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TALN research group at LS2N lab 14

34350068

Multi-Compartment Spatially-Derived Radiomics From Optical Coherence Tomography Predict Anti-VEGF Treatment Durability in Macular Edema Secondary to Retinal Vascular Disease: Preliminary Findings.

OBJECTIVE Diabetic macular edema (DME) and retinal vein occlusion (RVO) are the leading causes of visual impairments across the world. Vascular endothelial growth factor (VEGF) stimulates breakdown of blood-retinal barrier that causes accumulation of fluid within macula. Anti-VEGF therapy is the first-line treatment for both the diseases; however, the degree of response varies for individual patients. The main objective of this work was to identify the (i) texture-based radiomics features within individual fluid and retinal tissue compartments of baseline spectral-domain optical coherence tomography (SD-OCT) images and (ii) the specific spatial compartments that contribute most pertinent features for predicting therapeutic response. METHODS A total of 962 texture-based radiomics features were extracted from each of the fluid and retinal tissue compartments of OCT images, obtained from the PERMEATE study. Top-performing features selected from the consensus of different feature selection methods were evaluated in conjunction with four different machine learning classifiers: Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Random Forest (RF), and Support Vector Machine (SVM) in a cross-validated approach to distinguish eyes tolerating extended interval dosing (non-rebounders) and those requiring more frequent dosing (rebounders). RESULTS Combination of fluid and retinal tissue features yielded a cross-validated area under receiver operating characteristic curve (AUC) of 0.78±0.08 in distinguishing rebounders from non-rebounders. CONCLUSIONS This study revealed that the texture-based radiomics features pertaining to IRF subcompartment were most discriminating between rebounders and non-rebounders to anti-VEGF therapy. Clinical Impact: With further validation, OCT-based imaging biomarkers could be used for treatment management of DME patients.

['Sil Kar|Sudeshna|S|', 'Sevgi|Duriye Damla|DD|', 'Dong|Vincent|V|', 'Srivastava|Sunil K|SK|', 'Madabhushi|Anant|A|', 'Ehlers|Justis P|JP|']

2021

31137499

Roles of Natural Killer T Cells and Natural Killer Cells in Kidney Injury.

Mouse natural killer T (NKT) cells and natural killer (NK) cells are innate immune cells that are highly abundant in the liver. In addition to their already-known antitumor and antimicrobial functions, their pathophysiological roles in the kidney have recently become evident. Under normal circumstances, the proportion of activated NKT cells in the kidney increases with age. Administration of a synthetic sphingoglycolipid ligand (alpha-galactosylceramide) further activates NKT cells, resulting in injury to renal vascular endothelial cells via the perforin-mediated pathway and tubular epithelial cells via the TNF-α/Fas ligand pathway, causing acute kidney injury (AKI) with hematuria. Activation of NKT cells by common bacterial DNA (CpG-ODN) also causes AKI. In addition, NKT cells together with B cells play significant roles in experimental lupus nephritis in NZB/NZW F1 mice through their Th2 immune responses. Mouse NK cells are also assumed to be involved in various renal diseases, and there may be complementary roles shared between NKT and NK cells. Human CD56+ T cells, a functional counterpart of mouse NKT cells, also damage renal cells through a mechanism similar to that of mice. A subpopulation of human CD56+ NK cells also exert strong cytotoxicity against renal cells and contribute to the progression of renal fibrosis.

['Uchida|Takahiro|T|', 'Ito|Seigo|S|0000-0001-7080-3157', 'Kumagai|Hiroo|H|', 'Oda|Takashi|T|0000-0002-6131-7752', 'Nakashima|Hiroyuki|H|', 'Seki|Shuhji|S|']

2019

32987383

Relationship of Thrombospondin 1 to von Willebrand Factor and ADAMTS-13 in Sickle Cell Disease Patients of Arab Ethnicity.

BACKGROUND Thrombospondin 1 (TSP-1) is a multifunctional glycoprotein secreted by platelets. In sickle cell disease (SCD), TSP-1 promotes red cell adhesion to the endothelium by binding to von Willebrand factor (vWF) and inhibiting its degradation by the protease ADAMTS-13. We investigated a possible correlation between TSP-1, vWF and ADAMTS-13 in adult and pediatric SCD patients. METHODS Using commercially available ELISA kits, TSP-1, vWF and ADAMTS-13 levels were measured in 59 SCD patients (20 children and 39 adults) and compared with 59 age- and sex-matched controls. Associations between TSP-1 and parameters of interest were analyzed using Pearson's correlation coefficient. RESULTS Although TSP-1 levels were higher in adult and pediatric SCD patients than in controls, the increase was not statistically significant (p > 0.05). We found a significant positive correlation between TSP-1 and platelet count in both adult (r = 0.402, p = 0.01) and pediatric (r = 0.589, p = 0.01) patients, which is expected due to increased platelet activation in SCD. There was a positive correlation between TSP-1 and vWF in normal adults (r = 0.305, p = 0.049) and children (r = 0.633, p = 0.005) but not in patients (p > 0.05). A significant negative correlation between TSP-1 and ADAMTS-13 activity (r = -0.41, p = 0.01) was found in adult patients. Also, a significant negative correlation between TSP-1 and ADAMTS-13/vWF antigen ratio in both normal controls (r = -0.595, p = 0.009) and patients (r = -0.493, p = 0.032) is reported for the pediatric group. CONCLUSIONS Our findings confirm the inhibitory effects of TSP-1 on ADAMTS-13 activity in adult SCD patients. The negative correlation reported between TSP-1 and ADAMTS-13/vWF antigen ratio in pediatric subjects suggests a possible protective mechanism in younger individuals, although this is not related to the presence of SCD. This work emphasizes the impact of age on interpreting results related to the regulation of vWF expression and interaction with TSP-1 and ADAMTS-13 in SCD.

['Al-Awadhi|Anwar|A|', 'Adekile|Adekunle|A|', 'Marouf|Rajaa|R|']

2021

34240570

The evidence for pharmacist care in outpatients with heart failure: a systematic review and meta-analysis.

AIMS Patients with heart failure (HF) have poor outcomes, including poor quality of life, and high morbidity and mortality. In addition, they have a high medication burden due to the multiple drug therapies now recommended by guidelines. Previous reviews, including studies in hospital settings, provided evidence that pharmacist care improves outcomes in patients with HF. Because most HF is managed outside of hospitals, we aimed to synthesize the evidence for pharmacist care in outpatients with HF. METHODS AND RESULTS We conducted a systematic literature search in PubMed of randomized controlled trials (RCTs) and integrated the evidence on patient outcomes in a meta-analysis. We found 24 RCTs performed in 10 countries, including 8029 patients. The data revealed consistent improvements in medication adherence (independent of the measuring instrument) and knowledge, physical function, and disease and medication management. Sixteen RCTs were included in meta-analyses. Differences in all-cause mortality (odds ratio (OR) = 0.97 [95% CI, 0.84-1.12], Q-statistic, P = 0.49, I2  = 0%), all-cause hospitalizations (OR = 0.86 [0.73-1.03], Q-statistic, P = 0.01, I2  = 45.5%), and HF hospitalizations (OR = 0.89 [0.77-1.02], Q-statistic, P = 0.11, I2  = 0%) were not statistically significant. We also observed an improvement in the standardized mean difference for generic quality of life of 0.75 ([0.49-1.01], P < 0.01), with no indication of heterogeneity (Q-statistic, P = 0.64; I2  = 0%). CONCLUSIONS Results indicate that pharmacist care improves medication adherence and knowledge, symptom control, and some measures of quality of life in outpatients with HF. Given the increasing complexity of guideline-directed medical therapy, pharmacists' unique focus on medication management, titration, adherence, and patient teaching should be considered part of the management strategy for these vulnerable patients.

['Schumacher|Pia M|PM|0000-0002-5377-4021', 'Becker|Nicolas|N|', 'Tsuyuki|Ross T|RT|0000-0002-3724-598X', 'Griese-Mammen|Nina|N|0000-0002-8830-9031', 'Koshman|Sheri L|SL|', 'McDonald|Michael A|MA|', 'Bouvy|Marcel|M|0000-0002-4596-0684', 'Rutten|Frans H|FH|0000-0002-5052-7332', 'Laufs|Ulrich|U|0000-0003-2620-9323', 'Böhm|Michael|M|0000-0002-2976-2514', 'Schulz|Martin|M|0000-0002-5876-7322']

2021

30811722

Fast quantitative susceptibility reconstruction via total field inversion with improved weighted L0 norm approximation.

Quantitative susceptibility mapping (QSM) is a meaningful MRI technique owing to its unique relation to actual physical tissue magnetic properties. The reconstruction of QSM is usually decomposed into three sub-problems, which are solved independently. However, this decomposition does not conform to the causes of the problems, and may cause discontinuity of parameters and error accumulation. In this paper, a fast reconstruction method named fast TFI based on total field inversion was proposed. It can accelerate the total field inversion by using a specially selected preconditioner and advanced solution of the weighted L0 regularization. Due to the employment of an effective model, the proposed method can efficiently reconstruct the QSM of brains with lesions, where other methods may encounter problems. Experimental results from simulation and in vivo data verified that the new method has better reconstruction accuracy, faster convergence ability and excellent robustness, which may promote clinical application of QSM.

['Zhang|Li|L|', 'Chen|Xi|X|', 'Lin|Jianzhong|J|', 'Ding|Xinghao|X|', 'Bao|Lijun|L|', 'Cai|Congbo|C|0000-0002-0600-8594', 'Li|Jing|J|', 'Chen|Zhong|Z|', 'Cai|Shuhui|S|0000-0003-2767-9490']

2019

31616171

Association of diabetes knowledge with glycemic control and self-care practices among Pakistani people with type 2 diabetes mellitus.

Objective This study explored the relationship of disease knowledge with glycemic control and self-care practices in adult Pakistani people diabetes (PWD). Methods People diagnosed with type 2 diabetes (n=218) were selected from three health care centers, located in different cities of Pakistan. Disease knowledge and self-care practices were assessed by Urdu versions of Diabetes Knowledge Questionnaire (DKQ) and Diabetes Self-Management Questionnaire (DSMQ), using a cross-sectional design. Chi-square and correlation analysis were applied to explore the relationship of disease knowledge with glycemic control and self-care practices. Linear regression was used to explore the predictors for disease knowledge. Results Majority of the sample was >45-60 years old (48.8%), suffering from type 2 diabetes mellitus for <5 years (49.5%) and had poor glycemic control (HbA1C≥7%; n=181 participants). Disease knowledge was significantly associated (p<0.05) with patient's gender, level of education, family history of diabetes, nature of euglycemic therapy, and glycemic control. Correlation matrix showed strongly inverse correlations of DKQ with glycated hemoglobin levels (r=-0.62; p<0.001) and strongly positive with DSMQ sum scale (r=0.63; p<0.001). PWD having university-level education (β=0.22; 95% Confidence Interval (CI) 0.189, 0.872; p<0.01), doing job (β=0.22; 95% CI 0.009, 0.908]; p=0.046), and use of oral hypoglycemic agents in combination with insulin (β=-0.16; 95% CI [-1.224, -0.071]; p=0.028) were the significant predictors for disease knowledge. Conclusion Disease knowledge significantly correlated with glycated hemoglobin levels and self-care activities of PWD. These findings will help in designing patient-tailored diabetes educational interventions for yielding a higher probability of achieving target glycemic control.

['Bukhsh|Allah|A|', 'Khan|Tahir Mehmood|TM|', 'Sarfraz Nawaz|Muhammad|M|', 'Sajjad Ahmed|Hafiz|H|', 'Chan|Kok Gan|KG|', 'Goh|Bey-Hing|BH|']

2019

34227258

Substance P/Heparin-Conjugated PLCL Mitigate Acute Gliosis on Neural Implants and Improve Neuronal Regeneration via Recruitment of Neural Stem Cells.

The inflammatory host tissue response, characterized by gliosis and neuronal death at the neural interface, limits signal transmission and longevity of the neural probe. Substance P induces an anti-inflammatory response and neuronal regeneration and recruits endogenous stem cells. Heparin prevents nonspecific protein adsorption, suppresses the inflammatory response, and is beneficial to neuronal behavior. Poly(l-lactide-co-ε-caprolactone) (PLCL) is a soft and flexible polymer, and PLCL covalently conjugated with biomolecules has been widely used in tissue engineering. Coatings of heparin-conjugated PLCL (Hep-PLCL), substance P-conjugated PLCL (SP-PLCL), and heparin/substance P-conjugated PLCL (Hep/SP-PLCL) reduced the adhesion of astrocytes and fibroblasts and improved neuronal adhesion and neurite development compared to bare glass. The effects of these coatings are evaluated using immunohistochemistry analysis after implantation of coated stainless steel probes in rat brain for 1 week. In particular, Hep/SP-PLCL coating reduced the activation of microglia and astrocytes, the neuronal degeneration caused by inflammation, and indicated a potential for neuronal regeneration at the tissue-device interface. Suppression of the acute host tissue response by coating Hep/SP-PLCL could lead to improved functionality of the neural prosthesis.

['Kim|Donghak|D|', 'Park|DoYeun|D|', 'Kim|Tae Hee|TH|', 'Chung|Justin J|JJ|', 'Jung|Youngmee|Y|', 'Kim|Soo Hyun|SH|0000-0002-8391-3686']

2021

28754303

Type I IFN and not TNF, is Essential for Cyclic Di-nucleotide-elicited CTL by a Cytosolic Cross-presentation Pathway.

Cyclic di-nucleotides (CDN) are potent stimulators of innate and adaptive immune responses. Cyclic di-AMP (CDA) is a promising adjuvant that generates humoral and cellular immunity. The strong STING-dependent stimulation of type I IFN represents a key feature of CDA. However, recent studies suggested that this is dispensable for adjuvanticity. Here we demonstrate that stimulation of IFN-γ-secreting CD8+ cytotoxic T lymphocytes (CTL) is significantly decreased after vaccination in the absence of type I IFN signaling. The biological significance of this CTL response was confirmed by the stimulation of MHC class I-restricted protection against influenza virus challenge. We show here that type I IFN (and not TNF-α) is essential for CDA-mediated cross-presentation by a cathepsin independent, TAP and proteosome dependent cytosolic antigen processing pathway, which promotes effective cross-priming and further CTL induction. Our data clearly demonstrate that type I IFN signaling is critical for CDN-mediated cross-presentation.

['Lirussi|Darío|D|', 'Ebensen|Thomas|T|', 'Schulze|Kai|K|', 'Trittel|Stephanie|S|', 'Duran|Veronica|V|', 'Liebich|Ines|I|', 'Kalinke|Ulrich|U|', 'Guzmán|Carlos A|CA|']

2017

31794733

Prostaglandin D2 synthase and its functional association with immune and reproductive processes in a lepidopteran insect, Spodoptera exigua.

Several prostaglandins (PGs) have been identified in different insect species. However, their biosynthesis and physiological roles in insects remain unclear. PGD2 is synthesized by isomerization from PGH2 in mammals. This study identified a PGD2 synthase (SePGDS) in a lepidopteran insect, Spodoptera exigua. It showed sequence homology (32.8%) with human PGDS. Based on its conserved active site residues, its N-terminal tyrosine (Y8) was predicted to mediate electron relay from glutathione to PGH2 substrate, which was distinct from the catalysis of PGE2 (=PGD2 isomer) synthase (SePGES). SePGDS was highly expressed in larval and adult stages. RNA interference (RNAi) of SePGDS expression resulted in immunosuppression of cellular immune responses by suppressing the expression of actin polymerization-associated genes. It also suppressed the expression of some antimicrobial genes. Such immunosuppression induced by RNAi treatment was specifically rescued by the addition of PGD2, but not its precursor, arachidonic acid. Such RNAi treatment in adults prevented egg development in females by inhibiting choriogenesis. RNAi treatment also suppressed nurse cell dumping to growing oocytes. However, the addition of PGD2 rescued egg development of RNAi-treated females. These results suggest that SePGDS is responsible for the production of PGD2 which mediates immune and reproductive processes of S. exigua.

['Sajjadian|Seyede Minoo|SM|', 'Ahmed|Shabbir|S|', 'Al Baki|Md Abdullah|MA|', 'Kim|Yonggyun|Y|']

2020

31666017

More than a "touch of the flu": a response to Mayrhuber et al's ""with fever it's the real flu I would say": laypersons' perception of common cold and influenza and their differences - a qualitative study in Austria, Belgium and Croatia".

This short reply contests two assumptions made by the authors of Mayrhuber et al's. "With fever it's the real flu I would say." The first is that there is influenza can be reliably defined by a medical case definition. The second is that this small qualitative study can be generalisable. However, it does underline the important point that technical diagnostic terms may be used on different registers by a variety of actors in the medical setting.

['Jutel|Annemarie|A|0000-0001-7131-3838']

2019

26249772

The EFECT framework for interprofessional education in the patient centered medical home.

The very nature of the Patient-Centered Medical Home (PCMH) necessitates new instructional models that prepare learners for the roles they will have to assume in these transformed primary care practices. In this manuscript we describe a new instructional framework that seeks to blend the goals of patient-centered care and inter-professional education, and can be implemented in existing training environments while practice transformation continues to proceed. We propose a 5-step process, the EFECT framework, which is simultaneously a sequence of tasks for effective patient care and a guide for the learners and faculty in teaching and evaluating that care delivery. These steps include: (1) Eliciting a patient-centered narrative, (2) Facilitating an inter-professional team discussion, (3) Evaluating clinical evidence, (4) Creating a shared care plan, and (5) Tracking outcomes. We then report preliminary descriptive outcomes from the first EFECT pilot. Our proposed framework supports learners' abilities to construct a patient-centered narrative from multiple professional perspectives as the basis for developing an evidence-based, integrated care plan between the patient and the inter-professional care team and deliberately following up on outcomes. We present this framework to stimulate a process for creating new curricula and evaluative tools to measure and promote learner functioning in medical home environments.

['Bitton|Asaf|A|', 'Pereira|Anne G|AG|', 'Smith|C Scott|CS|', 'Babbott|Stewart F|SF|', 'Bowen|Judith L|JL|', '|||']

2013

30505574

The Effect of Functional Group Polarity in Palladium Immobilized Multiwalled Carbon Nanotube Catalysis: Application in Carbon-Carbon Coupling Reaction.

Carbon nanotubes (CNTs) are effective supports for nanometals and together they represent hybrids that combine the unique properties of both. A microwave-induced reaction was used to deposit nanopalladium on carboxylated and octadecylamine functionalized multiwall CNTs, which were used to carry out C-C coupling reactions in dimethylformamide (DMF) and toluene. These hybrids showed excellent catalytic activity with yield as high as 99.8%, while its enhancement with respect to commercially available Pd/C catalyst reached as high as 109%, and the reaction times were significantly lower. The polarity of the functionalized form was found to be a significant factor with the polar carboxylated CNT showing better activity in DMF while the relatively nonpolar octadecyl amine was better in toluene. The results suggest the possibility of tailor making functionalized CNTs when used as catalyst supports.

['Chandra|Boggarapu Praphulla|BP|', 'Wu|Zheqiong|Z|', 'Ntim|Susana Addo|SA|', 'Rao|Golakoti Nageswara|GN|', 'Mitra|Somenath|S|']

2018

27074926

Toxicity assessment of four insecticides with different modes of action on pupae and adults of Eriopis connexa (Coleoptera: Coccinellidae), a relevant predator of the Neotropical Region.

Pesticides can be toxic to nontarget organisms including the natural enemies of agricultural pests, thus reducing the biodiversity of agroecosystems. The lethal and sublethal effects of four insecticides with different modes of action-pyriproxyfen, teflubenzuron, acetamiprid, and cypermethrin-were evaluated on pupae and adults of Eriopis connexa, an effective predator in horticultural crops. Pupal survival was reduced by pyriproxyfen (26 %) and cypermethrin (41 %). Malformations in adults emerged from treated pupae were observed after acetamiprid (82.7 and 100 % for 100 and 200 mg a.i./l, respectively), pyriproxyfen (48.6 %), and cypermethrin (13.3 %) treatments. A longer mean oviposition time was also observed in adults emerged from pupae treated with cypermethrin. Moreover, the latter insecticide as well as teflubenzuron did not reduce reproductive parameters, whereas females emerged from pyriproxyfen-treated pupae were not be able to lay eggs even when females showed large abdomens. Upon exposure of adults, survival was reduced to approximately 90 % by acetamiprid, but no reduction occurred with pyriproxyfen, teflubenzuron, or cypermethrin though the fecundity at fifth oviposition time of the female survivors was reduced. Pyriproxyfen decreased the hatching at all the oviposition times tested, whereas fertility was reduced in the fourth and fifth ovipositions by teflubenzuron and in the first and third ovipositions by cypermethrin. In conclusion, all four insecticides tested exhibited lethal or sublethal effects, or both, on E. connexa. The neurotoxic insecticides were more harmful than the insect-growth regulators, and pupae were more susceptible than adults. The toxicity of insecticides on the conservation of predators in agroecosystems of the Neotropical Region is discussed.

['Fogel|Marilina Noelia|MN|', 'Schneider|Marcela Inés|MI|', 'Rimoldi|Federico|F|', 'Ladux|Lorena Sabrina|LS|', 'Desneux|Nicolas|N|', 'Ronco|Alicia Estela|AE|']

2016

34158207

Comparison of the Orientation Angles of Volar Locking Plate Distal Ulnar Locking Screw for Distal Radius Fractures.

PURPOSE This study aimed to measure the angles between the screw and plate in 16 commercially available volar locking plates (VLPs) to determine the fixable intra-articular fragment size. METHODS Ulnar orientation angles (axial plane) and elevation angles (sagittal plane) between the distal ulnar screw and plate were measured for 14 fixed-angle VLPs and 2 variable-angle VLPs. Each VLP was simulated by 2 surgeons to sit distally and ulnarly in 10 normal distal radius models. The distance between the screw and distal/ulnar end of the distal radius on both the volar and dorsal sides, designated as the longitudinal/lateral distance, was measured to identify the fixable size of the 2 intra-articular fragments: volar lunate fragment and dorsoulnar fragment. Relationships between the ulnar orientation angle and dorsal-side lateral length as well as the elevation angle and dorsal-side longitudinal distance were analyzed. RESULTS The ulnar orientation and elevation angles ranged from 6.5° to 16.9° and -5.8° to 34.3°, respectively, for fixed-angle VLPs and -12.5° to 32.2° and 3.1° to 42.1°, respectively, for variable-angle VLPs. The minimal longitudinal distances on the volar side with the fixed- and variable-angle VLPs were 4.3-10.9 mm and 5.8-5.9 mm, respectively. On the dorsal side, the lateral distance negatively correlated with the ulnar orientation angle (R = -0.74), and the longitudinal distance negatively correlated with the elevation angle (R = -0.89). CONCLUSIONS The Depuy Synthes variable-angle VLP provides an advantage for fixating small intra-articular fragments. For fixed-angle VLPs, the Mizuho VLP provides an advantage for fixating small volar lunate fragments. A narrow dorsoulnar fragment can be fixated using a plate with a large ulnar orientation angle, such as the Zimmer Biomet or Mizuho VLP. CLINICAL RELEVANCE The ability of each individual commercially available plate to capture specific intra-articular fragments should be known.

['Abe|Shingo|S|', 'Shimada|Toshiki|T|', 'Murase|Tsuyoshi|T|', 'Kuriyama|Kohji|K|']

2021

33893480

First Dose of BNT162b2 mRNA Vaccine in a Healthcare Worker Cohort Is Associated With Reduced Symptomatic and Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

Over the first 2 months of 2021, vaccination coverage of staff at Hull Teaching Hospitals with BNT162b2 increased from 8.3% to 82.5% and was associated with a significant reduction in symptomatic and asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. The proportion of positive lateral flow tests from asymptomatic screening was maintained over this period.

['Lillie|Patrick J|PJ|0000-0002-4811-4774', "O'Brien|Paul|P|", 'Lawtie|Michelle|M|', 'Jessop|Steve|S|', 'Easom|Nicholas J W|NJW|', 'Patmore|Russell|R|']

2021

29690505

Regression Analysis to Identify Factors Associated with Urinary Iodine Concentration at the Sub-National Level in India, Ghana, and Senegal.

Single and multiple variable regression analyses were conducted using data from stratified, cluster sample design, iodine surveys in India, Ghana, and Senegal to identify factors associated with urinary iodine concentration (UIC) among women of reproductive age (WRA) at the national and sub-national level. Subjects were survey household respondents, typically WRA. For all three countries, UIC was significantly different (p < 0.05) by household salt iodine category. Other significant differences were by strata and by household vulnerability to poverty in India and Ghana. In multiple variable regression analysis, UIC was significantly associated with strata and household salt iodine category in India and Ghana (p < 0.001). Estimated UIC was 1.6 (95% confidence intervals (CI) 1.3, 2.0) times higher (India) and 1.4 (95% CI 1.2, 1.6) times higher (Ghana) among WRA from households using adequately iodised salt than among WRA from households using non-iodised salt. Other significant associations with UIC were found in India, with having heard of iodine deficiency (1.2 times higher; CI 1.1, 1.3; p < 0.001) and having improved dietary diversity (1.1 times higher, CI 1.0, 1.2; p = 0.015); and in Ghana, with the level of tomato paste consumption the previous week (p = 0.029) (UIC for highest consumption level was 1.2 times lowest level; CI 1.1, 1.4). No significant associations were found in Senegal. Sub-national data on iodine status are required to assess equity of access to optimal iodine intake and to develop strategic responses as needed.

['Knowles|Jacky|J|', 'Kupka|Roland|R|', 'Dumble|Sam|S|', 'Garrett|Greg S|GS|', 'Pandav|Chandrakant S|CS|', 'Yadav|Kapil|K|', 'Touré|Ndeye Khady|NK|', 'Foriwa Amoaful|Esi|E|', 'Gorstein|Jonathan|J|']

2018

25014257

Assessment of the physiological responses to drought in different sugar beet genotypes in connection with their genetic distance.

Drought affects many physiological processes, which influences plant productivity. The aim of this study was to evaluate the degree of genotypic diversity in drought tolerance of sugar beet genotypes (Beta vulgaris L.) in connection with their genetic distance. Three hybrid genotypes produced by crossing double haploid genotype (P-pollinator) with cytoplasmic male-sterile female part (MS), as well as with two parent lines, were examined. Drought conditions were imposed by the cessation of watering at the 3-4 leaf stage for about three months, after which irrigation was resumed. Control plants were optimally irrigated throughout the entire vegetation period. Long-term drought significantly increased the wilting of leaves (Wilt.), specific leaf weight (SLW), the succulence index (Suc.I), leaf senescence and membrane damage (El-l). Simultaneously, the osmotic potential (ψs), leaf area index (LAI), absorption of photosynthetic active radiation (PAR) and the efficiency of the photosynthetic apparatus (Φ PSII) declined under water deficit conditions. The examined genotypes demonstrated a clear diversity in their physiological response to drought. Based on these findings, we suggest that traits that are strongly correlated with root and sugar yield, e.g. Φ PSII, LAI, PAR absorption and ψs, could be used as potential selection criteria in physiological-associated breeding strategies to improve drought tolerance in sugar beet. There was not a significant correlation between the genetic distance separating different sugar beet genotypes and the observed heterotic effect of root or sugar yields, with the exception of heterosis of root yield under optimal conditions, where the correlation was negative.

['Chołuj|Danuta|D|', 'Wiśniewska|Anita|A|', 'Szafrański|Kamil M|KM|', 'Cebula|Justyna|J|', 'Gozdowski|Dariusz|D|', 'Podlaski|Sławomir|S|']

2014

32755271

Mortality related to ambulatory care sensitive hospitalisations in Finland.

Aims: Hospitalisations for ambulatory care sensitive conditions are used as an outcome indicator of access to and quality of primary care. Evidence on mortality related to these hospitalisations is scarce. This study analysed the effect of ambulatory care sensitive condition hospitalisations to subsequent mortality and time or geographical trends in the mortality indicating variations in ambulatory care sensitive conditions outcomes. Methods: This retrospective cohort study used individual-level data from national registers concerning ambulatory care sensitive condition hospitalisations. Crude and age-adjusted 365-day mortality rates for the first ambulatory care sensitive condition-related admission were calculated for vaccine-preventable, acute, and chronic ambulatory care sensitive conditions separately, and for three time periods stratified by gender. The mortality rates were also compared to mortality in the general Finnish population to assess the excess mortality related to ambulatory care sensitive condition hospitalisations. Results: The data comprised a total of 712,904 ambulatory care sensitive condition hospital admissions with the crude 365-day mortality rate of 14.2 per 100 person-years. Mortality for those hospitalised for vaccine-preventable conditions was approximately 10-fold compared to the general population and four-fold in chronic and acute conditions. Of the 10 most common ambulatory care sensitive conditions, bacterial pneumonia and influenza and congestive heart failure were associated with highest age-standardised mortality rates.

['Partanen|Veli-Matti|VM|https://orcid.org/0000-0002-4623-3673', 'Arffman|Martti|M|', 'Manderbacka|Kristiina|K|', 'Keskimäki|Ilmo|I|']

2020

23129912

A rare association with patent ductus arteriosus.

Persistent fifth aortic arch (PFAA), also known as congenital double-lumen aortic arch, is a rare developmental anomaly of the aortic arch. A 5-month-old baby who presented with congestive cardiac failure was diagnosed to have a large patent ductus arteriosus with PFAA. Although this arch anomaly had no hemodynamic relevance in this case, preoperative diagnosis prevented surprises "on table."

['Warrier|Dhanya|D|', 'Shah|Sejal|S|', 'John|Colin|C|', 'Dayananda|L|L|']

2012

26373943

Production and characterization of surfactin-type lipopeptides as bioemulsifiers produced by a Pinctada martensii-derived Bacillus mojavensis B0621A.

Bacillus mojavensis B0621A was isolated from the mantle of a pearl oyster Pinctada martensii collected from South China Sea. Semi-purified surfactins (225 mg L(-1)) were obtained by acid precipitation and vacuum flash chromatography. The component of the semi-purified surfactins was preliminarily analyzed by liquid chromatography mass spectrometer system, and the results showed that all these surfactins could be a group of homologues. Eight surfactin homologues were isolated and afforded by reversed phase high-performance liquid chromatography. Furthermore, their structure was characterized by mass spectrometry analysis combined with nuclear magnetic resonance spectroscopy techniques. These surfactins shared seven amino acids as peptide backbone and a saturated β-hydroxy fatty acid chain residue (from C13 to C15), differed each other from peptide sequence in the position of Leu7 or Val7. All these surfactins had significant activity and stability of emulsification under various pH (from 7.0 to 12.0), temperature range (from 20 to 115 °C) and sodium chloride concentration (from 2.5 to 20.0 %, w/v). Taken all together, these results indicated that B. mojavensis B0621A have potential to be an alternative source as a biological-derived emulsifying agent.

['Ma|Zongwang|Z|', 'Hu|Jiangchun|J|']

2015

29766364

Binding of Cd(II), Pb(II), and Zn(II) to a type 1 metallothionein from maize (Zea mays).

Metallothioneins (MTs) are a family of ubiquitous, low-molecular-mass, cysteine-rich proteins that play a significant role in maintaining intracellular metal homeostasis, eliminating metal toxification, and protecting cells against oxidative damages. Research activity on plant MTs, although known for 30 years, has only moderately increased in the past few years. In this study, a type 1 MT from maize (Zea mays) (ZmMT1) was successfully expressed in Escherichia coli strain BL21 (DE3). The UV absorption spectra recorded after the reconstitution of apo-ZmMT1 with different metals demonstrated that ZmMT1 can coordinate up to six Zn(II) ions, six Cd(II) ions, and even higher amounts of Pb(II). In addition, the general metal ion coordination abilities of ZmMT1 characterized by pH-dependent zinc-, lead- and cadmium-binding stability and by the competitive reaction with 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) were evaluated. Results showed that the affinity of metal ions for the recombinant form of ZmMT1 can be arranged as follows: Cd(II) > Pb(II) > Zn(II). The observation revealed that chelating agents, such as ethylene diamine tetraacetic acid (EDTA) and ATP, accelerate the oxidation of ZmMT1 in the following order: EDTA ≫ L-histidine > ATP ≈ citrate. Meanwhile, commonly used buffers increase the reactivity of ZmMT1 with DTNB in the following order: PBS > Tris-HCl > HEPES.

['Duan|Lian|L|', 'Kong|Jing-Jing|JJ|', 'Wang|Tong-Qing|TQ|', 'Sun|Yue|Y|']

2018

24085596

Sieve estimation in semiparametric modeling of longitudinal data with informative observation times.

Analyzing irregularly spaced longitudinal data often involves modeling possibly correlated response and observation processes. In this article, we propose a new class of semiparametric mean models that allows for the interaction between the observation history and covariates, leaving patterns of the observation process to be arbitrary. For inference on the regression parameters and the baseline mean function, a spline-based least squares estimation approach is proposed. The consistency, rate of convergence, and asymptotic normality of the proposed estimators are established. Our new approach is different from the usual approaches relying on the model specification of the observation scheme, and it can be easily used for predicting the longitudinal response. Simulation studies demonstrate that the proposed inference procedure performs well and is more robust. The analyses of bladder tumor data and medical cost data are presented to illustrate the proposed method.

['Zhao|Xingqiu|X|', 'Deng|Shirong|S|', 'Liu|Li|L|', 'Liu|Lei|L|']

2014

32438863

The association of a single-nucleotide variant in the microRNA-146a with advanced colorectal cancer prognosis.

The aim of this study was to evaluate the association of single-nucleotide variant n.60G>C (rs2910164) of microRNA (miR)-146a, related to suppressing of BRCA1/2 DNA repair protein, with the risk and survival of colorectal cancer patients, as well as miR-146a and BRCA1/2 levels and miR binding efficiency. The genotypes were identified in 125 colorectal cancer patients and 276 controls using TaqMan polymerase chain reaction assay. The miR-146a and BRCA1/2 levels were assessed by quantitative-polymerase chain reaction protocols. Primary precursor of miR-146a containing G (wild-type) and C (variant) allele were cloned into pcDNA.3.3 vector and co-transfected in HT-29 colorectal cancer cell line. Luciferase reporter assay was performed to assess miR-146a binding to BRCA2 3'-untranslated region in HT-29. The differences between groups were calculated using chi-square or Fisher's exact test, logistic regression, and Mann-Whitney test. The prognostic impact of single-nucleotide variant genotypes on overall survival was evaluated by Kaplan-Meier estimate and Cox regression. The GC or CC genotypes prevalence was similar in patients and controls (50.4% vs 50.7%, p = 0.74). However, patients with tumors in advanced stage with miR-146a GG genotype had 2.41 more chance of dying than GC or CC genotypes. In addition, tumor tissues of patients with GG genotype presented higher miR-146a (p = 0.02) and lower BRCA1 (p = 0.01) and BRCA2 (p < 0.0001) levels when compared to those with GC or CC genotypes. In fact, pcDNA.3.3-miR-146a-G presented increased binding capacity to the 3'-untranslated region of BRCA2 (p = 0.001) compared to pcDNA.3.3-miR-146a-C. In addition, the G allele altered the binding affinity between miR-146a and its BRCA2 3'-untranslated region target (p < 0.001), thus enhancing suppression of BRCA2 expression. Our results suggest that single-nucleotide variant rs2910164 does not influence the colorectal cancer risk in Brazilian patients; however, the GG genotype could act as a factor of worse prognosis in patients with advanced disease due to suppression of BRCA1/2 modulated by miR-146a.

['Santos|Jéssica Silva Dos|JSD|', 'Zunta|Gabriella Lucatto|GL|', 'Negrini|Amanda Binatto|AB|', 'Ribeiro|Marina Silva Guinda|MSG|', 'Martinez|Carlos Augusto Real|CAR|', 'Ribeiro|Marcelo Lima|ML|', 'Lourenço|Gustavo Jacob|GJ|', 'Ortega|Manoela Marques|MM|https://orcid.org/0000-0003-4609-7074']

2020

31784273

Benthic hypoxia in anthropogenically-impacted rivers provides positive feedback enhancing the level of bioavailable metals at sediment-water interface.

We investigated the effect of hypoxic-anoxic range of dissolved oxygen (DO) on metal release/bioavailability at sediment-water interface (SWI) in the Ganga River. Here, we consider eight sites in the main river stem along 518 km; sixty sites downstream two point sources and two tributary confluences covering 630 km; and an incubation experiment to verify these results. We found higher concentrations of metals and bioavailable fractions at SWI at two locations of main stem and up to 700 m, 1000 m, 400 m and 500 m downstream Assi drain, Wazidpur drain, Ramganga confluence and Varuna confluence respectively where DO at SWI (DOsw) was <2.0 mgL-1. The incubation experiment did show higher levels of metal- and P-release and bioavailability under anoxic-hypoxic range of DO. The risk assessment code and eutrophication index indicated high to very high risks of contaminated river sediment and water to aquatic environment at sites with hypoxic-anoxic range of DOsw. Further, the principal component analyses separated metals and bioavailable fractions opposite to FDAase indicating greater risk at these locations. The study, which forms the first report on benthic hypoxia/anoxia-driven metal release, potential bioavailability and risk to the Ganga River ecosystem will help understanding how human-driven perturbations influence geochemical cycling of metals and ecosystem responses in large rivers.

['Jaiswal|Deepa|D|', 'Pandey|Jitendra|J|']

2020

32505178

Robust estimation of the effect of an exposure on the change in a continuous outcome.

BACKGROUND The change in two measurements of a continuous outcome can be modelled directly with a linear regression model, or indirectly with a random effects model (REM) of the individual measurements. These methods are susceptible to model misspecifications, which are commonly addressed by applying monotonic transformations (e.g., Box-Cox transformation) to the outcomes. However, transforming the outcomes complicates the data analysis, especially when variable selection is involved. We propose a robust alternative through a novel application of the conditional probit (cprobit) model. METHODS The cprobit model analyzes the ordered outcomes within each subject, making the estimate invariant to monotonic transformation on the outcome. By scaling the estimate from the cprobit model, we obtain the exposure effect on the change in the observed or Box-Cox transformed outcome, pending the adequacy of the normality assumption on the raw or transformed scale. RESULTS Using simulated data, we demonstrated a similar good performance of the cprobit model and REM with and without transformation, except for some bias from both methods when the Box-Cox transformation was applied to scenarios with small sample size and strong effects. Only the cprobit model was robust to skewed subject-specific intercept terms when a Box-Cox transformation was used. Using two real datasets from the breast cancer and inpatient glycemic variability studies which utilize electronic medical records, we illustrated the application of our proposed robust approach as a seamless three-step workflow that facilitates the use of Box-Cox transformation to address non-normality with a common underlying model. CONCLUSIONS The cprobit model provides a seamless and robust inference on the change in continuous outcomes, and its three-step workflow is implemented in an R package for easy accessibility.

['Ning|Yilin|Y|', 'Støer|Nathalie C|NC|', 'Ho|Peh Joo|PJ|', 'Kao|Shih Ling|SL|', 'Ngiam|Kee Yuan|KY|', 'Khoo|Eric Yin Hao|EYH|', 'Lee|Soo Chin|SC|', 'Tai|E-Shyong|ES|', 'Hartman|Mikael|M|', 'Reilly|Marie|M|', 'Tan|Chuen Seng|CS|']

2020

31707507

The effects of inulin on gut microbial composition: a systematic review of evidence from human studies.

BACKGROUND Inulin, consisting of repetitive fructosyl units linked by β(2,1) bonds, is a readily fermentable fiber by intestinal bacteria that generates large quantities of short-chain fatty acids (SCFA). In individuals with constipation, it was reported that inulin ingestion was associated with a significant increase in stool frequency, suggesting a potential impact of inulin on human gut microbiota composition. Progress in high-throughput technologies allow assessment of human-associated microbiomes in terms of diversity and taxonomic or functional composition, and can identify changes in response to a specific supplementation. Hence, to understand the effects of inulin on the human gut microbiome is pivotal to gain insight into their mechanisms of action. METHODS Here, we conducted a systematic review of human studies in adult individuals showing the effects of inulin on the gut microbiome. We searched in MEDLINE, EMBASE, Web of Science, and Scopus databases for articles in English published in peer-reviewed journals and indexed up until March 2019. We used multiple search terms capturing gut microbiome, gut microflora, intestinal microbiota, intestinal flora, gut microbiota, gut flora, microbial gut community, gut microbial composition, and inulin. RESULTS Overall, nine original articles reported the effects of inulin on microbiome composition in adult humans, most of them being randomized, double-blind, placebo-controlled trials (n = 7). Studies varied significantly in design (3 studies associated inulin and oligofructose), supplementation protocols (from 5 to 20 gr per day of inulin consumed) and in microbiome assessment methods (16S sequencing, n = 7). The most consistent change was an increase in Bifidobacterium. Other concordant results included an increase in relative abundance of Anaerostipes, Faecalibacterium, and Lactobacillus, and a decrease in relative abundance of Bacteroides after inulin supplementation. CONCLUSIONS Our systematic review assessed the evidence for the effects of inulin supplementation on the human gut microbiome. However, these in vivo studies did not confirm in vitro experiments as the taxonomic alterations were not associated with increase in short-chain fatty acids levels.

['Le Bastard|Quentin|Q|', 'Chapelet|Guillaume|G|', 'Javaudin|François|F|', 'Lepelletier|Didier|D|', 'Batard|Eric|E|', 'Montassier|Emmanuel|E|http://orcid.org/0000-0002-2313-1172']

2020

30351466

Proposed modifications and incorporation of plasma Epstein-Barr virus DNA improve the TNM staging system for Epstein-Barr virus-related nasopharyngeal carcinoma.

BACKGROUND The prognosis of patients who have Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without EBV-related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV-related NPC by incorporating the measurement of plasma EBV DNA. METHODS In total, 979 patients with NPC who received intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT. RESULTS The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression-free survival and overall survival in univariate analysis (all P < .001) and multivariate analysis (all P < .05). Recursive partitioning analysis of the primary cohort to incorporate EBV DNA generated the following proposed stage groupings: stage RI (T1N0), RIIA (T2-T3N0 or T1-T3N1, EBV DNA ≤2000 copies/mL), stage RIIB (T2-T3N0 or T1-T3N1, EBV DNA >2000 copies/mL; T1-T3N2, EBV DNA ≤2000 copies/mL), stage RIII (T1-T3N2, EBV DNA >2000 copies/mL; T4N0-N2), and stage RIVA (any T and N3). In the validation cohort, the 5-year progression-free survival rate was 100%, 87.9%, 76.7%, 68.7%, and 50.4% for proposed stage RI, RIIA, RIIB, RIII, and RIV NPC, respectively (P < .001). Compared with the eighth edition TNM stage groupings, the proposed stage groupings incorporating EBV DNA provided better hazard consistency, hazard discrimination, outcome prediction, and sample size balance. CONCLUSIONS The proposed stage groupings have better prognostic performance than the eighth edition of the TNM staging system. EBV DNA titers should be included in the TNM staging system to assess patients who have EBV-related NPC.

['Guo|Rui|R|', 'Tang|Ling-Long|LL|0000-0002-8561-1454', 'Mao|Yan-Ping|YP|', 'Du|Xiao-Jing|XJ|', 'Chen|Lei|L|', 'Zhang|Zi-Chen|ZC|', 'Liu|Li-Zhi|LZ|', 'Tian|Li|L|', 'Luo|Xiao-Tong|XT|', 'Xie|Yu-Bin|YB|', 'Ren|Jian|J|', 'Sun|Ying|Y|0000-0002-5888-2929', 'Ma|Jun|J|0000-0002-1137-9349']

2019

29616027

Detailed Characterization of T Cell Receptor Repertoires in Multiple Sclerosis Brain Lesions.

The antigen-specific activation of pathogenic T cells is considered essential in the initiation and maintenance of multiple sclerosis (MS). The site of activation, the differential involvement of CD4+, and CD8+ T cells, their functional phenotype, and specificity, are important aspects to understand MS pathogenesis. The analysis of clonal expansions of brain-infiltrating T cells may reveal local antigen-driven activation or specific brain homing and allow the identification of putatively pathogenic T cells. We used high-throughput T cell receptor β-chain variable gene (TRBV) sequencing (-seq) of genomic (g)DNA, which reflects the quantity and diversity of the TRBV repertoire, to characterize three white matter demyelinating lesions with different location and inflammatory activity, and paired peripheral blood memory CD4+ and CD8+ T cell pools from a secondary progressive (SP)MS patient. Our results revealed an important sharing of clonally expanded T cells with identical TRBV sequence (clonotypes) across MS lesions independently of their proximity or inflammatory activity. Comparison with circulating T cells showed that the most frequent brain-infiltrating CD8+, but not CD4+ clonotypes were also those with highest frequency in the peripheral blood, indicating clonal expansion inside the brain or specific brain homing of CD4+ but not CD8+ T cells. Parallel TRBV-seq of complementary (c)DNA that reflects the activation status of the cells, revealed differences between lesions regarding inflammatory activity and appears to facilitate the identification of putatively pathogenic T cells in active lesions. Approaches to identify pathogenic T cells in brain lesions using TRBV-seq may benefit from focusing on lesions with high inflammatory activity and from combining gDNA and cDNA sequencing.

['Planas|Raquel|R|', 'Metz|Imke|I|', 'Martin|Roland|R|', 'Sospedra|Mireia|M|']

2018

34392856

Upstream and downstream explanations of the harms of ultra-processed foods in national dietary guidelines.

OBJECTIVE Dietary advice about the potential health risks of unhealthy foods or diets has historically been communicated in terms of nutrients. Recent evidence has shown that the processing of food itself is independently attributable to harmful outcomes, particularly a new category of foods described to be 'ultra-processed'. Dietary guidelines (DG) are a key policy tool to translate and communicate nutrition research; however, there is little research exploring whether and how the harms of food processing are communicated and rationalised in dietary advice. DESIGN Nineteen publicly available DG were thematically analysed to explore: (1) the diversity of terms used to refer to processed foods and (2) the underlying explanations and rationales provided to reduce consumption of processed foods. SETTING International. PARTICIPANTS Sample of national dietary guidelines. RESULTS Seventeen different descriptive terms were used to refer to processed foods, with many countries using a large variation of terms within their DG. Six rationales to reduce consumption of processed foods were identified, which were grouped into four overarching domains: harmful outcomes (disease risk, environmental risk); food quality (food quality, nutrient content); diet quality and food environment. CONCLUSION The rationales provided to reduce the consumption of processed foods reflect upstream and downstream determinants of health. However, the persistence of nutrient-based rationales indicate that most DG do not apply an upstream understanding of the issues with ultra-processing. Further, the diversity of terms and foods referenced in DG suggest that the concept of ultra-processing is subject to multiple interpretations.

['Quinn|Madalyn|M|', 'Jordan|Helen|H|', 'Lacy-Nichols|Jennifer|J|']

2021

33640456

A conserved arginine residue is critical for stabilizing the N2 FeS cluster in mitochondrial complex I.

Respiratory complex I (NADH:ubiquinone oxidoreductase), the first enzyme of the electron-transport chain, captures the free energy released by NADH oxidation and ubiquinone reduction to translocate protons across an energy-transducing membrane and drive ATP synthesis during oxidative phosphorylation. The cofactor that transfers the electrons directly to ubiquinone is an iron-sulfur cluster (N2) located in the NDUFS2/NUCM subunit. A nearby arginine residue (R121), which forms part of the second coordination sphere of the N2 cluster, is known to be posttranslationally dimethylated but its functional and structural significance are not known. Here, we show that mutations of this arginine residue (R121M/K) abolish the quinone-reductase activity, concomitant with disappearance of the N2 signature from the electron paramagnetic resonance (EPR) spectrum. Analysis of the cryo-EM structure of NDUFS2-R121M complex I at 3.7 Å resolution identified the absence of the cubane N2 cluster as the cause of the dysfunction, within an otherwise intact enzyme. The mutation further induced localized disorder in nearby elements of the quinone-binding site, consistent with the close connections between the cluster and substrate-binding regions. Our results demonstrate that R121 is required for the formation and/or stability of the N2 cluster and highlight the importance of structural analyses for mechanistic interpretation of biochemical and spectroscopic data on complex I variants.

['Hameedi|Mikhail A|MA|', 'Grba|Daniel N|DN|', 'Richardson|Katherine H|KH|', 'Jones|Andrew J Y|AJY|', 'Song|Wei|W|', 'Roessler|Maxie M|MM|', 'Wright|John J|JJ|', 'Hirst|Judy|J|']

2021

24365325

Classification of and risk factors for estrogen deprivation pain syndromes related to aromatase inhibitor treatments in women with breast cancer: a prospective multicenter cohort study.

UNLABELLED Aromatase inhibitors (AIs) are the first-line treatment in women with breast cancer for total estrogen depletion. Half the treated women may develop pain, and this condition may therefore be seen as a clinical model of pain related to estrogen deprivation. In this prospective multicenter study, we classified AI-related pain syndromes and identified their predictors. A 1-year, prospective, multicenter cohort study, with 6 visits, was carried out on 135 women with early-stage breast cancer and no pain at the start of AI treatment. At initial assessment, we investigated clinical (demographic and psychosocial, cancer characteristics and treatment, sleep, quality of life), biological (sex hormones, vitamin D, bone biomarkers, oxidative stress, immunologic and inflammatory markers), environmental, and genetic (polymorphism for pain mechanisms) risk factors for pain. During 1 year of follow-up, 77 women (57%) developed pain, leading to AI discontinuation in 12 cases. Five pain syndromes were identified: joint pain (36%), diffuse pain (22%), tendinitis (22%), neuropathic pain (9%), and mixed pain (11%), which are mostly persistent (57%), with diffuse and joint pains the most intense. Risk factors for the development of pain included higher levels of anxiety and impaired quality of life at the initial assessment, whereas cancer characteristics, genetic background, inflammation, and immunologic and hormonal status at baseline were not significant predictors. PERSPECTIVE This article presents a classification of AI-related pain syndromes induced by estrogen deprivation that were previously described as arthralgia, but not as neuropathic, diffuse, and mixed pain. This estrogen deprivation-related condition represents a clinical model of pain, and our study identified mostly psychological risk factors for pain development.

['Laroche|Francoise|F|', 'Coste|Joël|J|', 'Medkour|Terkia|T|', 'Cottu|Paul Henri|PH|', 'Pierga|Jean-Yves|JY|', 'Lotz|Jean-Pierre|JP|', 'Beerblock|Karine|K|', 'Tournigand|Christophe|C|', 'Declèves|Xavier|X|', 'de Cremoux|Patricia|P|', 'Bouhassira|Didier|D|', 'Perrot|Serge|S|']

2014

29899068

On dangerous ground: the evolution of body armour in cordyline lizards.

Animal body armour is often considered an adaptation that protects prey against predatory attacks, yet comparative studies that link the diversification of these allegedly protective coverings to differential predation risk or pressure are scarce. Here, we examine the evolution of body armour, including spines and osteoderms, in Cordylinae, a radiation of southern African lizards. Using phylogenetic comparative methods, we attempt to identify the ecological and environmental correlates of body armour that may hint at the selective pressures responsible for defensive trait diversification. Our results show that species inhabiting arid environments are more likely to possess elaborated body armour, specifically osteoderms. We did not find any effect of estimated predation pressure or risk on the degree of body armour. These findings suggest that body armour might not necessarily evolve in response to direct interactions with predators, but rather as a result of increased habitat-mediated predation risk. Furthermore, we discuss the possibility that osteoderms might have been shaped by factors unrelated to predation.

['Broeckhoven|Chris|C|0000-0001-5597-0061', 'El Adak|Yousri|Y|', 'Hui|Cang|C|0000-0002-3660-8160', 'Van Damme|Raoul|R|0000-0002-4585-6940', 'Stankowich|Theodore|T|0000-0002-6579-7765']

2018

23275826

Aspergillus flavus keratitis after deep anterior lamellar keratoplasty.

PURPOSE To report the clinical, microbiologic, confocal scan and histopathologic features of Aspergillus flavus keratitis which developed immediately after deep anterior lamellar keratoplasty (DALK). CASE REPORT A 28-year-old woman underwent DALK using the big-bubble technique for keratoconus. The operation was uneventful, yielding a bare Descemet's membrane (DM) followed by transplantation of a corneal graft devoid of DM and endothelium. Four days after keratoplasty, mild infiltrates were noticed in the inferonasal margin of the graft, which rapidly progressed to involve the adjacent recipient cornea. Confocal scan findings suggested filamentous fungal keratitis, leading to initiation of topical and systemic antifungal medications followed by immediate replacement of the graft. Histopathologic examination disclosed keratitis caused by a filamentous fungus, which was determined by microbiologic cultures to be Aspergillus flavus. Early diagnosis and appropriate management resulted in complete recovery from this potentially devastating infection. CONCLUSION Aspergillus Flavus can cause graft ulcers immediately after DALK. Confocal scan proved to be a valuable tool for early diagnosis and prompt intervention to control this otherwise devastating infection.

['Jafarinasab|Mohammad-Reza|MR|', 'Feizi|Sepehr|S|', 'Yazdizadeh|Forouzan|F|', 'Rezaei Kanavi|Mozhgan|M|', 'Moein|Hamid-Reza|HR|']

2012

31161630

Glucose-containing polymer rings enable fed-batch operation in microtiter plates with parallel online measurement of scattered light, fluorescence, dissolved oxygen tension, and pH.

Bioprocesses operated in batch mode can induce adverse effects like overflow metabolism, substrate inhibition, osmotic inhibition, oxygen limitation, and catabolite repression. To avoid these adverse effects, fed-batch is the predominant operation mode in industrial production. Nevertheless, screening for optimal production strains is usually performed in microtiter plates and shake flasks operated in batch mode without any online monitoring. Recently, a polymer-based controlled-release fed-batch microtiter plate with stable glucose release characteristics was described. In this study, a glucose-containing polymer matrix was used to manufacture polymer rings that were placed at the bottom of a 48-well microtiter plate. Thereby, the liquid content of the well became accessible for optical measurement by the BioLector device. Reflections caused by the polymer ring were minimized by adjusting the scattered-light measurement position. Influences on the measurement of the dissolved oxygen tension and pH could be avoided by choosing appropriate polymer-ring geometries. These adjustments enabled parallel online measurement of scattered light, fluorescence, dissolved oxygen tension, and pH of Escherichia coli BL21 (DE3) fed-batch cultivations. The online monitoring and fed-batch operation capabilities of the fed-batch microtiter plate presented in this study finds optimal application in screenings and initial process development.

['Habicher|Tobias|T|0000-0001-9015-8650', 'Czotscher|Vroni|V|', 'Klein|Tobias|T|', 'Daub|Andreas|A|', 'Keil|Timm|T|0000-0003-0193-9418', 'Büchs|Jochen|J|0000-0002-2012-3476']

2019

29297575

Travel health prevention.

All around the world there has been a rapid growth in the number of international travels. According to the World Tourism Organisation the number of international tourist arrivals reached 1,235 billion in 2016 and continues to grow at a high rate. This has been much due to the development of air transport (including low-cost airlines), increasingly common economic migration, a growing number of travellers visiting friends and relatives, and an increase in medical tourism. With tropical destinations becoming increasingly popular among travellers, doctors have seen a rising number of patients who seek medical advice on health risks prevalent in hot countries and health prevention measures to be taken in tropical destinations, especially where sanitation is poor. The risk for developing a medical condition while staying abroad depends on a variety of factors, including the traveller's general health condition, health prevention measures taken before or during travel (vaccinations, antimalarial chemoprophylaxis, health precautions during air, road and sea travel, proper acclimatisation, prevention of heat injuries, protection against local flora and fauna, personal hygiene, water, food and feeding hygiene), as well as the prevalence of health risk factors in a given location. Health prevention is a precondition for safe travel and maintaining good physical health; in the era of a rapid growth in international tourism it has become of key importance for all travellers.

['Korzeniewski|Krzysztof|K|']

2017

27006093

Cross-modal symbolic processing can elicit either an N2 or a protracted N2/N400 response.

A cross-modal symbolic paradigm was used to elicit EEG activity related to semantic incongruence. Twenty-five undergraduate students viewed pairings of visual lexical cues (e.g., DOG) with congruent (50% of trials) or incongruent (50%) auditory nonlexical stimuli (animal vocalizations; e.g., sound of a dog woofing or a cat meowing). In one condition, many different pairs of congruent/incongruent stimuli were shown, whereas in a second condition only two pairs of stimuli were repeatedly shown. A typical N400-like pattern of incongruence-related activity (including activity in the N2 time window) was evident in the condition using many stimuli, whereas the incongruence-related activity in the two-stimuli condition was confined to differential N2-like activity. A supplementary analysis excluded stimulus characteristics as the source of this differential activity between conditions. We found that a single individual performing a fixed task can demonstrate either a protracted N400-like pattern of activity or a more temporally focused N2-like pattern of activity in response to the same stimulus, which suggests that the N2 may be a precursor to the protracted N400 response.

['Griffiths|Oren|O|0000-0002-9833-9998', 'Le Pelley|Mike E|ME|', 'Jack|Bradley N|BN|', 'Luque|David|D|', 'Whitford|Thomas J|TJ|']

2016

31589802

Pristine-Graphene-Supported Nitrogen-Doped Carbon Self-Assembled from Glucaminium-Based Ionic Liquids as Metal-Free Catalyst for Oxygen Evolution.

For the first time, graphene-supported N-doped carbon (G@NC) with a high degree of N doping was synthesized by in situ self-assembly of a glucaminium-based ionic liquid on pristine graphene under hydrothermal conditions. This 2D, metal-free nanohybrid exhibited much higher catalytic activity than most reported metal-free catalysts for the oxygen evolution reaction (OER) and even state-of-the-art Ir- and Ru-based catalysts because the high content of graphitic N greatly increased the number of OER-active sites, the pristine graphene significantly promoted the OER activity of the C sites adjacent to the graphitic N atoms, and N-doped graphitic carbon remarkably enhanced the charge-transfer rate. This work not only creates a facile and economical approach to controllably fabricate pristine-graphene-supported carbon with a high N-doping level for the development of highly efficient metal-free OER catalysts but also provides insight into the mechanisms for both the in situ self-assembly and the high OER catalytic activity of G@NC.

['Zhao|Ming|M|', 'Li|Tianhao|T|', 'Jia|Lichao|L|', 'Li|Huilin|H|', 'Yuan|Weiyong|W|http://orcid.org/0000-0003-2194-0301', 'Li|Chang Ming|CM|']

2019

25274900

Patients with rheumatoid arthritis in clinical remission manifest persistent joint inflammation on histology and imaging studies.

OBJECTIVE The purpose of our study was to test the hypothesis that synovitis on magnetic resonance imaging (MRI) and ultrasound (US) observed in patients with rheumatoid arthritis (RA) who meet remission criteria reflects active inflammation on histopathology. METHODS We analyzed 15 synovial specimens obtained during surgical procedures from 14 patients with RA in clinical remission as defined by the American College of Rheumatology criteria. Histological specimens were scored for hyperplasia of synovial lining and synovial stroma, inflammation, lymphoid follicles, and vascularity. The histology scores were classified as minimal, mild, moderate, or severe disease activity. US and MRI performed within a 4-month period of surgery were scored for disease activity. The correlation between histology and imaging scores was examined. RESULTS Four of 14 patients were receiving anti-tumor necrosis factor (TNF) therapy, 4 were receiving methotrexate (MTX) alone, 4 were taking MTX and hydroxychloroquine (HCQ), and 1 was taking HCQ and sulfasalazine. Four specimens had severe, 6 moderate, 3 mild, and 2 minimal disease activity on histology. Three of 4 specimens with minimal and mild histology were observed in subjects receiving anti-TNF therapy. Synovitis was noted on greyscale in 80% of joints and Doppler signal in 60%. MRI demonstrated synovitis and bone marrow edema in 86% of images. Positive but not significant correlations were noted between histology and synovitis scores on US. CONCLUSION Despite clinical remission, histology and imaging studies documented a persistently active disease state that may explain the mechanism for radiographic progression.

['Anandarajah|Allen|A|', 'Thiele|Ralf|R|', 'Giampoli|Ellen|E|', 'Monu|Johnny|J|', 'Seo|Gwy-Suk|GS|', 'Feng|Changyong|C|', 'Ritchlin|Christopher T|CT|']

2014

31972115

Evaluation of clinically indicated removal versus routine replacement of peripheral vascular catheters.

Latest clinical guidelines for peripheral vascular catheters (PVC) recommend that they should be removed only when clinically indicated and not routinely removed and replaced. In 2017, the authors' hospital policy was changed to align with the new recommendations and, between March and July 2019, 500 PVCs were audited at two main sites to evaluate the efficacy of the change. Of the 500 PVCs, 31% (n=155) were in situ for more than 3 days (range 4-22 days). Analysis of the combined data showed an overall prevalence of phlebitis at 8%, but variation in trends looking at each individual site (7% and 9% respectively) with a wide variation for PVCs in situ for more than 7 days. Implementing clinically indicated removal of PVCs has resulted in better patient experience with fewer PVCs for a course of treatment. Implementation has also resulted in cost savings for the Trust with a notable decrease in number of PVCs used.

['McGuire|Rose|R|', 'Coronado|Angela|A|']

2020

31138169

Aberrantly expressed miR-188-5p promotes gastric cancer metastasis by activating Wnt/β-catenin signaling.

BACKGROUND Gastric cancer (GC) is one of the most common human cancers with the high rate of recurrence, metastasis and mortality. Aberrantly expressed microRNAs (miRNAs) are associated with invasion and metastasis in various human cancers. Recently, miR-188-5p has been indicated as an oncogene in GC since it promotes GC cell growth and metastasis. However, the underlying molecular mechanism remains to be fully defined. METHODS Using Significance Analysis of Microarrays (SAM) screening, we identified that miR-188-5p is associated with overall survival and lymph node metastasis in patients with GC. The functional impact of miR-188-5p on GC metastasis was validated using in vitro and in vivo assays. The regulatory function of miR-188-5p on Wnt/β-catenin signaling activation through directly targeting PTEN was proven using quantitative real-time PCR, western blot analysis, a dual-luciferase assay, a Transwell assay, and immunofluorescence. Immunohistochemical analyses further confirmed the clinical significance of miR-188-5p in GC. RESULTS MiR-188-5p diminishes tumor suppressor PTEN expression, and further increases phospho-Ser9 of GSK3β to activate Wnt/β-catenin signaling in GC. Consequently, miR-188-5p enhanced the migration and invasion of GC cells in vitro and tumor metastasis in vivo, whereas inhibition of miR-188-5p had the opposite effects. Moreover, miR-188-5p was negatively correlated with PTEN expression but positively correlated with nuclear β-catenin staining in GC samples. CONCLUSIONS Our findings revealed a model of the miR-188-5p-PTEN-β-catenin axis in GC, which mediates the constitutive activation of Wnt/β-catenin signaling and promotes tumor metastasis, inferring that miR-188-5p is a potential therapeutic target to treat GC.

['Li|Yun|Y|', 'Yan|Xiaoli|X|', 'Shi|Jiajian|J|', 'He|Yun|Y|', 'Xu|Jie|J|', 'Lin|Liying|L|', 'Chen|Wannan|W|', 'Lin|Xinjian|X|', 'Lin|Xu|X|']

2019

33909182

Effects of tree species diversity and stand structure on carbon stocks of homestead forests in Maheshkhali Island, Southern Bangladesh.

BACKGROUND The homestead forests of Bangladesh occupy 0.27 million hectares (10% of the total forested area) and have potential to store carbon (C) and conserve biodiversity. Small scale forestry practices, however, are lacking reliable estimation of C stocks and tree species diversity. This may hinder successful implementation of REDD + and similar mechanisms as they concentrate on large-scale forests. This study aimed to estimate the above- and below-ground carbon stocks in homestead forests of Maheshkhali Island in Bangladesh and how tree species diversity and stand structural variation affect these C stocks. We randomly surveyed a total of 239 homestead forests in the hillside, beachside, and inland in 2019. RESULTS Tree biomass C stocks were 48-67% greater in the inland and hillside forests than in the beachside due to significantly greater stand density, basal area, tree diameter. In total we found 52 tree species, but most abundant species in the inland and hillside forests, Mangifera indica, Samanea saman, and Artocarpus heterophyllus stored the most C in tree biomass. Greater tree species richness and diversity index in the inland and hillside forests indicated greater above- and below-ground tree biomass C stocks. An increase in tree species richness and diversity index by one unit was found to increase the tree biomass C stock by 22 and 30 Mg C ha-1, respectively. The total soil C stock was also affected by tree species diversity, stand density, and their interaction with soil properties. Total soil C stocks were greatest (51 Mg ha-1) in the inland forests, having also the greatest stand density and tree species richness. C stock in soil surface was greatest in the hillside forests due to the greatest litterfall, but the average share of litterfall from the total biomass C was only 0.1%. CONCLUSIONS Homestead forest ecosystems could store 96 Mg C ha-1 in total, which can contribute to climate change mitigation by generating C credits for small-scale homestead forests owners. Above- and below-ground tree biomass C stocks were found to correlate with tree species diversity, which may also contribute to biodiversity conservation in the REDD + in Bangladesh and countries alike.

['Baul|Tarit Kumar|TK|http://orcid.org/0000-0002-0805-0657', 'Chakraborty|Avinanda|A|', 'Nandi|Rajasree|R|', 'Mohiuddin|Mohammed|M|', 'Kilpeläinen|Antti|A|', 'Sultana|Taslima|T|']

2021

26033922

Multicenter Observational Study of the First-Generation Intravenous Blood Glucose Monitoring System in Hospitalized Patients.

BACKGROUND Current methods of blood glucose (BG) monitoring and insulin delivery are labor intensive and commonly fail to achieve the desired level of BG control. There is great clinical need in the hospital for a user-friendly bedside device that can automatically monitor the concentration of BG safely, accurately, frequently, and reliably. METHODS A 100-patient observation study was conducted at 6 US hospitals to evaluate the first generation of the Intravenous Blood Glucose (IVBG) System (Edwards Lifesciences LLC & Dexcom Inc). Device safety, accuracy, and reliability were assessed. A research nurse sampled blood from a vascular catheter every 4 hours for ≤ 72 hours and BG concentration was measured using the YSI 2300 STAT Plus Analyzer (YSI Life Sciences). The IVBG measurements were compared to YSI measurements to calculate point accuracy. RESULTS The IVBG systems logged more than 5500 hours of operation in 100 critical care patients without causing infection or inflammation of a vein. A total of 44135 IVBG measurements were performed in 100 patients with 30231 measurements from the subset of 75 patients used for accuracy analysis. In all, 996 IVBG measurements were time-matched with reference YSI measurements. These pairs had a mean absolute difference (MAD) of 11.61 mg/dl, a mean absolute relative difference (MARD) of 8.23%, 93% met 15/20% accuracy defined by International Organization for Standardization 15197:2003 standard, and 93.2% were in zone A of the Clarke error grid. The IVBG sensors were exposed to more than 200 different medications with no observable effect on accuracy. CONCLUSIONS The IVBG system is an automated and user-friendly glucose monitoring system that provides accurate and frequent BG measurements with great potential to improve the safety and efficacy of insulin therapy and BG control in the hospital, potentially leading to improved clinical outcomes.

['Bochicchio|Grant V|GV|', 'Hipszer|Brian R|BR|', 'Magee|Michelle F|MF|', 'Bergenstal|Richard M|RM|', 'Furnary|Anthony P|AP|', 'Gulino|Angela M|AM|', 'Higgins|Michael J|MJ|', 'Simpson|Peter C|PC|', 'Joseph|Jeffrey I|JI|']

2015

24034748

Computer-aided diagnosis of breast cancer based on fine needle biopsy microscopic images.

Prompt and widely available diagnostics of breast cancer is crucial for the prognosis of patients. One of the diagnostic methods is the analysis of cytological material from the breast. This examination requires extensive knowledge and experience of the cytologist. Computer-aided diagnosis can speed up the diagnostic process and allow for large-scale screening. One of the largest challenges in the automatic analysis of cytological images is the segmentation of nuclei. In this study, four different clustering algorithms are tested and compared in the task of fast nuclei segmentation. K-means, fuzzy C-means, competitive learning neural networks and Gaussian mixture models were incorporated for clustering in the color space along with adaptive thresholding in grayscale. These methods were applied in a medical decision support system for breast cancer diagnosis, where the cases were classified as either benign or malignant. In the segmented nuclei, 42 morphological, topological and texture features were extracted. Then, these features were used in a classification procedure with three different classifiers. The system was tested for classification accuracy by means of microscopic images of fine needle breast biopsies. In cooperation with the Regional Hospital in Zielona Góra, 500 real case medical images from 50 patients were collected. The acquired classification accuracy was approximately 96-100%, which is very promising and shows that the presented method ensures accurate and objective data acquisition that could be used to facilitate breast cancer diagnosis.

['Kowal|Marek|M|', 'Filipczuk|Paweł|P|', 'Obuchowicz|Andrzej|A|', 'Korbicz|Józef|J|', 'Monczak|Roman|R|']

2013

33907708

Identification and Management of Pediatric Sepsis: A Medical Student Curricular Supplement for PICU and NICU Rotations.

Introduction Medical students frequently report lack of confidence and skill in managing ill pediatric patients. We aimed to implement targeted learning interventions to address these knowledge gaps, specifically focusing on pediatric sepsis. Our objective was to create a curriculum to advance knowledge and confidence in identifying and managing pediatric sepsis. Methods We designed this curriculum to augment medical student pediatric ICU (PICU) and neonatal ICU (NICU) rotations. We first emailed students a pretest and upon completion, we emailed students a series of brief educational videos. Students then participated in a simulation experience designed to assess their ability to diagnose and manage severe sepsis. We provided immediate debriefing after each session. Upon completion of the simulation experience, we emailed students a posttest (identical to the pretest). The pre-/posttest included multiple-choice questions to assess the students' ability to recognize and manage pediatric sepsis and septic shock, as well as Likert-scale questions assessing confidence levels in diagnosis and management of pediatric sepsis. We performed paired Student t tests comparing knowledge-based question scores and Likert-scale results. Results Of students, 40 enrolled in and 30 completed the curriculum between 2015 and 2020. When comparing pre- and posttest results, we found a significant improvement in knowledge scores (33% mean increase, 95% CI [22%-45%], p < .001) and confidence levels (mean increase in Likert scale score of 1.5, 95% CI [1.2-1.7], p < .001). Discussion Results suggested that the curriculum advanced students' knowledge scores and improved self-reported confidence in managing theoretical pediatric patients with sepsis.

['Anderson|Nicole B|NB|0000-0002-9342-5643', 'Chan|Mai-King|MK|', 'Gutierrez|Cristina|C|', 'Kambestad|Kristi|K|', 'Walker|Valencia|V|']

2021

32309567

Initiative for standardization of the format of the next-generation sequencing (NGS) results.

The number of published reports using next-generation sequencing (NGS) technology in cancer research is increasing. These technologies generate large amounts of data that need to be appropriately presented and available to other researchers for further use. Our goal was to create a comprehensive database with single nucleotide polymorphisms (SNPs) associated with different types of cancer to integrate them to our bioinformatics tools. We reviewed more than 200 scientific papers and extracted relevant information on mutations detected by NGS technology. The current version of the database contains more than 100.000 mutations in more than 70 types of cancer. However, our review of NGS studies revealed great variation in presentation of NGS data in scientific literature with almost no effort for standardization of the data format. NGS results are published in a variety of forms which hinders the gathering of information. Therefore we suggested a uniform format for presenting the NGS data. This will allow faster database development, easier access and data sharing between the laboratories. The database will be a useful tool to many researchers in the field of cancer research and can be a base for a range of studies such as genome-wide association studies, microRNA target binding, and development of cancer biomarkers research.

['Pipan|Veronika|V|', 'Kunej|Tanja|T|']

2015

25099875

Numerical simulation of pressure waves in the cochlea induced by a microwave pulse.

The pressure waves developing at the cochlea by the irradiation of the body with a plane wave microwave pulse are obtained by numerical simulation, employing a two-step finite-difference time-domain (FDTD) algorithm. First, the specific absorption rate (SAR) distribution is obtained by solving the Maxwell equations on a FDTD grid. Second, the temperature rise due to this SAR distribution is used to formulate the thermoelastic equations of motion, which are discretized and solved by the FDTD method. The calculations are performed for anatomically based full body human models, as well as for a head model. The dependence of the pressure amplitude at the cochlea on the frequency, the direction of propagation, and the polarization of the incident electromagnetic radiation, as well as on the pulse width, was investigated.

['Yitzhak|Nir M|NM|', 'Ruppin|Raphael|R|', 'Hareuveny|Ronen|R|']

2014

24478154

Spatiotemporal stimulus properties modulate responses to trajectory changes in a locust looming-sensitive pathway.

The lobula giant movement detector (LGMD) and descending contralateral movement detector (DCMD) constitute one motion-sensitive pathway in the locust visual system that is implicated in collision-avoidance behaviors. While this pathway is thought to respond preferentially to objects approaching on a direct collision course, emerging studies suggest the firing rate is able to monitor more complicated movements that would occur under natural conditions. While previous studies have compared the response of the DCMD to objects on collision courses that travel at different speeds, velocity has not been manipulated for other simple or compound trajectories. Here we test the possibility that the LGMD/DCMD pathway is capable of responding uniquely to complex aspects of object motion, including translation and trajectory changes at different velocities. We found that the response of the DCMD to translational motion initiated in the caudal visual field was a low-amplitude peak in firing rate that occurred before the object crossed 90° azimuth that was invariant to different object velocities. Direct looms at different velocities resulted in peak firing rates that occurred later in time and with greater amplitude for higher velocities. In response to transitions from translational motion to a collision course, the firing rate change depended on both the location within the visual field and the velocity. These results suggest that this pathway is capable of conveying information about multiple properties of a moving object's trajectory.

['Dick|Paul C|PC|', 'Gray|John R|JR|']

2014

27027030

HOW CAN BONE TUNNEL ENLARGEMENT IN ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION SURGERY BE MEASURED? DESCRIPTION OF A TECHNIQUE.

UNLABELLED To assess the presence of tibial bone tunnel enlargement after surgery to reconstruct the anterior cruciate ligament using quadruple flexor tendon grafts, and to propose a new technique for its measurement. METHODS The study involved 25 patients aged 18-43 years over a six-month period. The assessment was based on radiographs taken immediately postoperatively and in the third and sixth months of evolution after operations to reconstruct the anterior cruciate ligament using grafts from the tendons of the semitendinosus and gracilis muscles, fixed in the femur with a transverse metal screw and in the tibia with an interference screw. The radiographs were evaluated in terms of the relative value between the diameter of the tunnel and the bone, both at 2 cm below the medial tibial condyle. RESULTS There were significant increases in tunnel diameters: 20.56% for radiographs in anteroposterior view and 26.48% in lateral view. Enlargement was present in 48% of anteroposterior and lateral radiographs, but was present in both views in only 16% of the cases. CONCLUSIONS Bone tunnel enlargement is a phenomenon found in the first months after surgery to reconstruct the anterior cruciate ligament. The measurement technique proposed in this study was sufficient to detect it.

['Aguiar Leonardi|Adriano Barros de|AB|', 'Severino|Nilson Roberto|NR|', 'Junior|Aires Duarte|AD|']

2011

27890313

Laparoscopic fundoplication in neonates and young infants: Failure rate and need for redo at a high-volume center.

AIM OF THE STUDY Present the outcomes of patients younger than 2years who underwent laparoscopic fundoplication, highlighting the failure rate and need for redo fundoplication. METHODS Retrospective review of patients <2years who underwent laparoscopic fundoplication between January 2009 and December 2014. MAIN RESULTS 458 infants younger than 2years underwent laparoscopic fundoplication in the 6-year period (360 Nissen, 77 Toupet and 21 Thal fundoplications). Median age at surgery was 5 (1-23) months. Median follow-up was 3 (1-6) years. The conversion rate was 0.87% (4 of 458 cases). Patients did not undergo routine studies to assess the incidence of postoperative GER but were instead followed clinically. Failure of the fundoplication was determined when a patient was unable to gain weight and/or protect the airway while receiving gastric feedings because of GER. The failure rate in our experience was 2.6% (12 redo out of 458 cases [11/360 Nissen, 1/77 Toupet and 0/21 Thal]). All failed cases occurred because of migration of the fundoplication, confirmed preoperatively by a contrast study. Median time between the initial fundoplication and the redo was 13 (5-27) months. There were no failures within a contemporaneous group of 101 patients <2years who underwent open fundoplication. CONCLUSION The need for a redo fundoplication after a laparoscopic fundoplication was an uncommon event in our experience (12 of 458 cases). Our results contrast with published studies that report higher failure rates. Case volume per surgeon may explain in part the dissimilar results among studies. LEVEL OF EVIDENCE III.

['Laje|Pablo|P|', 'Blinman|Thane A|TA|', 'Nance|Michael L|ML|', 'Peranteau|William H|WH|']

2017

25890143

Repetitive transcranial magnetic stimulation for motor recovery of the upper limb after stroke.

OBJECTIVE Repetitive transcranial magnetic stimulation changes excitability of the motor cortex and it has hereby the potential to modulate changes in neural processing which impede motor recovery after stroke. METHODS This chapter presents an up-to-day systematic review of the treatment effects of repetitive transcranial magnetic stimulation (rTMS) in promoting motor recovery of the affected upper limb after stroke. RESULTS Thirty-seven trials were included in the analysis. The selected studies involved a total of 871 stroke subjects. All stimulation protocols pride on interhemispheric imbalance model. INTERPRETATION rTMS enhances motor recovery of the affected hand after stroke; however, the data available until today is too limited to support its routine use.

['Lüdemann-Podubecká|Jitka|J|', 'Bösl|Kathrin|K|', 'Nowak|Dennis Alexander|DA|']

2015

26173562

Register based study of anorectal anomalies over 26 years: Associated anomalies, prevalence, and trends.

BACKGROUND Anorectal anomalies are atresias or stenoses of the anal canal and rectum with or without fistulous connections with the bladder, urethra, perineum, or vestibule. The aim of this study was to describe the epidemiology of anorectal anomalies, including associated anomalies, prevalence, and temporal trends. METHODS Anorectal anomalies occurring in late miscarriages (>20 gestation weeks), terminations of pregnancy for fetal anomaly (any gestation), stillbirths (≥24 gestation weeks) and live births, delivered from 1985 to 2010, notified to the Northern Congenital Abnormality Survey (NorCAS) were included in this population-based case series. RESULTS There were 278 cases among 892,194 live births. Twenty (7.2%) cases occurred in twin pregnancies and 24 (8.7%) with chromosomal anomalies/genetic syndromes were excluded. There were 234 cases (total prevalence = 2.7, 95% confidence interval [CI]: 2.4, 3.1 per 10,000 live and stillbirths). There was no evidence of a trend in prevalence over time (Chi(2) test for trend: p = 0.789). There was a male predominance (70.9%). Of the 234 cases, 167 (71.4%) were live born, two (0.9%) were late miscarriages, seven (3.0%) were stillbirths, and 58 (24.8%) were terminations of pregnancy for fetal anomaly. There was no significant association with maternal age at delivery (p = 0.095). 7.2% of isolated cases (cases with no other congenital anomalies) were diagnosed prenatally. CONCLUSION The prevalence of anorectal anomalies in this study is comparable to other case series. There was no evidence of a temporal increase in prevalence. We confirmed a male predominance of anorectal anomalies and no significant association with maternal age. Birth Defects Research (Part A) 103:597-602, 2015. © 2015 Wiley Periodicals, Inc.

['Godse|Alok S|AS|', 'Best|Kate E|KE|', 'Lawson|Anne|A|', 'Rosby|Lucy|L|', 'Rankin|Judith|J|']

2015

31158693

Brain vascular changes in adults with congenital heart disease: A systematic review.

Less information is available on brain integrity in adults with congenital heart disease than on brain changes in newborns and children with heart defects. Nevertheless, the number of adults with congenital heart disease is increasing rapidly and it has been shown that adults with congenital heart disease develop dementia almost twice as frequently as adults in the general population. In the context of a rapidly growing congenital heart disease population, neuroradiological-oriented investigations of biomarkers distinctive for vascular damage, brain aging, and possible cognitive impairment is a crucial challenge. We provide an overview of the existing literature on neuroimaging studies in adults with congenital heart disease and discuss methodology issues to further investigate this subject. Overall, we aim to raise awareness of the importance of brain health studies in adults with congenital heart disease given the likely increasing impact on social and healthcare systems.

['Melazzini|Luca|L|', 'Codari|Marina|M|', 'Vitali|Paolo|P|', 'Sardanelli|Francesco|F|']

2019

31641414

Topical 15% Zinc Oxide Ointment Significantly Reduces the Size of Common Warts After Four Weeks: A Randomized, Triple-blinded, Placebo-controlled Trial.

Background: There are limited number of topical agents for the treatment of common warts. Few reports show efficacy of zinc oxide for such indication. Objectives: We sought to evaluate the efficacy of topical 15% zinc oxide ointment for the reduction in size of common warts. Materials and Methods: Sixteen patients with two comparable palmar warts or verruca vulgaris were randomized to receive either 15% zinc oxide ointment or placebo three times a day for four weeks. Diameter, surface area, and volume change of warts in both groups were used as objective assessments, while patient and physician assessments were also recorded. Results: At Week 4, zinc oxide significantly reduced the median surface area compared to baseline (P<0.037). However, when the median percent changes between groups were compared, there were no statistically significant differences. Conclusions: Zinc oxide can reduce the size of common hand warts after four weeks. We suggest that it can be used as an adjunctive therapy to enhance the efficacy of other treatments.

['Songsantiphap|Chankiat|C|', 'Asawanonda|Pravit|P|']

2019

34412576

The impact of a medical improv curriculum on wellbeing and professional development among pre-clinical medical students.

Medical students experience rising rates of burnout throughout their training. Efforts have been made to not only mitigate its negative effects, but also prevent its development. Medical improv takes the basic ideas of improvisational theatre and applies them to clinical situations. Given improv's focus on self-awareness and reflection, in addition to its spontaneous nature, we hypothesized it had the potential to serve as a creative outlet, a way to prevent and/or mitigate the negative effects of stress, burnout, and fatigue, and provide a learning environment to develop skills necessary to succeed as a physician. University of California (UC) San Diego School of Medicine developed a medical improv elective for pre-clinical students and assessed its effects on student development and wellbeing. Students enrolled in the elective between Fall 2019 and Fall 2020 at UC San Diego School of Medicine were surveyed pre- and post- course completion using both qualitative and quantitative methods. Students noted significant improvement in domains related to proactivity in their professional career (3.15 to 4.00, p = 0.02), wellbeing (3.0 to 4.4, p < 0.001), engagement with their studies (3.85 to 4.52, p = 0.02), and communication (3.75 to 4.3, p = 0.04) after completion of the medical improv elective. We describe a pilot-study demonstrating the positive effects of improv on medical student wellbeing and professional development, laying the groundwork for both future study of improv on student wellness and its implementation in the pre-clinical curriculum.

['Neel|Nicholas|N|', 'Maury|John-Michael|JM|', 'Heskett|Karen M|KM|', 'Iglewicz|Alana|A|', 'Lander|Lina|L|']

2021

24735499

Examining the role of parental self-regulation in family physical activity: a mixed-methods approach.

Physical activity (PA) is essential for good health. However, parents risk becoming less active because of the demands of parenting. This has consequences for children as parents are role models. The present study used a mixed-methods approach to explore parental self-regulation associated with PA. Data were collected from 36 parents with preschool-aged children. They were interviewed about their PA and their family's PA. Parents also completed PA and self-regulation questionnaires and wore an accelerometer for five days. Qualitative data were examined using an inductive approach to thematic analysis. It showed that parents felt that they had limited time for personal PA. Mothers' self-regulation was driven by an ethic of care and subjective norms, whereas fathers' self-regulation was driven by beliefs about the importance of autonomy. Nevertheless, both parents saw caring for their children as the main priority. Quantitative data were examined using multiple regression analyses. Results showed that different self-regulatory behaviours predicted the PA of mothers and fathers. Which predictors were significant depended on the type of activity and how it was measured. The findings warrant longitudinal research that would enable the effect of family dynamics on self-regulation associated with PA to be assessed.

['Butson|Michael L|ML|', 'Borkoles|Erika|E|', 'Hanlon|Clare|C|', 'Morris|Tony|T|', 'Romero|Vivian|V|', 'Polman|Remco|R|']

2014

30158905

The Culture Environment Influences Both Gene Regulation and Phenotypic Heterogeneity in Escherichia coli.

Microorganisms shape the composition of the medium they are growing in, which in turn has profound consequences on the reprogramming of the population gene-expression profile. In this paper, we investigate the progressive changes in pH and sugar availability in the medium of a growing Escherichia coli (E. coli) culture. We show how these changes have an effect on both the cellular heterogeneity within the microbial community and the gene-expression profile of the microbial population. We measure the changes in gene-expression as E. coli moves from lag, to exponential, and finally into stationary phase. We found that pathways linked to the changes in the medium composition such as ribosomal, tricarboxylic acid cycle (TCA), transport, and metabolism pathways are strongly regulated during the different growth phases. In order to quantify the corresponding temporal changes in the population heterogeneity, we measure the fraction of E. coli persisters surviving different antibiotic treatments during the various phases of growth. We show that the composition of the medium in which β-lactams or quinolones, but not aminoglycosides, are dissolved strongly affects the measured phenotypic heterogeneity within the culture. Our findings contribute to a better understanding on how the composition of the culture medium influences both the reprogramming in the population gene-expression and the emergence of phenotypic variants.

['Smith|Ashley|A|', 'Kaczmar|Agnieszka|A|', 'Bamford|Rosemary A|RA|', 'Smith|Christopher|C|', 'Frustaci|Simona|S|', 'Kovacs-Simon|Andrea|A|', "O'Neill|Paul|P|", 'Moore|Karen|K|', 'Paszkiewicz|Konrad|K|', 'Titball|Richard W|RW|', 'Pagliara|Stefano|S|']

2018

34891016

Estimation of the heavy metals released from cigarette butts to beaches and urban environments.

Cigarette butts (CB) are considered as a commonly littered waste. This hazardous waste contains a variety of pollutants. This study was developed to estimate the release of some heavy metals from CBs to the environment in different climatic conditions in different scenarios. To this end, CBs samples were obtained through artificial smoking from 10 high-consumption brands in the Iranian market, and their samples in urban areas were taken and analyzed in terms of heavy metals pollution. The results showed that the average concentrations of Lead, Cadmium, Chromium, Zinc, Copper, Nickel in the studied CBs were 1.71, 0.36, 1.59, 24.61, 12.83, and 2.66 µg/g, respectively. The long persistency of CBs in the environment leads to increased release of all heavy metals to 9.7%. In addition, the rainfall can accelerate the leaching of heavy metals to 17.7% compared to the control scenario. The total mean concentrations of the studied metals in the CBs samples collected from the urban areas in rainy and non-rainy conditions were measured to be 32.67-51.81 μg/g, respectively. According to the data obtained for the amount of each heavy metal releases in four scenarios, 147.5 kg/year and 57.3 kg/year heavy metals are released to the environment in the worst and the best-case scenarios. This study showed that CBs littering lead to the release of heavy metals into the environment; it is necessary to reduce the density of CBs in urban and public environments by training the smokers as well as increasing the efficiency of the urban cleaning system.

['Farzadkia|Mahdi|M|', 'Salehi Sedeh|Mina|M|', 'Ghasemi|Afsaneh|A|', 'Alinejad|Navid|N|', 'Samadi Kazemi|Malihe|M|', 'Jafarzadeh|Naghmeh|N|', 'Torkashvand|Javad|J|']

2021

28792272

Trigeminovascular calcitonin gene-related peptide function in Cacna1a R192Q-mutated knock-in mice.

Familial hemiplegic migraine type 1 (FHM1) is a rare migraine subtype. Whereas transgenic knock-in mice with the human pathogenic FHM1 R192Q missense mutation in the Cacna1a gene reveal overall neuronal hyperexcitability, the effects on the trigeminovascular system and calcitonin gene-related peptide (CGRP) receptor are largely unknown. This gains relevance as blockade of CGRP and its receptor are therapeutic targets under development. Hence, we set out to test these effects in FHM1 mice. We characterized the trigeminovascular system of wild-type and FHM1 mice through: (i) in vivo capsaicin- and CGRP-induced dural vasodilation in a closed-cranial window; (ii) ex vivo KCl-induced CGRP release from isolated dura mater, trigeminal ganglion and trigeminal nucleus caudalis; and (iii) peripheral vascular function in vitro . In mutant mice, dural vasodilatory responses were significantly decreased compared to controls. The ex vivo release of CGRP was not different in the components of the trigeminovascular system between genotypes; however, sumatriptan diminished the release in the trigeminal ganglion, trigeminal nucleus caudalis and dura mater but only in wild-type mice. Peripheral vascular function was similar between genotypes. These data suggest that the R192Q mutation might be associated with trigeminovascular CGRP receptor desensitization. Novel antimigraine drugs should be able to revert this complex phenomenon.

['Chan|Kayi Y|KY|', 'Labastida-Ramírez|Alejandro|A|', 'Ramírez-Rosas|Martha B|MB|', 'Labruijere|Sieneke|S|', 'Garrelds|Ingrid M|IM|', 'Danser|Alexander Hj|AH|0000-0002-5052-3585', 'van den Maagdenberg|Arn Mjm|AM|', 'MaassenVanDenBrink|Antoinette|A|']

2019

27347073

Establishment of a hybrid risk model to predict major cardiac adverse events in patients with non-ST-elevation acute coronary syndromes.

The present study aimed to generate a hybrid risk model for the prediction of major cardiac adverse events (MACE) in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS), by combining the Global Registry of Acute Coronary Events (GRACE) scoring system and the plasma concentration of N-terminal of the prohormone brain natriuretic peptide (lgNT-proBNP). A total of 640 patients with NSTE-ACS were randomly divided into either the model-establishing group (409 patients) or the prediction model group (231 patients). The clinical endpoint event was MACE, including cardiogenic death, myocardial infarction and heart failure-induced readmission. Among the 409 patients in the model-establishing group, 26 (6.6%) experienced MACE. The hybrid risk model was calculated using the following equation: Hybrid risk model = GRACE score + 20 × logarithm (lg)NT-proBNP + 15, in which the area under the receiver operating curves (ROCs) for the GRACE score and lgNT-proBNP were 0.807 and 0.798, respectively. From the equation, the area under the ROC for the hybrid risk model was 0.843; thus suggesting that the hybrid risk model may be better able to predict the occurrence of MACE compared with either of its components alone. Following re-stratification, 6% of patients in the hybrid risk model were re-grouped. A total of 15 patients in the prediction model group experienced MACE (6.5%). The areas under the ROCs for the hybrid risk model and the GRACE scores for the prediction model group were 0.762 and 0.748, respectively. The results of the present study suggested that the lgNT-proBNP and GRACE score-established hybrid risk model may improve the accuracy by which MACE are predicted.

['Zhang|Ning|N|', 'Liu|Wenxian|W|']

2016

27383399

Cloning and characterization of three ketoreductases from soil metagenome for preparing optically active alcohols.

OBJECTIVES To discover novel ketoreductases (KRED) from soil metagenome preparation of chiral alcohols. RESULTS Three putative KRED were cloned, heterologously expressed in Eschericha coli and characterized based on the sequence analysis of soil metagenome. All the three enzymes (KRED424, KRED432, and KRED433) had maximum activity at 55 °C and pH 7. KRED424 had a broader substrate spectrum compared with the other two. Three prochiral carbonyl compounds were used to evaluate the abilities of enantioselective reductions of the KRED. For N-Boc-3-pyrrolidone, all enzymes produced an (S)-type alcohol in enantiomeric excess (>99 % ee). For ethyl 2-oxo-4-phenylbutyrate, KRED424 showed a higher conversion (91.5 %) and enantioselectivity (S-type, >99 % ee) than KRED432 and KRED433. For ethyl 4-chloroacetoacetate (COBE), both of KRED424 and KRED433 completely converted 20 mM substrate and KRED433 could obtain an (R)-alcohol with 94 % ee. CONCLUSIONS The three ketoreductases have potential in the preparation of pharmaceuticals and fine chemicals.

['Zhao|Zhiqiang|Z|', 'Wang|Hualei|H|http://orcid.org/0000-0002-0111-753X', 'Zhang|Yiping|Y|', 'Chen|Lifeng|L|', 'Wu|Kai|K|', 'Wei|Dongzhi|D|']

2016

33747372

Cementless Hemiarthroplasty for Intracapsular Femoral Neck Fractures in the Octa- and Nonagenarians.

Backgroud Current evidence supports the use of cemented hemiarthroplasty for treatment of intracapsular femoral neck fractures since it is associated with a lower risk of implant-related complications. However, many medical centers employ the cementless technique for the frail elderly population because it is faster and has lower cardiovascular risks and perioperative mortality. This observational study reports the outcomes of cementless bipolar hemiarthroplasty for intracapsular femoral neck fractures in patients aged 80 years and older. Methods A total of 424 patients (female, 77.1%) with a mean age of 86.9 years were operated for intracapsular femoral neck fractures between January 2009 and December 2017. Of those, 66.7% had an American Society of Anaesthesiologists (ASA) score of 3 or more. All operations were performed with the posterolateral surgical approach and all patients received a cementless stem. Intraoperative and perioperative values and in-hospital outcomes were evaluated, and clinical and radiographical follow-up was done at 40 days, 90 days, and when possible between 5 months and 12 months postoperatively. Multivariate analysis was performed to evaluate if there were factors affecting mortality. Results The mean operative time was 50 minutes. There were no deaths intraoperatively. Intraoperative periprosthetic fractures occurred in 2.1% of the cases with 66.7% of them fixed through cerclage wires intraoperatively. The median length of hospitalization was 11 days (interquartile range, 8.75-15) and 2.4% of patients died while in hospital after surgery. Approximately 91.5% of patients presented with perioperative anemia. Only 1.9% of the complications were related to the implant, 62.5% of which were dislocations. More than 90% of patients were ambulatory either autonomously or with support at each follow-up assessment. Age, male sex, and higher ASA score were related to increased mortality. Conclusions Despite some limitations, this observational study underlines that a cementless femoral stem of modern design can give good clinical outcomes, thus being an appropriate solution especially for the frail elderly.

['Masoni|Virginia|V|', 'Staletti|Leda|L|', 'Berlusconi|Marco|M|', 'Castagna|Alessandro|A|', 'Morenghi|Emanuela|E|']

2021

28419632

Factors influencing beliefs about intimate partner violence among adults in South Korea.

OBJECTIVES This study aimed to identify factors influencing beliefs about intimate partner violence among Korean adults. DESIGN AND SAMPLE This is a cross-sectional descriptive study that analyzed data from 466 adults. MEASURES Beliefs about intimate partner violence were measured using a self-report questionnaire with a total of 28 items consisting of four subscales: perpetrator's justification for beating women, blaming women for violence against them, perpetrator's responsibility for violence, and giving help to victims. RESULTS Men and women had significantly different beliefs about intimate partner violence (t = -7.19, p < .001). Some characteristics were identified that led to unhealthy beliefs about intimate partner violence. Four variables-gender, age, educational level, and witnessing parental violence-had an explanatory power of 20% with regard to beliefs about IPV (F = 10.50, p = .000). CONCLUSIONS In South Korea, men, older individuals, and those with less formal education or who have witnessed parental violence need education to foster healthier beliefs about intimate partner violence. Nurses can play a vital role in efforts to decrease intimate partner violence.

['Han|Young Ran|YR|', 'Jeong|Geum Hee|GH|0000-0002-2254-1962', 'Kim|Shin-Jeong|SJ|']

2017

29117348

Delivering Patient-Centered Care in a Fragile State: Using Patient-Pathway Analysis to Understand Tuberculosis-Related Care Seeking in Pakistan.

Background Pakistan has the sixth largest population in the world and boasts the fifth greatest burden of tuberculosis. The Government of Pakistan has set the ambitious goal of zero deaths due to tuberculosis and universal access to tuberculosis care by 2020. Successfully reaching these goals is dependent on the country's capacity to diagnose and successfully treat an estimated 200000 unnotified or missing patients with tuberculosis. Methods A patient-pathway analysis (PPA) was conducted at the national level, as well as for each of the 4 provinces, to assess the alignment between patient care seeking and the availability of tuberculosis diagnostic and treatment services. Results Almost 90% of patients initiated care in the private sector, which accounts for only 15% of facilities with the capacity for tuberculosis diagnosis and treatment. Across the country, nearly 50% of tuberculosis microscopy laboratories were located in public-sector-basic health units and regional health centers. However, very few patients initiated care in these facilities. Overall, tuberculosis case detection was high given the low likelihood of patients reaching facilities with the capacity for tuberculosis service delivery during their first visit. Discussion Improving the engagement of the informal sector and lower-level clinicians will improve the efficiency and timeliness of tuberculosis diagnosis for patients in Pakistan. Concurrently, the apparent strength of the referral networks connecting community-level workers and private clinicians to the public sector for tuberculosis diagnosis and treatment suggests that strengthening the capacity of the public sector could be valuable.

['Fatima|Razia|R|', 'Haq|Mahboob Ul|MU|', 'Yaqoob|Aashifa|A|', 'Mahmood|Nasir|N|', 'Ahmad|Khawaja Laeeq|KL|', 'Osberg|Mike|M|', 'Makayova|Julia|J|', 'Hymoff|Aaron|A|', 'Hanson|Christy|C|']

2017

25582275

Cytidine deaminase polymorphism predicts toxicity of gemcitabine-based chemotherapy.

BACKGROUND The aim of this study was to ascertain whether single nucleotide polymorphisms of cytidine deaminase (CDA), a key enzyme in the metabolism pathway of gemcitabine, could predict clinical outcomes of cancer patients with gemcitabine-based chemotherapy. METHODS We searched MEDLINE and EMBASE up to January 2013 to identify eligible studies. A rigorous quality assessment of eligible studies was conducted according to the Newcastle-Ottawa Quality Assessment Scale. For each included study, the overall survival (OS), overall response rate (ORR) and toxicities were extracted and pooled using random-effects model. RESULTS In total, data from 13 studies were included. CDA 208A>G and CDA 435C>T were not included in quantified synthesis due to limited data. CDA 79A>C polymorphism was not significantly associated with OS; however, patients carrying the variant CDA 79C allele were likely to have a poor survival, hazard ratio (HR)=1.03, 95% CI 0.957-1.27 (AC+CC vs. AA). CDA 79A>C polymorphism did not correlated with ORR, odds ratio (OR)=0.719, 95% CI 0.363-1.425 (AC+CC vs. AA). However, patients with the variant CDA 79C allele would experience more grade ≥ 3 leucopenia (OR=2.933, 95% CI 1.357-6.605) and tended to have more severe neutropenia (OR=1.313, 95% CI 0.157-10.981). CONCLUSIONS These results suggest that CDA 79A>C polymorphisms is a potential biomarker for toxicity of gemcitabine-based chemotherapy and a CDA testing before gemcitabine administration is preferred.

['Ding|Xiangxiang|X|', 'Chen|Wenwei|W|', 'Fan|Haijian|H|', 'Zhu|Bin|B|']

2015

32099500

Acquired Factor XIII Deficiency Inducing Recurrent and Fatal Bleeding, Description of a Case.

Factor XIII deficiency may be inherited or acquired. Inherited deficiency is associated with signs and symptoms of minor bleeding from a young age, and possible major bleeding complications, in particular during pregnancy. On the other hand, acquired factor XIII deficiency is usually associated with severe symptoms of major bleeding, in particular during surgery. In this paper, we report an interesting case of recurrent major bleeding with subsequent fatal bleeding in an adult man diagnosed with acquired factor XIII deficiency.

['Di Micco|Pierpaolo|P|', 'Gussoni|Gualberto|G|', 'Pieralli|Filippo|F|', 'Campanini|Mauro|M|', 'Dentali|Francesco|F|', 'Fontanella|Andrea|A|']

2020

26019420

Methotrexate-induced chemical meningitis in patients with acute lymphoblastic leukemia/lymphoma.

BACKGROUND Intrathecal methotrexate (ITMTX) is an important component in the treatment as well as prophylaxis of leukemia/lymphoma. ITMTX can cause chemical meningitis characterized by vomiting, headache, and fever lasting 2-5 days with spontaneous resolution of symptoms which differentiates this syndrome from bacterial meningitis. OBJECTIVE This prospective observational study was carried out to determine incidence of post-ITMTX syndrome in patients receiving prophylactic ITMTX as part of Berlin-Frankfurt-Munster (BFM) protocol. MATERIALS AND METHODS Patients aged 15-50 years receiving BFM 90 or BFM 95 protocol for acute lymphoblastic leukemia or lymphoblastic lymphoma were followed up for post-ITMTX syndrome, defined as vomiting, headache and fever between 38° and 39°C following ITMTX. RESULTS Thirty-three patients received a total of 297 courses of ITMTX. Of the 297 doses of ITMTX, 20 episodes (6.7%) of post-ITMTX syndrome were observed. The incidence of post-ITMTX syndrome was highest after the second dose of ITMTX (24%). The most common symptom of post-ITMTX syndrome was headache which was seen in 17 (85%) patients. Seventeen (85%) patients had vomiting, 10 (50%) patients had fever, and 4 (20%) patients had backache. Meningeal signs were present in 2 (10%) patients. CONCLUSIONS Post-ITMTX syndrome is not uncommon in adult patients receiving prophylactic ITMTX for treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Patients develop a toxic syndrome closely mimicking acute bacterial meningitis but spontaneous recovery is seen without any neurological sequelae.

['Jacob|Linu A|LA|', 'Sreevatsa|Aparna|A|', 'Chinnagiriyappa|Lakshmaiah K|LK|', 'Dasappa|Lokanatha|L|', 'Suresh|T M|TM|', 'Babu|Govind|G|']

2015

32229312

Detection of Salmonella Typhimurium and Listeria monocytogenes biofilm cells exposed to different drying and pre-enrichment times using conventional and rapid methods.

The capacity of real-time PCR (RT-PCR), the VIDAS immunoassay system, and the conventional count method for detecting Salmonella enterica serovar Typhimurium and Listeria monocytogenes biofilm cells was evaluated in this study. After biofilm formation, tests were performed under different drying times (0, 6, 12, 24, and 72 h) and pre-enrichment times (0, 6, 18, and 25 h). The direct epifluorescence microscopic results demonstrated that Salmonella Typhimurium and L. monocytogenes biofilm cells can remain viable for 72 h under drying conditions. Pre-enrichment time and type of medium played an essential role in the detection of both microorganisms after drying. Furthermore, RT-PCR was more sensitive than VIDAS and the conventional method for detecting Salmonella Typhimurium and L. monocytogenes cells at different drying times and without pre-enrichment (0 h), with a detection range between 102 and 107 CFU/mL. TSBYE-T80 used as a pre-enrichment medium was effective for detecting both bacteria and was more effective than Demi Fraser-T80 medium for detecting L. monocytogenes. Therefore, pre-enrichment is recommended to avoid false positives and false negatives due to the presence of dead cells or a very low initial concentration of cells after drying.

['Ríos-Castillo|A G|AG|', 'Ripolles-Avila|C|C|', 'Rodríguez-Jerez|J J|JJ|']

2020

31230525

Current opinions about herbivore-associated molecular patterns and plant intracellular signaling.

Elicitor-associated compounds included in oral secretions of herbivorous arthropods, defined as herbivore-associated molecular patterns (HAMPs), induce defense responses in plants. Recognition of HAMPs by the host plants triggers the activation of downstream intracellular and intercellular signaling, resulting in the production of defensive secondary metabolites and volatile emissions to defend against herbivore attack. Thus far, several chemical classes of HAMPs, e.g., fatty acid-amino acid conjugates, peptides, enzymes, and oligosaccharides, have been characterized from not only plant-chewing arthropod herbivores but also plant-sucking arthropod herbivores. Here, we introduce the latest insights about HAMPs and the HAMPs-induced defense signaling network in host plants.

['Uemura|Takuya|T|', 'Arimura|Gen-Ichiro|GI|']

2019

28491059

Elucidation of the Role of 3-Hydroxy Fatty Acids in Cryptococcus-amoeba Interactions.

We previously reported that 3-hydroxy fatty acids promoted the survival of cryptococcal cells when acted upon by amoebae. To expand on this, the current study sought to explain how these molecules may protect cells. Our data suggest that 3-hydroxy fatty acids may subvert the internalization of cryptococcal cells via suppression of the levels of a fetuin A-like amoebal protein, which may be important for enhancing phagocytosis. Additionally, we show that an acapsular strain (that is devoid of 3-hydroxy fatty acids) was protected against the effects of hydrogen peroxide when exogenous 3-hydroxy fatty acids were present, but not in the absence of 3-hydroxy fatty acids. A similar response profile was noted when a strain with a capsule was challenged with hydrogen peroxide. We also show that cryptococcal cells that naturally produce 3-hydroxy fatty acids were more resistant to the effects of amoebapore (an amoeba-specific hydrolytic enzyme), compared to cells that do not produce these molecules. Taken together, our findings suggest that 3-hydroxy fatty acids possess an anti-phagocytic activity that may be expressed when cells interact with macrophages. This may allow the yeast cells to evade immuno-processing.

['Madu|Uju L|UL|', 'Ogundeji|Adepemi O|AO|', 'Pohl|Carolina H|CH|', 'Albertyn|Jacobus|J|', 'Sebolai|Olihile M|OM|']

2017

23857909

An MEKC assay for the therapeutic drug monitoring of cefepime.

The development of a robust assay based on MEKC for cefepime in human serum and plasma with internal quality assurance is reported. Sample preparation comprises protein precipitation in the presence of SDS at pH 4.5. This is a gentle approach for which decomposition of cefepime during sample handling is negligible. After hydrodynamic sample injection of the supernatant, analysis occurs in a phosphate/borate buffer at pH 9.1 with 75 mM SDS using normal polarity and analyte detection at 257 nm. The MEKC run time interval and throughput are about 5 min and seven samples per hour, respectively. The calibration range for cefepime is 1-60 μg/mL, with 1 μg/mL being the LOQ. The performance of the assay with multilevel internal calibration was assessed with calibration and control samples. The assay is shown to be simple, inexpensive, reproducible, and robust. It was applied to determine cefepime levels in the sera of critically ill patients and to assess the instability of cefepime in patient and control samples. Our data revealed that serum containing cefepime can be stored at -20°C for a short time, whereas for long-term storage, samples have to be kept at -70°C.

['Theurillat|Regula|R|', 'Sendi|Parham|P|', 'Thormann|Wolfgang|W|']

2013

31040856

Loss-of-Function of a Tomato Receptor-Like Kinase Impairs Male Fertility and Induces Parthenocarpic Fruit Set.

Parthenocarpy arises when an ovary develops into fruit without pollination/fertilization. The mechanisms involved in genetic parthenocarpy have attracted attention because of their potential application in plant breeding and also for their elucidation of the mechanisms involved in early fruit development. We have isolated and characterized a novel small parthenocarpic fruit and flower (spff) mutant in the tomato (Solanum lycopersicum) cultivar Micro-Tom. This plant showed both vegetative and reproductive phenotypes including dwarfism of floral organs, male sterility, delayed flowering, altered axillary shoot development, and parthenocarpic production of small fruits. Genome-wide single nucleotide polymorphism array analysis coupled with mapping-by-sequencing using next generation sequencing-based high-throughput approaches resulted in the identification of a candidate locus responsible for the spff mutant phenotype. Subsequent linkage analysis and RNA interference-based silencing indicated that these phenotypes were caused by a loss-of-function mutation of a single gene (Solyc04g077010), which encodes a receptor-like protein kinase that was expressed in vascular bundles in young buds. Cytological and transcriptomic analyses suggested that parthenocarpy in the spff mutant was associated with enlarged ovarian cells and with elevated expression of the gibberellin metabolism gene, GA20ox1. Taken together, our results suggest a role for Solyc04g077010 in male organ development and indicate that loss of this receptor-like protein kinase activity could result in parthenocarpy.

['Takei|Hitomi|H|', 'Shinozaki|Yoshihito|Y|', 'Yano|Ryoichi|R|', 'Kashojiya|Sachiko|S|', 'Hernould|Michel|M|', 'Chevalier|Christian|C|', 'Ezura|Hiroshi|H|', 'Ariizumi|Tohru|T|']

2019

32899866

Targeting Cell Cycle in Breast Cancer: CDK4/6 Inhibitors.

Deregulation of cell cycle, via cyclin D/CDK/pRb pathway, is frequently observed in breast cancer lending support to the development of drugs targeting the cell cycle control machinery, like the inhibitors of the cycline-dependent kinases (CDK) 4 and 6. Up to now, three CDK4/6 inhibitors have been approved by FDA for the treatment of hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. These agents have been effective in improving the clinical outcomes, but the development of intrinsic or acquired resistance can limit the efficacy of these treatments. Clinical and translational research is now focused on investigation of the mechanism of sensitivity/resistance to CDK4/6 inhibition and novel therapeutic strategies aimed to improve clinical outcomes. This review summarizes the available knowledge regarding CDK4/6 inhibitor, the discovery of new biomarkers of response, and the biological rationale for new combination strategies of treatment.

['Piezzo|Michela|M|0000-0002-1730-3900', 'Cocco|Stefania|S|0000-0003-3169-1580', 'Caputo|Roberta|R|', 'Cianniello|Daniela|D|', 'Gioia|Germira Di|GD|', 'Lauro|Vincenzo Di|VD|', 'Fusco|Giuseppina|G|0000-0001-7405-3074', 'Martinelli|Claudia|C|', 'Nuzzo|Francesco|F|', 'Pensabene|Matilde|M|', 'De Laurentiis|Michelino|M|0000-0001-9009-1572']

2020

34239430

Neurofeedback Training of Auditory Selective Attention Enhances Speech-In-Noise Perception.

Selective attention enhances cortical responses to attended sensory inputs while suppressing others, which can be an effective strategy for speech-in-noise (SiN) understanding. Emerging evidence exhibits a large variance in attentional control during SiN tasks, even among normal-hearing listeners. Yet whether training can enhance the efficacy of attentional control and, if so, whether the training effects can be transferred to performance on a SiN task has not been explicitly studied. Here, we introduce a neurofeedback training paradigm designed to reinforce the attentional modulation of auditory evoked responses. Young normal-hearing adults attended one of two competing speech streams consisting of five repeating words ("up") in a straight rhythm spoken by a female speaker and four straight words ("down") spoken by a male speaker. Our electroencephalography-based attention decoder classified every single trial using a template-matching method based on pre-defined patterns of cortical auditory responses elicited by either an "up" or "down" stream. The result of decoding was provided on the screen as online feedback. After four sessions of this neurofeedback training over 4 weeks, the subjects exhibited improved attentional modulation of evoked responses to the training stimuli as well as enhanced cortical responses to target speech and better performance during a post-training SiN task. Such training effects were not found in the Placebo Group that underwent similar attention training except that feedback was given only based on behavioral accuracy. These results indicate that the neurofeedback training may reinforce the strength of attentional modulation, which likely improves SiN understanding. Our finding suggests a potential rehabilitation strategy for SiN deficits.

['Kim|Subong|S|', 'Emory|Caroline|C|', 'Choi|Inyong|I|']

2021

24329871

A global analysis of bidirectional interactions in alpine plant communities shows facilitators experiencing strong reciprocal fitness costs.

Facilitative interactions are defined as positive effects of one species on another, but bidirectional feedbacks may be positive, neutral, or negative. Understanding the bidirectional nature of these interactions is a fundamental prerequisite for the assessment of the potential evolutionary consequences of facilitation. In a global study combining observational and experimental approaches, we quantified the impact of the cover and richness of species associated with alpine cushion plants on reproductive traits of the benefactor cushions. We found a decline in cushion seed production with increasing cover of cushion-associated species, indicating that being a benefactor came at an overall cost. The effect of cushion-associated species was negative for flower density and seed set of cushions, but not for fruit set and seed quality. Richness of cushion-associated species had positive effects on seed density and modulated the effects of their abundance on flower density and fruit set, indicating that the costs and benefits of harboring associated species depend on the composition of the plant assemblage. Our study demonstrates 'parasitic' interactions among plants over a wide range of species and environments in alpine systems, and we consider their implications for the possible selective effects of interactions between benefactor and beneficiary species.

['Schöb|Christian|C|', 'Michalet|Richard|R|', 'Cavieres|Lohengrin A|LA|', 'Pugnaire|Francisco I|FI|', 'Brooker|Rob W|RW|', 'Butterfield|Bradley J|BJ|', 'Cook|Bradley J|BJ|', 'Kikvidze|Zaal|Z|', 'Lortie|Christopher J|CJ|', 'Xiao|Sa|S|', 'Al Hayek|Patrick|P|', 'Anthelme|Fabien|F|', 'Cranston|Brittany H|BH|', 'García|Mary-Carolina|MC|', 'Le Bagousse-Pinguet|Yoann|Y|', 'Reid|Anya M|AM|', 'le Roux|Peter C|PC|', 'Lingua|Emanuele|E|', 'Nyakatya|Mawethu J|MJ|', 'Touzard|Blaise|B|', 'Zhao|Liang|L|', 'Callaway|Ragan M|RM|']

2014

34813921

The effects of molecular weight of hyaluronic acid on transdermal delivery efficiencies of dissolving microneedles.

Hyaluronic acid (HA) is widely adopted to fabricate dissolving microneedles for transdermal drug delivery applications, yet the structure-activity relationship between molecular weight of HA and transdermal delivery efficiency of microneedles (HA-MNs) has not been fully explored, particularly in the transdermal delivery of small molecule drugs. Herein, we report the fabrication of three types of HA-MNs of various molecular weights (10k, 74k and 290k Da), which incorporate rhodamine B as the model drug. We assess the influence of molecular weight of HA on the mechanical properties of HA-MNs and transdermal delivery of rhodamine B in vitro and in vivo. The mechanical strength of all types of HA-MNs exceeds the minimal force requirement for skin penetration, with the highest values of compression force found in 10k-HA-MN. Interestingly, 74k-HA-MN that owns a medium mechanical strength, exhibits the highest efficiency in transdermal delivery of rhodamine B in a porcine skin and a Franz cell transdermal model. Further in vivo fluorescence imaging of HA-MN-treated mice reveals a tunable transdermal delivery of rhodamine B, which is controllable according to the molecular weight of HA. Importantly, 74k-HA-MN treatment demonstrates the highest initial delivering amount and longest retention time of rhodamine B in mice. In addition, histological examinations of puncture sites of the skin tissues confirm the complete recovery of skin and excellent biocompatibility of HA-MNs.

['Chi|Yuquan|Y|', 'Huang|Yanping|Y|', 'Kang|Yixin|Y|', 'Dai|Guoru|G|', 'Liu|Ziqi|Z|', 'Xu|Keming|K|', 'Zhong|Wenying|W|']

2021

32298614

Plastic Circuits: Regulatory Flexibility in Fine Tuning Pathogen Success.

Bacterial pathogens employ diverse fitness and virulence mechanisms to gain an advantage in competitive niches. These lifestyle-specific traits require integration into the regulatory network of the cell and are often controlled by pre-existing transcription factors. In this review, we highlight recent advances that have been made in characterizing this regulatory flexibility in prominent members of the Enterobacteriaceae. We focus on the direct global interactions between transcription factors and their target genes in pathogenic Escherichia coli and Salmonella revealed using chromatin immunoprecipitation coupled with next-generation sequencing. Furthermore, the implications and advantages of such regulatory adaptations in benefiting distinct pathogenic lifestyles are discussed.

["O'Boyle|Nicky|N|", 'Turner|Natasha C A|NCA|', 'Roe|Andrew J|AJ|', 'Connolly|James P R|JPR|']

2020

27340853

Human ApoE ɛ2 Promotes Regulatory Mechanisms of Bioenergetic and Synaptic Function in Female Brain: A Focus on V-type H+-ATPase.

Humans possess three major isoforms of the apolipoprotein E (ApoE) gene encoded by three alleles: ApoE ɛ2 (ApoE2), ApoE ɛ3 (ApoE3), and ApoE ɛ4 (ApoE4). It is established that the three ApoE isoforms confer differential susceptibility to Alzheimer's disease (AD); however, an in-depth molecular understanding of the underlying mechanisms is currently unavailable. In this study, we examined the cortical proteome differences among the three ApoE isoforms using 6-month-old female, human ApoE2, ApoE3, and ApoE4 gene-targeted replacement mice and two-dimensional proteomic analyses. The results reveal that the three ApoE brains differ primarily in two areas: cellular bioenergetics and synaptic transmission. Of particular significance, we show for the first time that the three ApoE brains differentially express a key component of the catalytic domain of the V-type H+-ATPase (Atp6v), a proton pump that mediates the concentration of neurotransmitters into synaptic vesicles and thus is crucial in synaptic transmission. Specifically, our data demonstrate that ApoE2 brain exhibits significantly higher levels of the B subunit of Atp6v (Atp6v1B2) when compared to both ApoE3 and ApoE4 brains, with ApoE4 brain exhibiting the lowest expression. Our additional analyses show that Atp6v1B2 is significantly impacted by aging and AD pathology and the data suggest that Atp6v1B2 deficiency could be involved in the progressive loss of synaptic integrity during early development of AD. Collectively, our findings indicate that human ApoE isoforms differentially modulate regulatory mechanisms of bioenergetic and synaptic function in female brain. A more efficient and robust status in both areas-in which Atp6v may play a role-could serve as a potential mechanism contributing to the neuroprotective and cognition-favoring properties associated with the ApoE2 genotype.

['Woody|Sarah K|SK|', 'Zhou|Helen|H|', 'Ibrahimi|Shaher|S|', 'Dong|Yafeng|Y|', 'Zhao|Liqin|L|']

2016

34606228

Heteroepitaxial Growth of High Optical Quality, Wafer-Scale van der Waals Heterostrucutres.

Transition metal dichalcogenides (TMDs) are materials that can exhibit intriguing optical properties like a change of the bandgap from indirect to direct when being thinned down to a monolayer. Well-resolved narrow excitonic resonances can be observed for such monolayers although only for materials of sufficient crystalline quality and so far mostly available in the form of micrometer-sized flakes. A further significant improvement of optical and electrical properties can be achieved by transferring the TMD on hexagonal boron nitride (hBN). To exploit the full potential of TMDs in future applications, epitaxial techniques have to be developed that not only allow the growth of large-scale, high-quality TMD monolayers but also allow the growth to be performed directly on large-scale epitaxial hBN. In this work, we address this problem and demonstrate that MoSe2 of high optical quality can be directly grown on epitaxial hBN on an entire 2 in. wafer. We developed a combined growth theme for which hBN is first synthesized at high temperature by metal organic vapor phase epitaxy (MOVPE) and as a second step MoSe2 is deposited on top by molecular beam epitaxy (MBE) at much lower temperatures. We show that this structure exhibits excellent optical properties, manifested by narrow excitonic lines in the photoluminescence spectra. Moreover, the material is homogeneous on the area of the whole 2 in. wafer with only ±0.14 meV deviation of excitonic energy. Our mixed growth technique may guide the way for future large-scale production of high quality TMD/hBN heterostructures.

['Ludwiczak|Katarzyna|K|https://orcid.org/0000-0002-7279-4669', 'Da Browska|Aleksandra Krystyna|AK|', 'Binder|Johannes|J|https://orcid.org/0000-0002-0461-7716', 'Tokarczyk|Mateusz|M|', 'Iwański|Jakub|J|', 'Kurowska|Bogusława|B|', 'Turczyński|Jakub|J|', 'Kowalski|Grzegorz|G|', 'Bożek|Rafał|R|', 'Stȩpniewski|Roman|R|', 'Pacuski|Wojciech|W|https://orcid.org/0000-0001-8329-5278', 'Wysmołek|Andrzej|A|']

2021

27317498

Beyond p-values in the evaluation of brain-computer interfaces: A Bayesian estimation approach.

BACKGROUND To statistically evaluate the performance of brain-computer interfaces (BCIs), researchers usually rely on null hypothesis significance testing (NHST), i.e. p-values. However, over-reliance on NHST is often identified as one of the causes of the recent reproducibility crisis in psychology and neuroscience. NEW METHOD In this paper we propose Bayesian estimation as an alternative to NHST in the analysis of BCI performance data. For the three most common experimental designs in BCI research - which would usually be analyzed using a t-test, a linear regression, or an ANOVA - we develop hierarchical models and estimate their parameters using Bayesian inference. Furthermore, we show that the described models are special cases of the hierarchical generalized linear model (HGLM), which we propose as a general framework for the analysis of BCI performance. RESULTS We demonstrate the effectiveness of the proposed models on three real datasets and show how the results obtained with Bayesian estimation can give a nuanced insight into BCI performance data. Additionally, we provide all the data and code necessary to reproduce the presented results. COMPARISON WITH EXISTING METHOD(S) Compared to NHST, Bayesian estimation with the HGLM allows more flexibility in the analysis of BCI performance data from nested experimental designs, and the obtained results have a more straightforward interpretation. CONCLUSIONS Besides gains in flexibility and interpretability, a wider adoption of the Bayesian estimation approach in BCI studies could bring about greater transparency in data analysis, allow accumulation of knowledge across studies, and reduce questionable practices such as "p-hacking".

['Melinscak|Filip|F|', 'Montesano|Luis|L|']

2016

27236535

Design of an Internal Model Control strategy for single-phase grid-connected PWM inverters and its performance analysis with a non-linear local load and weak grid.

This paper presents the design of a controller based on Internal Model Control (IMC) applied to a grid-connected single-phase PWM inverter. The mathematical modeling of the inverter and the LCL output filter, used to project the 1-DOF IMC controller, is presented and the decoupling of grid voltage by a Feedforward strategy is analyzed. A Proportional - Resonant Controller (P+Res) was used for the control of the same plant in the running of experimental results, thus moving towards the discussion of differences regarding IMC and P+Res performances, which arrived at the evaluation of the proposed control strategy. The results are presented for typical conditions, for weak-grid and for non-linear local load, in order to verify the behavior of the controller against such situations.

['Chaves|Eric N|EN|', 'Coelho|Ernane A A|EAA|', 'Carvalho|Henrique T M|HTM|', 'Freitas|Luiz C G|LCG|', 'Júnior|João B V|JBV|', 'Freitas|Luiz C|LC|']

2016

24529435

Analysis of adipose tissue lipid using mass spectrometry.

Mass spectrometry technology has enabled significant advances in detailing the alterations of the lipidome in response to pathological conditions or experimental manipulations. Lipids comprise a wide range of compounds with functions that include structural, intracellular signaling, trafficking, and storage. Characterization of lipid species has evolved significantly over recent years due to the progress made in the area of mass spectrometry. This chapter details the methods used for the analysis of lipids tailored to the intrinsic characteristics of adipose tissue. Particular attention is given to the analysis of triglycerides, diacylglycerols, and phospholipid.

['Baker|Rodney C|RC|', 'Nikitina|Yana|Y|', 'Subauste|Angela R|AR|']

2014

25105208

Isotope-labeling studies on the formation pathway of acrolein during heat processing of oils.

Acrolein (2-propenal) is classified as a foodborne toxicant and was shown to be present in significant amounts in heated edible oils. Up to now, its formation was mainly suggested to be from the glycerol part of triacylglycerides, although a clear influence of the unsaturation of the fatty acid moiety was also obvious in previous studies. To unequivocally clarify the role of the glycerol and the fatty acid parts in acrolein formation, two series of labeled triacylglycerides were synthesized: [(13)C(3)]-triacylglycerides of stearic, oleic, linoleic, and linolenic acid and [(13)C(54)]-triacylglycerides with labeled stearic, oleic, and linoleic acid, but with unlabeled glycerol. Heating of each of the seven intermediates singly in silicon oil and measurement of the formed amounts of labeled and unlabeled acrolein clearly proved the fatty acid backbone as the key precursor structure. Enzymatically synthesized pure linoleic acid and linolenic acid hydroperoxides were shown to be the key intermediates in acrolein formation, thus allowing the discussion of a radical-induced reaction pathway leading to the formation of the aldehyde. Surprisingly, although several oils contained high amounts of acrolein after heating, deep-fried foods themselves, such as donuts or French fries, were low in the aldehyde.

['Ewert|Alice|A|', 'Granvogl|Michael|M|', 'Schieberle|Peter|P|']

2014

34610325

Low-cost structured alginate-immobilized bentonite beads designed for an effective removal of persistent antibiotics from aqueous solution.

The removal of persistent antibiotics from the water bodies can be quite challenging. The present study deals with the removal of doripenem, one of the most stable and persistent antibiotics, from aqueous solution via adsorption technique using the low-cost structured alginate-immobilized bentonite (Alg@iB) beads which can be easily recovered after the process. Alg@iB possesses a porous interior and higher basal spacing compared with the acid-activated bentonite (iB). Its adsorption/desorption isotherm corresponds to type IV IUPAC classification and H4-type hysteresis loops, implying the presence of slit- or plane-shaped pores. The influences of four independent adsorption parameters, e.g., pH, initial doripenem concentrations (md), temperature (T), and Alg@iB loading (mc), on the removal rate of doripenem (Yd) are investigated. The maximum Yd (95.8% w/w) is obtained at pH = 5, mc = 1.4% w/v, T = 50 °C, and md = 250 mg/l. The study suggests that the adsorption of doripenem is spontaneous and endothermic. Further analysis using the multi-linear intra-particle diffusion (IPD) model indicates that the rate-governing step in this adsorption process is the physical diffusion from the bulk solution to the boundary layer of Alg@iB. However, the mechanism study also considers the chemical hydrogen binding between the hydronium ions of Alg@iB and hydroxyl groups of doripenem as one of the driving forces that promote adsorption. Alg@iB shows good reusability with Yd > 90% w/w up to five adsorption cycles. Based on the study, the Alg@iB beads exhibit excellent affinity to doripenem, indicating that an effective doripenem removal can be achieved using this sorbent material.

['Yuliana|Maria|M|', 'Ismadji|Suryadi|S|', 'Lie|Jenni|J|', 'Santoso|Shella Permatasari|SP|', 'Soetaredjo|Felycia Edi|FE|', 'Waworuntu|Gladdy|G|', 'Putro|Jindrayani Nyoo|JN|', 'Wijaya|Christian Julius|CJ|']

2021

28824457

High Intensity Interval Training Leads to Greater Improvements in Acute Heart Rate Recovery and Anaerobic Power as High Volume Low Intensity Training.

The purpose of the current study was to explore if training regimes utilizing diverse training intensity distributions result in different responses on neuromuscular status, anaerobic capacity/power and acute heart rate recovery (HRR) in well-trained endurance athletes. Methods: Thirty-six male (n = 33) and female (n = 3) runners, cyclists, triathletes and cross-country skiers [peak oxygen uptake: (VO2peak): 61.9 ± 8.0 mL·kg-1·min-1] were randomly assigned to one of three groups (blocked high intensity interval training HIIT; polarized training POL; high volume low intensity oriented control group CG/HVLIT applying no HIIT). A maximal anaerobic running/cycling test (MART/MACT) was performed prior to and following a 9-week training period. Results: Only the HIIT group achieved improvements in peak power/velocity (+6.4%, P < 0.001) and peak lactate (P = 0.001) during the MART/MACT, while, unexpectedly, in none of the groups the performance at the established lactate concentrations (4, 6, 10 mmol·L-1) was changed (P > 0.05). Acute HRR was improved in HIIT (11.2%, P = 0.002) and POL (7.9%, P = 0.023) with no change in the HVLIT oriented control group. Conclusion: Only a training regime that includes a significant amount of HIIT improves the neuromuscular status, anaerobic power and the acute HRR in well-trained endurance athletes. A training regime that followed more a low and moderate intensity oriented model (CG/HVLIT) had no effect on any performance or HRR outcomes.

['Stöggl|Thomas L|TL|', 'Björklund|Glenn|G|']

2017

26081684

Fourth-derivative synchronous spectrofluorimetry and HPLC with fluorescence detection as two analytical techniques for the simultaneous determination of itopride and domperidone.

Two simple, rapid and sensitive methods, namely, fourth-derivative synchronous spectrofluorimetry (method I) and HPLC with fluorescence detection (method II) were developed for the simultaneous analysis of a binary mixture of itopride HCl (ITP) and domperidone (DOM) without prior separation. The first method was based on measuring the fourth derivative of the synchronous fluorescence spectra of the two drugs at Δλ = 40 nm in methanol. The different experimental parameters affecting the synchronous fluorescence of the studied drugs were carefully optimized. Chromatographic separation was performed in < 6.0 min using a RP C18 column (250 mm × 4.6 mm i.d., 5 µm particle size) with fluorescence detection at 344 nm after excitation at 285 nm. A mobile phase composed of a mixture of 0.02 M phosphate buffer with acetonitrile in a ratio of 55 : 45, pH 4.5, was used at a flow rate of 1 mL/min. Linearity ranges were found to be 0.1-2 µg/mL for ITP in both methods, whereas those for DOM were found to be 0.08-2 and 0.05-1.5 µg/mL in methods I and II, respectively. The proposed methods were successfully applied for the determination of the studied drugs in synthetic mixtures and laboratory-prepared tablets.

['Ibrahim|Fawzia|F|', 'Nasr|Jenny Jeehan|JJ|http://orcid.org/0000-0002-2423-7315']

2016

30505007

Cross-sectional analysis of the associations between fibromyalgia and diabetes mellitus.

Background The fibromyalgia syndrome (FMS) is a chronic condition consisting of widespread musculoskeletal pain and tenderness together with mood and cognitive dysfunction. Diabetes mellitus (DM) is a common condition causing significant and detrimental morbidity and mortality. Data on the association between the two conditions is scarce and mainly based on small populations therefore lack solid evidence. Objectives To evaluate the association of FMS with DM. Material and methods This cross-sectional study used the Clalit Health Services database, the largest Health Maintenance Organization in Israel, serving 4,400,000 members. FMS patients were compared to age- and sex-matched controls regarding chronic comorbid conditions. χ2 and student's t-tests were used for univariate analysis. Results The study included 14,296 FMS patients and 71,324 age- and sex-matched controls. The FMS group had a significantly higher proportion of DM patients compared to non-FMS controls (19.8% and 17.4 respectively; OR 1.17 , 95% CI: 1.12-1.23, p < 0.001). Conclusions DM was found to be more common amongst FMS patients compared to matched controls to suggest that the pathophysiology of DM might lead a patient to develop FMS. Consequently, physicians treating DM patients should be aware of the possible risk and asses for clinical signs of FMS in order to diagnose and treat it in time to better their patients' quality of life and disease management.

['Lichtenstein|Adi|A|', 'Tiosano|Shmuel|S|', 'Comaneshter|Doron|D|', 'Amital|Howard|H|', 'Cohen|Arnon D|AD|', 'Amital|Daniela|D|']

2018

29201229

Antimicrobial resistance and prevalence of CvfB, SEK and SEQ genes among Staphylococcus aureus isolates from paediatric patients with bloodstream infections.

Staphylococcus aureus (S. aureus) is one of the most frequently isolated pathogens in neonatal cases of early and late-onset sepsis. Drug resistance profiles and carriage of toxin genes may affect the treatment and outcome of an infection. The present study aimed to determine the antimicrobial resistance patterns and frequencies of the toxin-associated genes conserved virulence factor B (CvfB), staphylococcal enterotoxin Q (SEQ) and staphylococcal enterotoxin K (SEK) among S. aureus isolates recovered from paediatric patients with bloodstream infections (BSIs) in Guangzhou (China). Of the 53 isolates, 43.4% were methicillin-resistant S. aureus (MRSA), and resistance rates to penicillin, erythromycin, clindamycin, trimethoprim/sulfamethoxazole, tetracycline, and ciprofloxacin of 92.5, 66.0, 62.3, 13.2, 20.8 and 1.9% were recorded, respectively. However, no resistance to nitrofurantoin, dalfopristin/quinupristin, rifampicin, gentamicin, linezolid or vancomycin was detected. Resistance to erythromycin, clindamycin and tetracycline in the MRSA group was significantly higher than that in the methicillin-susceptible S. aureus (MSSA) group. No significant differences in antimicrobial resistance patterns were noted between two age groups (≤1 year and >1 year). The proportion of S. aureus isolates positive for CvfB, SEQ and SEK was 100, 34.0 and 35.8%, respectively, with 24.5% (13/53) of strains carrying all three genes. Compared with those in MSSA isolates, the rates of SEK, SEQ and SEK + SEQ carriage among MRSA isolates were significantly higher. Correlations were identified between the carriage of SEQ, SEK and SEQ + SEK genes and MRSA (contingency coefficient 0.500, 0.416, 0.546, respectively; P<0.01). In conclusion, MRSA isolated from the blood of paediatric patients with BSIs not only exhibited higher rates of antimicrobial resistance than MSSA from the same source, but also more frequently harboured SEK and SEQ genes. The combination of the two aspects influenced the dissemination of MRSA among children. The present study clarified the characteristics of BSI-associated S. aureus and enhanced the current understanding of the pathogenicity and treatment of MRSA.

['Liang|Bing-Shao|BS|', 'Huang|Yan-Mei|YM|', 'Chen|Yin-Shuang|YS|', 'Dong|Hui|H|', 'Mai|Jia-Liang|JL|', 'Xie|Yong-Qiang|YQ|', 'Zhong|Hua-Min|HM|', 'Deng|Qiu-Lian|QL|', 'Long|Yan|Y|', 'Yang|Yi-Yu|YY|', 'Gong|Si-Tang|ST|', 'Zhou|Zhen-Wen|ZW|']

2017

34452432

Gut Microbiome Changes Associated with Epithelial Barrier Damage and Systemic Inflammation during Antiretroviral Therapy of Chronic SIV Infection.

Gut dysbiosis is a common feature associated with the chronic inflammation of HIV infection. Toward understanding the interplay of chronic treated HIV infection, dysbiosis, and systemic inflammation, we investigated longitudinal fecal microbiome changes and plasma inflammatory markers in the nonhuman primate model. Following simian immunodeficiency virus (SIV) infection in rhesus macaques, significant changes were observed in several members of the phylum Firmicutes along with an increase in Bacteroidetes. Viral suppression with antiretroviral therapy (ART) resulted in an early but partial recovery of compositional changes and butyrate producing genes in the gut microbiome. Over the course of chronic SIV infection and long-term ART, however, the specific loss of Faecalibacterium prausnitzii and Treponema succinifaciens significantly correlated with an increase in plasma inflammatory cytokines including IL-6, G-CSF, I-TAC, and MIG. Further, the loss of T. succinifaciens correlated with an increase in circulating biomarkers of gut epithelial barrier damage (IFABP) and microbial translocation (LBP and sCD14). As F. prausnitzii and T. succinifaciens are major short-chain fatty acid producing bacteria, their sustained loss during chronic SV-ART may contribute to gut inflammation and metabolic alterations despite effective long-term control of viremia. A better understanding of the correlations between the anti-inflammatory bacterial community and healthy gut barrier functions in the setting of long-term ART may have a major impact on the clinical management of inflammatory comorbidities in HIV-infected individuals.

['Tanes|Ceylan|C|', 'Walker|Edith M|EM|', 'Slisarenko|Nadia|N|', 'Gerrets|Giovanni L|GL|', 'Grasperge|Brooke F|BF|', 'Qin|Xuebin|X|', 'Jazwinski|S Michal|SM|', 'Bushman|Frederic D|FD|', 'Bittinger|Kyle|K|', 'Rout|Namita|N|']

2021

32133920

Quantification of In Planta Zymoseptoria tritici Progression Through Different Infection Phases and Related Association with Components of Aggressiveness.

In planta growth of Zymoseptoria tritici, causal agent of Septoria tritici blotch of wheat, during the infection process has remained an understudied topic due to the long symptomless latent period before the emergence of fruiting bodies. In this study, we attempted to understand the relationship between in planta growth of Z. tritici relative to the primary components of aggressiveness, i.e., latent period and pycnidia coverage in regard to contrasting host resistance. We tested isolates collected from Ireland against the susceptible cultivar Gallant and cultivar Stigg, which has strong partial resistance. A clear isolate-host interaction effect (F = 3.018; P = 0.005, and F = 6.008; P < 0.001) for latent period and pycnidia coverage, respectively, was identified. Furthermore, during the early infection phase of latency from 5 to 11 days postinoculation (dpi), in planta growth rate of fungal biomass was significantly (F = 30.06; P < 0.001) more affected by host resistance than isolate specificity (F = 1.27; P = 0.27), indicating the importance of host resistance in the early infection phase. In planta Z. tritici growth rates in cultivar Gallant spiked between 11 and 16 dpi followed by a continuous fall onward, whereas in cultivar Stigg it was slowly progressive in nature. From correlation and regression analysis, we found that the in planta growth rate preceding the average latent period of cultivar Gallant has more influence on latency duration and pycnidia production. Likewise, correlation between component of aggressiveness and in planta growth rate of pathogen supports our understanding of aggressiveness to be driven by the pathogen's multiplication capacity within host tissue.

['Rahman|Atikur|A|http://orcid.org/0000-0002-3623-4664', 'Doohan|Fiona|F|', 'Mullins|Ewen|E|']

2020

25722769

Duane retraction syndrome in a Nigerian child.

We report a case of a four year old Nigerian girl who presented to the paediatric unit of our eye clinic with complaints of a squint on looking to the right side and reduction in the size of the right eye when looking to the left. On examination, she had right exotropia in the primary position of gaze. There was limitation of abduction and widening of the palpebral fissure of the right eye on right gaze. On left gaze there was narrowing of the palpebral fissure of the right eye with marked limitation of adduction and an upshoot, or occasionally a downshoot, of the eyeball. This report demonstrates that Duane's syndrome occurs in West Africa. Therefore, detailed examination of all patients with squints is important to ensure accurate diagnosis and appropriate management of the patient's condition.

['Olawoye|Olusola Oluyinka|OO|', 'Olusanya|Bolutife Ayokunnu|BA|', 'Baiyeroju|Aderonke Mojisola|AM|']

2014

27748256

Presurgical mapping of basal cell carcinoma or squamous cell carcinoma by confocal laser endomicroscopy compared to traditional micrographic surgery: a single-centre prospective feasibility study.

BACKGROUND At present, no ideal diagnostic tools exist in the market to excise cancer tissue with the required safety margins and to achieve optimal aesthetic results using tissue-conserving techniques. OBJECTIVES In this prospective study, confocal laser endomicroscopy (CLE) and the traditional gold standard of magnifying glasses (MG) were compared regarding the boundaries of in vivo basal cell carcinoma and squamous cell carcinoma. MATERIALS & METHODS Tumour diameters defined by both methods were measured and compared with those determined by histopathological examination. Nineteen patients were included in the study. RESULTS The CLE technique was found to be superior to excisional margins based on MG only. Re-excision was required in 68% of the cases following excision based on MG evaluation, but only in 27% of the cases for whom excision margins were based on CLE. CONCLUSION Our results are promising regarding the distinction between tumour and healthy surrounding tissue, and indicate that presurgical mapping of basal cell carcinoma and squamous cell carcinoma is possible. The tool itself should be developed further with special attention to early detection of skin cancer.

['Schulz|Alexandra|A|', 'Daali|Samira|S|', 'Javed|Mehreen|M|', 'Fuchs|Paul Christian|PC|', 'Brockmann|Michael|M|', 'Igressa|Alhadi|A|', 'Charalampaki|Patra|P|']

2016

25933498

Oral supplementation with L-glutamine alters gut microbiota of obese and overweight adults: A pilot study.

OBJECTIVE The aim of this study was to determine whether oral supplementation with L-glutamine (GLN) modifies the gut microbiota composition in overweight and obese adults. METHODS Thirty-three overweight and obese adults, ages between 23 and 59 y and body mass index between 25.03 and 47.12 kg/m(2), were randomly assigned to receive either oral supplementation with 30 g of L-alanine (ALA group control) or 30 g of GLN (GLN group) daily for 14 d. We analyzed the gut microbiota composition with new-generation sequencing techniques and bioinformatics analysis. RESULTS After 14 d of supplementation, adults in the GLN group exhibited statistically significant differences in the Firmicutes and Actinobacteria phyla compared with those in the ALA group. The ratio of Firmicutes to Bacteroidetes, a good biomarker for obesity, decreased in the GLN group from 0.85 to 0.57, whereas it increased from 0.91 to 1.12 in the ALA group. At the genus level, Dialister, Dorea, Pseudobutyrivibrio, and Veillonella, belonging to the Firmicutes phylum, had statistically significant reduction. CONCLUSION Oral supplementation with GLN, for a short time, altered the composition of the gut microbiota in overweight and obese humans reducing the Firmicutes to Bacteroidetes ratio, which resembled weight loss programs already seen in the literature.

['de Souza|Alessandra Zanin Zambom|AZ|', 'Zambom|Adriano Zanin|AZ|', 'Abboud|Kahlile Youssef|KY|', 'Reis|Sabrina Karen|SK|', 'Tannihão|Fabiana|F|', 'Guadagnini|Dioze|D|', 'Saad|Mario J A|MJ|', 'Prada|Patricia Oliveira|PO|']

2015

28978544

Intramuscular triglyceride synthesis: importance in muscle lipid partitioning in humans.

Intramuscular triglyceride (IMTG) concentration is elevated in insulin-resistant individuals and was once thought to promote insulin resistance. However, endurance-trained athletes have equivalent concentration of IMTG compared with individuals with type 2 diabetes, and have very low risk of diabetes, termed the "athlete's paradox." We now know that IMTG synthesis is positively related to insulin sensitivity, but the exact mechanisms for this are unclear. To understand the relationship between IMTG synthesis and insulin sensitivity, we measured IMTG synthesis in obese control subjects, endurance-trained athletes, and individuals with type 2 diabetes during rest, exercise, and recovery. IMTG synthesis rates were positively related to insulin sensitivity, cytosolic accumulation of DAG, and decreased accumulation of C18:0 ceramide and glucosylceramide. Greater rates of IMTG synthesis in athletes were not explained by alterations in FFA concentration, DGAT1 mRNA expression, or protein content. IMTG synthesis during exercise in Ob and T2D indicate utilization as a fuel despite unchanged content, whereas IMTG concentration decreased during exercise in athletes. mRNA expression for genes involved in lipid desaturation and IMTG synthesis were increased after exercise and recovery. Further, in a subset of individuals, exercise decreased cytosolic and membrane di-saturated DAG content, which may help explain insulin sensitization after acute exercise. These data suggest IMTG synthesis rates may influence insulin sensitivity by altering intracellular lipid localization, and decreasing specific ceramide species that promote insulin resistance.

['Bergman|Bryan C|BC|', 'Perreault|Leigh|L|', 'Strauss|Allison|A|', 'Bacon|Samantha|S|', 'Kerege|Anna|A|', 'Harrison|Kathleen|K|', 'Brozinick|Joseph T|JT|', 'Hunerdosse|Devon M|DM|', 'Playdon|Mary C|MC|', 'Holmes|William|W|', 'Bui|Hai Hoang|HH|', 'Sanders|Phil|P|', 'Siddall|Parker|P|', 'Wei|Tao|T|', 'Thomas|Melissa K|MK|', 'Kuo|Ming Shang|MS|', 'Eckel|Robert H|RH|']

2018

34830885

Quantitative Imaging Biomarkers of the Whole Liver Tumor Burden Improve Survival Prediction in Metastatic Pancreatic Cancer.

Finding prognostic biomarkers with high accuracy in patients with pancreatic cancer (PC) remains a challenging problem. To improve the prediction of survival and to investigate the relevance of quantitative imaging biomarkers (QIB) we combined QIB with established clinical parameters. In this retrospective study a total of 75 patients with metastatic PC and liver metastases were analyzed. Segmentations of whole liver tumor burden (WLTB) from baseline contrast-enhanced CT images were used to derive QIBs. The benefits of QIBs in multivariable Cox models were analyzed in comparison with two clinical prognostic models from the literature. To discriminate survival, the two clinical models had concordance indices of 0.61 and 0.62 in a statistical setting. Combined clinical and imaging-based models achieved concordance indices of 0.74 and 0.70 with WLTB volume, tumor burden score (TBS), and bilobar disease being the three WLTB parameters that were kept by backward elimination. These combined clinical and imaging-based models have significantly higher predictive performance in discriminating survival than the underlying clinical models alone (p < 0.003). Radiomics and geometric WLTB analysis of patients with metastatic PC with liver metastases enhances the modeling of survival compared with models based on clinical parameters alone.

['Gebauer|Leonie|L|', 'Moltz|Jan H|JH|0000-0002-7880-1014', 'Mühlberg|Alexander|A|', 'Holch|Julian W|JW|', 'Huber|Thomas|T|', 'Enke|Johanna|J|', 'Jäger|Nils|N|', 'Haas|Michael|M|', 'Kruger|Stephan|S|', 'Boeck|Stefan|S|', 'Sühling|Michael|M|', 'Katzmann|Alexander|A|', 'Hahn|Horst|H|', 'Kunz|Wolfgang G|WG|0000-0002-5021-1952', 'Heinemann|Volker|V|', 'Nörenberg|Dominik|D|0000-0001-7726-9006', 'Maurus|Stefan|S|']

2021

28612682

Culturally prescribed beliefs about mental illness among the Akan of Ghana.

Mental illness is a culturally laden phenomenon, and different cultures have unique ways of constructing mental illness. In this study, conceptions of mental illness were explored among 30 participants of Akan descent in Ghana through individual and group interviews. Participants demonstrated a wide range of knowledge on mental illness indicating that poor self-care, deficits in social functioning, and disordered behaviors are the cardinal features of mental illness. The data revealed that Akan cultural beliefs influenced notions of etiology of mental illness and care of the mentally ill. While participants recognized the role of multiple factors such as genetics, substance abuse, daily hassles (for example, concerns about basic needs such as food, clothing, and shelter), and trauma in the cause of mental illness, the predominant belief was that mental illness is a retributive and/or a spiritual illness. This belief encourages pluralistic health-seeking behaviors: use of hospitals, prayer camps, herbalists, and traditional healers. The implications of these findings for public health education on mental illness, and clinical training and practice are discussed.

['Opare-Henaku|Annabella|A|', 'Utsey|Shawn O|SO|']

2017

32828796

Effect of pH and denaturants on the fold and metal status of anthrax lethal factor.

Anthrax lethal factor (LF) is a critical component of the anthrax toxin, and functions intracellularly as a zinc-dependent endopeptidase targeting proteins involved in maintaining critical host signaling pathways. To reach the cytoplasm, LF requires to be unfolded and guided through the narrow protective antigen pore in a pH-dependent process. The current study sought to address the question as to whether LF is capable of retaining its metal ion when exposed to a low-pH environment (similar to that found in late endosomes) and an unfolding stress (induced by urea). Using a combination of tryptophan fluorescence spectroscopy and chelation studies, we show that a decrease in the pH value (from 7.0 to 5.0) leads to a pronounced shift in the onset of structural alterations in LF to lower urea concentrations. More importantly, the enzyme was found to retain its Zn2+ ion beyond the unfolding transitions monitored by Trp fluorescence, a finding indicative of tight metal binding to LF in a non-native state. In addition, an analysis of red-edge excitation shift (REES) spectra suggests the protein to maintain residual structure (a feature necessary for metal binding) even at very high denaturant concentrations. Furthermore, studies using the chromophoric chelator 4-(2-pyridylazo)resorcinol (PAR) revealed LF's Zn2+ ion to become accessible to complexation at urea concentrations in between those required to cause structural changes and metal dissociation. This phenomenon likely originates from the conversion of a PAR-inaccessible (closed) to a PAR-accessible (open) state of LF at intermediate denaturant concentrations.

['Lo|Suet Y|SY|', 'Goulet|Danica L|DL|', 'Fraaz|Usama|U|', 'Siemann|Stefan|S|']

2020

34001505

Task-specific movement training improves kinematics and pain during the Y-balance test and hip muscle strength in females with patellofemoral pain.

OBJECTIVES Task-specific movement training is a proposed intervention for patellofemoral pain aimed to optimise movement during daily tasks. Focused, progressive task practice emphasising optimal limb alignment may yield improvements in performance-based function and hip muscle strength, and transfer learnt movement patterns to untrained tasks. The purpose of this study was to determine if task-specific movement training improves performance-based function (composite score, movement, pain during movement) in an untrained task. Our secondary purpose was to test whether hip muscle strength improved following the movement training intervention. METHODS This study was a secondary analysis of a prospective, non-randomised, within-group, double-baseline study. Twenty-three females with patellofemoral pain underwent task-specific movement training two times/week for 6 weeks. Outcomes were collected at three time points: enrolment (baseline), 6 weeks (preintervention) and 12 weeks (postintervention). A repeated measures analysis of variance tested whether the change during the intervention phase was greater than the change during the control phase. Y-balance composite score, hip and knee kinematics and pain during the Y-balance test were primary outcome measures; strength of the hip lateral rotator, abductor and extensor muscles was a secondary outcome measure. RESULTS The change in composite score for the Y-balance test was not statistically significantly different between the intervention and control phases (p=0.16). The change during the intervention phase exceeded the change during the control phase for hip and knee kinematics and pain during the Y-balance test, with all variables improving (p<0.0001). The change during the intervention phase was greater than the control phase for hip muscle strength, with all variables improving (p<0.04). CONCLUSION Although the Y-balance test composite score did not improve, performance-based function during an untrained task, measured by movement and pain during the test, improved following task-specific movement training. Hip muscle strength improved, despite no focused muscle strengthening. LEVEL OF EVIDENCE Level II.

['Arhos|Elanna K|EK|0000-0001-9829-1624', 'Lang|Catherine E|CE|', 'Steger-May|Karen|K|', 'Van Dillen|Linda R|LR|', 'Yemm|Barbara|B|', 'Salsich|Gretchen B|GB|']

2021

23885172

Novel thermosensitive hydrogel for preventing formation of abdominal adhesions.

Adhesions can form after almost any type of abdominal surgery. Postoperative adhesions can be prevented by improved surgical techniques, such as reducing surgical trauma, preventing ischemia, and avoiding exposure of the peritoneal cavity to foreign materials. Although improved surgical techniques can potentially reduce formation of adhesions, they cannot be eliminated completely. Therefore, finding more effective methods to prevent postoperative adhesions is imperative. Recently, we found that a novel thermosensitive hydrogel, ie, poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC) had the potential to prevent postoperative adhesions. Using the ring-opening polymerization method we prepared a PCEC copolymer which could be dissolved and assembled at 55°C into PCEC micelles with mean size of 25 nm. At body temperature, a solution containing PCEC micelles could convert into a hydrogel. The PCEC copolymer was biodegradable and had low toxicity in vitro and in vivo. We found that most animals in a hydrogel-treated group (n = 10) did not develop adhesions. In contrast, 10 untreated animals developed adhesions that could only be separated by sharp dissection (P < 0.001). The hydrogel could adhere to peritoneal wounds and degraded gradually over 7-9 days, transforming into a viscous fuid that was completely absorbed within 12 days. The injured parietal and visceral peritoneum remesothelialized over about seven and nine days, respectively. This study confirms that PCEC hydrogel has potential application in the prevention of postoperative adhesions.

['Gao|Xiang|X|', 'Deng|Xiaohui|X|', 'Wei|Xiawei|X|', 'Shi|Huashan|H|', 'Wang|Fengtian|F|', 'Ye|Tinghong|T|', 'Shao|Bin|B|', 'Nie|Wen|W|', 'Li|Yuli|Y|', 'Luo|Min|M|', 'Gong|Changyang|C|', 'Huang|Ning|N|']

2013

28289143

Transcription factor Wilms' tumor 1 regulates developmental RNAs through 3' UTR interaction.

Wilms' tumor 1 (WT1) is essential for the development and homeostasis of multiple mesodermal tissues. Despite evidence for post-transcriptional roles, no endogenous WT1 target RNAs exist. Using RNA immunoprecipitation and UV cross-linking, we show that WT1 binds preferentially to 3' untranslated regions (UTRs) of developmental targets. These target mRNAs are down-regulated upon WT1 depletion in cell culture and developing kidney mesenchyme. Wt1 deletion leads to rapid turnover of specific mRNAs. WT1 regulates reporter gene expression through interaction with 3' UTR-binding sites. Combining experimental and computational analyses, we propose that WT1 influences key developmental and disease processes in part through regulating mRNA turnover.

['Bharathavikru|Ruthrothaselvi|R|', 'Dudnakova|Tatiana|T|', 'Aitken|Stuart|S|', 'Slight|Joan|J|', 'Artibani|Mara|M|', 'Hohenstein|Peter|P|', 'Tollervey|David|D|', 'Hastie|Nick|N|']

2017

26749528

Platelet immunoreceptor tyrosine-based activation motif (ITAM) and hemITAM signaling and vascular integrity in inflammation and development.

Platelets are essential for maintaining hemostasis following mechanical injury to the vasculature. Besides this established function, novel roles of platelets are becoming increasingly recognized, which are critical in non-injury settings to maintain vascular barrier integrity. For example, during embryogenesis platelets act to support the proper separation of blood and lymphatic vessels. This role continues beyond birth, where platelets prevent leakage of blood into the lymphatic vessel network. During the course of inflammation, platelets are necessary to prevent local hemorrhage due to neutrophil diapedesis and disruption of endothelial cell-cell junctions. Surprisingly, platelets also work to secure tumor-associated blood vessels, inhibiting excessive vessel permeability and intra-tumor hemorrhaging. Interestingly, many of these novel platelet functions depend on immunoreceptor tyrosine-based activation motif (ITAM) signaling but not on signaling via G protein-coupled receptors, which plays a crucial role in platelet plug formation at sites of mechanical injury. Murine platelets express two ITAM-containing receptors: the Fc receptor γ-chain (FcRγ), which functionally associates with the collagen receptor GPVI, and the C-type lectin-like 2 (CLEC-2) receptor, a hemITAM receptor for the mucin-type glycoprotein podoplanin. Human platelets express an additional ITAM receptor, FcγRIIA. These receptors share common downstream effectors, including Syk, SLP-76 and PLCγ2. Here we will review the recent literature that highlights a critical role for platelet GPVI/FcRγ and CLEC-2 in vascular integrity during development and inflammation in mice and discuss the relevance to human disease.

['Lee|R H|RH|', 'Bergmeier|W|W|']

2016