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TALN research group at LS2N lab 11

31703611

Recommendations for performance optimizations when using GATK3.8 and GATK4.

BACKGROUND Use of the Genome Analysis Toolkit (GATK) continues to be the standard practice in genomic variant calling in both research and the clinic. Recently the toolkit has been rapidly evolving. Significant computational performance improvements have been introduced in GATK3.8 through collaboration with Intel in 2017. The first release of GATK4 in early 2018 revealed rewrites in the code base, as the stepping stone toward a Spark implementation. As the software continues to be a moving target for optimal deployment in highly productive environments, we present a detailed analysis of these improvements, to help the community stay abreast with changes in performance. RESULTS We re-evaluated multiple options, such as threading, parallel garbage collection, I/O options and data-level parallelization. Additionally, we considered the trade-offs of using GATK3.8 and GATK4. We found optimized parameter values that reduce the time of executing the best practices variant calling procedure by 29.3% for GATK3.8 and 16.9% for GATK4. Further speedups can be accomplished by splitting data for parallel analysis, resulting in run time of only a few hours on whole human genome sequenced to the depth of 20X, for both versions of GATK. Nonetheless, GATK4 is already much more cost-effective than GATK3.8. Thanks to significant rewrites of the algorithms, the same analysis can be run largely in a single-threaded fashion, allowing users to process multiple samples on the same CPU. CONCLUSIONS In time-sensitive situations, when a patient has a critical or rapidly developing condition, it is useful to minimize the time to process a single sample. In such cases we recommend using GATK3.8 by splitting the sample into chunks and computing across multiple nodes. The resultant walltime will be nnn.4 hours at the cost of $41.60 on 4 c5.18xlarge instances of Amazon Cloud. For cost-effectiveness of routine analyses or for large population studies, it is useful to maximize the number of samples processed per unit time. Thus we recommend GATK4, running multiple samples on one node. The total walltime will be ∼34.1 hours on 40 samples, with 1.18 samples processed per hour at the cost of $2.60 per sample on c5.18xlarge instance of Amazon Cloud.

['Heldenbrand|Jacob R|JR|', 'Baheti|Saurabh|S|', 'Bockol|Matthew A|MA|', 'Drucker|Travis M|TM|', 'Hart|Steven N|SN|', 'Hudson|Matthew E|ME|', 'Iyer|Ravishankar K|RK|', 'Kalmbach|Michael T|MT|', 'Kendig|Katherine I|KI|', 'Klee|Eric W|EW|', 'Mattson|Nathan R|NR|', 'Wieben|Eric D|ED|', 'Wiepert|Mathieu|M|', 'Wildman|Derek E|DE|', 'Mainzer|Liudmila S|LS|http://orcid.org/0000-0001-7121-0214']

2019

27338850

Diffusion-weighted magnetic resonance imaging predicts malignant potential in small hepatocellular carcinoma.

BACKGROUND Poor differentiation and microvascular invasion are indicators of poor outcome after hepatectomy for patients with small hepatocellular carcinoma (HCC). AIMS We investigated whether gadoxetic acid-enhanced and diffusion-weighted magnetic resonance imaging (MRI) could predict these factors before hepatectomy. METHODS Between July 2008 and April 2012, 75 patients who underwent hepatectomy for small HCCs (diameter: ≤3cm, tumor number: ≤3) were consecutively enrolled. In gadoxetic acid-enhanced MRI, the signal intensity in the tumor was corrected to that in the paraspinous muscles, and the relative enhancement was calculated. In diffusion-weighted imaging, we measured the apparent diffusion coefficient (ADC). We then investigated the correlations between relative enhancement or ADC and histological grade, microvascular invasion and recurrence-free survival. RESULTS Poorly differentiated HCCs showed significantly lower ADC than well-differentiated and moderately differentiated HCCs. There was no significant difference in the hepatobiliary phase. Only ADC was an independent predictor of microvascular invasion, and the best cut-off point of its prediction was 1.175×10(-3)mm(2)/s. Additionally, the recurrence-free survival was significantly shorter in low-ADC group than in high-ADC group. CONCLUSION ADC is useful for predicting poorly differentiated HCCs and microvascular invasion, and low ADC is associated with increased recurrence risk for small HCCs after hepatectomy.

['Okamura|Shusuke|S|', 'Sumie|Shuji|S|', 'Tonan|Tatsuyuki|T|', 'Nakano|Masahito|M|', 'Satani|Manabu|M|', 'Shimose|Shigeo|S|', 'Shirono|Tomotake|T|', 'Iwamoto|Hideki|H|', 'Aino|Hajime|H|', 'Niizeki|Takashi|T|', 'Tajiri|Nobuyoshi|N|', 'Kuromatsu|Ryoko|R|', 'Okuda|Koji|K|', 'Nakashima|Osamu|O|', 'Torimura|Takuji|T|']

2016

29961655

Utility of narrow band imaging in the diagnosis of middle turbinate head edema.

PURPOSE Middle turbinate head edema has recently been found to have high specificity for diagnosis of inhalant allergy. However, subtle mucosal edema can be difficult to appreciate under white light endoscopy. Narrow band imaging (NBI) has the potential to demonstrate edema by identifying reduced mucosal vascularity and improve sensitivity for the detection of mucosal edema. Narrow band imaging was assessed to determine its utility in objectifying mucosal edema. MEATERIALS AND METHODS A cross-sectional diagnostic study was performed on patients with edematous mucosa of the middle turbinate head. Under traditional white light endoscopy, areas of edematous mucosa were identified. Using NBI, these areas were compared to areas of normal mucosa on the middle turbinate head. NBI images of these same areas were then converted to grey scale and a vascularity index was created by pixel analysis and brightness in Fiji Image J software (Wisconsin, US). RESULTS Thirty-three middle turbinates were assessed (age 42.4 ± 12.5, 42.4% female). NBI discriminated between areas identified under white light endoscopy as edematous and normal (158.2 ± 48.4 v 96.9 ± 32.7 p < 0.01). Receiver operating curve (ROC) analysis suggested a threshold of 115 brightness units to define endoscopically visible edematous mucosa with sensitivity 70% and specificity 79% (ROC AUC, p = 0.85). CONCLUSIONS NBI can differentiate edematous from normal mucosa. The potential for an objective measure of mucosal edema may assist research efforts and may provide a more sensitive tool for subtle mucosal inflammatory changes.

['Wong|Eugene|E|', 'Hamizan|Aneeza W|AW|', 'Alvarado|Raquel|R|', 'Orgain|Carolyn A|CA|', 'Kalish|Larry|L|', 'Sacks|Raymond|R|', 'Harvey|Richard J|RJ|']

2018

31900651

Current issues and perspectives in PD-1 blockade cancer immunotherapy.

Programmed cell death 1 (PD-1) signal receptor blockade has revolutionized the field of cancer therapy. Despite their considerable potential for treating certain cancers, drugs targeting PD-1 still present two main drawbacks: the substantial number of unresponsive patients and/or patients showing recurrences, and side effects associated with the autoimmune response. These drawbacks highlight the need for further investigation of the mechanisms underlying the therapeutic effects, as well as the need to develop novel biomarkers to predict the lack of treatment response and to monitor potential adverse events. Combination therapy is a promising approach to improve the efficacy of PD-1 blockade therapy. Considering the increasing number of patients with cancer worldwide, solving the above issues is central to the field of cancer immunotherapy. In this review, we discuss these issues and clinical perspectives associated with PD-1 blockade cancer immunotherapy.

['Chamoto|Kenji|K|', 'Hatae|Ryusuke|R|', 'Honjo|Tasuku|T|']

2020

29366431

Prednisolone Effects on Urine Cross-Linked N-Telopeptides of Type I Collagen (Ntx) Diurnal Rhythms in Children.

BACKGROUND Recently, methods for mimicking endogenous cortisol rhythms hereby potentially reducing the risk of systemic adverse effects of exogenous corticosteroids have been patented. Methods for sensitive detection of adverse effects on bone turnover of various doses, administration routes and regimens of exogenous corticosteroids have been patented. Urine cross-linked Ntelopeptides of Type I collagen (Ntx) have been established as a sensitive bone resorption marker and urine levels of Ntx have been found to exhibit a distinct diurnal rhythm. OBJECTIVE To assess whether the timing of administration of prednisolone affects the diurnal rhythm of Ntx in urine. METHODS Four girls and four boys aged 10.6 to 15.8 (mean 13.2) years with normal weight and height and pubertal stages I-IV were studied in an open randomized 2-periods cross-over trial, with a 1-day run in, and two 4-day periods of 5mg prednisolone in the morning and in the evening, respectively, separated by a 3-week washout period. At run in and on the last day of each treatment period, the first sample of urine was collected from 24.00 to 08.00h in the morning of the day of investigation. Thereafter, urine was collected in 4~hour intervals until 24.00 and in another 08.00h interval from 24.00 to 08.00h. RESULTS Compared to run in and morning prednisolone treatment urine Ntx levels were suppressed from 24.00 to 8.00h during treatment with prednisolone in the evening (P < 0.01 for both comparisons) and no statistically significant circadian rhythm was observed. During morning prednisolone treatment Ntx trough and peak levels occurred from 16.00 to 20.00 and 24.00 to 08.00h, respectively, and the Ntx levels were significantly reduced from 12.00 to 20.00h as compared to run in (P < 0.005) and prednisolone treatment in the evening (P < 0.01). CONCLUSIONS Depending on the time of administration, prednisolone interferes with diurnal rhythms in urine Ntx.

['Wolthers|Ole D|OD|', 'Heuck|Carsten|C|']

2018

31616540

Using induced pluripotent stem cells for modeling Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative disease caused by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. As DA neurons degenerate, PD patients gradually lose their ability of movement. To date no effective therapies are available for the treatment of PD and its pathogenesis remains unknown. Experimental models that appropriately mimic the development of PD are certainly needed for gaining mechanistic insights into PD pathogenesis and identifying new therapeutic targets. Human induced pluripotent stem cells (iPSCs) could provide a promising model for fundamental research and drug screening. In this review, we summarize various iPSCs-based PD models either derived from PD patients through reprogramming technology or established by gene-editing technology, and the promising application of iPSC-based PD models for mechanistic studies and drug testing.

['Ke|Minjing|M|', 'Chong|Cheong-Meng|CM|', 'Su|Huanxing|H|']

2019

26198278

Atypical presentation of moyamoya disease in an infant with a de novo RNF213 variant.

Variants in RNF213 lead to susceptibility to moyamoya disease, a rare cerebral angiopathy characterized by bilateral stenosis of the internal carotid arteries and development of a compensatory collateral network. We describe a 3-month-old female with seizures, arterial narrowing involving the internal carotid and intracranial arteries and inferior abdominal aorta, and persistently elevated transaminases. Whole exome sequencing demonstrated a novel de novo variant in RNF213, securing a molecular diagnosis and directing appropriate intervention. This report underscores the role of whole exome sequencing in cases for which a complex and atypical presentation may mask diagnosis. Furthermore, the early and severe presentation in our patient, in conjunction with a novel de novo RNF213 variant, suggests that specific variants in RNF213 may lead to a Mendelian form of disease rather than simply conferring susceptibility to multifactorial disease.

['Harel|Tamar|T|', 'Posey|Jennifer E|JE|', 'Graham|Brett H|BH|', 'Walkiewicz|Magdalena|M|', 'Yang|Yaping|Y|', 'Lalani|Seema R|SR|', 'Belmont|John W|JW|']

2015

33563567

The voices of people with an intellectual disability and a carer about orthopaedic and trauma hospital care in the UK: An interpretative phenomenological study.

INTRODUCTION People with intellectual disabilities have a greater prevalence of musculoskeletal conditions and injuries than the general population. Orthopaedic and trauma hospital care has not been investigated with this group who seldom have their voices heard or their experiences valued and interpreted. AIM To understand the orthopaedic and trauma hospital experiences from the perspective of people with intellectual disabilities. METHODS A qualitative approach, focusing on peoples' lived experiences was utilised. A purposive sample of five participants was recruited and one-to-one, semi-structured interviews were undertaken. Analysis of the interviews employed an interpretative phenomenological analytical framework. FINDINGS There were communication challenges, a lack of person-centred care, issues with pain management, a lack of confidence in hospital care, valuable support and expertise of carers, incompetence of hospital staff and isolation and loneliness. DISCUSSION AND CONCLUSIONS There were significant short comings as people with intellectual disabilities and a carer perceived they were unsupported and received poor care. Recommendations for practice: Person-centred care is needed along with specific education and training, including close liaison with the experts by experience - people with intellectual disabilities, their carers as well as the specialists in intellectual disability.

['Drozd|Mary|M|', 'Chadwick|Darren|D|', 'Jester|Rebecca|R|']

2021

34800719

KIF11, a plus end-directed kinesin, as a key gene in benzo(a)pyrene-induced non-small cell lung cancer.

Evidence indicates that Benzo(a)pyrenediol-epoxide (BPDE) can damage lung cells, resulting in carcinogenesis with complex mechanisms. We aimed to explore the genes and pathway variations in this process. First, the key gene was screened out and identified through data mining, and then, it was in turn validated by bioinformatics analysis and experimental methods. Consequently, 106 up-regulated and 260 down-regulated differentially expressed genes were yielded, which were enriched in various pathways, such as Cell cycle, and p53 signaling pathway. Then, KIF11 was identified as the key gene. Overexpression of KIF11 in lung cancer had a correlation with advanced pathological grade, advanced T stage, and presence of lymph node metastasis, which predicted poor prognosis. In summary, the present study revealed that KIF11 might be a key gene in the tumorigenesis of BPDE-related lung cancer, raising the possibility of KIF11 as a target for BPDE-induced lung cancer prevention and therapy.

['Ling|Junjun|J|', 'Wang|Yuhong|Y|', 'Ma|Lihai|L|', 'Zheng|Yu|Y|', 'Tang|Hongqu|H|', 'Meng|Lingzhan|L|', 'Zhang|Liang|L|']

2021

31595877

Antenatal HIV screening: results from the National Perinatal Survey, France, 2016.

BackgroundUniversal antenatal HIV screening programmes are an effective method of preventing mother-to-child transmission.AimsTo assess the coverage and yield of the French programme on a nationally representative sample of pregnant women, and predictive factors for being unscreened or missing information on the performance/ result of a HIV test.MethodsData came from the medical records of women included in the cross-sectional 2016 French National Perinatal Survey. We calculated odds ratios (OR) to identify factors for being unscreened for HIV and for missing information by multivariable analyses.ResultsOf 13,210 women, 12,782 (96.8%) were screened for HIV and 134 (1.0%) were not; information was missing for 294 (2.2%). HIV infection was newly diagnosed in 19/12,769 (0.15%) women screened. The OR for being unscreened was significantly higher in women in legally registered partnerships (OR: 1.3; 95% CI: 1.1-1.6), with 1-2 years of post-secondary schooling (OR: 1.6; 95% CI: 1.2-2.1), part-time employment (OR: 1.4; 95% CI: 1.1-1.8), inadequate antenatal care (OR: 1.9; 95% CI: 1.5-2.4) and receiving care from > 1 provider (OR: 1.8; 95% CI: 1.1-2.8). The OR of missing information was higher in multiparous women (OR: 1.4; 95% CI: 1.2-1.5) and women cared for by general practitioners (OR: 1.4; 95% CI: 1.1-1.9).ConclusionsThe French antenatal HIV screening programme is effective in detecting HIV among pregnant women. However, a few women are still not screened and awareness of the factors that predict this could contribute to improved screening levels.

['Tran|Thi-Chiên|TC|', 'Pillonel|Josiane|J|', 'Cazein|Françoise|F|', 'Sommen|Cécile|C|', 'Bonnet|Camille|C|', 'Blondel|Béatrice|B|', 'Lot|Florence|F|']

2019

31807400

Nitrogen-vacancy centers in diamond for nanoscale magnetic resonance imaging applications.

The nitrogen-vacancy (NV) center is a point defect in diamond with unique properties for use in ultra-sensitive, high-resolution magnetometry. One of the most interesting and challenging applications is nanoscale magnetic resonance imaging (nano-MRI). While many review papers have covered other NV centers in diamond applications, there is no survey targeting the specific development of nano-MRI devices based on NV centers in diamond. Several different nano-MRI methods based on NV centers have been proposed with the goal of improving the spatial and temporal resolution, but without any coordinated effort. After summarizing the main NV magnetic imaging methods, this review presents a survey of the latest advances in NV center nano-MRI.

['Boretti|Alberto|A|https://orcid.org/0000-0002-3374-0238', 'Rosa|Lorenzo|L|https://orcid.org/0000-0002-9210-5680', 'Blackledge|Jonathan|J|', 'Castelletto|Stefania|S|']

2019

29288110

Cerebral Radiation Necrosis: An Analysis of Clinical and Quantitative Imaging and Volumetric Features.

BACKGROUND Radiation therapy is an effective treatment for primary brain tumors and intracranial metastases but can occasionally precede new enhancing lesions on imaging studies that are difficult to discern between tumor recurrence (TR) and radiation necrosis (RN). The aim of this study was to identify clinical presentation and imaging patterns of RN compared with TR that may obviate the need for invasive definitive biopsy. METHODS Patients who received radiation therapy and subsequently presented with a new intracranial lesion were reviewed from 2001 to 2016; 27 patients were identified with adequate records and confirmed pathology to have RN present or TR only. Patient and lesion characteristics were assessed using univariate and multivariate logistic regression analyses. Sensitivity and specificities were calculated for imaging features and quantitatively segmented lesion and edema volumes for identifying RN. RESULTS Karnofsky performance scale score at presentation significantly predicted pathologic diagnosis on univariate analysis (P = 0.044). Radiation dosage and time from radiation therapy to lesion onset did not differ among pathologic diagnosis groups. No differences existed between RN and TR on quantitative imaging analyses. Multivariate logistic regression found higher Karnofsky performance scale score to be an independent factor associated with TR relative to RN (odds ratio 1.26, 95% confidence interval 1.02-1.56, P = 0.030). CONCLUSIONS Diagnostic imaging can often be inaccurate in detecting RN alone, even with quantitative volume assessment. Functional status on repeat presentation may increase the likelihood of accurate diagnosis before definitive biopsy when neuroimaging remains unclear.

['Feng|Rui|R|', 'Loewenstern|Joshua|J|', 'Aggarwal|Amit|A|', 'Pawha|Puneet|P|', 'Gilani|Ahmed|A|', 'Iloreta|Alfred Marc|AM|', 'Bakst|Richard|R|', 'Miles|Brett|B|', 'Bederson|Joshua|J|', 'Costa|Anthony|A|', 'Gupta|Vishal|V|', 'Shrivastava|Raj K|RK|']

2018

33877641

#SayHerName: Should Obstetrics and Gynecology Reckon with the Legacy of JM Sims?

Dr. James Marion Sims has been heralded as the "father of modern gynecology" for his groundbreaking surgical technique to repair post-partum vesicovaginal fistulas (VVF); however, the ethical concerns around his inhumane practices and the contributions of the enslaved women he refined his technique on are rarely recognized. Acknowledging the personal sacrifice of the enslaved women and addressing the truth behind the immoral practices of Sims, encourages reconciliation of the race-based medical atrocities of the past and sets the tone for moral, more equitable medical care moving forward.

['Christmas|Monica|M|0000-0001-9640-2992']

2021

24892023

Effect of silica coating on bond strength between a gold alloy and metal bracket bonded with chemically cured resin.

OBJECTIVE The purpose of this study was to evaluate the effects of three different surface conditioning methods on the shear bond strength (SBS) of metal brackets bonded directly to gold alloy with chemically cured resin. METHODS Two hundred ten type III gold alloy specimens were randomly divided into six groups according to the combination of three different surface conditioning methods (aluminum oxide sandblasting only, application of a metal primer after aluminum oxide sandblasting, silica coating and silanation) and thermocycling (with thermocycling, without thermocycling). After performing surface conditioning of specimens in accordance with each experimental condition, metal brackets were bonded to all specimens using a chemically cured resin. The SBS was measured at the moment of bracket debonding, and the resin remnants on the specimen surface were evaluated using the adhesive remnant index. RESULTS Application of metal primer after aluminum oxide sandblasting yielded a higher bond strength than that with aluminum oxide sandblasting alone (p < 0.001), and silica coating and silanation yielded a higher bond strength than that with metal primer after aluminum oxide sandblasting (p < 0.001). There was no significant change in SBS after thermocycling in all groups. CONCLUSIONS With silica coating and silanation, clinically satisfactory bond strength can be attained when metal brackets are directly bonded to gold alloys using a chemically cured resin.

['Ryu|Min-Ju|MJ|', 'Gang|Sung-Nam|SN|', 'Lim|Sung-Hoon|SH|']

2014

34654485

Developing Personal Resilience Questionnaire for rural doctors: an indigenous approach study in Indonesia.

BACKGROUND Resilience is recognized as a critical component of well-being and is an essential factor in coping with stress. There are issues of using a standardized resilience scale developed for one cultural population to be used in the different cultural populations. This study aimed to create a specific measurement scale for measuring doctors' resilience levels in the rural Indonesian context. METHOD A total of 527 rural doctors and health professional educators joined this study (37 and 490 participants in the pilot studies and the survey, respectively). An indigenous psychological approach was implemented in linguistic and cultural adaptation and validation of an existing instrument into the local Indonesian rural health context. A combined method of back-translation, committee approach, communication with the original author, and exploratory qualitative study in the local context was conducted. The indigenous psychological approach was implemented in exploring the local context and writing additional local items. RESULT The final questionnaire consisted of six dimensions and 30 items with good internal consistency (Cronbach's α ranged 0.809-0.960 for each dimension). Ten locally developed items were added to the final questionnaire as a result of the indigenous psychological approach. CONCLUSION An indigenous psychological approach may enrich the linguistic and cultural adaptation and validation process of an existing scale.

['Handoyo|Nicholas Edwin|NE|http://orcid.org/0000-0002-9191-518X', 'Rahayu|Gandes Retno|GR|', 'Claramita|Mora|M|', 'Keraf|Marselino K P Abdi|MKPA|', 'Octrisdey|Karol|K|', 'Yuniarti|Kwartarini Wahyu|KW|', 'Ash|Julie|J|', 'Schuwirth|Lambert|L|']

2021

23550921

α-Amylase is a potential growth inhibitor of Porphyromonas gingivalis, a periodontal pathogenic bacterium.

BACKGROUND AND OBJECTIVE Porphyromonas gingivalis is a major etiological agent in the development and progression of periodontal diseases. In this study, we isolated a cell growth inhibitor against P. gingivalis species from rice protein extract. MATERIAL AND METHODS The cell growth inhibitor active against P. gingivalis was purified from polished rice extract using a six-step column chromatography process. Its antimicrobial properties were investigated through microscope analysis, spectrum of activity and general structure. RESULTS The inhibitor was identified as AmyI-1, an α-amylase, and showed significant cell growth inhibitory activity against P. gingivalis species. Scanning electron microscopy micrograph analysis and bactericidal assay indicated an intriguing possibility that the inhibitor compromises the cell membrane structure of the bacterial cells and leads to cell death. Moreover, α-amylases from human saliva and porcine pancreas showed inhibitory activity similar to that of AmyI-1. CONCLUSIONS This is the first study to report that α-amylases cause cell death of periodontal pathogenic bacteria. This finding highlights the potential importance and therapeutic potential of α-amylases in treating periodontal diseases.

['Ochiai|A|A|', 'Harada|K|K|', 'Hashimoto|K|K|', 'Shibata|K|K|', 'Ishiyama|Y|Y|', 'Mitsui|T|T|', 'Tanaka|T|T|', 'Taniguchi|M|M|']

2014

34430825

Update on the safety of anesthesia in young children presenting for adenotonsillectomy.

Tonsillectomy with and without adenoidectomy is a frequently performed surgical procedure in children. Although a common procedure, it is not without significant risk. It is critical for anesthesiologists to consider preoperative, intraoperative, and postoperative patient factors and events to optimize safety, especially in young children. In the majority of cases, the indication for adenotonsillectomy in young children is obstructive breathing. Preoperative evaluation for patient comorbidities, especially obstructive sleep apnea, risk factors for a difficult airway, and history of recent illness are crucial to prepare the patient for surgery and develop an anesthetic plan. Communication and collaboration with the otolaryngologist is key to prevent and treat intraoperative events such as airway fires or hemorrhage. Postoperative analgesia planning is critical for safe pain control especially for those patients with a history of obstructive sleep apnea and opioid sensitivity. In young children, it is important to also consider the impact of anesthetic medications on the developing brain. This is an area of continuing research but needs to be weighed when planning for surgical treatment and when discussing risks and benefits with patients' families.

['McGuire|Stephanie R|SR|', 'Doyle|Nichole M|NM|']

2021

30853728

Drought attenuates the impact of fish on aquatic macroinvertebrate richness and community composition.

Identifying ecological niche filters that shape species community composition is a critical first step in understanding the relative contributions of deterministic and stochastic processes in structuring communities. Systems with harsh ecological filters often have a more deterministic basis to community structure. Although these filters are often treated as static, investigations into their stability through time are rare, particularly in combination with extreme forms of environmental change such as drought.We examined the richness and composition of aquatic macroinvertebrate communities from 36 ponds over four years during the onset of a megadrought to answer the following questions: (1) what are the relative influences of non-native fish presence and pond permanence in structuring communities? And (2) how do the magnitudes of such filters vary through time?As predicted, fish presence had a strong, negative effect on both alpha and gamma diversity, lowering average invertebrate richness in pond communities by 23%. However, fish presence and sample year interacted to determine both richness and taxa composition: as drought conditions intensified, the effects of fish weakened such that there were no differences in the richness or composition between fish and fishless ponds by the later sampling years. Moreover, large-bodied invertebrate groups - often considered highly vulnerable to fish predation - were detected within fish-occupied sites by the final year of the study.This pattern was associated with progressive decreases in precipitation due to a severe drought in California, emphasizing the importance of exogenous, regional factors in moderating the strength of biotic niche filters on local community structure over time. Given that all detected fish species were non-native, these results also have application to understanding and forecasting changes in the diversity of native insects and other aquatic invertebrates.

['McDevitt-Galles|Travis|T|0000-0002-4929-5431', 'Johnson|Pieter T J|PTJ|']

2018

25995653

Effects of training and anthropometric factors on marathon and 100 km ultramarathon race performance.

BACKGROUND Marathon (42 km) and 100 km ultramarathon races are increasing in popularity. The aim of the present study was to investigate the potential associations of anthropometric and training variables with performance in these long-distance running competitions. METHODS Training and anthropometric data from a large cohort of marathoners and 100 km ultramarathoners provided the basis of this work. Correlations between training and anthropometric indices of subjects and race performance were assessed using bivariate and multiple regression analyses. RESULTS A combination of volume and intensity in training was found to be suitable for prediction of marathon and 100 km ultramarathon race pace. The relative role played by these two variables was different, in that training volume was more important than training pace for the prediction of 100 km ultramarathon performance, while the opposite was found for marathon performance. Anthropometric characteristics in terms of body fat percentage negatively affected 42 km and 100 km race performance. However, when this factor was relatively low (ie, less than 15% body fat), the performance of 42 km and 100 km races could be predicted solely on the basis of training indices. CONCLUSION Mean weekly training distance run and mean training pace were key predictor variables for both marathon and 100 km ultramarathon race performance. Predictive correlations for race performance are provided for runners with a relatively low body fat percentage.

['Tanda|Giovanni|G|', 'Knechtle|Beat|B|']

2015

33198737

DNA sequencing of anatomy lab cadavers to provide hands-on precision medicine introduction to medical students.

BACKGROUND Medical treatment informed by Precision Medicine is becoming a standard practice for many diseases, and patients are curious about the consequences of genomic variants in their genome. However, most medical students' understanding of Precision Medicine derives from classroom lectures. This format does little to foster an understanding for the potential and limitations of Precision Medicine. To close this gap, we implemented a hands-on Precision Medicine training program utilizing exome sequencing to prepare a clinical genetic report of cadavers studied in the anatomy lab. The program reinforces Precision Medicine related learning objectives for the Genetics curriculum. METHODS Pre-embalmed blood samples and embalmed tissue were obtained from cadavers (donors) used in the anatomy lab. DNA was isolated and sequenced and illustrative genetic reports provided to the students. The reports were used to facilitate discussion with students on the implications of pathogenic genomic variants and the potential correlation of these variants in each "donor" with any anatomical anomalies identified during cadaver dissection. RESULTS In 75% of cases, analysis of whole exome sequencing data identified a variant associated with increased risk for a disease/abnormal condition noted in the donor's cause of death or in the students' anatomical findings. This provided students with real-world examples of the potential relationship between genomic variants and disease risk. Our students also noted that diseases associated with 92% of the pathogenic variants identified were not related to the anatomical findings, demonstrating the limitations of Precision Medicine. CONCLUSION With this study, we have established protocols and classroom procedures incorporating hands-on Precision Medicine training in the medical student curriculum and a template for other medical educators interested in enhancing their Precision Medicine training program. The program engaged students in discovering variants that were associated with the pathophysiology of the cadaver they were studying, which led to more exposure and understanding of the potential risks and benefits of genomic medicine.

['Anandakrishnan|Ramu|R|', 'Carpenetti|Tiffany L|TL|', 'Samuel|Peter|P|', 'Wasko|Breezy|B|', 'Johnson|Craig|C|', 'Smith|Christy|C|', 'Kim|Jessica|J|', 'Michalak|Pawel|P|', 'Kang|Lin|L|', 'Kinney|Nick|N|', 'Santo|Arben|A|', 'Anstrom|John|J|', 'Garner|Harold R|HR|', 'Varghese|Robin T|RT|http://orcid.org/0000-0001-6244-8220']

2020

25999828

Pre-stimulus BOLD-network activation modulates EEG spectral activity during working memory retention.

Working memory (WM) processes depend on our momentary mental state and therefore exhibit considerable fluctuations. Here, we investigate the interplay of task-preparatory and task-related brain activity as represented by pre-stimulus BOLD-fluctuations and spectral EEG from the retention periods of a visual WM task. Visual WM is used to maintain sensory information in the brain enabling the performance of cognitive operations and is associated with mental health. We tested 22 subjects simultaneously with EEG and fMRI while performing a visuo-verbal Sternberg task with two different loads, allowing for the temporal separation of preparation, encoding, retention and retrieval periods. Four temporally coherent networks (TCNs)-the default mode network (DMN), the dorsal attention, the right and the left WM network-were extracted from the continuous BOLD data by means of a group ICA. Subsequently, the modulatory effect of these networks' pre-stimulus activation upon retention-related EEG activity in the theta, alpha, and beta frequencies was analyzed. The obtained results are informative in the context of state-dependent information processing. We were able to replicate two well-known load-dependent effects: the frontal-midline theta increase during the task and the decrease of pre-stimulus DMN activity. As our main finding, these two measures seem to depend on each other as the significant negative correlations at frontal-midline channels suggested. Thus, suppressed pre-stimulus DMN levels facilitated later task related frontal midline theta increases. In general, based on previous findings that neuronal coupling in different frequency bands may underlie distinct functions in WM retention, our results suggest that processes reflected by spectral oscillations during retention seem not only to be "online" synchronized with activity in different attention-related networks but are also modulated by activity in these networks during preparation intervals.

['Kottlow|Mara|M|', 'Schlaepfer|Anthony|A|', 'Baenninger|Anja|A|', 'Michels|Lars|L|', 'Brandeis|Daniel|D|', 'Koenig|Thomas|T|']

2015

29378821

Anterior Pituitary Transcriptome Suggests Differences in ACTH Release in Tame and Aggressive Foxes.

Domesticated species exhibit a suite of behavioral, endocrinological, and morphological changes referred to as "domestication syndrome." These changes may include a reduction in reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and specifically reduced adrenocorticotropic hormone release from the anterior pituitary. To investigate the biological mechanisms targeted during domestication, we investigated gene expression in the pituitaries of experimentally domesticated foxes (Vulpes vulpes). RNA was sequenced from the anterior pituitary of six foxes selectively bred for tameness ("tame foxes") and six foxes selectively bred for aggression ("aggressive foxes"). Expression, splicing, and network differences identified between the two lines indicated the importance of genes related to regulation of exocytosis, specifically mediated by cAMP, organization of pseudopodia, and cell motility. These findings provide new insights into biological mechanisms that may have been targeted when these lines of foxes were selected for behavior and suggest new directions for research into HPA axis regulation and the biological underpinnings of domestication.

['Hekman|Jessica P|JP|0000-0002-7296-8307', 'Johnson|Jennifer L|JL|', 'Edwards|Whitney|W|', 'Vladimirova|Anastasiya V|AV|', 'Gulevich|Rimma G|RG|', 'Ford|Alexandra L|AL|', 'Kharlamova|Anastasiya V|AV|', 'Herbeck|Yury|Y|', 'Acland|Gregory M|GM|', 'Raetzman|Lori T|LT|', 'Trut|Lyudmila N|LN|', 'Kukekova|Anna V|AV|0000-0001-7027-3715']

2018

27282083

Search for a reliable model for bisphosphonate-related osteonecrosis of the jaw: establishment of a model in pigs and description of its histomorphometric characteristics.

The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains unknown, and the development of a reliable experimental model would help to improve our understanding of it. We used 12 domestic pigs of which 6 made up the experimental group and were treated with zoledronate 4mg intravenously weekly for 5 weeks, while the control group (n=6) were given no drugs. On day 60 the right second maxillary and mandibular third molars were extracted. Thirty days later 3 animals in each group were killed; the rest were killed 90 days later. Histopathological specimens from the extraction sites were analysed for bone density, collagen architecture, density of osteons, and the amount of non-mineralised bone. Bone density, amount of non-mineralised bone, and density of osteons differed significantly between the 2 groups (p<0.001 in each case), but the chromatic pattern dictated by the collagen architecture did not. Our results correspond to the observations that have been made in patients with BRONJ, which means that the histomorphometric conditions seen in patients can be reproduced in this experimental setting.

['Mitsimponas|K T|KT|', 'Moest|T|T|', 'Iliopoulos|C|C|', 'Rueger|T|T|', 'Mueller|C|C|', 'Lutz|R|R|', 'Shakib|K|K|', 'Neukam|F W|FW|', 'Schlegel|K A|KA|']

2016

30619231

Iron Regulation in Clostridioides difficile.

The response to iron limitation of several bacteria is regulated by the ferric uptake regulator (Fur). The Fur-regulated transcriptional, translational and metabolic networks of the Gram-positive, pathogen Clostridioides difficile were investigated by a combined RNA sequencing, proteomic, metabolomic and electron microscopy approach. At high iron conditions (15 μM) the C. difficile fur mutant displayed a growth deficiency compared to wild type C. difficile cells. Several iron and siderophore transporter genes were induced by Fur during low iron (0.2 μM) conditions. The major adaptation to low iron conditions was observed for the central energy metabolism. Most ferredoxin-dependent amino acid fermentations were significantly down regulated (had, etf, acd, grd, trx, bdc, hbd). The substrates of these pathways phenylalanine, leucine, glycine and some intermediates (phenylpyruvate, 2-oxo-isocaproate, 3-hydroxy-butyryl-CoA, crotonyl-CoA) accumulated, while end products like isocaproate and butyrate were found reduced. Flavodoxin (fldX) formation and riboflavin biosynthesis (rib) were enhanced, most likely to replace the missing ferredoxins. Proline reductase (prd), the corresponding ion pumping RNF complex (rnf) and the reaction product 5-aminovalerate were significantly enhanced. An ATP forming ATPase (atpCDGAHFEB) of the F0F1-type was induced while the formation of a ATP-consuming, proton-pumping V-type ATPase (atpDBAFCEKI) was decreased. The [Fe-S] enzyme-dependent pyruvate formate lyase (pfl), formate dehydrogenase (fdh) and hydrogenase (hyd) branch of glucose utilization and glycogen biosynthesis (glg) were significantly reduced, leading to an accumulation of glucose and pyruvate. The formation of [Fe-S] enzyme carbon monoxide dehydrogenase (coo) was inhibited. The fur mutant showed an increased sensitivity to vancomycin and polymyxin B. An intensive remodeling of the cell wall was observed, Polyamine biosynthesis (spe) was induced leading to an accumulation of spermine, spermidine, and putrescine. The fur mutant lost most of its flagella and motility. Finally, the CRISPR/Cas and a prophage encoding operon were downregulated. Fur binding sites were found upstream of around 20 of the regulated genes. Overall, adaptation to low iron conditions in C. difficile focused on an increase of iron import, a significant replacement of iron requiring metabolic pathways and the restructuring of the cell surface for protection during the complex adaptation phase and was only partly directly regulated by Fur.

['Berges|Mareike|M|', 'Michel|Annika-Marisa|AM|', 'Lassek|Christian|C|', 'Nuss|Aaron M|AM|', 'Beckstette|Michael|M|', 'Dersch|Petra|P|', 'Riedel|Katharina|K|', 'Sievers|Susanne|S|', 'Becher|Dörte|D|', 'Otto|Andreas|A|', 'Maaß|Sandra|S|', 'Rohde|Manfred|M|', 'Eckweiler|Denitsa|D|', 'Borrero-de Acuña|Jose M|JM|', 'Jahn|Martina|M|', 'Neumann-Schaal|Meina|M|', 'Jahn|Dieter|D|']

2018

27552340

Symptoms of Depression, Positive Symptoms of Psychosis, and Suicidal Ideation Among Adults Diagnosed With Schizophrenia Within the Clinical Antipsychotic Trials of Intervention Effectiveness.

Suicide is among leading causes of death for adults diagnosed with schizophrenia. While symptoms of depression are consistently supported factors involved in suicidal ideation, findings on the role of positive symptoms of psychosis have been mixed with limited understandings of risk. Accordingly, this study aimed to identify the pathways of influence between symptoms of depression, positive symptoms of psychosis (i.e. hallucinations and delusions), and suicidal ideation. Data were obtained from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE; n = 1,460). Suicidal ideation and symptoms of depression were measured by the Calgary Depression Scale (CDRS) and hallucinations and delusions by the Positive and Negative Syndrome Scale (PANSS). The data were analyzed using Structural Equation Modeling (SEM). As symptoms of depression and positive symptoms of psychosis independently increased, on average there were associated increases in suicidal ideation. The present study provides support for the relationship between positive symptoms of psychosis, specifically hallucinations and delusions, and suicidal ideation. Future prospective longitudinal study designs are needed to further increase understandings of the roles that hallucinations, delusions, and additional symptoms of schizophrenia play in both suicidal ideation and attempt to ultimately inform evidence-based interventions aiming to reduce suicidal death.

['Bornheimer|Lindsay A|LA|', 'Jaccard|James|J|']

2017

34813063

Expression and In Vivo Loading of De Novo Proteins with Tetrapyrrole Cofactors.

Tetrapyrrole cofactors such as heme and chlorophyll imprint their intrinsic reactivity and properties on a multitude of natural proteins and enzymes, and there is much interest in exploiting their functional and catalytic capabilities within minimal, de novo designed protein scaffolds. Here we describe how, using only natural biosynthetic and post-translational modification pathways, de novo designed soluble and hydrophobic proteins can be equipped with tetrapyrrole cofactors within living Escherichia coli cells. We provide strategies to achieve covalent and non-covalent heme incorporation within the de novo proteins and describe how the heme biosynthetic pathway can be co-opted to produce the light sensitive zinc protoporphyrin IX for loading into proteins in vivo. In addition, we describe the imaging of hydrophobic proteins and cofactor-rich protein droplets by electron and fluorescence microscopy, and how cofactors can be stripped from the de novo proteins to aid in vitro identification.

['Curnow|Paul|P|', 'Anderson|J L Ross|JLR|']

2022

34724097

Role of Akt isoforms in neuronal insulin signaling and resistance.

The aim of the present study was to determine the role of Akt isoforms in insulin signaling and resistance in neuronal cells. By silencing Akt isoforms individually and in pairs, in Neuro-2a and HT22 cells we observed that, in insulin-sensitive condition, Akt isoforms differentially reduced activation of AS160 and glucose uptake with Akt2 playing the major role. Under insulin-resistant condition, phosphorylation of all isoforms and glucose uptake were severely affected. Over-expression of individual isoforms in insulin-sensitive and resistant cells differentially reversed AS160 phosphorylation with concomitant reversal in glucose uptake indicating a compensatory role of Akt isoforms in controlling neuronal insulin signaling. Post-insulin stimulation Akt2 translocated to the membrane the most followed by Akt3 and Akt1, decreasing glucose uptake in the similar order in insulin-sensitive cells. None of the Akt isoforms translocated in insulin-resistant cells or high-fat-diet mediated diabetic mice brain cells. Based on our data, insulin-dependent differential translocation of Akt isoforms to the plasma membrane turns out to be the key factor in determining Akt isoform specificity. Thus, isoforms play parallel with predominant role by Akt2, and compensatory yet novel role by Akt1 and Akt3 to regulate neuronal insulin signaling, glucose uptake, and insulin-resistance.

['Sharma|Medha|M|', 'Dey|Chinmoy Sankar|CS|http://orcid.org/0000-0003-0667-915X']

2021

29749031

Amphiphilic Block Copolymers Directed Interface Coassembly to Construct Multifunctional Microspheres with Magnetic Core and Monolayer Mesoporous Aluminosilicate Shell.

Core-shell magnetic porous microspheres have wide applications in drug delivery, catalysis and bioseparation, and so on. However, it is great challenge to controllably synthesize magnetic porous microspheres with uniform well-aligned accessible large mesopores (>10 nm) which are highly desired for applications involving immobilization or adsorption of large guest molecules or nanoobjects. In this study, a facile and general amphiphilic block copolymer directed interfacial coassembly strategy is developed to synthesize core-shell magnetic mesoporous microspheres with a monolayer of mesoporous shell of different composition (FDUcs-17D), such as core-shell magnetic mesoporous aluminosilicate (CS-MMAS), silica (CS-MMS), and zirconia-silica (CS-MMZS), open and large pores by employing polystyrene-block-poly (4-vinylpyridine) (PS-b-P4VP) as an interface structure directing agent and aluminum acetylacetonate (Al(acac)3 ), zirconium acetylacetonate, and tetraethyl orthosilicate as shell precursors. The obtained CS-MMAS microspheres possess magnetic core, perpendicular mesopores (20-32 nm) in the shell, high surface area (244.7 m2 g-1 ), and abundant acid sites (0.44 mmol g-1 ), and as a result, they exhibit superior performance in removal of organophosphorus pesticides (fenthion) with a fast adsorption dynamics and high adsorption capacity. CS-MMAS microspheres loaded with Au nanoparticles (≈3.5 nm) behavior as a highly active heterogeneous nanocatalyst for N-alkylation reaction for producing N-phenylbenzylamine with a selectivity and yields of over 90% and good magnetic recyclability.

['Zhang|Yu|Y|', 'Yue|Qin|Q|', 'Yu|Lei|L|', 'Yang|Xuanyu|X|', 'Hou|Xiu-Feng|XF|', 'Zhao|Dongyuan|D|', 'Cheng|Xiaowei|X|', 'Deng|Yonghui|Y|http://orcid.org/0000-0002-0657-9397']

2018

24301325

Artesunate-amodiaquine combination therapy in the absence of malarial parasite infection induces oxidative damage in female rats.

Artesunate-amodiaquine is among the most widely available artemisinin combination therapy used as treatment regimen for uncomplicated Plasmodium falciparum malaria. Our aim was to evaluate clinical routine markers of liver and renal functions, lipid profile levels and lipid peroxidation status in a female mammalian rat model. This was an attempt to simulate a scenario where the drugs are taken without malarial parasite infection, which is a common practice in settings where drug misuse is a common practice. Twenty female Wistar rats were randomly divided into four study groups of five animals each. Group 1 (control) received distilled water, group 2 was exposed to artesunate [2 mg/kg body weight (b.w.)], group 3 was administered with amodiaquine (6.12 mg/kg b.w.) and group 4 was co-administered with artesunate (2 mg/kg b.w.) and amodiaquine (6.12 mg/kg b.w.) for 3 days. At the end of the treatment period, animals were fasted overnight and sacrificed. Markers of liver and renal functions and lipid profile indices were evaluated in the plasma, whereas lipid peroxidation status, GSH concentration and G6PD activity were assessed in the erythrocytes. The results showed that the co-administration of artesunate and amodiaquine altered liver function markers and lipid profile indices. The drugs also induced lipid peroxidation as evidenced by the elevated level of oxidative stress marker malondialdehyde (p < 0.05). We recommend therefore that the drugs should be taken with prescription only with clinical evidence of malarial parasite infection.

['Abolaji|Amos O|AO|', 'Osedeme|Fenose|F|', 'Olusemire|Oluwatosin|O|']

2014

26131613

Molecular Characterization of the Multidrug Resistant Escherichia coli ST131 Clone.

Escherichia coli ST131 is a recently emerged and globally disseminated multidrug resistant clone associated with urinary tract and bloodstream infections in both community and clinical settings. The most common group of ST131 strains are defined by resistance to fluoroquinolones and possession of the type 1 fimbriae fimH30 allele. Here we provide an update on our recent work describing the globally epidemiology of ST131. We review the phylogeny of ST131 based on whole genome sequence data and highlight the important role of recombination in the evolution of this clonal lineage. We also summarize our findings on the virulence of the ST131 reference strain EC958, and highlight the use of transposon directed insertion-site sequencing to define genes associated with serum resistance and essential features of its large antibiotic resistance plasmid pEC958.

['Schembri|Mark A|MA|', 'Zakour|Nouri L Ben|NL|', 'Phan|Minh-Duy|MD|', 'Forde|Brian M|BM|', 'Stanton-Cook|Mitchell|M|', 'Beatson|Scott A|SA|']

2015

34802898

Differentially expressed proteins in the interaction of Paracoccidioides lutzii with human monocytes.

BACKGROUND Fungi of the genus Paracoccidioides are the etiological agents of paracoccidioidomycosis, a highly prevalent mycosis in Latin America. Infection in humans occurs by the inhalation of conidia, which later revert to the form of yeast. In this context, macrophages are positioned as an important line of defense, assisting in the recognition and presentation of antigens, as well as producing reactive oxygen species that inhibit fungal spreading. AIMS The objective of this study was to identify differentially expressed proteins during the interaction between Paracoccidioides lutzii Pb01 strain and human U937 monocytes. METHODS Two-dimensional electrophoresis, combined with mass spectrometry, was used to evaluate the differential proteomic profiles of the fungus P. lutzii (Pb01) interacting with U937 monocytes. RESULTS It was possible to identify 25 proteins differentially expressed by Pb01 alone and after interacting with U937 monocytes. Most of these proteins are directly associated with fungal metabolism for energy generation, such as glyceraldehyde-3-phosphate dehydrogenase, and intracellular adaptation to monocytes. Antioxidant proteins involved in the response to oxidative stress, such as peroxiredoxin, cytochrome, and peroxidase, were expressed in greater quantity in the interaction with monocytes, suggesting their association with survival mechanisms inside phagocytic cells. We also identified 12 proteins differentially expressed in monocytes before and after the interaction with the fungus; proteins involved in the reorganization of the cytoskeleton, such as vimentin, and proteins involved in the response to oxidative stress, such as glioxalase 1, were identified. CONCLUSIONS The results of this proteomic study of a P. lutzii isolate are novel, mimicking in vitro what occurs in human infections. In addition, the proteins identified may aid to understand fungal-monocyte interactions and the pathogenesis of paracoccidioidomycosis.

['Oliveira|Flamélia Carla Silva|FCS|', 'Pessoa|Wallace Felipe Blohem|WFB|', 'Mares|Joise Hander|JH|', 'Freire|Herbert Pina Silva|HPS|', 'Souza|Ednara Almeida de|EA|', 'Pirovani|Carlos Priminho|CP|', 'Romano|Carla Cristina|CC|']

2021

33292673

Associations between animal and herd management factors, serological response to three respiratory pathogens and pluck lesions in finisher pigs on a farrow-to-finish farm.

BACKGROUND Serological screening is a common method to monitor antibody response to pathogen exposure, but results could vary due to several factors. This study aimed to quantify animal and management related factors associated with variation in antibody levels in finisher pigs at slaughter, in an Irish farrow-to-finish farm endemically infected with Actinobacillus pleuropneumonia (App), Mycoplasma hyopneumoniae (Mhyo) and swine influenza virus (SIV). A second objective was to estimate differences in antibody levels in pigs presenting pluck lesions. This was an observational study whereby pigs were managed as per routine farm practice. Data on sow parity, number of born alive (NBA) pigs per litter, cross-fostering status, birth and weaning body weight were recorded from 1016 pigs born from one farrowing batch. At slaughter, blood samples were collected for serological analysis and pigs were inspected for presence of enzootic pneumonia (EP)-like lesions, pleurisy, pericarditis and heart condemnations. Pigs were retrospectively classified into three production flows, depending on time spent in each production stage: flow 1 (F1; pigs followed the normal production flow); flow 2 (F2; pigs which were delayed by 1 week from advancing forward); and flow 3 (F3; pigs delayed by > 1 week from advancing forward). A nested case-control design was applied by matching pigs from each flow by sow parity, birth weight and NBA. RESULTS Pigs born from primiparous sows had higher antibody levels for App than those born to parity ≥5 sows (P < 0.05) and there was no association between any of the pathogens investigated and other early life indicators (P > 0.05). Pigs in F1 had lower antibody levels for App but higher antibody levels for SIV than F2 and F3 pigs (P < 0.05). There was no association between pluck lesions and respiratory pathogens (P > 0.05), except for increased antibody levels for Mhyo when EP-like lesions were present (P = 0.006). CONCLUSION Results indicate that offspring from primiparous sows develop higher antibody levels for App IV toxin when exposed to this disease and that enforcement of a strict all-in/all-out production system would reduce on-farm disease circulation. A high percentage of pigs were affected with EP-like lesions which were associated with higher antibody levels for Mhyo.

['Fitzgerald|Rose Mary|RM|https://orcid.org/0000-0002-0847-1830', "O'Shea|Helen|H|", 'Manzanilla|Edgar García|EG|https://orcid.org/0000-0002-2301-2560', 'Moriarty|John|J|', 'McGlynn|Hugh|H|', 'Calderón Díaz|Julia Adriana|JA|https://orcid.org/0000-0002-6313-9283']

2020

29383448

A comparison of CRISPR/Cas9 and siRNA-mediated ALDH2 gene silencing in human cell lines.

Gene knockdown and knockout using RNAi and CRISPR/Cas9 allow for efficient evaluation of gene function, but it is unclear how the choice of technology can influence the results. To compare the phenotypes obtained using siRNA and CRISPR/Cas9 technologies, aldehyde dehydrogenase 2 (ALDH2) was selected as an example. In this study, we constructed one HepG2 cell line with a homozygous mutation in the fifth exon of ALDH2 (ALDH2-KO1 cell) using the eukaryotic CRISPR/Cas9 expression system followed by the limited dilution method and one HepG2 cell line with different mutations in the ALDH2 gene (ALDH2-KO2 cell) using the lentivirus CRISPR/Cas9 system. Additionally, one ALDH2-knockdown (KD) HepG2 cell line was created using siRNA. The reproducibility of these methods was further verified in the HEK293FT cell line. We found that the mRNA expression level of ALDH2 was significantly decreased and the protein expression level of ALDH2 was completely abolished in the ALDH2-KO cell lines, but not in ALDH2-KD cells. Furthermore, the functional activity of ALDH2 was also markedly disrupted in the two ALDH2-KO cell lines compared with ALDH2-KD and wild-type cells. The lack of ALDH2 expression mediated by CRIPSR/Cas9 resulted in a more dramatic increase in the cellular susceptibility to chemical-induced reactive oxygen species generation, cytotoxicity, apoptosis, and inflammation, especially at low concentrations compared with ALDH2-KD and WT cells. Therefore, we consider the gene knockout cell line created by CRISPR/Cas9 to be a more useful tool for identifying the function of a gene.

['Wang|Fei|F|', 'Guo|Tao|T|', 'Jiang|Hongmei|H|', 'Li|Ruobi|R|', 'Wang|Ting|T|', 'Zeng|Ni|N|', 'Dong|Guanghui|G|', 'Zeng|Xiaowen|X|', 'Li|Daochuan|D|', 'Xiao|Yongmei|Y|', 'Hu|Qiansheng|Q|', 'Chen|Wen|W|', 'Xing|Xiumei|X|', 'Wang|Qing|Q|']

2018

31988860

Nonalcoholic Fatty Liver Diseases among Recently Diagnosed Patients with Diabetes Mellitus and Risk Factors.

Aim Prevalence of obesity and type 2 diabetes mellitus (T2DM), both of which represent are related to nonalcoholic fatty liver disease (NAFLD), is an increasing trend among Asian people. The study aimed to assess the prevalence of NAFLD in T2DM with their risk factors in the Southern part of Pakistan. Materials and methods A cross-sectional study was accomplished during 2008-2013 at The Aga Khan University Hospital, Karachi, Pakistan. Adult patients diagnosed with T2DM during last 6 months were enrolled in this study. NAFLD was identified using ultrasound of the liver. Clinical and biochemical relevant measurements were accomplished. Results Out of a total of 203 patients with T2DM, NAFLD was detected in 146 patients (71.9%). Multivariate analysis revealed that NAFLD was significantly associated with dyslipidemia (OR 2.38, 95% CI 1.06-5.34, p = 0.035), higher LDL (OR 1.02, 95%CI 1.01-1.03, p = 0.003), H bA1c (OR1.27, 95% CI 0.97-1.68, p = 0.045) and diastolic blood pressure (OR 1.05, 95% CI 1.01-1.10, p = 0.009). The highest odds of 10.8 for NAFLD (95% CI 4.9-24, p = 0.001) was found for the combination of hypertension, dyslipidemia, body mass index (BMI), waist circumference, lack of physical inactivity, triglycerides, lower HDL, LDL, HbA1c, and ALT (multiplicative analysis). Conclusion High incidence of NAFLD with the association of different lifestyle-related factors has been analyzed. It unmasks the need for screening for NAFLD in newly diagnosed DM patients in Pakistan with the assessment of parameters of risk factors. How to cite this article Butt AS, Hamid S, et al. Nonalcoholic fatty Liver Diseases Among Recently Diagnosed Patients With Diabetes Mellitus and Risk Factors. Euroasian J Hepatogastroenterol 2019;9(1):9-13.

['Butt|Amna S|AS|', 'Hamid|Saeed|S|', 'Haider|Zishan|Z|', 'Sharif|Fatima|F|', 'Salih|Mohammad|M|', 'Awan|Safia|S|', 'Khan|Aatif A|AA|', 'Akhter|Jaweed|J|']

2019

28585391

Understanding mortality rates after hip fracture repair using ASA physical status in the National Hip Fracture Database.

Hip fracture is the most common reason for older patients to need emergency anaesthesia and surgery. Up to one-third of patients die in the year after hip fracture, but this view of outcome may encourage therapeutic nihilism in peri-operative decisions and discussions. We used a multicentre national dataset to examine relative and absolute mortality rates for patients presenting with hip fracture, stratified by ASA physical status. We analysed ASA physical status, dates of surgery, death and hospital discharge for 59,369 out of 64,864 patients in the 2015 National Hip Fracture Database; 3914 (6.6%) of whom died in hospital. Rates of death in hospital were 1.8% in ASA 1-2 patients compared with 16.5% in ASA 4 patients. Survival rates for ASA 4 patients on each of the first three postoperative days were: 98.8%, 99.1% and 99.1% (compared with figures of > 99.9% in ASA 1-2 patients over these days). Survival on postoperative day 6 was 99.4% for ASA 4 patients. Nearly half (48.6%) of the 1427 patients who did not have surgery died in hospital. Although technically sound, a focus on cumulative and relative risk of mortality may frame discussions in an unduly negative fashion, discouraging surgeons and anaesthetists from offering an operation, and deterring patients and their loved ones from agreeing to it. A more optimistic and pragmatic explanation that over 98% of ASA 4 patients survive both the day of surgery and the day after it, may be more appropriate.

['Johansen|A|A|', 'Tsang|C|C|', 'Boulton|C|C|', 'Wakeman|R|R|', 'Moppett|I|I|']

2017

30648290

Efficacy and safety of 308-nm excimer lamp in the treatment of scalp psoriasis: a retrospective study.

BACKGROUND Scalp psoriasis is a major therapeutic challenge due to the hindrance caused by hair. Treatment with the 308-nm excimer lamp is purported to provide many benefits over conventional phototherapy. This retrospective study evaluates the efficacy, safety, and effective dosage of 308-nm excimer light in the treatment of scalp psoriasis. METHODS We retrospectively reviewed the medical records of patients with scalp psoriasis who received treatment with 308-nm excimer light. Clinical and epidemiological data as well as details regarding treatment were statistically analyzed to determine the treatment outcomes. RESULTS Twenty patients with scalp psoriasis were included in the study. Their mean age was 47.45 ± 17.93 years. Eleven patients responded to treatment at the end of 10 sessions. The median baseline Psoriatic Scalp Severity Index (PSSI) was 12 (range, 3-32). At the end of the protocol, the median PSSI was 4.5 (range, 0-24), indicating a statistically significant reduction (P < 0.001). Common adverse effects included erythema, irritation, and desquamation. CONCLUSION The 308-nm excimer light appears to be an effective and safe modality that requires short treatment time. The modality could be considered as an alternative or adjuvant treatment for scalp psoriasis.

['Rattanakaemakorn|Ploysyne|P|', 'Phusuphitchayanan|Phanitchanat|P|', 'Pakornphadungsit|Kallapan|K|', 'Thadanipon|Kunlawat|K|', 'Suchonwanit|Poonkiat|P|https://orcid.org/0000-0001-9723-0563']

2019

27100924

Prior renovascular hypertension does not predispose to atherosclerosis in mice.

BACKGROUND Hypertension is a major risk factor for development of atherosclerotic cardiovascular disease (ASCVD). Although lowering blood pressure with antihypertensive drugs reduces the increased risk of ASCVD, residual increased risk still remains, suggesting that hypertension may cause chronic changes that promote atherosclerosis. Thus, we tested the hypothesis that hypertension increases the susceptibility to atherosclerosis in mice even after a period of re-established normotension. METHODS We used the 2-kidney, 1-clip (2K1C) technique to induce angiotensin-driven renovascular hypertension, and overexpression of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene to cause severe hypercholesterolemia and atherosclerosis. RESULTS First, we performed 2K1C (n = 8) or sham surgery (n = 9) in PCSK9 transgenic mice before they were fed a high fat diet for 14 weeks. As expected, 2K1C did not affect cholesterol levels, but induced cardiac hypertrophy and significantly increased the atherosclerotic lesion area compared to sham mice (1.8 fold, p < 0.01). Next, we performed 2K1C (n = 13) or sham surgery (n = 14) in wild-type mice but removed the clipped/sham-operated kidney after 10 weeks to eliminate hypertension, and subsequently induced hypercholesterolemia by way of adeno-associated virus-mediated hepatic gene transfer of PCSK9 combined with high-fat diet. After 14 weeks of hypercholesterolemia, atherosclerotic lesion areas were not significantly different in mice with or without prior 2K1C hypertension (0.95 fold, p = 0.35). CONCLUSION Renovascular hypertension in mice does not induce pro-atherogenic changes that persist beyond the hypertensive phase. These results indicate that hypertension only promotes atherogenesis when coinciding temporally with hypercholesterolemia.

['Mortensen|Martin Bødtker|MB|', 'Nilsson|Line|L|', 'Larsen|Tore G|TG|', 'Espeseth|Eirild|E|', 'Bek|Marie|M|', 'Bjørklund|Martin M|MM|', 'Hagensen|Mette K|MK|', 'Wolff|Anne|A|', 'Gunnersen|Stine|S|', 'Füchtbauer|Ernst-Martin|EM|', 'Boedtkjer|Ebbe|E|', 'Bentzon|Jacob F|JF|']

2016

22529802

Cellulitis with leukocytopenia as an initial sign of acute promyelocytic leukemia.

Patients with hematologic malignancies are immunosuppressive and may develop cutaneous or invasive infections as a primary sign of immune suppression. Acute promyelocytic leukemia (acute myeloid leukemia M3) is caused by translocation of reciprocal chromosomal rearrangement t(15;17), which produces an oncogenic protein. We herein describe a 71-year-old man having cellulitis with leukocytopenia as a first sign of acute promyelocytic leukemia. Dermatologists and hematologists should keep in mind that patients with a hematologic malignancy, such as acute promyelocytic leukemia, can develop cellulitis with leukocytopenia.

['Sakamoto|Sachiko|S|', 'Oiso|Naoki|N|', 'Emoto|Masakatsu|M|', 'Uchida|Shusuke|S|', 'Hirao|Ayaka|A|', 'Tatsumi|Yoichi|Y|', 'Matsumura|Itaru|I|', 'Kawada|Akira|A|']

2012

29403643

Down syndrome and microRNAs.

In recent years numerous studies have indicated the importance of microRNAs (miRNA/miRs) in human pathology. Down syndrome (DS) is the most prevalent survivable chromosomal disorder and is attributed to trisomy 21 and the subsequent alteration of the dosage of genes located on this chromosome. A number of miRNAs are overexpressed in down syndrome, including miR-155, miR-802, miR- 125b-2, let-7c and miR-99a. This overexpression may contribute to the neuropathology, congenital heart defects, leukemia and low rate of solid tumor development observed in patients with DS. MiRNAs located on other chromosomes and with associated target genes on or off chromosome 21 may also be involved in the DS phenotype. In the present review, an overview of miRNAs and the haploinsufficiency and protein translation of specific miRNA targets in DS are discussed. This aimed to aid understanding of the pathogenesis of DS, and may contribute to the development of novel strategies for the prevention and treatment of the pathologies of DS.

['Brás|Aldina|A|', 'Rodrigues|António S|AS|', 'Gomes|Bruno|B|', 'Rueff|José|J|']

2018

31390272

Ten-Year Epidemiology of Ankle Injuries in Men's and Women's Collegiate Soccer Players.

CONTEXT Data from the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP) have indicated that ankle injuries are the most common injuries among NCAA soccer players. OBJECTIVE To review 10 years of NCAA-ISP data for soccer players' ankle injuries to understand how the time period (2004-2005 through 2008-2009 versus 2009-2010 through 2013-2014), anatomical structure injured, and sex of the athlete affected the injury rate, mechanism, and prognosis. DESIGN Descriptive epidemiology study. SETTING Online injury surveillance. MAIN OUTCOME MEASURE(S) The NCAA-ISP was queried for men's and women's soccer ankle data from 2004 to 2014. Ankle-injury rates were calculated on the basis of injuries per 1000 athlete-exposures. Rate ratios (RRs) were used to compare injury rates. Injury proportion ratios (IPRs) were used to compare injury characteristics. RESULTS When compared with the 2004-2005 through 2008-2009 seasons, the 2009-2010 through 2013-2014 seasons showed a similar rate of injuries (RR = 0.94, 95% confidence interval [CI] = 0.85, 1.04) but fewer days missed (P < .001) and fewer recurrent injuries (IPR = 0.55, 95% CI = 0.41, 0.74). The 4 most common ankle injuries, which accounted for 95% of ankle injuries, were lateral ligament complex tears (65.67%), tibiofibular ligament (high ankle) sprains (10.3%), contusions (10.1%), and medial (deltoid) ligament tears (9.77%). Of these injuries, high ankle sprains were most likely to cause athletes to miss ≥30 days (IPR = 1.9, 95% CI = 1.24, 2.90). Men and women had similar injury rates (RR = 1.02, 95% CI = 0.94, 1.11). Men had more contact injuries (IPR = 1.28, 95% CI = 1.16, 1.41) and contusion injuries (IPR = 1.34, CI = 1.03, 1.73) but fewer noncontact injuries (IPR = 0.86, 95% CI = 0.78, 0.95) and lateral ligamentous complex injuries (IPR = 0.92, 95% CI = 0.86, 0.98). CONCLUSIONS Although the rate of ankle injuries did not change between the 2004-2005 through 2008-2009 seasons and the 2009-2010 through 2013-2014 seasons, the prognoses improved. Among the 4 most common ankle injuries, high ankle sprains resulted in the worst prognosis. Overall, male and female NCAA soccer players injured their ankles at similar rates; however, men were more likely to sustain contact injuries.

['Gulbrandsen|Matthew|M|', 'Hartigan|David E|DE|', 'Patel|Karan A|KA|', 'Makovicka|Justin L|JL|', 'Tummala|Sailesh V|SV|', 'Chhabra|Anikar|A|']

2019

24147265

Acute effects of stochastic resonance whole body vibration.

AIM To investigate the acute effects of stochastic resonance whole body vibration (SR-WBV) training to identify possible explanations for preventive effects against musculoskeletal disorders. METHODS Twenty-three healthy, female students participated in this quasi-experimental pilot study. Acute physiological and psychological effects of SR-WBV training were examined using electromyography of descending trapezius (TD) muscle, heart rate variability (HRV), different skin parameters (temperature, redness and blood flow) and self-report questionnaires. All subjects conducted a sham SR-WBV training at a low intensity (2 Hz with noise level 0) and a verum SR-WBV training at a higher intensity (6 Hz with noise level 4). They were tested before, during and after the training. Conclusions were drawn on the basis of analysis of variance. RESULTS Twenty-three healthy, female students participated in this study (age = 22.4 ± 2.1 years; body mass index = 21.6 ± 2.2 kg/m(2)). Muscular activity of the TD and energy expenditure rose during verum SR-WBV compared to baseline and sham SR-WBV (all P < 0.05). Muscular relaxation after verum SR-WBV was higher than at baseline and after sham SR-WBV (all P < 0.05). During verum SR-WBV the levels of HRV were similar to those observed during sham SR-WBV. The same applies for most of the skin characteristics, while microcirculation of the skin of the middle back was higher during verum compared to sham SR-WBV (P < 0.001). Skin redness showed significant changes over the three measurement points only in the middle back area (P = 0.022). There was a significant rise from baseline to verum SR-WBV (0.86 ± 0.25 perfusion units; P = 0.008). The self-reported chronic pain grade indicators of pain, stiffness, well-being, and muscle relaxation showed a mixed pattern across conditions. Muscle and joint stiffness (P = 0.018) and muscular relaxation did significantly change from baseline to different conditions of SR-WBV (P < 0.001). Moreover, muscle relaxation after verum SR-WBV was higher than after sham SR-WBV (P < 0.05). CONCLUSION Verum SR-WBV stimulated musculoskeletal activity in young healthy individuals while cardiovascular activation was low. Training of musculoskeletal capacity and immediate increase in musculoskeletal relaxation are potential mediators of pain reduction in preventive trials.

['Elfering|Achim|A|', 'Zahno|Jasmine|J|', 'Taeymans|Jan|J|', 'Blasimann|Angela|A|', 'Radlinger|Lorenz|L|']

2013

28092205

Effect of polidocanol foam administration into rat peripheral veins on pulmonary parenchyma.

Background Sclerotherapy has been gaining increased acceptance and popularity as an effective therapy for the treatment of varicose veins. This attention has fed growing interest into the safety and potential complications of this procedure. There is no evidence of pulmonary complications from foam sclerotherapy in humans; however, animal studies have shown possible damage. The aim of this study is to show the changes in rat pulmonary parenchyma after the injection of 1% polidocanol Tessari foam into the peripheral vein using histological analysis of the inflammatory and fibrosis processes. Methods Twenty-four Wistar rats were divided into the following four groups: 24 h polidocanol, seven-day polidocanol, 28-day polidocanol, and control group. After the foam was injected into the lateral saphenous vein, the lungs of the rats were removed for histological analysis. Results Alveolar edema was observed in only the 24 h group (P < 0.005). Vessel thickening was observed in the seven-and 28-day groups (P < 0.001). Interstitial fibrosis was found in only the 28-day group (P = 0.006). There was no evidence of venous or arterial thrombosis in either group. Conclusion Polidocanol Tessari foam injection into rat peripheral veins causes alveolar edema, vessel thickening, and interstitial fibrosis.

['de Moraes Silva|Melissa A|MA|', 'Ferreira|Rimarcs G|RG|', 'de Jesus-Silva|Seleno G|SG|', 'Cardoso|Rodolfo S|RS|', 'Miranda|Fausto|F|']

2018

28187461

Lysosomal accumulation of anticancer drugs triggers lysosomal exocytosis.

We have recently shown that hydrophobic weak base anticancer drugs are highly sequestered in acidic lysosomes, inducing TFEB-mediated lysosomal biogenesis and markedly increased lysosome numbers per cell. This enhanced lysosomal sequestration of chemotherapeutics, away from their intracellular targets, provoked cancer multidrug resistance. However, little is known regarding the fate of lysosome-sequestered drugs. While we suggested that sequestered drugs might be expelled from cancer cells via lysosomal exocytosis, no actual drug-induced lysosomal exocytosis was demonstrated. By following the subcellular localization of lysosomes during exposure to lysosomotropic chemotherapeutics, we herein demonstrate that lysosomal drug accumulation results in translocation of lysosomes from the perinuclear zone towards the plasma membrane via movement on microtubule tracks. Furthermore, following translocation to the plasma membrane in drug-treated cells, lysosomes fused with the plasma membrane and released their cargo to the extracellular milieu, as also evidenced by increased levels of the lysosomal enzyme cathepsin D in the extracellular milieu. These findings suggest that lysosomal exocytosis of chemotherapeutic drug-loaded lysosomes is a crucial component of lysosome-mediated cancer multidrug resistance. We further argue that drug-induced lysosomal exocytosis bears important implications on tumor progression, as several lysosomal enzymes were found to play a key role in tumor cell invasion, angiogenesis and metastasis.

['Zhitomirsky|Benny|B|', 'Assaraf|Yehuda G|YG|']

2017

26477519

Rapid screening of edible oils for phthalates using phase-transfer catalyst-assisted hydrolysis and liquid phase microextraction coupled to high performance liquid chromatography-tandem mass spectrometry.

Edible oil is easily contaminated with phthalic acid esters (PAEs). Conventional procedures to analyze individual PAEs require very rigorous experimental conditions that are extremely labor-intensive due to significant procedural contaminations generated by the ubiquitous presence of PAEs in the laboratory environment. In this study, a rapid screening method for PAEs in edible oil was successfully developed. Using a phase-transfer catalyst (terabutylammonium bromide) during oil/water biphasic base hydrolysis of PAEs, the hydrolysis time was decreased from a previously reported time of 20 h to 10 min (80 °C). The resulting phthalic acid in the acidified hydrolysate was extracted with 600 μL of tributyl phosphate and then analyzed by high performance liquid chromatography-tandem mass spectrometry in 6 min. Parameters affecting the hydrolysis of PAEs and the extraction of phthalic acid were optimized, and the analytical method was validated. No obvious matrix effect existed in the edible oils whether an external or internal standard method was used. The detection limit was 1.0 μmol kg(-1), and the quantification limit was 1.3 μmol kg(-1). The recovery rates varied from 86 to 107% with relative standard deviations equal to or lower than 9.9% in all of the tested conditions. Twenty-six samples were analyzed, and the background corrected total PAE content was found to be in the range of <LOD-52.1 μmol kg(-1). This fast and reliable method was not only a practical way to screen oil samples but can also be used as an indicator of false positive or overestimated results in conventional analysis of PAEs. In addition, it presents a new and promising methodology to deal with oil matrices.

['Liu|Shuhui|S|', 'Liu|Laping|L|', 'Han|Yangying|Y|', 'Sun|Jingru|J|', 'Feng|Jing|J|', 'Wang|Jin|J|', 'Zhong|Chongming|C|']

2015

31637962

Metamorphosis of a Gerontological Social Work Scholar.

My participation in the Pre-Dissertation Fellows Program (PDFP) was a defining moment in the development of my career. This commentary focuses on how my participation helped me transition from mentee to mentor and from PhD student to faculty member and scholar in gerontological social work and end-of-life care. While many students have limited mentorship from gerontological faculty in their own program, the PDFP offers a bridge to gerontological scholars and peer support across the US. Beyond that, opportunities are readily available for participation with the Association for Gerontology Education in Social Work (AGESW) and for collaboration across this network. Like myself, many awardees move into faculty positions and their accomplishments are varied and impressive. It is difficult to fully separate these from the connections, mentorship, and support received from the AGESW network and through participation in this program.

['Wallace|Cara L|CL|0000-0002-6739-1910']

2019

34028963

Effect of auto flash margin on superficial dose in breast conserving radiotherapy for breast cancer.

PURPOSE To investigate the dose-effect of Auto Flash Margin (AFM) on breast cancer's superficial tissues based on the Treatment Planning System (TPS) in the breast-conserving radiotherapy plan. METHODS A total of 16 breast-conserving patients with early stage breast cancer were selected, using the X-ray Voxel Monte Carlo (XVMC) algorithm. Then, every included case plan was designed using a 2 cm-AFM (the value of AFM is 2 cm) and N-AFM (without AFM). Under the condition of ensuring the same configuration of #MU and collimator, the absorbed dose after a simulated inspiratory motion was calculated again using the new plan center, which moved backward to the linac source. The dose difference between the measurement points between AFM and N-AFM groups was compared. RESULTS In the dose results, PTVV50Gy of the AFM group was superior to that of the N-AFM group, PTVD2% , PTVDmean , Lung_IpsiV20Gy , Lung_IpsiDmean , and BodyDmax . Also, the dose results of the N-AFM group were significantly higher than those of the AFM group. However, there was no significant difference between Lung_ContraV5Gy , HeartDmean , and Breast_ContraV10Gy in the two groups. In the collimator alignments at the same angle between groups, the AFM group formed an apparent air region outside the collimator compared with the N-AFM group. In the XVMC algorithm feature parameter, the AFM group had less #MU, higher QE, and slightly longer optimization time. The #segments of both groups were close to the 240 control points preset by the plan. The validation results of EBT3 film in both groups were more significant than 95%, meeting the clinical plan's application requirements. The difference in film results between groups was mainly reflected in the dose distribution at the near-source. 4DCT was used to summarize the maximum and minimum inspiratory motion distances of 7.31 ± 0.45 and 3.42 ± 0.91 mm respectively. CONCLUSIONS These results suggest that the AFM function application could significantly reduce the possibility of insufficient tumor target caused by inspiratory motion and ensure sufficient tumor target exposure.

['Wang|Lu|L|', 'Qiu|Gang|G|', 'Yu|Jianhe|J|', 'Zhang|Qunhui|Q|', 'Man|Li|L|', 'Chen|Li|L|', 'Zhang|Xiaoxiao|X|', 'Ren|Qun|Q|', 'Xu|Hongxia|H|', 'Hua|Xiaolong|X|']

2021

27235899

Environmental occurrence and ecological risk assessment of organic UV filters in marine organisms from Hong Kong coastal waters.

Organic UV filters, now considered to be emerging contaminants in aquatic ecosystems, are being intensively tracked in environmental waters worldwide. However, their environmental fate and impact of these contaminants on marine organisms remains largely unknown, especially in Asia. This work elucidates the occurrence and the ecological risks of seven UV filters detected in farmed fish, wild mussels and some other wild organisms collected from local mariculture farms in Hong Kong. For all of the organisms, ethylhexyl methoxycinnamate (EHMC) and octyl dimethyl p-aminobenzoic acid (OD-PABA) were the predominant contaminants with the highest concentrations up to 51.3 and 24.1ng/g (dw), respectively; lower levels were found for benzophenone-8 (BP-8), octocrylene (OC) and benzophenone-3 (BP-3) from <LOQ to <14.4ng/g (dw); 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC) were rarely detected. Additionally, the detection frequencies and measured concentrations of all targets were clearly higher in mussels than in fish. Spatial distribution of studied UV filters indicated a positive correlation between their measured concentrations and the anthropogenic activities responsible for their direct emission. The ecological risk assessment specific to the marine aquatic environment was carried out. The risk quotient (RQ) values of EHMC and BP-3 were calculated as 3.29 and 2.60, respectively, indicating these two UV filters may pose significant risks to the marine aquatic environment.

['Sang|Ziye|Z|', 'Leung|Kelvin Sze-Yin|KS|']

2016

30227369

The variation of mitochondrial NADH dehydrogenase subunit 4 (mtND4) and molecular dynamics simulation of SNPs among Iranian women with breast cancer.

Breast cancer is the second cause of death among women all around the world. One out of every eight women is diagnosed with breast cancer in Iran. There are many reasons for cancer, one of which is the mutations in the mitochondrial genome observed in most breast cancer studies. However, the aim of this study is to evaluate the genetic region of NADH dehydrogenase subunit 4 in patients with breast cancer. First, the genomic DNA was extracted from a tissue. The NADH dehydrogenase subunit 4 coding region was amplified by PCR, and then the SSCP was sequenced. After that, the molecular dynamics were employed. The association between the mutations and the prognostic factors such as ER, PR, HER-2, and age were statistically examined. The sequence of the ND4 area was determined in 24 suspected patients, and 15 nucleotide changes were reported. The role of this variations was investigated by in-silico. The harmful mutations were predicted based on some servers. The molecular dynamics results showed that there is a significant relationship between the mutant protein and the changes in the structural conformation. Our results showed that the mutation in the ND4 area plays an important role in developing breast cancer. So, it can be concluded that the mitochondrial NADH dehydrogenase analysis may help to detect breast cancer in the early stages.

['Arezi|Parastoo|P|', 'Rezvani|Zahra|Z|']

2018

27351940

Immunoglobulin A nephropathy: a pathophysiology view.

BACKGROUND AND AIM IgA nephropathy is one of the leading causes of primary glomerulonephritis worldwide and an important etiology of renal disease in young adults. IgA nephropathy is considered an immune complex-mediated disease. METHODS This review article summarizes recent evidence on the pathophysiology of IgA nephropathy. RESULTS Current studies indicate an ordered sequence of multi-hits as fundamental to disease occurrence. Altered glycan structures in the hinge region of the heavy chains of IgA1 molecules act as auto-antigens, potentially triggering the production of glycan-specific autoantibodies. Recognition of novel epitopes by IgA and IgG antibodies leads to the formation of immune complexes galactose deficient-IgA1/anti-glycan IgG or IgA. Immune complexes of IgA combined with FcαRI/CD89 have also been implicated in disease exacerbation. These nephritogenic immune complexes are formed in the circulation and deposited in renal mesangium. Deposited immune complexes ultimately induce glomerular injury, through the release of pro-inflammatory cytokines, secretion of chemokines and the resultant migration of macrophages into the kidney. The TfR1/CD71 receptor has a pivotal role in mesangial cells. New signaling intracellular mechanisms have also been described. CONCLUSION The knowledge of the whole pathophysiology of this disease could provide the rational bases for developing novel approaches for diagnosis, for monitoring disease activity, and for disease-specific treatment.

['Fabiano|Rafaela Cabral Gonçalves|RC|', 'Pinheiro|Sérgio Veloso Brant|SV|', 'Simões E Silva|Ana Cristina|AC|http://orcid.org/0000-0001-9222-3882']

2016

27554070

Correlation of Breast Ultrasound Classifications with Breast Cancer in Chinese Women.

The aim of this study was to identify potential links between ultrasonographic breast parenchymal patterns and the risk of breast cancer in Chinese women. The population of Chinese women at high risk for breast cancer was explored using the ultrasonographic classification. Ultrasonographic parenchymal patterns were classified into four types: heterogeneous type, ductal type, mixed type and fibrous type. A total of 5879 Chinese women underwent breast ultrasound examination from May 2010 to April 2014. Of the 5879 women, 256 women had pathology-confirmed breast cancer. Among the remaining 5623 women, 512 randomly selected, age-matched women were recruited into the present study. The correlation between ultrasonographic type and breast cancer revealed that the odds ratio (OR) was highest for the heterogeneous type (odds ratio = 4.11, 95% confidence interval: 2.01-8.41, p < 0.001), followed by the fibrous type (odds ratio = 2.05, 95% confidence interval: 1.51-2.78, p < 0.001). The odds ratios of the ductal and mixed types were both less than 1 (p < 0.05). This study indicates that the heterogeneous and fibrous types in the ultrasonographic classification are associated with an increased risk of breast cancer and, therefore, can be used as a marker of breast cancer risk in the female population of China.

['Hou|Xin-Yan|XY|', 'Niu|Hai-Yan|HY|', 'Huang|Xiao-Ling|XL|', 'Gao|Yu|Y|']

2016

22589370

At risk for schizophrenic or affective psychoses? A meta-analysis of DSM/ICD diagnostic outcomes in individuals at high clinical risk.

BACKGROUND The clinical high-risk state for psychosis (HRP) is associated with an enhanced probability of developing a psychotic episode over a relatively short period of time. However, the extent to which different diagnostic types of illness develop remains unclear. METHODS A systematic review was performed to identify studies of HRP participants reporting International Classfication of Diseases/Diagnostic and Statistical Manual of Mental Disorders diagnostic outcomes at follow-up. Demographic, clinical, and methodological variables were extracted from each publication or obtained directly from its authors. A meta-analysis was performed of transition to schizophrenic (SP) or affective psychoses (AP) and to specific diagnostic categories. Statistical heterogeneity and small study bias were assessed, and meta-regressions were performed. RESULTS Twenty-three studies were retrieved, including a total of 2182 HRP participants, 560 (26%) of them developed a frank psychotic disorder over the follow-up time (mean = 2.35 y). Among HRP participants who developed psychosis, 73% were diagnosed with SP and only 11% with AP (Risk Ratio, RR = 5.43, 95% CI from 3.35 to 8.83). The specific transition risk to ICD/DSM schizophrenia was of 15.7% (over 2.35y). Heterogeneity was statistically significant and moderate in magnitude. Use of basic symptoms criteria in the baseline clinical assessment was associated with a further increase in the proportion progressing to SP vs AP (RR = 17.1). There was no evidence of publication bias and the sensitivity analysis confirmed robustness of the above results. CONCLUSIONS The HRP state is heterogeneous in term of longitudinal diagnoses; however, the current HRP diagnostic criteria appear strongly biased toward an identification of early phases of SP rather than AP.

['Fusar-Poli|Paolo|P|', 'Bechdolf|Andreas|A|', 'Taylor|Matthew John|MJ|', 'Bonoldi|Ilaria|I|', 'Carpenter|William T|WT|', 'Yung|Alison Ruth|AR|', 'McGuire|Philip|P|']

2013

32523251

Effects of a short-term increase in physical activity on arterial stiffness during hyperglycemia.

We examined the effects of increasing physical activity on arterial stiffness during hyperglycemia. Nineteen glucose-intolerant elderly participated in the study. We randomly assigned 10 participants to increase their daily activity in everyday life, regardless of the time or intensity, for 1 month (PAI group) (age, 74.6 ± 1.3 years; mean ± SE) and nine participants to maintain their level of activity (CON group) (age, 79.2 ± 2.1 years; mean ± SE). The 75-g oral glucose tolerance test was conducted in each participant in both groups before and after the start of the intervention to confirm glucose intolerance. Brachial-ankle pulse wave velocity and cardio-ankle vascular index significantly increased from baseline at 30, 60, and 90 min after the 75-g glucose ingestion after the intervention in the CON group (p<0.05), but not in the PAI group. Heart-brachial pulse wave velocity did not change compared to baseline after the 75-g glucose ingestion in either group and did not change from baseline at 30, 60, and 90 min after the 75-g glucose ingestion before and after the intervention in both groups. The present findings indicate that a short-term increase in physical activity suppresses the increase in arterial stiffness after glucose intake.

['Kobayashi|Ryota|R|', 'Sato|Kaori|K|', 'Takahashi|Toshihiko|T|', 'Asaki|Kenji|K|', 'Iwanuma|Soichiro|S|', 'Ohashi|Nobuyuki|N|', 'Hashiguchi|Takeo|T|']

2020

24891268

T wave inversions in leads with ST elevations in patients with acute anterior ST elevation myocardial infarction is associated with patency of the infarct related artery.

OBJECTIVES Following reperfusion therapy, early T wave inversions (TWI) have been shown to be a marker of successful reperfusion. We aimed to evaluate the relationship of TWI on the presenting ECG with spontaneous reperfusion as assessed by coronary angiography in patients with ST elevation (STE) myocardial infarction (STEMI). METHODS Data of 146 consecutive patients presenting to the St. Luke's Episcopal Hospital Emergency Department with acute STEMI undergoing primary percutaneous coronary intervention (p-PCI) between January, 2007 and October, 2010 were retrospectively analyzed. Clinical data, ECG and angiographic data were reviewed. Patients were dichotomized based on T wave morphology on the presenting ECG into 2 groups - those with TWI and those with positive T waves (PTW). RESULTS Thirty-one patients (21.2%) had TWI, while 115 (78.8%) had PTW. Sixty-four (43.8%) patients had anterior STE and 75 (51.3%) had inferior STE. Anterior STE was more likely to have TWI than non-anterior (29.7% vs. 14.6; p=0.014). By angiography, infarct related artery (IRA) patency (TIMI 2-3 flow) was seen in 45 (30.8%). TWI was more likely to be associated with IRA patency compared to PTW (51.6% vs. 25.2%; p=0.008). In patients with anterior STEMI and TWI, patent IRA was seen more frequently compared to those with PTW (68.4% vs. 20%; p<0.001). There was no association of T wave morphology and TIMI flow in patients with non-anterior STEMI. Patients presenting with stuttering symptoms were more likely to have TWI (70.4% vs. 10.2%; p <0.001) suggesting recurrent episodes of reperfusion and ischemia. CONCLUSIONS In anterior STEMI patients, TWI on the presenting ECG is associated with spontaneous reperfusion. This relationship was not found among patients with non-anterior STEMI.

['Hira|Ravi S|RS|', 'Moore|Curtiss|C|', 'Huang|Henry D|HD|', 'Wilson|James M|JM|', 'Birnbaum|Yochai|Y|']

2014

24114798

Droplet Array Platform for High-Resolution Melt Analysis of DNA Methylation Density.

High-resolution melting (HRM) has garnered significant interest as an analytical technique for a number of applications, including DNA methylation detection, due to its inherent sensitivity and robustness. In this study, we describe a miniaturized assay platform for quantitative methylation density analysis using a microfluidic droplet array cartridge. We demonstrate that the DNA methylation level of the RASSF1A promoter can be directly analyzed using HRM. PCR products were generated by amplifying bisulfite-treated DNA with varying CpG densities using CpG island-flanking primer sets. Subsequent HRM analysis on the miniaturized droplet platform shows distinct melting curve profiles associated with methylation levels, which was verified using a conventional benchtop PCR-HRM system. The characteristic melting temperature (Tm) of the PCR products was used to directly quantify the respective levels of DNA methylation density. Our approach provides a key advantage over current gold standard methods such as methylation-specific PCR (MSP), which are incapable of providing specific information regarding the overall methylation density of the target genes. The miniaturized platform establishes a practical approach to methylation density profiling from multiple DNA samples with a potential application in point-of-care diagnostics.

['Athamanolap|Pornpat|P|', 'Shin|Dong Jin|DJ|', 'Wang|Tza-Huei|TH|']

2014

26476066

Comparative test of ecological assessment methods of lowland streams based on long-term monitoring data of macrophytes.

Ecological assessment of water courses is required by the European Water Framework Directive (WFD). Assessment by means of macrophytes is impeded by insufficient knowledge on the relations between assessment scores and the dynamics of environmental parameters. Data from a long-term observation of macrophyte dynamics over 21 years in two lowland rivers were used for testing the performance of six widely used assessment methods. Six sample sites situated in two lowland streams were selected. Four sites were classified as of moderate habitat quality and two sites as of poor habitat quality in the context of WFD. Assessment methods generally showed a poor performance in recognizing the ecological status of the annual observations. Status was more often over- than underestimated. Performance of methods differed among individual rivers and among river zones. Assessment scores mostly showed a steady decline, even though all sites obviously remained in the same habitat quality class throughout the observation period. Variation of most environmental factors was largely unrelated to assessment scores. Fluctuations of assessment scores were partly related to single natural disturbance events such as high discharge. Increased shading by marginal trees was reflected negatively by most assessment scores. Assessment scores were highly correlated with species richness and total abundance. The best overall performance was shown by the North-Rhine Westphalian (NRW) method. In contrast to single metric methods it can be adapted to individual properties of a reach in a flexible way. Macrophyte assessment based on the pressure-impact framework did not lead to a satisfying result in our case study. Improvement of species assessment scores and inclusion of functional properties such as growth form may help to overcome the present difficulties.

['Wiegleb|Gerhard|G|', 'Gebler|Daniel|D|', 'van de Weyer|Klaus|K|', 'Birk|Sebastian|S|']

2016

24133478

Virtual sensory feedback for gait improvement in neurological patients.

We review a treatment modality for movement disorders by sensory feedback. The natural closed-loop sensory-motor feedback system is imitated by a wearable virtual reality apparatus, employing body-mounted inertial sensors and responding dynamically to the patient's own motion. Clinical trials have shown a significant gait improvement in patients with Parkinson's disease using the apparatus. In contrast to open-loop devices, which impose constant-velocity visual cues in a "treadmill" fashion, or rhythmic auditory cues in a "metronome" fashion, requiring constant vigilance and attention strategies, and, in some cases, instigating freezing in Parkinson's patients, the closed-loop device improved gait parameters and eliminated freezing in most patients, without side effects. Patients with multiple sclerosis, previous stroke, senile gait, and cerebral palsy using the device also improved their balance and gait substantially. Training with the device has produced a residual improvement, suggesting virtual sensory feedback for the treatment of neurological movement disorders.

['Baram|Yoram|Y|']

2013

32389619

Attention allocation to subliminally presented affective faces in high and low social anxiety.

Attention bias to affective stimuli, particularly threatening stimuli, has been well documented, with attention bias to affective faces often reported in populations with social anxiety (SA). However, inconsistencies exist in the literature regarding the direction of the bias, with some studies reporting a bias to attend toward social threat, and others reporting a bias to avoid social threat. This variability in the attention bias literature could be related to fluctuations in how attentional resources are allocated toward social stimuli over time. This study aimed to isolate early processing of affective faces using a backward masking paradigm in participants with high and low levels of subclinical SA. We used prepulse inhibition (PPI) of startle to index the amount of early attention allocated to masked affective faces. There was greater PPI to masked angry faces compared to neutral faces across all participants, suggesting that more attention was allocated to threatening faces. This effect was similar across face genders and participant SA levels. There was also a trend for more attention to be allocated to masked affective faces (angry and happy) compared to neutral faces across all participants. These findings demonstrate that attention bias to subliminal affect, and threat specifically, may not be modulated by subclinical levels of SA at very early stages of attention processing.

['Duval|Elizabeth R|ER|', 'Lovelace|Christopher T|CT|', 'Filion|Diane L|DL|']

2020

28558873

Mechanism for ginkgolic acid (15 : 1)-induced MDCK cell necrosis: Mitochondria and lysosomes damages and cell cycle arrest.

Ginkgolic acids (GAs), primarily found in the leaves, nuts, and testa of ginkgo biloba, have been identified with suspected allergenic, genotoxic and cytotoxic properties. However, little information is available about GAs toxicity in kidneys and the underlying mechanism has not been thoroughly elucidated so far. Instead of GAs extract, the renal cytotoxicity of GA (15 : 1), which was isolated from the testa of Ginkgo biloba, was assessed in vitro by using MDCK cells. The action of GA (15 : 1) on cell viability was evaluated by the MTT and neutral red uptake assays. Compared with the control, the cytotoxicity of GA (15 : 1) on MDCK cells displayed a time- and dose-dependent manner, suggesting the cells mitochondria and lysosomes were damaged. It was confirmed that GA (15 : 1) resulted in the loss of cells mitochondrial trans-membrane potential (ΔΨm). In propidium iodide (PI) staining analysis, GA (15 : 1) induced cell cycle arrest at the G0/G1 and G2/M phases, influencing on the DNA synthesis and cell mitosis. Characteristics of necrotic cell death were observed in MDCK cells at the experimental conditions, as a result of DNA agarose gel electrophoresis and morphological observation of MDCK cells. In conclusion, these findings might provide useful information for a better understanding of the GA (15 : 1) induced renal toxicity.

['Yao|Qing-Qing|QQ|', 'Liu|Zhen-Hua|ZH|', 'Xu|Ming-Cheng|MC|', 'Hu|Hai-Hong|HH|', 'Zhou|Hui|H|', 'Jiang|Hui-Di|HD|', 'Yu|Lu-Shan|LS|', 'Zeng|Su|S|']

2017

27940259

Inflammation-induced anorexia and fever are elicited by distinct prostaglandin dependent mechanisms, whereas conditioned taste aversion is prostaglandin independent.

Systemic inflammation evokes an array of brain-mediated responses including fever, anorexia and taste aversion. Both fever and anorexia are prostaglandin dependent but it has been unclear if the cell-type that synthesizes the critical prostaglandins is the same. Here we show that pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not of COX-1, attenuates inflammation-induced anorexia. Mice with deletions of COX-2 selectively in brain endothelial cells displayed attenuated fever, as demonstrated previously, but intact anorexia in response to peripherally injected lipopolysaccharide (10μg/kg). Whereas intracerebroventricular injection of a cyclooxygenase inhibitor markedly reduced anorexia, deletion of COX-2 selectively in neural cells, in myeloid cells or in both brain endothelial and neural cells had no effect on LPS-induced anorexia. In addition, COX-2 in myeloid and neural cells was dispensable for the fever response. Inflammation-induced conditioned taste aversion did not involve prostaglandin signaling at all. These findings collectively show that anorexia, fever and taste aversion are triggered by distinct routes of immune-to-brain signaling.

['Nilsson|Anna|A|', 'Wilhelms|Daniel Björk|DB|', 'Mirrasekhian|Elahe|E|', 'Jaarola|Maarit|M|', 'Blomqvist|Anders|A|', 'Engblom|David|D|']

2017

30838824

Noble Metal Coated Central Venous Catheters Are Not Superior To Uncoated Catheters In Preventing Infectious And Non-Infectious Complications In Immunocompromised Patients.

Background Patients with haematological malignancies and stem cell transplant recipients are at high risk of opportunistic infections. Little international and no national data is available comparing noble metal coated versus uncoated central venous catheters (CVC) in this special population of severely immunocompromised patients. Objective of the study is to compare infectious and non-infectious complications of noble metal coated versus uncoated central venous catheters in patients undergoing stem cell transplantation and receiving chemotherapy for acute myeloid leukaemia. Methods This is a prospective, cross-sectional, randomized study (January to December 2016), enrolling 45 consecutive patients undergoing stem cell transplantation or chemotherapy for acute myeloid leukaemia. Patients were randomized in 2 groups. Twenty 23 patients received standard CVC and 22 patients received CVC catheters coated with three noble metals (Gold, Silver, Palladium). Patients were observed for catheter related infectious and noninfectious complications. Data was analysed using SPSS. Results Mean age was 24.3 (±4.91) in uncoated and 25.09 (±5.22) in coated CVL group. CRBSI infection was detected in 2 (8.6%) and 3 (13.6%) patients in uncoated and coated group respectively with p-value of .279. There was no statistically significant difference in febrile episodes between coated (95.4%) and uncoated (91.3%) group. While we considered non-infectious complications, 2 patients in coated (8.6%) and 1 in uncoated CVCs group (4.3%) had CVC thrombosis which was not significant statistically. Conclusion There was no efficacy of BG-thin noble metal coated CVCs in reducing infectious and non-infectious complications (thrombosis) in our study.

['Iftikhar|Raheel|R|', 'Chaudhry|Qamar Un Nisa|QUN|', 'Satti|Tariq Mehmood|TM|', 'Mahmood|Syed Kamran|SK|', 'Satti|Humayun Shafique|HS|', 'Ghafoor|Tariq|T|', 'Khan|Mehreen Ali|MA|']

2018

31287949

Scanning Probe-Directed Assembly and Rapid Chemical Writing Using Nanoscopic Flow of Phospholipids.

Nanofluidic systems offer a huge potential for discovery of new molecular transport and chemical phenomena that can be employed for future technologies. Herein, we report on the transport behavior of surface-reactive compounds in a nanometer-scale flow of phospholipids from a scanning probe. We have investigated microscopic deposit formation on polycrystalline gold by lithographic printing and writing of 1,2-dioleoyl-sn-glycero-3-phosphocholine and eicosanethiol mixtures, with the latter compound being a model case for self-assembled monolayers (SAMs). By analyzing the ink transport rates, we found that the transfer of thiols was fully controlled by the fluid lipid matrix allowing to achieve a certain jetting regime, i.e., transport rates previously not reported in dip-pen nanolithography (DPN) studies on surface-reactive, SAM-forming molecules. Such a transport behavior deviated significantly from the so-called molecular diffusion models, and it was most obvious at the high writing speeds, close to 100 μm s-1. Moreover, the combined data from imaging ellipsometry, scanning electron microscopy, atomic force microscopy (AFM), and spectroscopy revealed a rapid and efficient ink phase separation occurring in the AFM tip-gold contact zone. The force curve analysis indicated formation of a mixed ink meniscus behaving as a self-organizing liquid. Based on our data, it has to be considered as one of the co-acting mechanisms driving the surface reactions and self-assembly under such highly nonequilibrium, crowded environment conditions. The results of the present study significantly extend the capabilities of DPN using standard AFM instrumentation: in the writing regime, the patterning speed was already comparable to that achievable by using electron beam systems. We demonstrate that lipid flow-controlled chemical patterning process is directly applicable for rapid prototyping of solid-state devices having mesoscopic features as well as for biomolecular architectures.

['Navikas|Vytautas|V|', 'Gavutis|Martynas|M|', 'Rakickas|Tomas|T|http://orcid.org/0000-0002-1231-7545', 'Valiokas|Ramu Nas|RN|http://orcid.org/0000-0003-4807-9136']

2019

27242652

Idiopathic Inflammatory Myopathies: Clinical Approach and Management.

Idiopathic inflammatory myopathies (IIM) are a group of chronic, autoimmune conditions affecting primarily the proximal muscles. The most common types are dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myopathy (NAM), and sporadic inclusion body myositis (sIBM). Patients typically present with sub-acute to chronic onset of proximal weakness manifested by difficulty with rising from a chair, climbing stairs, lifting objects, and combing hair. They are uniquely identified by their clinical presentation consisting of muscular and extramuscular manifestations. Laboratory investigations, including increased serum creatine kinase (CK) and myositis specific antibodies (MSA) may help in differentiating clinical phenotype and to confirm the diagnosis. However, muscle biopsy remains the gold standard for diagnosis. These disorders are potentially treatable with proper diagnosis and initiation of therapy. Goals of treatment are to eliminate inflammation, restore muscle performance, reduce morbidity, and improve quality of life. This review aims to provide a basic diagnostic approach to patients with suspected IIM, summarize current therapeutic strategies, and provide an insight into future prospective therapies.

['Malik|Asma|A|', 'Hayat|Ghazala|G|', 'Kalia|Junaid S|JS|', 'Guzman|Miguel A|MA|']

2016

27614563

Benthic surveys of the historic pearl oyster beds of Qatar reveal a dramatic ecological change.

The study aimed to confirm the presence of historic oyster banks of Qatar and code the biotopes present. The research also collated historical records and scientific publications to create a timeline of fishery activity. The oyster banks where once an extremely productive economic resource however, intense overfishing, extreme environmental conditions and anthropogenic impacts caused a fishery collapse. The timeline highlighted the vulnerability of ecosystem engineering bivalves if overexploited. The current status of the oyster banks meant only one site could be described as oyster dominant. This was unexpected as the sites were located in areas which once supported a highly productive oyster fishery. The research revealed the devastating effect that anthropogenic impacts can have on a relatively robust marine habitat like an oyster bed and it is hoped these findings will act as a driver to investigate and map other vulnerable habitats within the region before they too become compromised.

['Smyth|D|D|', 'Al-Maslamani|I|I|', 'Chatting|M|M|', 'Giraldes|B|B|']

2016

34823527

Acceptability and feasibility of malaria prophylaxis for forest goers: findings from a qualitative study in Cambodia.

BACKGROUND In the Greater Mekong Subregion, adults are at highest risk for malaria, particularly those who visit forests. The absence of effective vector control strategies and limited periods of exposure during forest visits suggest that chemoprophylaxis could be an appropriate strategy to protect forest goers against malaria. METHODS Alongside a clinical trial of anti-malarial chemoprophylaxis in northern Cambodia, qualitative research was conducted, including in-depth interviews and observation, to explore the acceptability of malaria prophylaxis for forest goers, the implementation opportunities, and challenges of this strategy. RESULTS Prophylaxis with artemether-lumefantrine for forest goers was found to be acceptable under trial conditions. Three factors played a major role: the community's awareness and perception of the effectiveness of prophylaxis, their trust in the provider, and malaria as a local health concern. The findings highlight how uptake and adherence to prophylaxis are influenced by the perceived balance between benefits and burden of anti-malarials which are modulated by the seasonality of forest visits and its influence on malaria risk. CONCLUSIONS The implementation of anti-malarial prophylaxis needs to consider how the preventive medication can be incorporated into existing vector-control measures, malaria testing and treatment services. The next step in the roll out of anti-malarial prophylaxis for forest visitors will require support from local health workers.

['Jongdeepaisal|Monnaphat|M|', 'Ean|Mom|M|', 'Heng|Chhoeun|C|', 'Buntau|Thoek|T|', 'Tripura|Rupam|R|', 'Callery|James J|JJ|', 'Peto|Thomas J|TJ|', 'Conradis-Jansen|Franca|F|', 'von Seidlein|Lorenz|L|', 'Khonputsa|Panarasri|P|', 'Pongsoipetch|Kulchada|K|', 'Soviet|Ung|U|', 'Sovannaroth|Siv|S|', 'Pell|Christopher|C|', 'Maude|Richard J|RJ|http://orcid.org/0000-0002-5355-0562']

2021

23989188

An investigative peptide-acyclovir combination to control herpes simplex virus type 1 ocular infection.

PURPOSE To investigate the efficacy of a combination treatment composed of the cationic, membrane-penetrating peptide G2, and acyclovir (ACV) in both in vitro and ex vivo models of herpes simplex virus 1 (HSV-1) ocular infection. METHODS The antiviral activity of a combined G2 peptide and ACV therapy (G2-ACV) was assessed in various treatment models. Viral entry, spread, and plaque assays were performed in vitro to assess the prophylactic efficacy of G2, G2-ACV, and ACV treatments. In the ex vivo model of HSV-1 infection, the level of viral inhibition was also compared among the three treatment groups via Western blot analysis and immunohistochemistry. The potential change in expression of the target receptor for G2 was also assessed using immunohistochemistry and RT-PCR. RESULTS Statistically significant effects against HSV-1 infection were seen in all treatment groups in the viral entry, spread, and plaque assays. The greatest effects against HSV-1 infection in vitro were seen in the G2-ACV group. In the ex vivo model, statistically significant anti-HSV-1 effects were also noted in all control groups. At 24 hours, the greatest inhibitory effect against HSV-1 infection was seen in the ACV group. At 48 hours, however, the G2-ACV-treated group demonstrated the greatest antiviral activity. Syndecan-1, a target of G2, was found to be upregulated at 12-hours postinfection. CONCLUSIONS This study shows that G2-ACV may be an effective antiviral against HSV-1 (KOS) strain when applied as single prophylactic applications with or without continuous doses postinfection.

['Park|Paul J|PJ|', 'Antoine|Thessicar E|TE|', 'Farooq|Asim V|AV|', 'Valyi-Nagy|Tibor|T|', 'Shukla|Deepak|D|']

2013

30836741

Effect of tDCS on Aberrant Functional Network Connectivity in Refractory Hallucinatory Schizophrenia: A Pilot Study.

We aim to investigate the effect of fronto-temporal transcranial direct current stimulation (tDCS) on the interactions among functional networks and its association with psychotic symptoms. In this pilot study, we will determine possible candidate functional networks and an adequate sample size for future research. Seven schizophrenia patients with treatment-refractory auditory hallucinations underwent tDCS twice daily for 5 days. Resting-state fMRI data and measures of the severity of psychotic symptoms were acquired at baseline and after completion of the tDCS sessions. At baseline, decreased functional network interaction was negatively correlated with increased hallucinatory behavior. After tDCS, the previously reduced functional network connectivity significantly increased. Our results showed that fronto-temporal tDCS could possibly remediate aberrant hallucination-related functional network interactions in patients with schizophrenia.

['Yoon|Youngwoo Bryan|YB|', 'Kim|Minah|M|', 'Lee|Junhee|J|', 'Cho|Kang Ik K|KIK|', 'Kwak|Seoyeon|S|', 'Lee|Tae Young|TY|', 'Kwon|Jun Soo|JS|']

2019

32044695

The impact of balance specific physiotherapy, intensity of therapy and disability on static and dynamic balance in people with multiple sclerosis: A multi-center prospective study.

BACKGROUND A high-quality research identifying the best physiotherapeutic approach for the improvement of balance in people with multiple sclerosis is missing. This study compared aspects of balance improvement such as therapy specificity to balance, therapy method and category, country, intensity and medical conditions. METHODS A multicentric randomised rater-blinded controlled trial comprised three different physiotherapy programs (Czech and Italian outpatient or inpatient programs). All patients received 20 therapy sessions. Experimental group underwent balance specific physiotherapy (it was Motor Program Activating Therapy in the Czech cohort and Sensory-motor Integration Training in the Italian cohort), control group underwent non-balance specific physiotherapy (it was Vojta reflex locomotion in the Czech cohort and conventional dynamic strengthening exercises in the Italian cohort, respectively). Static balance was evaluated by Berg Balance Scale and dynamic balance was assessed by Timed Up-and-Go Test. RESULTS A total of 149 patients entered the study. Physiotherapy significantly improved static balance (p < 0.0001, increase by mean 2.6 points (95% confidence interval 2.0-3.5) in BBS score). Balance specific approach had a higher effect than non-specific balance approach (increase in BBS by 1.9 points, 95% confidence interval 0.9-3.7 points). The intensity of the physiotherapy significantly influenced static balance (BBS by 2.7 points higher in the inpatient setting, p= 0.007). Dynamic balance was also improved (TUG decrease by -0.8 s (95% CI -1.4 - -0.1s, p = 0.011)); the balance specificity had no impact. The level of disability played the most important role (p= 0.022). CONCLUSION Although the overall changes in static and dynamic balance were statistically significant, they were quite small in a clinical sense. A small statistically significant difference between balance specific and non-specific treatment was found. It seems that a high intensity of the therapy is critical to maximize the effectiveness.

['Pavlikova|M|M|', 'Cattaneo|D|D|', 'Jonsdottir|J|J|', 'Gervasoni|E|E|', 'Stetkarova|I|I|', 'Angelova|G|G|', 'Markova|M|M|', 'Prochazkova|M|M|', 'Prokopiusova|T|T|', 'Hruskova|N|N|', 'Reznickova|J|J|', 'Zimova|D|D|', 'Spanhelova|S|S|', 'Rasova|K|K|']

2020

24941982

Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase.

Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for B-cell survival and proliferation. In preclinical studies, ibrutinib bound to Bruton's tyrosine kinase with high affinity, leading to inhibition of B-cell receptor signaling, decreased B-cell activation and induction of apoptosis. In clinical studies, ibrutinib has been well-tolerated and has demonstrated profound anti-tumor activity in a variety of hematologic malignancies, most notably chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), leading to US FDA approval for relapsed CLL and MCL. Ongoing studies are evaluating ibrutinib in other types of non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and Waldenström's macrogobulinemia, in larger Phase III studies in CLL and MCL, and in combination studies with monoclonal antibodies and chemotherapy. Future studies will combine ibrutinib with other promising novel agents currently in development in hematologic malignancies.

['Davids|Matthew S|MS|', 'Brown|Jennifer R|JR|']

2014

24195032

Effects of intraocular rifampicin on retinal ganglion cell structure: a stereological and histopathological study.

AIM To determine the histopathological changes of rifampicin applied intravitreally on retinal ganglion cells by means of stereological and histopathological methods. METHODS For this study twenty-four New Zealand adult rabbits were divided into four groups (n=6 for each group). 50µg/0.1mL (group 1), 100µg/0.1mL (group 2), 150µg/0.1mL (group 3) and 200µg/0.1mL (group 4), rifampicin were injected into the vitreous of the right eyes of animals, their left eyes were used as control (group 5). After the 28(th) day of application, animals were anesthetised with xylazine (8mg/kg, IM) and then their eyes were enucleated immediately. Patterns were taken away and eyes were prepared for both stereological and electromicroscopic observation. RESULTS Depending on the high dose of rifampicin, some histopathological changes such as cytoplasmic dilatation and damaged membrane were observed on the electromicroscopic level. Using quantitative examination, which was done at the light microscopic level, it was shown that the number of neurons decreased linearly as rifampicin dose increased when compared with the control group. CONCLUSION Based on these findings, low-dose rifampicin (50µg/0.1mL) may be useful for treatment of the ocular diseases.

['Cakici|Ozgür|O|', 'Aksak|Selina|S|', 'Unal|Deniz|D|', 'Sipal|Sare|S|', 'Keles|Sadullah|S|', 'Dumlu|Talha|T|', 'Karamese|Murat|M|']

2013

32725149

Obeticholic acid ameliorates hepatorenal syndrome in ascitic cirrhotic rats by down-regulating the renal 8-iso-PGF2α-activated COX-TXA2 pathway.

BACKGROUNDS/AIMS The present study explores the potential of chronic treatment with the Foresaid X receptor (FXR) agonist obeticholic acid (OCA), which inhibits oxidative stress-related pathogenesis, in ascitic cirrhotic rats with hepatorenal syndrome (HRS) developed 6 weeks after bile duct ligation (BDL). METHODS Systemic, splanchnic, and renal hemodynamics and pathogenic cascades were measured in ascitic BDL and sham rats receiving 2-weeks of either vehicle or OCA treatments (sham-OCA and BDL-OCA groups), and NRK-52E cells, rat kidney tubular epithelial cells. RESULTS Chronic OCA treatment significantly normalized portal hypertension, glomerular filtration rate, urine output, renal blood flow; decreased ascites, renal vascular resistance, serum creatinine, and the release of renal tubular damage markers, including urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury moleculae-1 (uKim-1) in BDL-OCA rats. In the BDL group, inhibition of the renal oxidative stress (8-iso-PGF2α)-activated cyclooxygenase-thromboxane A2 [COX-TXA2] pathway, apoptosis, and tubular injury accompanied by a decrease in hyper-responsiveness to the vasoconstrictor 8-iso-PGF2α in perfused kidneys. In vitro experiments revealed that 8-iso-PGF2α induced oxidative stress, release of reactive oxygen species, and cell apoptosis, which were reversed by concomitant incubation with the FXR agonist. CONCLUSIONS Through the inhibition of renal 8-iso-PGF2α production and the down-regulation of the COX-TXA2 pathway, our study suggests that chronic OCA treatment can ameliorate the HRS in ascitic cirrhotic rats. Thus, OCA is an agent with antioxidative stress, antivasoconstrictive, antiapoptotic properties which benefit ascitic, cirrhotic rats with systemic, hepatic, and renal abnormalities.

['Tsai|Yu-Lien|YL|', 'Liu|Chih-Wei|CW|', 'Hsu|Chien-Fu|CF|', 'Huang|Chia-Chang|CC|', 'Lin|Ming-Wei|MW|', 'Huang|Shiang-Fen|SF|', 'Li|Tzu-Hao|TH|', 'Lee|Kuei-Chuan|KC|', 'Hsieh|Yun-Cheng|YC|', 'Yang|Ying-Ying|YY|', 'Lee|Tzung-Yan|TY|', 'Liu|Hsuan-Miao|HM|', 'Huang|Yi-Hsiang|YH|', 'Hou|Ming-Chih|MC|', 'Lin|Han-Chieh|HC|']

2020

29371216

Bmal1 in Perivascular Adipose Tissue Regulates Resting-Phase Blood Pressure Through Transcriptional Regulation of Angiotensinogen.

BACKGROUND The perivascular adipose tissue (PVAT) surrounding vessels constitutes a distinct functional integral layer of the vasculature required to preserve vascular tone under physiological conditions. However, there is little information on the relationship between PVAT and blood pressure regulation, including its potential contributions to circadian blood pressure variation. METHODS Using unique brown adipocyte-specific aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and angiotensinogen knockout mice, we determined the vasoactivity of homogenized PVAT in aortic rings and how brown adipocyte peripheral expression of Bmal1 and angiotensinogen in PVAT regulates the amplitude of diurnal change in blood pressure in mice. RESULTS We uncovered a peripheral clock in PVAT and demonstrated that loss of Bmal1 in PVAT reduces blood pressure in mice during the resting phase, leading to a superdipper phenotype. PVAT extracts from wild-type mice significantly induced contractility of isolated aortic rings in vitro in an endothelium-independent manner. This property was impaired in PVAT from brown adipocyte-selective Bmal1-deficient (BA-Bmal1-KO) mice. The PVAT contractile properties were mediated by local angiotensin II, operating through angiotensin II type 1 receptor-dependent signaling in the isolated vessels and linked to PVAT circadian regulation of angiotensinogen. Indeed, angiotensinogen mRNA and angiotensin II levels in PVAT of BA-Bmal1-KO mice were significantly reduced. Systemic infusion of angiotensin II, in turn, reduced Bmal1 expression in PVAT while eliminating the hypotensive phenotype during the resting phase in BA-Bmal1-KO mice. Angiotensinogen, highly expressed in PVAT, shows circadian expression in PVAT, and selective deletion of angiotensinogen in brown adipocytes recapitulates the phenotype of selective deletion of Bmal1 in brown adipocytes. Furthermore, angiotensinogen is a transcriptional target of Bmal1 in PVAT. CONCLUSIONS These data indicate that local Bmal1 in PVAT regulates angiotensinogen expression and the ensuing increase in angiotensin II, which acts on smooth muscle cells in the vessel walls to regulate vasoactivity and blood pressure in a circadian fashion during the resting phase. These findings will contribute to a better understanding of the cardiovascular complications of circadian disorders, alterations in the circadian dipping phenotype, and cross-talk between systemic and peripheral regulation of blood pressure.

['Chang|Lin|L|', 'Xiong|Wenhao|W|', 'Zhao|Xiangjie|X|', 'Fan|Yanbo|Y|', 'Guo|Yanhong|Y|', 'Garcia-Barrio|Minerva|M|', 'Zhang|Jifeng|J|', 'Jiang|Zhisheng|Z|', 'Lin|Jiandie D|JD|', 'Chen|Y Eugene|YE|']

2018

33923675

Laser Discoloration in Acrylic Painting of Visual Art: Experiment and Modeling.

This study discloses a method for painting artwork using a CO2 laser. The continuous-wave laser beam, at a predetermined heat flux and a predetermined number of laser beam passes, mixes and displaces the plurality of colored polymer-based compositions, respectively, by way of melting and vaporizing them. Experiments showed a great accuracy of colors and designed patterns between the computer aided design (CAD) drawing and what was achieved after laser discoloration. It was found that lower values of power and speed provide sufficient energy and time to make a melt pool of colors and cause their vaporization from the surface. A detailed numerical simulation was performed to obtain a detailed understanding of the physics of laser interaction with paint using ABAQUS software. The comparative analysis indicated that the top layer of paint (including yellow and green colors) melted upon increasing cutting speed and employing one laser pass. For blue and red paints, two passes of lasers are required; in the case of red color, lower laser speed is also necessary to intensify the heat. This method can be applied for making art designs on each surface color because it is based on melting and vaporization using a laser.

['Tamrin|Khairul Fikri|KF|0000-0003-2180-9610', 'Moghadasi|Kaveh|K|', 'Jalil|Marzie Hatef|MH|', 'Sheikh|Nadeem Ahmed|NA|0000-0003-2405-1358', 'Mohamaddan|Shahrol|S|']

2021

28117128

How consumers of plastic water bottles are responding to environmental policies?

Although plastic induces environmental damages, almost all water bottles are made from plastic and the consumption never stops increasing. This study evaluates the consumers' willingness to pay (WTP) for different plastics used for water packaging. Successive messages emphasizing the characteristics of plastic are delivered to consumers allowing explaining the influence of information on the consumers' WTP. We find that information has a manifest effect on the WTP. We show there is a significant premium associated with recycled plastic packaging and biodegradable bioplastic packaging. As there is no consensus on the plastic which is the most or the least dangerous for the environment, we propose different policies for protecting the environment. We discuss about the impact of these policies on consumer's purchasing decisions: switching one plastic packaging for another, or leaving water plastic bottles market. We present the environmental policies that are effective according to the point of view adopted. Choosing between these policies then depends on the priorities of the regulator and pressure of lobbies.

['Orset|Caroline|C|', 'Barret|Nicolas|N|', 'Lemaire|Aurélien|A|']

2017

27283535

Implementation of an extended ZINB model in the study of low levels of natural gastrointestinal nematode infections in adult sheep.

BACKGROUND In this study, two traits related with resistance to gastrointestinal nematodes (GIN) were measured in 529 adult sheep: faecal egg count (FEC) and activity of immunoglobulin A in plasma (IgA). In dry years, FEC can be very low in semi-extensive systems, such as the one studied here, which makes identifying animals that are resistant or susceptible to infection a difficult task. A zero inflated negative binomial model (ZINB) model was used to calculate the extent of zero inflation for FEC; the model was extended to include information from the IgA responses. RESULTS In this dataset, 64% of animals had zero FEC while the ZINB model suggested that 38% of sheep had not been recently infected with GIN. Therefore 26% of sheep were predicted to be infected animals with egg counts that were zero or below the detection limit and likely to be relatively resistant to nematode infection. IgA activities of all animals were then used to decide which of the sheep with zero egg counts had been exposed and which sheep had not been recently exposed. Animals with zero FEC and high IgA activity were considered resistant while animals with zero FEC and low IgA activity were considered as not recently infected. For the animals considered as exposed to the infection, the correlations among the studied traits were estimated, and the influence of these traits on the discrimination between unexposed and infected animals was assessed. CONCLUSIONS The model presented here improved the detection of infected animals with zero FEC. The correlations calculated here will be useful in the development of a reliable index of GIN resistance that could be of assistance for the study of host resistance in studies based on natural infection, especially in adult sheep, and also the design of breeding programs aimed at increasing resistance to parasites.

['Atlija|M|M|', 'Prada|J M|JM|', 'Gutiérrez-Gil|B|B|', 'Rojo-Vázquez|F A|FA|', 'Stear|M J|MJ|', 'Arranz|J J|JJ|', 'Martínez-Valladares|M|M|']

2016

33568995

Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines.

Many studies have shown that the efficacy and risk of side effects of drug treatment is influenced by genetic variants. Evidence based guidelines are essential for implementing pharmacogenetic knowledge in daily clinical practice to optimize pharmacotherapy of individual patients. A literature search was performed to select committees developing guidelines with recommendations being published in English. The Dutch Pharmacogenetics Working Group (DPWG), the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Canadian Pharmacogenomics Network for Drug Safety (CPNDS), and the French National Network (Réseau) of Pharmacogenetics (RNPGx) were selected. Their guidelines were compared with regard to the methodology of development, translation of genotypes to predicted phenotypes, pharmacotherapeutic recommendations and recommendations on genotyping. A detailed overview of all recommendations for gene-drug combinations is given. The committees have similar methodologies of guideline development. However, the objectives differed at the start of their projects, which have led to unique profiles and strengths of their guidelines. DPWG and CPIC have a main focus on pharmacotherapeutic recommendations for a large number of drugs in combination with a patient's genotype or predicted phenotype. DPWG, CPNDS and RNPGx also recommend on performing genetic testing in daily clinical practice, with RNPGx even describing specific clinical settings or medical conditions for which genotyping is recommended. Discordances exist, however committees also initiated harmonizing projects. The outcome of a consensus project was to rename "extensive metabolizer (EM)" to "normal metabolizer (NM)". It was decided to translate a CYP2D6 genotype with one nonfunctional allele (activity score 1.0) into the predicted phenotype of intermediate metabolizer (IM). Differences in recommendations are the result of the methodologies used, such as assessment of dose adjustments of tricyclic antidepressants. In some cases, indication or dose specific recommendations are given for example for clopidogrel, codeine, irinotecan. The following drugs have recommendations on genetic testing with the highest level: abacavir (HLA), clopidogrel (CYP2C19), fluoropyrimidines (DPYD), thiopurines (TPMT), irinotecan (UGT1A1), codeine (CYP2D6), and cisplatin (TPMT). The guidelines cover many drugs and genes, genotypes, or predicted phenotypes. Because of this and their unique features, considering the totality of guidelines are of added value. In conclusion, many evidence based pharmacogenetics guidelines with clear recommendations are available for clinical decision making by healthcare professionals, patients and other stakeholders.

['Abdullah-Koolmees|Heshu|H|', 'van Keulen|Antonius M|AM|', 'Nijenhuis|Marga|M|', 'Deneer|Vera H M|VHM|']

2020

24327493

Off-label drug use in a single-center pediatric cardiac intensive care unit.

BACKGROUND The frequency of off-label drug use and its association with morbidity and mortality in the cardiac intensive care unit (CICU) has not been previously studied. METHODS Patients less than 18 years of age admitted to the CICU from June to August 2008 were retrospectively identified. Patient demographics were collected for 30 days or until CICU discharge. Off-label drug use was defined as the prescription of a medication that lacked a labeled indication based on patient's age as reported in the Micromedex drug database and electronic Physician's Desk Reference. RESULTS Eighty-two patients were admitted to the CICU during the study period. In all, 40 (46%) patients were male; the median age was 10.6 months. Common diagnoses were left-to-right shunt lesions (20.7%) and single-ventricle lesions (20.7%), with an overall mortality of 2.4%. Of all drugs prescribed, 36% were off-label. In all, 94% of the patients received ≥1 drug off-label. The median number of drugs prescribed off-label was four. Patients receiving more than four off-label medications were younger, had longer CICU lengths of stay (median 9.5 vs 2 days, P < .001), and increased ventilator days (median two vs one day, P < .001). CONCLUSIONS Off-label drug use in the CICU is common. Frequency of use is likely higher in patients with a higher severity of illness. Further safety, efficacy, and pharmaceutical trials are warranted to optimize the use of these drugs to improve outcomes.

['Maltz|Lily A|LA|', 'Klugman|Darren|D|', 'Spaeder|Michael C|MC|', 'Wessel|David L|DL|']

2013

27957206

ICD Implantation Practice Within Europe: How To Explain The Differences Beyond Economy?

Implantable cardioverter defibrillators (ICD) offer the potential to prevent sudden cardiac death and demonstrated a survival benefit in high risk cardiac patients. ICD implantation rates vary significantly throughout the countries all over Europe although there are no major differences in cardiovascular morbidity among countries. ICD implantation rates in each European country may be influenced by economic factors, including the gross domestic product, its percentage devoted to public health, and organization of the health system. However, ICD implantation rates vary substantially also among countries with a high gross domestic product. Beyond economy, other important factors that may influence ICD implantation rates are lack of guidelines awareness and poor guidelines adherence especially when treating specific subgroup of patients (such as elderly and those with non ischemic cardiomyopathies).

['Stella|Baccillieri Maria|BM|', 'Alessandro|Zorzi|Z|']

2015

32459647

Intra-Rater and Inter-Rater Reliability of Tongue Coating Diagnosis in Traditional Chinese Medicine Using Smartphones: Quasi-Delphi Study.

BACKGROUND There is a growing trend in the use of mobile health (mHealth) technologies in traditional Chinese medicine (TCM) and telemedicine, especially during the coronavirus disease (COVID-19) outbreak. Tongue diagnosis is an important component of TCM, but also plays a role in Western medicine, for example in dermatology. However, the procedure of obtaining tongue images has not been standardized and the reliability of tongue diagnosis by smartphone tongue images has yet to be evaluated. OBJECTIVE The first objective of this study was to develop an operating classification scheme for tongue coating diagnosis. The second and main objective of this study was to determine the intra-rater and inter-rater reliability of tongue coating diagnosis using the operating classification scheme. METHODS An operating classification scheme for tongue coating was developed using a stepwise approach and a quasi-Delphi method. First, tongue images (n=2023) were analyzed by 2 groups of assessors to develop the operating classification scheme for tongue coating diagnosis. Based on clinicians' (n=17) own interpretations as well as their use of the operating classification scheme, the results of tongue diagnosis on a representative tongue image set (n=24) were compared. After gathering consensus for the operating classification scheme, the clinicians were instructed to use the scheme to assess tongue features of their patients under direct visual inspection. At the same time, the clinicians took tongue images of the patients with smartphones and assessed tongue features observed in the smartphone image using the same classification scheme. The intra-rater agreements of these two assessments were calculated to determine which features of tongue coating were better retained by the image. Using the finalized operating classification scheme, clinicians in the study group assessed representative tongue images (n=24) that they had taken, and the intra-rater and inter-rater reliability of their assessments was evaluated. RESULTS Intra-rater agreement between direct subject inspection and tongue image inspection was good to very good (Cohen κ range 0.69-1.0). Additionally, when comparing the assessment of tongue images on different days, intra-rater reliability was good to very good (κ range 0.7-1.0), except for the color of the tongue body (κ=0.22) and slippery tongue fur (κ=0.1). Inter-rater reliability was moderate for tongue coating (Gwet AC2 range 0.49-0.55), and fair for color and other features of the tongue body (Gwet AC2=0.34). CONCLUSIONS Taken together, our study has shown that tongue images collected via smartphone contain some reliable features, including tongue coating, that can be used in mHealth analysis. Our findings thus support the use of smartphones in telemedicine for detecting changes in tongue coating.

['Wang|Zhi Chun|ZC|0000-0002-9045-6831', 'Zhang|Shi Ping|SP|0000-0002-6413-5778', 'Yuen|Pong Chi|PC|0000-0002-9343-2202', 'Chan|Kam Wa|KW|0000-0002-3175-1574', 'Chan|Yi Yi|YY|0000-0002-9226-0576', 'Cheung|Chun Hoi|CH|0000-0003-2936-2921', 'Chow|Chi Ho|CH|0000-0002-1894-8903', 'Chua|Ka Kit|KK|0000-0002-0446-3155', 'Hu|Jun|J|0000-0002-7954-9965', 'Hu|Zhichao|Z|0000-0003-1628-4274', 'Lao|Beini|B|0000-0002-0600-143X', 'Leung|Chun Chuen|CC|0000-0002-7294-1454', 'Li|Hong|H|0000-0002-6897-9257', 'Zhong|Linda|L|0000-0002-3877-1914', 'Liu|Xusheng|X|0000-0002-0931-4925', 'Liu|Yulong|Y|0000-0003-3630-6936', 'Liu|Zhenjie|Z|0000-0003-1008-0043', 'Lun|Xin|X|0000-0002-2071-4137', 'Mo|Wei|W|0000-0003-1039-2047', 'Siu|Sheung Yuen|SY|0000-0003-0234-9348', 'Xiong|Zhoujian|Z|0000-0003-2541-7446', 'Yeung|Wing Fai|WF|0000-0002-7980-3126', 'Zhang|Run Yun|RY|0000-0003-1803-2249', 'Zhang|Xuebin|X|0000-0002-3678-8149']

2020

32151263

Serious games for serious crises: reflections from an infectious disease outbreak matrix game.

BACKGROUND While there is widespread recognition of global health failures when it comes to infectious disease outbreaks, there is little discussion on how policy-makers and global health organizations can learn to better prepare and respond. Serious games provide an underutilized tool to promote learning and innovation around global health crises. In order to explore the potential of Serious Games as a policy learning tool, Global Affairs Canada, in collaboration with the Department of National Defense and academic partners, developed and implemented a matrix game aimed at prompting critical reflection and gender-based analysis on infectious disease outbreak preparedness and response. This commentary, written by the core development team, reflects on the process and outcomes of the gaming exercise, which we believe will be of interest to others hoping to promote innovative thinking and learning around global health policy and crisis response, as well as the application of serious games more broadly. MAIN BODY Participants reported, through discussions and a post-game survey, that they felt the game was reflective of real-world decision-making and priority-setting challenges during a crisis. They reflected on the challenges that emerge around global health co-operation and outbreak preparedness, particularly noting the importance of learning to work with private actors. While participants only sporadically applied gender-based analysis or considered the social determinants of health during the game, post-game discussions led to reflection on the ways in which equity concerns are put aside during a crisis scenario and on why this happens, offering critical learning opportunities. CONCLUSION Matrix games provide opportunities for policy-makers and health professionals to experience the challenges of global health co-operation, test ideas and explore how biases, such as those around gender, influence policy-making and implementation. Due to their flexibility, adaptability and accessibility, serious games offer a potentially powerful learning tool for global health policy-makers and practitioners.

['Smith|Julia|J|0000-0002-5175-1109', 'Sears|Nathan|N|', 'Taylor|Ben|B|', 'Johnson|Madeline|M|']

2020

30497226

Endoscope-assisted hemispherotomy: translation of technique from cadaveric anatomical feasibility study to clinical implementation.

OBJECTIVEAppropriately chosen candidates with medically refractory epilepsy may benefit from hemispheric disconnection. Traditionally, this involves a large surgical exposure with significant associated morbidity. Minimally invasive approaches using endoscopic assistance have been described by only a few centers. Here, the authors report on the feasibility of endoscope-assisted functional hemispherotomy in a cadaver model and its first translation into clinical practice in appropriately selected patients.METHODSThree silicone-injected, formalin-fixed cadaver heads were used to establish the steps of the procedure in the laboratory. The steps of disconnection were performed using standard surgical instruments and a straight endoscope. The technique was then applied in two patients who had been referred for hemispherectomy and had favorable anatomy for an endoscope-assisted approach.RESULTSAll disconnections were performed in the cadaver model via a 4 × 2-cm paramedian keyhole craniotomy using endoscopic assistance. An additional temporal burr hole approach was marked in case the authors were unable to completely visualize the frontobasal and insular cuts from the paramedian vertical view. Their protocol was subsequently used successfully in two pediatric patients. Full disconnection was verified with postoperative tractography.CONCLUSIONSFull hemispheric disconnection can be accomplished with minimally invasive endoscope-assisted functional hemispherotomy. The procedure is technically feasible and can be safely applied in patients with favorable anatomy and pathology; it may lead to less surgical morbidity and faster recovery.

['Wagner|Kathryn|K|', 'Vaz-Guimaraes|Francisco|F|', 'Camstra|Kevin|K|', 'Lam|Sandi|S|']

2018

28508022

Impact of Health Literacy on Senior Citizen Engagement in Health Care IT Usage.

Objective: Patient engagement in health care information technology (IT) is required for government reimbursement programs. This research surveyed one older adult group to determine their willingness to use health information from a variety of sources. Health literacy was also measured using the Newest Vital Sign (NVS) and eHealth Literacy Scale (eHEALS) tools. Method: Regression models determined engagement in health care IT usage and impact of literacy levels based on survey data collected from the group. Results: Although most participants have adequate literacy, they are not more likely to use health care IT than those with limited literacy scores. Knowledge of how to use the Internet to answer questions about health was statistically associated with IT usage. Discussion: Health care IT usage is important for healthy aging. The ability of older adults to understand information provided to them can impact population health including medication usage and other important factors.

['Noblin|Alice M|AM|', 'Rutherford|Ashley|A|']

2017

30676086

Bounds on Identification of Genome Evolution Pacemakers.

Several studies have pointed out that the tight correlation between genes' evolutionary rate is better explained by a model denoted as the

['Snir|Sagi|S|']

2019

29945915

Linoleic Acid in Adipose Tissue and Development of Ischemic Stroke: A Danish Case-Cohort Study.

BACKGROUND We investigated the association between the content of linoleic acid in adipose tissue, a biomarker of long-term intake of linoleic acid, and the risk of ischemic stroke and its subtypes. METHODS AND RESULTS The Danish cohort study Diet, Cancer and Health included 57 053 patients aged 50 to 65 years at enrollment. All participants had an adipose tissue biopsy performed at enrollment, while information on ischemic stroke during follow-up was obtained from the Danish National Patient Register. Stroke diagnoses were all validated and classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Cases and a randomly drawn subcohort of 3500 patients had their fatty acid composition in adipose tissue determined by gas chromatography. Hazard ratios with 95% confidence intervals were calculated using weighted Cox proportional hazard regression. During 13.5 years of follow-up, 1879 ischemic stroke cases were identified, for which 1755 adipose biopsies were available, while adipose biopsies were available for 3203 participants in the subcohort. When comparing the highest and the lowest quartiles of adipose tissue content of linoleic acid there was a negative association with the rate of total ischemic stroke (hazard ratio, 0.78; 95% confidence interval, 0.65-0.93) and large artery atherosclerosis (hazard ratio, 0.61; 95% confidence interval, 0.43-0.88), while there was an indication of a negative association with small-vessel occlusion (hazard ratio, 0.87; 95% confidence interval, 0.69-1.11). There was no clear association with the rate of cardioembolism. CONCLUSIONS The content of linoleic acid in adipose tissue was inversely associated with the risk of total ischemic stroke and stroke caused by large artery atherosclerosis.

['Venø|Stine Krogh|SK|', 'Bork|Christian Sørensen|CS|', 'Jakobsen|Marianne Uhre|MU|', 'Lundbye-Christensen|Søren|S|', 'Bach|Flemming Winther|FW|', 'Overvad|Kim|K|', 'Schmidt|Erik Berg|EB|']

2018

28979769

Single-incision laparoscopic surgery in gynecologic surgery: a single-institutional experience from Saudi Arabia.

Background: Laparoscopy is rapidly replacing laparotomy in the field of gynecologic surgery. Generally, there are limited data concerning the utility of single-incision laparoscopic surgery (SILS) in gynecologic surgery. Specifically, in Saudi Arabia, a third-world country, data are further limited; only one related study has been conducted so far. The purpose of this study is to retrospectively report our single-institutional experience of SILS in terms of feasibility, safety and perioperative outcomes in the management of various gynecologic conditions. Methods: The study took place at the Women's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia. From January 2012 to May 2016, all gynecologic patients who underwent SILS procedures were analyzed for pre-, intra- and post-operative details. SILS was performed using a single multi-port trocar and standard laparoscopic instruments. Results: A total of 54 patients underwent 66 SILS procedures. The median age and body mass index (BMI) were 36 years and 28.2 kg/m 2, respectively. Fourteen patients (26%) had ≥ 1 previous abdominal and/or pelvic surgeries. Twenty-four patients (44.4%) were nulliparous. The three most commonly performed SILS procedures were unilateral salpingo-oophorectomy (45.5%) and unilateral ovarian cystectomy (27.3%) and adhesiolysis (6.1%). The median operative time, estimated blood loss and hospital stay were 74 min, 50 ml and 1 day, respectively. Three patients required conversion to laparotomy, as follows: unidentified non-stopping bleeding source (n=1) and endometriosis stage IV resulting in difficult dissection (n=2). One patient developed post-operative incisional hernia that was treated surgically. The median patients' post-operative pain (according to Wong-Baker FACES Foundation pain rating scale) within 4 hours was 2. At 4-week post-operatively, the median wound scar length (measured at outpatient clinic) was 2 cm. Conclusions: SILS is feasible, safe and associated with acceptable clinical and surgical outcomes.

['Salamah|Kareemah|K|', 'Abuzaid|Mohammed|M|', 'Abu-Zaid|Ahmed|A|https://orcid.org/0000-0003-2286-2181']

2017

28235537

The concentration of desflurane preventing spectral entropy change during surgical stimulation: A prospective randomized trial.

STUDY OBJECTIVE To determine the concentration of desflurane necessary to blunt changes in spectral entropy during surgical incision when two different target-controlled effect-site concentrations of remifentanil (1 and 3ng/ml) were infused. DESIGN Prospective, randomized controlled study. SETTING Operating room of a university hospital. INTERVENTIONS Forty-two patients undergoing general anesthesia for elective surgery were enrolled and randomly allocated to the R1 (1ng/ml of remifentanil, n=21) or R3 (3ng/ml of remifentanil, n=21) group. After at least a 10-min administration of target-controlled remifentanil concentration and predetermined end-tidal desflurane following endotracheal intubation, changes in spectral entropy in response to surgical incision were evaluated. MEASUREMENTS Concentration of desflurane necessary to blunt changes in spectral entropy during surgical incision for each group was determined using Dixon's up-and-down method. Hemodynamic variables including mean arterial pressure (MAP) and heart rate (HR) were measured. MAIN RESULTS Concentration of desflurane necessary to blunt changes in spectral entropy during surgical incision in 50% of patients (EC50) was 4.1% (95% CI: 3.5-4.7%) for the R1 group and 3.4% (95% CI: 3.0-3.8%) for the R3 group (P=0.033). Additionally, the calculated EC95 values using the logistic regression analysis for the R1 and R3 groups were 5.8% (95% CI: 5.0-10.8%) and 5.1% (95% CI: 4.3-10.6%), respectively. MAPs and HRs were significantly higher in the R1 than in the R3 group after surgical incision. CONCLUSIONS Desflurane 4.1% with remifentanil 1ng/ml and desflurane 3.4% with remifentanil 3ng/ml significantly blunt the change in spectral entropy after surgical incision in 50% of patients.

['Han|Sun-Sook|SS|', 'Han|Sunghee|S|', 'Kim|Byung-Gook|BG|', 'Kim|Dong-Ho|DH|', 'Ryu|Jung-Hee|JH|']

2017

25344370

Ten-year follow-up of the 'minimal MRI lesion' subgroup from the original CHAMPS Multiple Sclerosis Prevention Trial.

BACKGROUND Patients with clinically isolated syndrome (CIS) and characteristic magnetic resonance imaging (MRI) lesions are at high risk for multiple sclerosis (MS). However, patients with a minimal MRI lesion burden (a low T2-hyperintense [low T2] lesion count) may have borderline formal diagnostic criteria, presenting a clinical management challenge. OBJECTIVE Compare the 10-year disease progression of patients with low and higher T2 lesion counts treated over most intervals. METHODS CIS patients from the original CHAMPS MS trial were retrospectively assigned to low-T2 (first quartile; 2-8 lesions) or higher-T2 (second through fourth quartiles; ≥ 9 lesions) groups using baseline T2 lesion counts. The 5- and 10-year open-label extension of CHAMPS (CHAMPIONS) evaluated conversion to clinically definite MS (CDMS), MRI activity, relapses, and disability. RESULTS The vast majority of patients showed new disease activity by MRI and/or clinical criteria at 10 years (low-T2 86%; higher-T2 98%). Fewer low-T2 than higher-T2 patients developed CDMS (40% vs. 63%; p = 0.013); low-T2 patients also had fewer new brain lesions, less brain volume loss, and less disability progression. CONCLUSION CIS patients with low T2 lesion counts show continued disease activity. However, all assessments of disease progression over 10 years indicated a significantly less severe disease course for low-T2 patients.

['Simon|J H|JH|', 'Kinkel|R P|RP|', 'Kollman|C|C|', "O'Connor|P|P|", 'Fisher|E|E|', 'You|X|X|', 'Hyde|R|R|', '|||']

2015

31068888

Severity of Tinnitus Distress Negatively Impacts Quality of Life in Patients With Vestibular Schwannoma and Mimics Primary Tinnitus.

Objective: Quality of life (QoL) and subjective symptoms are predominantly used to evaluate treatment outcome of patients with vestibular schwannoma (VS). However, for patients undergoing conservative treatment-the most frequently used intervention-the association between QoL and subjective symptoms is unclear. Moreover, it is unknown whether VS-related tinnitus could be associated with the audiological and psychological status of the patient. Our overall aim is to provide objective evidence of this association to better guide treatment of VS. Methods: In a prospective study, we analyzed factors that influence VS-related tinnitus and QoL in 72 patients receiving conservative management of unilateral sporadic VS. This was done through questionnaires that assessed QoL, anxiety, depression, and audiological examinations. We used the SF-36 Short Form to assess QoL; the Tinnitus Handicap Inventory, Dizziness Handicap Inventory, Facial Clinimetric Evaluation Scale, Visual Analog Scale for hearing impairment to assess symptoms subjectively; and pure tone audiometry, the speech discrimination for hearing measurements. For psychological status, we used the Hospital Anxiety and Depression Scale. For analyses, we used Pearson correlation analysis and multiple regression between variables and QoL. Results: Correlation and regression analyses revealed that the severity of tinnitus distress had the largest negative impact on QoL in all domains of SF-36. The severity of tinnitus was significantly associated with subjective hearing impairment and the degree of depression and anxiety. Hearing thresholds had no statistical association with severity of tinnitus. Conclusions: To our knowledge, this is the first study to investigate VS-related tinnitus with respect to both patients' hearing status and psychological condition. Our results suggest that tinnitus distress strongly affects VS patients' QoL and that its characteristics are similar to primary tinnitus. An intervention for VS-related tinnitus, therefore, should assess to what extent tinnitus bothers patients, and it should reduce any unpleasant emotions that may exacerbate symptoms. This approach should improve their QoL.

['Kojima|Takashi|T|', 'Oishi|Naoki|N|', 'Nishiyama|Takanori|T|', 'Ogawa|Kaoru|K|']

2019

31482624

Outcome of catheter ablation of supraventricular tachyarrhythmias in cardiac sarcoidosis.

BACKGROUND Sarcoidosis is a multisystem granulomatous disease of not sufficiently understood origin. Some patients develop cardiac involvement in course of the disease which is mostly responsible for adverse outcome. In addition to complications like high degree atrioventricular (AV) block or ventricular tachyarrhythmias, there is a certain percentage of patients developing atrial tachyarrhythmias. Data is limited and the role of catheter ablation uncertain. Therefore, we studied sarcoid patients who presented with supraventricular tachyarrhythmias. HYPOTHESIS Treatment and ablation of supraventricular tachycardia could be hampered by inflammation in patients with cardiac sarcoidosis. METHODS We enrolled 37 consecutive patients with cardiac sarcoidosis who presented with atrial tachyarrhythmias and underwent an electrophysiologic study over a period of 6 years (03/2013-04/2019). In total, 16 catheter ablations for atrial tachyarrhythmias were performed. Mean follow-up duration was 2.5 years. RESULTS Most common ablation performed was cavo-tricuspid isthmus ablation for typical atrial flutter in seven patients (54%). Pulmonary vein isolation for treatment of atrial fibrillation (AF) was performed in five patients (38%). Two patients received slow-pathway modulation for treatment of recurrent atrioventricular nodal reentry tachycardia (AVNRT). All but two patients with AF had no clinical recurrence during follow-up. Two patients had recurrence of AF but still reported markedly improved european heart rhythm association (EHRA) class. Periprocedural safety was very high. There were no adverse events related to the ablation procedure. One patient died during follow-up in the presence of electrical storm. CONCLUSION Catheter ablations of supraventricular tachycardias seem to be safe and effective in patients with cardiac sarcoidosis. Outcome is comparable to patients without inflammatory heart disease, although data from larger patient collectives are mandatory to make recommendations in this special entity.

['Willy|Kevin|K|https://orcid.org/0000-0003-1259-3213', 'Dechering|Dirk G|DG|', 'Wasmer|Kristina|K|', 'Köbe|Julia|J|', 'Bögeholz|Nils|N|', 'Ellermann|Christian|C|', 'Leitz|Patrick|P|', 'Reinke|Florian|F|', 'Frommeyer|Gerrit|G|https://orcid.org/0000-0002-1431-9886', 'Eckardt|Lars|L|']

2019

33328202

Boys are more likely to be undernourished than girls: a systematic review and meta-analysis of sex differences in undernutrition.

BACKGROUND Excess male morbidity and mortality is well recognised in neonatal medicine and infant health. In contrast, within global nutrition, it is commonly assumed that girls are more at risk of experiencing undernutrition. We aimed to explore evidence for any male/female differences in child undernutrition using anthropometric case definitions and the reasons for differences observed. METHODS We searched: Medline, Embase, Global health, Popline and Cochrane databases with no time limits applied. Eligible studies focused on children aged 0-59 months affected by undernutrition where sex was reported. In the meta-analysis, undernutrition-specific estimates were examined separately for wasting, stunting and underweight using a random-effects model. RESULTS 74 studies were identified: 44/74 studies were included in the meta-analysis. In 20 which examined wasting, boys had higher odds of being wasted than girls (pooled OR 1.26, 95% CI 1.13 to 1.40). 38 examined stunting: boys had higher odds of stunting than girls (pooled OR 1.29 95% CI 1.22 to 1.37). 23 explored underweight: boys had higher odds of being underweight than girls (pooled OR 1.14, 95% CI 1.02 to 1.26). There was some limited evidence that the female advantage, indicated by a lower risk of stunting and underweight, was weaker in South Asia than other parts of the world. 43/74 (58%) studies discussed possible reasons for boy/girl differences; 10/74 (14%) cited studies with similar findings with no further discussion; 21/74 (28%) had no sex difference discussion. 6/43 studies (14%) postulated biological causes, 21/43 (49%) social causes and 16/43 (37%) to a combination. CONCLUSION Our review indicates that undernutrition in children under 5 is more likely to affect boys than girls, though the magnitude of these differences varies and is more pronounced in some contexts than others. Future research should further explore reasons for these differences and implications for nutrition policy and practice.

['Thurstans|Susan|S|0000-0002-7102-446X', 'Opondo|Charles|C|0000-0001-8155-4117', 'Seal|Andrew|A|0000-0003-3656-4054', 'Wells|Jonathan|J|0000-0003-0411-8025', 'Khara|Tanya|T|', 'Dolan|Carmel|C|', 'Briend|André|A|', 'Myatt|Mark|M|', 'Garenne|Michel|M|0000-0001-6073-7803', 'Sear|Rebecca|R|0000-0002-4315-0223', 'Kerac|Marko|M|0000-0002-3745-7317']

2020

25128567

Histone acetylation in astrocytes suppresses GFAP and stimulates a reorganization of the intermediate filament network.

Glial fibrillary acidic protein (GFAP) is the main intermediate filament in astrocytes and is regulated by epigenetic mechanisms during development. We demonstrate that histone acetylation also controls GFAP expression in mature astrocytes. Inhibition of histone deacetylases (HDACs) with trichostatin A or sodium butyrate reduced GFAP expression in primary human astrocytes and astrocytoma cells. Because splicing occurs co-transcriptionally, we investigated whether histone acetylation changes the ratio between the canonical isoform GFAPα and the alternative GFAPδ splice variant. We observed that decreased transcription of GFAP enhanced alternative isoform expression, as HDAC inhibition increased the GFAPδ∶GFAPα ratio. Expression of GFAPδ was dependent on the presence and binding of splicing factors of the SR protein family. Inhibition of HDAC activity also resulted in aggregation of the GFAP network, reminiscent of our previous findings of a GFAPδ-induced network collapse. Taken together, our data demonstrate that HDAC inhibition results in changes in transcription, splicing and organization of GFAP. These data imply that a tight regulation of histone acetylation in astrocytes is essential, because dysregulation of gene expression causes the aggregation of GFAP, a hallmark of human diseases like Alexander's disease.

['Kanski|Regina|R|', 'Sneeboer|Marjolein A M|MA|', 'van Bodegraven|Emma J|EJ|', 'Sluijs|Jacqueline A|JA|', 'Kropff|Wietske|W|', 'Vermunt|Marit W|MW|', 'Creyghton|Menno P|MP|', 'De Filippis|Lidia|L|', 'Vescovi|Angelo|A|', 'Aronica|Eleonora|E|', 'van Tijn|Paula|P|', 'van Strien|Miriam E|ME|', 'Hol|Elly M|EM|']

2014

27807673

Correlation of geographic distributions of haptoglobin alleles with prevalence of multiple sclerosis (MS) - a narrative literature review.

We have proposed that the myelin damage observed in multiple sclerosis (MS) may be partly mediated through the long-term release and degradation of extracellular hemoglobin (Hb) and the products of its oxidative degradation [Cellular and Molecular Life Sciences, 71, 1789-1798, 2014]. The protein haptoglobin (Hpt) binds extracellular Hb as a first line of defense, and can serve as a vascular antioxidant. Humans have two different Hpt alleles: Hpt1 and Hpt2, giving either homozygous Hpt1-1 or Hpt2-2 phenotypes, or a heterozygous Hpt1-2 phenotype. We questioned whether those geographic regions with higher frequency of the Hpt2 allele (conversely, lower frequency of Hpt1 allele) would correlate with an increased incidence of MS, because different Hpt phenotypes will have variable anti-oxidative potentials in protecting myelin from damage inflicted by extracellular Hb and its degradation products. To test this hypothesis, we undertook a systematic analysis of the literature on reported geographic distributions of Hpt alleles to compare them with data reported in the World Health Organization Atlas of worldwide MS prevalence. We found the frequency of the Hpt1 allele to be low in European and North American countries with a high prevalence of MS, consistent with our hypothesis. However, this correlation was not observed in China and India, countries with the lowest Hpt1 frequencies, yet low reported prevalence of MS. Nevertheless, this work shows the need for continued refinement of geographic patterns of MS prevalence, including data on ethnic or racial origin, and for new clinical studies to probe the observed correlation and evaluate Hpt phenotype as a predictor of disease variability and progression, severity, and/or comorbidity with cardiovascular disorders.

['Bamm|Vladimir V|VV|', 'Geist|Arielle M|AM|', 'Harauz|George|G|0000-0002-6114-9947']

2017

25523879

Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies? A systematic review.

OBJECTIVE Systematically review the scientific evidence for efficiency of anti-inflammatory agents against gingivitis, either as solo treatments or adjunctive therapies. METHODS A protocol was developed aimed to answer the following focused question: "Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies?" RCTs and cohort studies on anti-inflammatory agents against gingivitis studies were searched electronically. Screening, data extraction and quality assessment were conducted. The primary outcome measures were indices of gingival inflammation. A sub-analysis was performed dividing the active agents into anti-inflammatory and other drugs. RESULTS The search identified 3188 studies, of which 14 RCTs met the inclusion criteria. The use of anti-inflammatory or other agents, in general showed a higher reduction in the test than in the control in terms of gingival indexes and bleeding scores. Only two RCTs on inflammatory drugs could be meta-analysed, showing a statistically significant reduction in the GI in the experimental group [WMD = -0.090; 95% CI (-0.105; -0.074); p = 0.000]. However, the contribution of both studies to the global result was unbalanced (% weight: 99.88 and 0.12 respectively). CONCLUSIONS Most of the tested material showed beneficial effect as anti-inflammatory agents against gingivitis, either as a single treatment modality or as an adjunctive therapy.

['Polak|David|D|', 'Martin|Conchita|C|', 'Sanz-Sánchez|Ignacio|I|', 'Beyth|Nurit|N|', 'Shapira|Lior|L|']

2015

34867223

Cortical Hub for Flavor Sensation in Rodents.

The experience of eating is inherently multimodal, combining intraoral gustatory, olfactory, and somatosensory signals into a single percept called flavor. As foods and beverages enter the mouth, movements associated with chewing and swallowing activate somatosensory receptors in the oral cavity, dissolve tastants in the saliva to activate taste receptors, and release volatile odorant molecules to retronasally activate olfactory receptors in the nasal epithelium. Human studies indicate that sensory cortical areas are important for intraoral multimodal processing, yet their circuit-level mechanisms remain unclear. Animal models allow for detailed analyses of neural circuits due to the large number of molecular tools available for tracing and neuronal manipulations. In this review, we concentrate on the anatomical and neurophysiological evidence from rodent models toward a better understanding of the circuit-level mechanisms underlying the cortical processing of flavor. While more work is needed, the emerging view pertaining to the multimodal processing of food and beverages is that the piriform, gustatory, and somatosensory cortical regions do not function solely as independent areas. Rather they act as an intraoral cortical hub, simultaneously receiving and processing multimodal sensory information from the mouth to produce the rich and complex flavor experience that guides consummatory behavior.

['Samuelsen|Chad L|CL|', 'Vincis|Roberto|R|']

2021

33333393

Experience of using tocilizumab for treatment in Indonesian patients with severe COVID-19.

COVID-19 is a public health emergency of international concern with millions confirmed cases globally including in Indonesia with more than two hundred thousand confirmed cases to date COVID-19. (1) COVID-19 has wide clinical manifestation ranging from asymptomatic, acute respiratory illness, respiratory failure that necessitates mechanical ventilation and support in an ICU, to MODS. (2) Several comorbidities have been demonstrated to be associated with the development of severe outcomes from COVID-19 infection, such as hypertension, diabetes, cardiovascular disease, dyslipidemia, thyroid disease, and pulmonary disease. (3)-(5) Severe COVID-19 is associated with increased plasma concentrations of IL-6, resulting in cytokine storm. (6) Tocilizumab, an interleukin-6 inhibitor, might alleviates the cytokine storm, prevents significant lungs and organs damage, thus improving clinical outcomes. (7) Therefore, tocilizumab, might be one of the promising therapies for severe COVID-19. (8) However there were limited studies regarding the efficacy in COVID-19 patients, especially with control group. We would like to report our experience in using tocilizumab as treatment in severe COVID-19 patients in Indonesia, which is the first in Indonesia to the best of our knowledge.

['Widysanto|Allen|A|', 'Kurniawan|Andree|A|', 'Lugito|Nata Pratama Hardjo|NPH|', 'Yuniarti|Mira|M|', 'Gunawan|Catherine|C|', 'Angela|||', 'Wiryanto|Jessica|J|', 'Levinna|||', 'Pradhana|Tasya Meidy|TM|']

2021

28916400

Assessing Changes in the Activity Levels of Breast Cancer Patients During Radiation Therapy.

BACKGROUND Radiation therapy (RT) is often delivered after lumpectomy for women with breast cancer. A common perceived side effect of RT is fatigue, yet its exact effect on activity levels and sleep is unknown. In this study we analyzed the change in activity levels and sleep using an activity tracking device before, during, and after RT for women with early stage breast cancer and ductal carcinoma in situ who underwent adjuvant RT. PATIENTS AND METHODS After institutional review board approval, activity levels were quantified before, during, and after RT with measurements of steps, miles walked, calories burned, and sleep metrics in 10 women fitted with activity trackers. All data were uploaded and tabulated on a secure database. Multivariable linear regressions were used to evaluate changes in these variables over time during the RT course. RESULTS Median step count was 5047 per day (range, 2741-15,508) and distance traveled was 1.6 miles per day (range, 0.9-5.3). Step count, distance, and calories decreased by an average of 54 steps per day, 0.02 miles per day, and 3 calories per day (median calories 1822; range, 1461-2712) during RT, respectively. These changes were statistically significant (P < .001), but not clinically relevant. There was no significant change in sleep (average 6.8 hours per night; range, 5.5-8.3). CONCLUSION RT has a minimal effect on activity or sleep in women undergoing treatment for breast cancer. Activity levels varied greatly between patients in a population of women undergoing hypofractionated RT. Because increased activity levels correlate with improved outcomes, further studies evaluating attempts to increase physical activity during as well as after treatment with radiation are warranted.

['Champ|Colin E|CE|', 'Ohri|Nitin|N|', 'Klement|Rainer J|RJ|', 'Cantor|Matthew|M|', 'Beriwal|Sushil|S|', 'Glaser|Scott M|SM|', 'Smith|Ryan P|RP|']

2018

28690422

Detection methods for stochastic gravitational-wave backgrounds: a unified treatment.

We review detection methods that are currently in use or have been proposed to search for a stochastic background of gravitational radiation. We consider both Bayesian and frequentist searches using ground-based and space-based laser interferometers, spacecraft Doppler tracking, and pulsar timing arrays; and we allow for anisotropy, non-Gaussianity, and non-standard polarization states. Our focus is on relevant data analysis issues, and not on the particular astrophysical or early Universe sources that might give rise to such backgrounds. We provide a unified treatment of these searches at the level of detector response functions, detection sensitivity curves, and, more generally, at the level of the likelihood function, since the choice of signal and noise models and prior probability distributions are actually what define the search. Pedagogical examples are given whenever possible to compare and contrast different approaches. We have tried to make the article as self-contained and comprehensive as possible, targeting graduate students and new researchers looking to enter this field.

['Romano|Joseph D|JD|', 'Cornish|Neil J|NJ|']

2017

25767516

Pimpinella anisum in the treatment of functional dyspepsia: A double-blind, randomized clinical trial.

BACKGROUND We aimed to evaluate the effects of Pimpinella anisum (anise) from Apiaceae family on relieving the symptoms of postprandial distress syndrome (PDS) in this double-blind randomized clinical trial. MATERIALS AND METHODS Totally, 107 patients attending the gastroenterology clinic, aged 18-65 years, diagnosed with PDS according to ROME III criteria and signed a written consent form were enrolled. They were randomized to receive either anise or placebo, blindly, for 4 weeks. Anise group included 47 patients and received anise powders, 3 g after each meal (3 times/day). Control group involved 60 patients and received placebo powders (corn starch), 3 gafter each meal (3 times/day). The severity of Functional dyspepsia (FD) symptoms was assessed by FD severity scale. Assessments were done at baseline and by the end of weeks 2, 4 and 12. Mean scores of severity of FD symptoms and the frequency distribution of patients across the study period were compared. RESULTS The age, sex, body mass index, smoking history, and coffee drinking pattern of the intervention and control groups were not significantly different. Mean (standard deviation) total scores of FD severity scale before intervention in the anise and control groups were 10.6 (4.1) and 10.96 (4.1), respectively (P = 0.6). They were 7.04 (4.1) and 12.30 (4.3) by week 2, respectively (P = 0.0001), 2.44 (4.2) and 13.05 (5.2) by week 4, respectively (P = 0.0001), and 1.08 (3.8) and 13.30 (6.2) by week 12, respectively (P = 0.0001). CONCLUSION This study showed the effectiveness of anise in relieving the symptoms of postpartum depression. The findings were consistent across the study period at weeks 2, 4 and 12.

['Ghoshegir|S Ashraffodin|SA|', 'Mazaheri|Mohammad|M|', 'Ghannadi|Alireza|A|', 'Feizi|Awat|A|', 'Babaeian|Mahmoud|M|', 'Tanhaee|Maryam|M|', 'Karimi|Mehrdad|M|', 'Adibi|Peyman|P|']

2015

34840803

Primary Hyperoxaluria Type 1 (PH1) Presenting With End-Stage Kidney Disease and Cutaneous Manifestations in Adulthood: A Case Report.

Rationale Primary hyperoxaluria (PH) is a rare autosomal recessive disorder more commonly diagnosed in children or adolescents. Owing to its rarity and heterogeneous phenotype, it is often underrecognized, resulting in delayed diagnosis, including diagnosis after end-stage kidney disease (ESKD) has occurred or recurrence after kidney-only transplantation. Case Presentation A 40-year-old Caucasian Canadian woman with a history of recurrent nephrolithiasis since age 19 presented with ESKD and cutaneous symptoms. She had no known prior kidney disease and no family history of kidney disease or nephrolithiasis. Diagnosis A diagnosis of primary hyperoxaluria type 1 (PH1) due to homozygous splice donor mutation (AGXT c.680+1G>A) was made with kidney and cutaneous pathology demonstrating calcium oxalate deposition and ultrasound suggestive of nephrocalcinosis. Interventions She was initiated on frequent, high-efficiency, high-flux conventional hemodialysis and oral pyridoxine. Lumasiran was added 11 months later, after she developed bilateral swan-neck deformities. Outcomes After 14 months of high-intensity dialysis and 3 months of lumasiran, there have been no signs of renal recovery, and extra-renal involvement has increased with progressive swan-neck deformities, reduced cardiac systolic function, and pulmonary hypertension. The patient has been waitlisted for kidney-liver transplantation. Teaching Points This case report describes an adult presentation of PH1. The case highlights the importance of timely workup of metabolic causes of recurrent nephrolithiasis or nephrocalcinosis in adults which can be a presenting sign of PH and genetic testing for PH to facilitate early diagnosis and treatment especially in the era of novel therapeutics that may alter disease course and outcomes. The case also demonstrates the value of testing for PH in adults presenting with unexplained ESKD and a history of recurrent nephrolithiasis or nephrocalcinosis due to implications for organ transplantation strategy and presymptomatic family screening.

['Poyah|Penelope|P|https://orcid.org/0000-0002-7575-2835', 'Bergman|Joel|J|', 'Geldenhuys|Laurette|L|', 'Wright|Glenda|G|', 'Walsh|Noreen M|NM|', 'Hull|Peter|P|', 'Roche|Kristina|K|', 'West|Michael L|ML|']

2021

25339258

Outcomes and treatments of mal fractures caused by the split-crest technique in the mandible.

In this study, we investigated cases of mal fracture occurring during the split-crest procedure. In all subjects (six patients), the free cortical bone segment caused by the mal fracture was carefully maintained in the lateral position without fixation using a titanium plate or screw. On pre- and postoperative multiplanar reconstruction CT, the average total alveolar increase was 5.0 mm in the lower portion 1 mm from the top of the alveolar ridge, and the average total alveolar increase in the lower portion 11 mm from the top of the alveolar ridge was 2.2 mm. A total of 11 dental implants were placed immediately at the same time as the split-crest procedure, while three dental implants were placed after a waiting period of 4-11 months from bone augmentation. During an average follow-up of 27.8 months, there were no complications or cases of failed implants. Consequently, among the patients who experienced mal fracture during the split-crest technique, a sufficient volume of alveolar bone was obtained without the need for rigid fixation of the free bone segment, and the dental implants placed within the area of the mal fracture showed a good prognosis.

['Shibuya|Yasuyuki|Y|', 'Yabase|Akiko|A|', 'Ishida|Suguru|S|', 'Kobayashi|Masaki|M|', 'Komori|Takahide|T|']

2014

34732286

The genetic basis of urate control and gout: Insights into molecular pathogenesis from follow-up study of genome-wide association study loci.

This review focuses on the post-genome-wide association study (GWAS) era in gout, i.e., the translation of GWAS genetic association signals into biologically informative knowledge. Analytical and experimental follow-up of individual loci, based on the identification of causal genetic variants, reveals molecular pathogenic pathways. We summarize in detail the largest GWAS in urate to date, then we review follow-up studies and molecular insights from ABCG2, HNF4A, PDZK1, MAF, GCKR, ALDH2, ALDH16A1, SLC22A12, SLC2A9, ABCC4, and SLC22A13, including the role of insulin signaling. One common factor in these pathways is the importance of transcriptional control, including the HNF4α transcription factor. The new molecular knowledge reveals new targets for intervention to manage urate levels and prevent gout.

['Leask|Megan P|MP|', 'Merriman|Tony R|TR|']

2021