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Grass strip corridors in agricultural landscapes enhance nest-site colonization by solitary wasps. Corridors that connect otherwise isolated habitats have often been proposed as a management strategy to mitigate negative effects of habitat fragmentation. Non-crop corridors may have the potential to enhance the connectivity for arthropod predators in cropland landscapes, especially for species that require multiple habitats, such as cavity-nesting wasps which use wooded habitat for nesting and grassland habitat for foraging. However, the effects of corridors in nonexperimental landscapes have been rarely examined. We studied the species richness and abundance of cavity-nesting wasps and their parasitoids in standardized trap nests located in three habitat types (forest edge, hedge, grass strip) and in three grass-strip types (connected to a forest edge, slightly isolated, highly isolated from a forest edge). Species richness and the abundance of wasps (Hymenoptera: Sphecidae, Eumenidae, Pompilidae) were highest at forest edges, which provide natural nesting sites, and lowest in grass strips, with few natural nesting sites. Wasp abundance in grass strips connected to forest edges was 270% higher than in slightly isolated grass strips and 600% higher than in highly isolated grass strips. The abundance of caterpillar-hunting eumenid wasps was 600% higher in connected grass strips than in slightly and highly isolated grass strips. Species richness of wasps was enhanced by 180% in connected grass strips compared to highly isolated grass strips. Parasitism rates were not directly influenced by habitat or grass-strip type, but increased with increasing parasitoid diversity that was higher at forest edges than in grass strips. We conclude that grass-strip corridors enhance the colonization of nesting sites, presumably by facilitating wasp movements. In agricultural landscapes, where nesting sites are limited and food availability changes frequently, rapid colonization of nests may enhance population viability. Higher wasp abundance in connected nesting sites may be directly linked to higher biocontrol of pest caterpillars within the foraging range around nests. Although grass strips can reduce the negative effects of habitat fragmentation, non-crop habitats such as forest habitats and hedges providing nesting sites are required within the home range of wasps to allow reproduction in agricultural landscapes.

[Quality of fundamental movement patterns in chronic low back pain patients: a quasi-experimental cross-sectional study]. Chronic back pain may be associated with alterations of motor control and maladaptive movement. However, instruments that systematically screen fundamental movement patterns are rare. Using a newly developed functional movement analysis, this study aims to examine whether persons with chronic unspecific low back pain display altered quality of fundamental movement patterns and whether asymmetry exists between body sides. 20 patients with chronic back pain (♀ = 8, ♂ = 12; 49.4 ± 11.3 years) and 20 healthy controls (♀ = 12, ♂ = 8; 47.7 ± 10.7 years) completed the functional movement analysis. It consists of 11 items screening movements of daily life. Eight of them were to complete left and right. The overall score and the number of observed asymmetries (in items to complete left and right) constituted the primary outcomes. A preliminary analysis of reliability (four raters, four subjects) with pilot character was conducted using intraclass correlation (ICC). To compare differences in means, independent t-tests were performed. In case of significance, we calculated the effect size (Cohen's d). The reliability analysis showed an ICC (2.1) of 0.82 (95 % CI: 0.72 - 0.90). Patients with chronic low back pain (31.95 ± 5.82) scored significantly lower than healthy subjects (44.01 ± 5.27; p < 0.001, d = 2.17). Additionally, patients averaged 3.8 ± 1.28 asymmetries while pain-free participants only demonstrated 1.4 ± 0.94 (p < 0.001; d = 2.14). Faulty and dysbalanced movement patterns appear to be linked to chronic low back pain. Nonetheless, given an existing relation, it remains unclear whether the detected deficiencies are causes or consequences of pain. Further studies about the reliability of the presented screening tool are needed.

Sense of coherence contributes to physical and mental health in general hospital patients in China. The sense of coherence (SOC) may explain why some people become ill under stress whereas others remain healthy. SOC is strongly related to perceived health, particularly mental health. Little is known about the physical and mental health statuses associated with SOC among general hospital outpatients in China. This multicentre cross-sectional study analysed 491 outpatients from four large Chinese general hospitals located in Beijing, Shanghai, Chengdu and Kunming. Patients completed questionnaires examining their SOC (SOC-9), somatic symptom severity (PHQ-15), depression (PHQ-9), generalised anxiety disorder (GAD), health anxiety (WI-7), quality of life (QoL; SF-12) and socio-demographic and clinical characteristics. SOC was negatively correlated with daily-life impairment, symptom duration, somatic symptom severity, depression, GAD and health anxiety, but was positively correlated with age as well as physical and mental QoL. Using a multiple linear regression model, the three strongest correlates of SOC were mental QoL, depression and age. These three variables explained 52% of the variance. SOC may be an important contributor to both mental and physical health in Chinese general hospital outpatients, which is consistent with the results obtained for primary care patients in Western countries. Longitudinal studies are needed to investigate how SOC predicts physical and mental health statuses over time and how these statuses respond to treatment for low SOC.

MUC1 and breast cancer. The development of an effective immunotherapeutic approach to cancer is now a major focus of research, and despite impressive progress over the last 10 years there are still many hurdles to overcome to elicit an effective immune response which will totally eradicate the cancer. Mucins (MUC1) have attracted interest as potential targets for immunotherapy of cancers of breast, pancreas, ovary and others, and we have demonstrated that mannan, a polymannose carbohydrate is an effective carrier for MUC1 in eliciting a cellular immune response. Several clinical trials are in progress to evaluate the immunogenicity of MUC1 and its suitability as to use for immunotherapy/vaccine for breast cancer.

Air-breathing behaviour of the Colombian catfish Eremophilus mutisii (Trichomycteridae, Siluriformes). Eremophilus mutisii uses the vascularized central portion of its stomach for aerial respiration, and is a frequent but not obligatory air breather. Air ventilation takes place during a rapid dash to the surface with the expiration of old air preceding inspiration. The frequency of air breathing is affected by aquatic O2 concentration. E. mutisii can survive at least 10 days without air breathing in normoxic water but cannot survive without air access in water containing less than 2.0 ppm O2.

Quantification of Enterococcus faecalis and Enterococcus faecium in different foods using rRNA-targeted oligonucleotide probes. The abundance of Enterococcus faecalis and Enterococcus faecium in different Spanish foods was evaluated by using taxon-specific oligonucleotide probes targeted against extracted rRNA. Two satisfactory methods were developed for RNA extraction. Although the yield and purity of total RNA obtained largely depended on the type of food, method 1 should be recommended. The quantitative results obtained with the oligonucleotide probes DB6 for E. faecium and DB8 for E. faecalis showed that these two species accounted for less than 0.5% of the active microflora in all the food samples tested. These results suggest that enterococci form only a minor portion of the microflora of these products.

[A comparative analysis of the intracellular potassium content for the cardiomyocyte in papillary muscle tissue and in a primary heart culture]. This work was aimed to examine potassium contents in heart myocytes. The intracellular concentration of this element was measured with electron probe microanalysis (EPMA). The cardiomyocyte was studied in samples of the papillary muscle tissue and in heart primary culture. The low temperature fixation was applied to the sample preparation. As a result, cells of the primary heart culture were shown to be separated into three kinds of myocytes, defined by their different shape, size and cellular potassium content. The rod cardial cell, to be used for electrophysiological assays, has potassium and sodium concentrations close to those of the papillary muscle. The difference in potassium concentrations is to be explained presumably by the injury of cell membrane during the primary culture preparation. Healing over the membrane is likely to parallel with the membrane damage resulting from a continuous destruction of the cellular assembly in primary culture.

Are antipredator behaviours of hatchery Salmo salar juveniles similar to wild juveniles? This study explores how antipredator behaviour of juvenile Atlantic salmon Salmo salar developed during conventional hatchery rearing of eggs from wild brood stock, compared with the behaviour of wild-caught juveniles from the same population. Juveniles aged 1+ years were tested in two unfamiliar environments; in one S. salar were presented with simulated predator attacks and in the other they were given the opportunity to explore an open-field arena. No difference was found in their spontaneous escape responses or ventilation rate (reflex responses) after simulated predator attacks. Hatchery-reared juveniles were more risk-prone in their behaviours than wild-caught individuals. Hatchery juveniles stayed less time in association with shelter. In the open-field arena, hatchery juveniles were more active than wild juveniles. Hatchery juveniles were also immobile for less time and spent a shorter amount of time than wild juveniles in the fringe of the open-field arena. Salmo salar size had no effect on the observed behaviour. Overall, this study provides empirical evidence that one generation of hatchery rearing does not change reflex responses associated with threats, whereas antipredator behaviour, typically associated with prior experience, was less developed in hatchery-reared than in wild individuals.

Degree of molecular self-sorting in multicomponent systems. Self-sorting represents the spontaneous and high fidelity self and/or non-self-recognition of two or more related components within a complex mixture. While the effective management of self-sorting principles perceptibly requires some key expertise in molecular programming, at a higher stage of operation it is of supreme interest to guide the process to increasingly higher degrees of self-sorting. In this article, we present the emerging principles of how to guide several components toward formation of self-sorted multicomponent architectures. To provide further guidance in denominating such systems, we suggest to utilise a systematic classification as well as a formula to evaluate their degree of self-sorting (M).

Characterization of serum tartrate-resistant acid phosphatase and development of a direct two-site immunoassay. Osteoclasts secrete tartrate-resistant acid phosphatase (TRAP) to the circulation, where the amount of TRAP is expected to correlate with the bone resorption rate. We have developed two monoclonal antibodies, O1A and J1B, using purified human bone TRAP as antigen. The antibodies recognized different epitopes, allowing us to develop a two-site fluoroimmunoassay. The immunoreactivity in fresh serum specimens was less than 10% of the concentrations measured from the same specimens after 24 h of storage at 4 degrees C, or after addition of 5 mM EDTA or EGTA to them. When fresh serum was gel filtrated using Sephacryl S-200 column, all of the enzyme eluted in the void volume as a complex with a molecular weight of more than 250 kDa. If the serum was treated with EDTA before the gel filtration, the complex was destroyed and the enzyme eluted in fractions corresponding to a molecular weight of 30 kDa, the size of monomeric purified human bone TRAP. The immunoassay was used to measure TRAP concentrations from serum samples that had been stored at 4 degrees C for 24 h. According to the assay, premenopausal women had 13.1 +/- 3.1, postmenopausal women 17.6 +/- 4.2, and children 32.6 +/- 12.2 microg TRAP/l of serum. We conclude that TRAP circulates in the serum as part of a complex, which also contains Ca2+, and that TRAP-immunoassay is a potentially useful method for determining bone resorption rates, as long as the complex is destroyed before the assay.

Neuroendocrine neoplasms arising in inflammatory bowel disease: a report of 14 cases. Inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), is a premalignant condition, because these patients are at increased risk of adenocarcinoma. Neuroendocrine neoplasms (NENs) have rarely been described in this setting. We evaluated 14 cases of NEN arising in a setting of IBD. All of the tumors arose in areas involved by IBD, and all showed immunohistochemical or ultrastructural evidence of neuroendocrine differentiation. The cohort included seven men and seven women (range, 28-71 yr; median, 43 yr). Eight patients had Crohn's disease (CD), and six had UC. Duration of disease ranged from 4 months to 50 years (median, 15 yr), with one of unknown duration. Of the eight patients with CD, five had ileocolitis, one had ileitis, one had colitis, and in one case, the extent of disease was unknown. Of the six patients with UC, four had extensive UC, one had left-sided UC, and the extent of UC was unknown in one case. Reasons for surgery included CD complications (five patients), refractory disease (three patients), dysplasia/carcinoma (five patients), and incontinence (one patient). The NENs were well differentiated in 11 cases and poorly differentiated mixed adenocarcinoma/small cell carcinomas in 3 cases. Tumor sites included the rectum (six cases), appendix (four cases), small bowel (two cases), and sigmoid colon (two cases). High-grade dysplasia was present in adjacent mucosa in four cases, and low-grade dysplasia was present in distant mucosa in two cases. Two patients with poorly differentiated NENs died from the disease at 3 and 11 months after tumor excision. All of the other patients were alive without tumor as of last follow-up. We concluded that NENs rarely arise in a setting of IBD. Most are well-differentiated tumors and are clinically indolent. Dysplasia is found in adjacent mucosa in more than one-third of cases, suggesting that neuroendocrine differentiation might evolve from multipotential cells in dysplastic epithelium.

Atraumatic osteolysis of the distal clavicle: MR findings. The purpose of this study was to describe the MRI appearance in atraumatic osteolysis of the distal clavicle (AODC). We retrospectively evaluated MRI, medical records, ancillary diagnostic imaging studies and clinical course in five men and two women (mean age, 39 years) in whom the final clinical diagnosis of AODC was established. None of the patients had significant shoulder injury, but all participated in activities involving repetitive strain of the acromioclavicular (AC) joint. In three of these patients, we performed follow-up MRI (ranging from 5 1/2 to 15 months after the initial MRI). In all seven patients, signal intensity changes within the intramedullary portion of the distal clavicle on MRI were consistent with diffuse bone marrow edema. Marrow edema was most conspicuous on STIR imaging and occasionally could be misinterpreted as normal marrow signal patterns on spin-echo imaging. Cortical thinning or irregularity of the distal clavicle was seen in six cases and tiny subchondral cysts were seen in three, corresponding to subtle cystic changes on shoulder radiography. Limited bone scans obtained in two patients showed markedly increased uptake of radiotracer at the distal clavicle and AC joint. Histologic examination in one case showed disruption of articular cartilage, subchondral cysts, and metaplastic bone formation with increased osteoclastic activity. Follow-up MRI in three patients who were asymptomatic following conservative therapy showed normalization of marrow signal intensity. Atraumatic osteolysis of the distal clavicle is a relatively uncommon but important cause of shoulder pain. Particularly when the clinical history is suggestive of repetitive AC joint stress, MRI of the distal clavicle should be examined closely for marrow edema, cortical irregularity, and cystic changes. Such abnormalities may be especially conspicuous when STIR imaging techniques are used.

The role of p21-activated kinases in pancreatic cancer. Pancreatic cancer is an aggressive cancer with a poor prognosis and an overall 5-year survival rate of less than 5%. Management has not improved significantly over the last 30 years, and a better understanding of the genetic and molecular changes that occur is urgently required. Many of these changes appear to involve the p21-activated kinases (PAKs). The PAK family consists of 6 isoforms, 2 of which, PAK1 and PAK4, are up-regulated and/or hyperactivated in pancreatic cancer. p21-Activated kinases can mediate many different cellular processes especially those contributing to cancer development and progression. These processes include the regulation of cytoskeletal dynamics and cell adhesion, the evasion of apoptosis, and the promotion of cell survival, proliferation, migration, and invasion. p21-Activated kinases may also be involved in characteristics unique to pancreatic tumors, such as interplay with the pancreatic stroma, the re-emergence of embryonic pathways, and the involvement of a subset of microRNAs and heat shock proteins. This review highlights the potential role of PAKs in pancreatic cancer and provides a foundation for more effective therapeutics to improve our current treatment of pancreatic cancer.

Is patient outcome compromised during the initial experience with robot-assisted radical cystectomy? Results of 164 consecutive cases. • Robot-assisted radical cystectomy (RARC) remains controversial in terms of oncologic outcomes, especially during the initial experience. The purpose of this study was to evaluate the impact of initial experience of robotic cystectomy programs on oncologic outcomes and overall survival. • Utilizing a prospectively maintained, single institution robotic cystectomy database, we identified 164 consecutive patients who underwent RARC since November 2005. • After stratification by age group, gender, pathologic T stage, lymph node status, surgical margin status, and sequential case number; we used chi-squared analyses to correlate sequential case number to operative time, surgical blood loss, lymph node yield, and surgical margin status. • We also addressed the relationship between complications and sequential case number. We then utilized Cox proportional hazard modeling and Kaplan-Meier survival analyses to correlate variables to overall mortality. • Sequential case number was not significantly associated with increased incidence of complications, surgical blood loss, or positive surgical margins (P= 0.780, P= 0.548, P= 0.545). Case number was, however, significantly associated with shorter operative time and mean number of lymph nodes retrieved (P < 0.001, P < 0.001). • Sequential case number was not significantly associated with survival; however, tumour stage, the presence of lymph node metastases, and positive surgical margins were significantly associated with death. • Although being the largest of its kind, this was a small study with short follow-up when compared to open cystectomy series. • Initial experience with RARC did not affect the incidence of positive surgical margins, operative/postoperative complications, or overall survival in a single-institution series.

Acute phase protein levels in pregnancy and oestrus cycle in bitches. The purpose of this study was to evaluate the acute phase protein (serum amyloid A, C-reactive protein, haptoglobin, ceruloplasmin and fibrinogen) profiles in pregnant dogs as well as bitches at various stages of the estrus cycle and to verify possible relationship(s) among the APPs profile and hormonal status. A total of 60 bitches of various breeds were enrolled. The animals were divided into six groups. B-mode ultrasonographic scanner (concept M/C) was used for pregnancy diagnosis, involving the first and second halves of pregnancy. Proestrus, estrus, diestrus and anestrus stages of sexual cycles were differentiated by use of vaginal cytology and blood progesterone and estradiol 17-beta levels. Serum C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin, ceruloplasmin and fibrinogen levels were determined. No statistically significant differences were observed between the groups with regard to the serum SAA and CRP concentrations. Haptoglobin, ceruloplasmin and fibrinogen concentrations were elevated in pregnant dogs compared to non-pregnant groups', independently from the pregnancy stage. No statistically significant differences in acute phase protein concentrations in dogs at various stages of estrus could be detected. Results of this study indicated that ceruloplasmin and fibrinogen levels may have potential importance in the diagnosis of pregnancy, and acute phase proteins may be used for monitoring the health status of the pregnant dogs.

[Energetic changes in heart cells of white rats in stress conditions induced by violated diurnal cycle]. The aim of the study was to investigate the content and dynamics of nitric oxide (NO) and enzymes involved in generation and preservation of energy in cardiomyocytes under chronic stress condition, induced by circadian rhythm disturbances and isolation. For the present investigation white rats were selected as the experimental animal model. Quantitative decline in NO and decrease in enzyme activity (creatine/creatinphosphokinase/phosphocreatine and succinatedehydrogenase) under 30-day stress was found. Enzyme activity in white rat cardiomyocytes declined, and NO as a signal molecule increased. In accordance with experimental data it is supposed that the lack of ATP in cardiomyocytes is the main cause of various heart disorders.

The Women's Initiative for Nonsmoking (WINS) XI: age-related differences in smoking cessation responses among women with cardiovascular disease. Smoking cessation has immediate health benefits; however, the efficacy of smoking cessation interventions among older adults and women has received limited research attention. The original Women's Initiative for Nonsmoking (WINS) study was a randomized controlled trial that tested the efficacy of a smoking cessation intervention for Bay Area women hospitalized with cardiovascular disease. The current study, which used the WINS dataset, compares participants 62 and older with those younger than 62 years. The sample (n=277) contained 136 older smokers and 141 younger smokers. At the 6-month follow-up, 52.1% of older smokers had quit smoking compared with 40.6% of younger smokers. At the 12-month follow-up, 52.0% of older smokers had quit smoking compared with 38.1% of younger smokers. The difference at 12 months was statistically significant, and a Kaplan-Meier survival analysis further supported these findings. Clinicians should be sure to also include older smokers in smoking assessments and smoking cessation interventions.

Spoken words can make the invisible visible-Testing the involvement of low-level visual representations in spoken word processing. The notion that processing spoken (object) words involves activation of category-specific representations in visual cortex is a key prediction of modality-specific theories of representation that contrasts with theories assuming dedicated conceptual representational systems abstracted away from sensorimotor systems. In the present study, we investigated whether participants can detect otherwise invisible pictures of objects when they are presented with the corresponding spoken word shortly before the picture appears. Our results showed facilitated detection for congruent ("bottle" → picture of a bottle) versus incongruent ("bottle" → picture of a banana) trials. A second experiment investigated the time-course of the effect by manipulating the timing of picture presentation relative to word onset and revealed that it arises as soon as 200-400 ms after word onset and decays at 600 ms after word onset. Together, these data strongly suggest that spoken words can rapidly activate low-level category-specific visual representations that affect the mere detection of a stimulus, that is, what we see. More generally, our findings fit best with the notion that spoken words activate modality-specific visual representations that are low level enough to provide information related to a given token and at the same time abstract enough to be relevant not only for previously seen tokens but also for generalizing to novel exemplars one has never seen before. (PsycINFO Database Record

Impact of a standardized titration protocol with carvedilol in heart failure: safety, tolerability, and efficacy-a report from the GESICA registry. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA) studied whether a standardized protocol for the initiation and titration of the beta-blocker carvedilol in a multicenter, open-label program would optimize beta-blocker use in heart failure (HF) patients. The program included: (1) the carvedilol initiation and titration period, and (2) long-term follow-up at 6 and 12 months. Of 1299 patients in the registry, 504 were excluded due to current therapy; of the remaining 795 eligible patients, 293 were excluded due to contraindications. Of the included patients with follow-up data (n = 316), 93.3% tolerated carvedilol initiation and 47.7% of the patients reached the target dose of 50 mg/day for a mean dose of 39 mg/day. Rates were comparable in the elderly (n = 83), of which 53% achieved a target dose for a mean dose of 43.08 mg/day. This protocol improved therapy rates and achieved target doses quickly (average of 4 visits). Concomitant medications did not have to be adjusted and there were low withdrawal rates (10%) and hospital admissions (7.2%) for HF. Patients were able to maintain carvedilol therapy at 6 and 12 months. These results indicate that a standardized titration protocol, as used in GESICA, for the initiation and titration of beta-blockers is well tolerated and may improve beta-blocker use in carefully selected heart failure patients.

Bend and helical twist associated with a symmetric internal loop from 5S ribosomal RNA. We have used gel electrophoretic mobility measurements to investigate the conformation of the symmetric eubacterial loop E sequence of 5S rRNA (seven nucleotides in each strand). The loop strongly retarded the gel mobility of duplex RNAs containing it. In contrast, only asymmetric A5.An or U5.Un internal loops (n not equal to 5) strongly affected duplex RNA gel mobility. A phasing experiment, in which an A2 bulge and loop E were placed in the same duplex RNA and the number of base pairs between them varied, showed that loop E has a permanent bend and is torsionally stiff. A second phasing experiment substituting loop E for duplex sequences between two A2 bulges measured the helical twist associated with loop E; it is about 30 degrees (+/- 15 degrees) overwound compared to a duplex RNA of the same number of bases. Ribosomal protein L25 specifically recognizes loop E but had little or no effect on the twist of the loop. These results suggest that loop E adopts a specific, roughly helical structure.

Ultrasonic diagnosis of oral and neck malignant lymphoma. A series of 14 patients with nodal and extranodal non-Hodgkin's lymphoma of the oral and neck region was analyzed by ultrasonogram evaluation. Eight nodal lymphomas and six extranodal lymphomas commonly exhibited almost completely similar ultrasonographic findings, specifically, clear delineation of the boundary echo and a homogeneous, weak internal echo, the so-called pseudo-liquid-like images. The results derived from our study suggest that ultrasonic diagnosis is also helpful in evaluating patients with lymphoma during the initial diagnosis and initial treatment like other diagnostic imaging modalities.

Molecular cloning, characterization and expression analysis of grass carp (Ctenopharyngodon idellus) NF45 (ILF2) cDNA, a subunit of the nuclear factor of activated T-cells (NF-AT). NF45 (ILF2) and NF90 (ILF3) regulate the IL-2 gene transcription via interaction with the antigen receptor response element. Much work on NF45 has been done in human and mammals while little in fish. In the present study, we have cloned and characterized the full-length cDNA of NF45 in grass carp (Ctenopharyngodon idellus). The grass carp NF45 cDNA of 1563bp contains a short 5'UTR of 24bp, a 3'UTR of 375bp and an open reading frame of 1164bp coding for a protein of 387 aa with a predicted molecular mass of 42.8kDa. The encoded protein shares 86.3-96.7% identities to other homologues. RT-PCR was optimized to estimate the expression level of NF45 in grass carp. The results showed that NF45 is constitutively expressed in most selected tissues, including head kidney, spleen, heart, brain, liver, and gill, although low levels were observed in spleen, liver and gill. The ubiquitous expression of NF45 is consistent with a postulated role in gene regulation at the level of transcription. Stimulating the fish with PHA significantly up-regulated the expression of NF45 in most tissues examined, which potentially indicated that NF45 was involved in the immune responses triggered by PHA.

Clinical research evidence and clinical practice. An informal survey among colleagues turns up the far-from surprising information that the average patient contact involves at least three or four judgements and decisions: judgements about aetiology and prognosis, decisions about diagnosis and therapy, and sometimes discussions about costs and side-effects. And so it goes: 20 patients a day, 60 decisions; 100 patients a week, 300 decisions. Who makes these decisions, the doctor or the patient? What factors govern the final choice in each case? Evidence-based medicine (EBM) is the factor getting a lot of attention these days, but clinical decisions depend on many different elements. Good doctors have always made use of experience and judgement as well as the best available evidence.

The crystal structure of pectate lyase Pel9A from Erwinia chrysanthemi. The "family 9 polysaccharide lyase" pectate lyase L (Pel9A) from Erwinia chrysanthemi comprises a 10-coil parallel beta-helix domain with distinct structural features including an asparagine ladder and aromatic stack at novel positions within the superhelical structure. Pel9A has a single high affinity calcium-binding site strikingly similar to the "primary" calcium-binding site described previously for the family Pel1A pectate lyases, and there is strong evidence for a common second calcium ion that binds between enzyme and substrate in the "Michaelis" complex. Although the primary calcium ion binds substrate in subsite -1, it is the second calcium ion, whose binding site is formed by the coming together of enzyme and substrate, that facilitates abstraction of the C5 proton from the sacharride in subsite +1. The role of the second calcium is to withdraw electrons from the C6 carboxylate of the substrate, thereby acidifying the C5 proton facilitating its abstraction and resulting in an E1cb-like anti-beta-elimination mechanism. The active site geometries and mechanism of Pel1A and Pel9A are closely similar, but the catalytic base is a lysine in the Pel9A enzymes as opposed to an arginine in the Pel1A enzymes.

Stereoselective acylation of the E,E-vinylketene silyl N,O-acetal and its application to the synthesis of khafrefungin. Stereoselective acylation of the E,E-vinylketene silyl N,O-acetal possessing a chiral auxiliary has been achieved by using acid anhydrides and SnCl4. Acid anhydrides having alkyl chains gave the adducts in excellent stereoselectivity. The formal synthesis of khafrefungin has been accomplished by the methodology.

Low Tie Compared to High Tie Vascular Ligation of the Inferior Mesenteric Artery in Rectal Cancer Surgery Decreases Postoperative Complications Without Affecting Overall Survival. The aim of this study was to determine the clinical impact of low tie ligation (LT) of the inferior mesenteric artery (IMA) below the left colic artery versus high tie ligation (HT) at the origin of the IMA in patients undergoing rectal cancer surgery. Between January 2005 and December 2017, all consecutive patients who underwent rectal resection for non-metastatic cancer were retrospectively included. Patients who had LT were compared to those who had HT. Overall, 200 patients were identified (101 HT and 99 LT). Postoperative 30-day mortality rate was nil in both groups. There were significantly higher severe postoperative complications in HT versus LT patients (Clavien-Dindo III-IV) (18.8% vs. 9.1%, p=0.048). Median follow-up was 38.5 months and overall survival at 5 years was 91.5% and there was no difference between the two groups (90.1% vs. 92.9%; HT vs. LT p=0.640). LT ligation of IMA significantly decreased the severe postoperative complication rate without affecting recurrence-free or overall survival.

Thymic extracellular matrix in human malnutrition. Previous studies have shown that malnutrition severely affects both lymphoid and epithelial components of the thymus. Yet, few data are available concerning the extracellular matrix (ECM) of the thymic microenvironment in malnutrition. We studied by histological, ultrastructural, and immunohistochemical means thymuses obtained in necropsies from 19 malnourished children. We observed a consistent increase in the intralobular ECM-containing network which could be ascertained histologically by the dense reticulin staining. This abnormally dense ECM network contained fibronectin, laminin, and type IV collagen. Importantly, the enhancement of thymic ECM in malnourished individuals positively correlated with the degree of thymocyte depletion. This correlation may represent a cause-effect relationship in which the contact of thymocytes with abnormally high amounts of thymic ECM triggers and/or enhances programmed cell death.

Detecting and detering employee theft. Physician group practices can limit their vulnerability to employee theft by taking steps to detect theft when it occurs and to deter future occurrences. Steps for detecting theft include being wary of an employee's refusal to take earned time off, conducting periodic credit checks on employees, rotating employees' duties, and conducting impromptu reviews of the practice's finances. Steps for detering theft include routing the practice's checks to a lock box; reviewing cash reports; reconciling check with deposit statements; separating employees' duties; reviewing bank, credit card, and ATM statements; setting the tone for prudent financial management; and reporting cases of theft when they occur.

Outcomes of the Arterial Switch Operation in Children Less Than 2.5 Kilograms. Children with body weight less than 2.5 kg who undergo the arterial switch operation (ASO) represent a challenging group. We sought to determine outcomes of patients with weight less than 2.5 kg at ASO at a single institution. All patients who underwent an ASO with biventricular repair and weighed less than 2.5 kg at time of surgery were identified from the hospital database and reviewed retrospectively. From 1983 to 2014, 870 patients underwent an ASO with biventricular repair at our institution. At the time of ASO, 31 patients (3.6%, 31 of 870) weighed less than 2.5 kg (mean 2.1; median 2.1; range, 1.1 to 2.4). Twenty-nine patients underwent an ASO for d-transposition of the great arteries, and 2 patients had an ASO for Taussig-Bing anomaly. Mean age at operation was 16 days (median 11; range, 3 to 66). There were 6 hospital deaths (19%, 6 of 31) among patients weighing less than 2.5 kg compared with a hospital mortality of 1.9% (16 of 839) among patients weighing more than 2.5 kg (p < 0.0001). Mortality for children weighing 2.0 kg or less was 50% (5 of 10) compared with a mortality of 2.8% (1 of 21) for children weighing more than 2.0 kg but less than 2.5 kg. Four patients (13%, 4 of 31) required reoperation during hospital admission. Follow-up was available for 24 survivors (96%, 24 of 25). Mean follow-up was 13.2 years (median 11.9; range, 6 months to 25 years). There were no late deaths. Two patients (8%, 2 of 24) required late reoperation. No patient had more than mild neoaortic valve regurgitation, and all survivors were in New York Heart Association class I at last follow-up. Early mortality for children weighing less than 2.5 kg undergoing the ASO remains high; however, most of the mortality occurred in children weighing 2.0 kg or less. Long-term outcomes for survivors are excellent.

Non-suicidal self-injury and suicidality in trans people: A systematic review of the literature. Literature has described high levels of mental health problems among trans people, such as depression, resulting in increased levels of non-suicidal self-injury (NSSI) behaviour and suicidality (suicidal thoughts, suicide attempts and suicide rates). With the aim of systematically reviewing the available literature in this field, this study identifies 31 papers that explore the rates of NSSI and suicidality in trans people. From reviewing the literature, it was revealed that trans people have a higher prevalence of NSSI and suicidality compared to the cisgender (non-trans) population. There appear to be some gender differences within these rates, with trans men at a greater risk for NSSI behaviour. Prevalence rates differ depending on the different stages of transition, but they are still overall greater than the cisgender population. The study concludes that trans individuals are at a greater risk of NSSI behaviour and suicidality than the cisgender population, and discusses risk factors and the need to develop effective preventative interventions.

[Gallbladder cancer in chronic calculous cholecystitis]. 127 cases of gallbladder cancer are analysed. Among them there were 99(78%) women and 28(22%) men. The majority of the patients were at the age from 61 to 70 years; 19 (15%) patients were younger than 50 years. Mean average age of the patients was 61.7 years. Chronic calculous cholecystitis was detected in 116 (91.3%) patients. In 75 (59%) patients the duration of the disease exceeded 5 years. Women suffer more frequently than men because of higher rate of calculous cholecystitis in women. Radical surgery was possible only in 51 of 97 (52.7%) patients as a result of late diagnosis of the cancer. Cholecystectomy was performed in 32 patients, cholecystectomy in combination with liver resection in 9 patients, tumor removal in borderes of the healthy tissues in 10 patients. Palliative operations were performed in 46 (36.2%) patients. Long-term results of the surgery were followed up in 93 patients. 5 year survival after the radical surgery was 40%, 10 year survival--20%. Mean survival after the palliative surgery was 7 months. Gallbladder cancer is difficult for diagnosis and the results of its treatment are unsatisfactory. Timery surgery of chronic calculous cholecystitis is important in prevention of gallbladder cancer.

Lithium niobate nanoparticle-coated Y-coupler optical fiber for enhanced electro-optic sensitivity. Single crystals of lithium niobate (LiNbO3), possessing high birefringence and anisotropic properties have been explored, for a long time, to harness their excellent electro-optic properties. However, their nanoforms are comparatively less explored. In this context, dielectric constant and polarization (P) versus electric-field (E) characteristics of LiNbO3 nanomaterials have been studied. A nonideal P-E loop and a dielectric constant of 20 at the onset of 1 kHz were seen. The electro-optic sensitivity was found to be 4 times as compared to the bulk LiNbO3 crystals. The results are attributed to oxygen vacancies, antisite defects, and grain boundary effects in an already congruent structural matrix of LiNbO3.

Maintaining motivation and health among recreational runners: Panel study of factors associated with self-rated performance outcomes at competitions. To investigate health-related factors associated with self-rated race performance outcomes among recreational long-distance runners. Panel study. Data were collected from runners one month before and after a community-level race event including distances from 8 to 42.2 km. The primary outcome measure was self-rated race performance outcome. The explanatory variables represented health complaints suffered during the build-up year, the pre-race month, and the race and among full marathon runners predicted objective performance outcome (mean pace equal to training pace or faster). Multiple logistic regression was used to determine factors associated with the self-rated performance outcome. Two-hundred forty-five runners (29%) provided complete data sets. Seventy-four percent of the runners reached their desired race performance outcome. Achievement of the performance outcome was more likely when having avoided illness during the build-up and pre-race periods (OR = 3.8; 95% CI:1.8-8.0, p < 0.001), having avoided per-race injury (OR=3.0; 95% CI:1.2-7.4, p = 0.02) and avoided per-race illness (OR = 4.1; 95% CI:1.3-15, p = 0.020). Having obtained the self-rated performance outcome was also associated with running a shorter distance (OR=3.6; 95% CI: 1.7-8.0, p = 0.001) and being younger than 50 years of age (OR = 2.4; 95% CI:1.1-5.3-8.3, p = 0.03). Having met the predicted objective performance outcome predisposed marathon runners to also obtain the self-rated performance outcome (OR = 4.7, 95% CI: 1.5-16, p < 0.01). Having avoided illness during build-up and pre-race was positively associated with self-rated race performance outcome among recreational runners. Adjusting the desired performance outcomes with regard to recent illness and age may help recreational runners to more often achieve their goals and thereby prevent them from leaving the sport.

Comparison of weights for left and right breast muscle of broilers. Two studies were conducted to investigate the differences in the yield of broiler breast meat (pectoralis muscles) between the left and right sides of the bird. In the first study, 42-day-old male broilers had 3.3% more meat on the left side of the breast than on the right side. This difference was observed for both the Pectoralis superficialis and Pectoralis profundis muscles. In the second study, male broilers were sampled at 50, 57, and 64 days of age. There was 2.7% more meat on the left side of the breast than on the right side, and the percentage difference was not affected by age. The results indicated that both sides of the breast should be sampled in studies concerning the yield of breast meat.

State-of-the-art-myocardial perfusion stress testing: Static CT perfusion. Large multicenter studies and meta-analysis have documented the diagnostic accuracy and the prognostic implications of stress echocardiography, cardiac magnetic resonance and, mainly, nuclear stress tests. However, none of them provides a comprehensive anatomical and functional evaluation within the same study as stress CT perfusion. Myocardial CT perfusion is the only non-invasive modality that allows to quantifying coronary stenosis and determining its functional relevance, constituting a potential "one-stop-shop" method for the diagnosis and global management of patients with known or suspected coronary artery disease. In comparison with the dynamic modality, that requires increased radiation, precise acquisition protocols and dedicated post-processing softwares, static CT perfusion was associated with less radiation exposure, non-inferior diagnostic accuracy, easier interpretation of images and is nowadays more widely available.

HPV status predicts for improved survival following chemotherapy in metastatic squamous cell carcinoma of the oropharynx. We sought to further define prognostic and predictive value of human papillomavirus (HPV) status in metastatic squamous cell carcinoma of the oropharynx (OPC). A Surveillance, Epidemiology, and End Results custom database identified 5940 adult patients, >18-years-old, with primary SCCHN and known HPV status, diagnosed from 2013 to 2014. Wilcoxon rank-sum and Mantel-Haenszel χ2 tests compared distributions of continuous and categorical covariates. Fine-Gray competing risks regressions estimated hazard ratios by HPV status, and predictive analyses were performed including the interaction term HPV status × Receipt of Chemotherapy. 182 of 5940 patients (4.0%) had metastatic OPC at diagnosis (106/3925 [2.7%] HPV+ and 76/1894 [4.0%] HPV-). HPV+ disease was prognostic for improved 20-month cancer-specific mortality (CSM) (47.1% vs 72.5%, HR 0.43, 95% CI 0.26-0.74, p = 0.002) on univariable analysis. HPV status was predictive of response to chemotherapy-adjusted HRs for receipt of chemotherapy were 0.11 (95% CI 0.03-0.37) and 0.34 (95% CI 0.18-0.64) for HPV+ versus HPV- disease, respectively (PHPV status∗Chemotherapy = 0.036). HPV status has known prognostic value in locally advanced OPC, but data on metastatic OPC are sparse. In this work, we demonstrate that HPV status is strongly prognostic for CSM in metastatic OPC and show for the first time that HPV status predicts for response to chemotherapy.

Epidermal growth factor receptor mutations in small cell lung cancer: a brief report. Knowledge about the current status of the epidermal growth factor receptor (EGFR) has resulted in an improvement in the treatment of non-small cell lung cancer. In contrast, small cell lung cancer (SCLC) continues to frustrate clinicians with its tendency toward early metastasis and chemotherapy resistance. Recent studies have reported the EGFR mutation and its response to gefitinib treatment in SCLC. We would like to share our experience of EGFR studies on SCLC patients. Between 2004 and 2009, we prospectively collected 76 specimens from patients with SCLC at the National Taiwan University Hospital, Taiwan. These specimens included 10 computed tomography-guided biopsy specimens, 17 echo-guided aspiration specimens, 37 echo-guided biopsy specimens, 1 surgical lobectomy specimen, and 11 malignant pleural effusion specimens. Molecular genetic analysis of the specimens was conducted to detect the EGFR mutation. Among the 76 SCLC specimens we examined, 2 (2.6%) tested positive for the EGFR mutation and both were deletions in exon 19. One patient was administered gefitinib after several lines of chemotherapy but showed no treatment response. To date, only 11 EGFR mutant-positive SCLC patients, including our 2 patients, have been reported. Most of these patients were never smokers. The SCLC harboring EGFR mutation were more likely to be combined with adenocarcinoma compared with the whole SCLC population. The EGFR mutation is rare in SCLC patients. Despite the presence of the EGFR mutation, gefitinib may not be effective in treating SCLC patients.

Demography, hunting ecology, and pathogen exposure of domestic dogs in the Isoso of Bolivia. Disease is increasingly recognized as a threat to the conservation of wildlife, and in many cases the source of disease outbreaks in wild carnivores is the domestic dog. For disease to spill over from a domestic to a wild population, three conditions must be satisfied: susceptibility of the wild species, presence of the disease agent in the domestic population, and contact between the two populations of interest. We investigated the potential for disease spillover from the domestic dog population to the wild carnivore population in the Isoso of Bolivia, an area of tropical dry forest contiguous with a national park. Using questionnaires and discussions with residents, we gathered data on the demography of dogs in the Isoso, including adult and neonatal mortality, litter size, and hunting frequency. We analyzed a large data set containing self-recorded information on hunting in various communities of the Isoso to determine the extent of dog participation in hunting and the duration of hunting trips. Finally, we took blood samples from dogs in the Isoso for a serosurvey of common canine pathogens. More than 95% of dogs had positive titers to canine distemper virus and canine parvovirus. There was also a high seroprevalence in dogs for other pathogens, a high population turnover of dogs (which may allow diseases to be maintained endemically), and frequent opportunities for contact between domestic and wild carnivores. Based on our results and the susceptibility of wild species previously reported in the literature, domestic dogs represent a disease risk for wildlife in the Bolivian Isoso.

Crescent fractures of the pelvis treated by open reduction and internal fixation: a critique of Day's guidelines. Day's classification and treatment guidelines are considered the gold standard in crescent fractures of the pelvis. The objective of this study was to retrospectively evaluate 10 surgically treated crescent fractures of the pelvis in the context of Day's recommendations. This is a retrospective cohort study. Ten consecutive cases of crescent fractures that were treated surgically at a level 1 trauma center formed the cohort. Six were operated anteriorly, three posteriorly and one percutaneously. Classification and treatment strategy were compared to Day's guidelines. The minimum follow-up was 13 months. Outcomes were assessed using the modified Majeed's scoring system. Three out of 10 cases were difficult to classify by Day's criteria. There were 4 type I, three type III and no type II cases. Our surgical strategy was independent of Day's recommendations in this series and based on ease of access, ability to restore the sacroiliac joint anatomy and other associated injuries. All the patients were mobilized early and the fractures united without any major incident. The results of these cases were quite good with outcome scores over 67/96. Assigning Day's classification to a given case can be difficult in up to 33% patients with crescent fractures due to the obliquity of the iliac fracture line in axial sections. Sacroiliac articular alignment is the primary factor determining the surgical approach. Besides the fracture configuration, additional factors like delay in surgery, locking of the fracture fragments, comminution of the iliac or sacral fragment as well as access to the additional injuries contribute to the decision making.

Developmental changes in heart and muscle phosphofructokinase isozymes. Phosphofructokinase isozymes of fetal, neonatal, and adult rat heart and skeletal muscle were characterized by DEAE-cellulose chromatography, agarose gel electrophoresis, and immunodiffusion with specific antisera. The results of these studies indicate that in skeletal muscle and heart the levels of the major liver phosphofructokinase isozyme (PFK-L2) and the muscle phosphofructokinase isozyme (PFK-M) are dependent on the developmental status of the rat. For example, PFK-L2 and PFK-M are present in fetal and early neonatal skeletal muscle; whereas in adult skeletal muscle, only PFK-M is detectable. By DEAE- cellulose chromatography, PFK-L2 activity was estimated to be 2.4 units/g (41% of total phosphofructokinase activity) in fetal muscle, very low and not resolved from PFK-M in 7-day neonatal muscle, and not detectable in adult muscle. Further, PFK-M activity was found to be 3.4 units/g (59% of total phosphofructokinase activity), 10 units/g, and 31.6 units/g in fetal, 7-day neonatal, and adult skeletal muscle, respectively. The developmental changes of heart phosphofructokinase isozymes differ considerably from that of the skeletal muscle phosphofructokinase isozymes. In fetal heart, PFK-L2 is the major phosphofructokinase isozyme (5.6 units/g), constituting 67% of total phosphofructokinase activity. Further, in fetal heart another phosphofructokinase isozyme (33% of total phosphofructokinase activity) was found by DEAE-cellulose chromatography which is different from PFK-M and PFK-L2. In 7-day neonatal and adult heart, PFK-M and PFK-L2 are the only detectable phosphofructokinase isozymes. Varying from 5.6 units/g (44% of total) in 7-day neonatal to 5.9 units/g (40% of total) in adult heart, PFK-L2 activity remains fairly constant. Also, PFK-M is very low in fetal heart but increases within 1 week postpartum to 5.5 units/g (50% of total activity) and to 8.9 units/g (60% of total activity) in adult heart.

Retrospective detection of potential medication errors involving drugs with similar names. To estimate frequencies of potential errors involving similarly named drugs using a retrospective claims database and measure the association between frequencies of potential errors and two measures of drug name similarity, edit distance (minimum number of insertions, substitutions, or deletions of characters required to change a given word into another target word) and normalized edit distance (proportion of letters that must be changed to commute one word to another, and ranges from 0 to 1, with 0 indicating identical words, and 1 indicating a pair of words with no common letters). Retrospective database analysis. Idaho Medicaid claims data from 1993 to 2000. Not applicable. Potential errors were detected using adjacent claims generated by dispensing of one drug followed by dispensing of the other drug with a similar name. In all, four potential error criteria were developed: two for detecting potential refill errors and two for detecting potential initial errors. A total of 10 drug pairs were randomly selected from the Idaho Medicaid claims database for each value of edit distance, which ranged from 1 to 30 (n = 300). Frequencies of potential medication errors in claims sequences for initial and refill claims, edit distance, and normalized edit distance. Of 300 drug pairs studied, 106 (35.33%) were involved in at least one potential error. A total of 1,138 dispensing episodes satisfied the criteria for potential errors. Frequencies of potential errors per drug pair were negatively associated with edit distance (r = -0.133, P < .05) and normalized edit distance (r = -0.226, P < .01). Frequencies of potential initial errors also were negatively associated with edit distance (r = -0.126, P < .05) and normalized edit distance (r = -0.222, P < .01). Potential refill errors also had negative association with edit distance (r = -0.134, P < .05) and normalized edit distance (r = -0.226, P < .01). Error criteria were successfully applied to a retrospective claims database to detect potential initial and refill errors that involved similarly named drugs.

Evolution of the apolipoproteins. Structure of the rat apo-A-IV gene and its relationship to the human genes for apo-A-I, C-III, and E. We have determined the nucleotide sequence of the rat apolipoprotein (apo-) A-IV gene and analyzed its structural and evolutionary relationships to the human apolipoprotein A-I, E, and C-III genes. The rat A-IV gene is 2.4 kilobases in size and consists of three exons (142, 126, and 1157 base pairs) interrupted by two introns (277 and 673 base pairs). The 5'-nontranslated region and most of the signal peptide are encoded by the first exon. Thus, the apo-A-IV gene lacks an intron in the 5'-nontranslated region of its mRNA in contrast to all other known apolipoprotein genes. Sequences coding for amphipathic docosapeptides span both the second and third exons of the rat A-IV gene. We demonstrate that this is also true for the human apolipoprotein genes. This gene family seems to have evolved by the duplication of an ancestral minigene that resulted in the formation of two exons. Thereafter, evolution of these sequences was dominated by intraexonic amplification of repeating units coding for amphipathic peptides. Sequence divergence of these repeats resulted in the functional differentiation of the apolipoproteins. However, conservation of the fundamental amphipathic pattern allowed members of this protein family to retain their lipid-binding properties.

Glycoligand-targeted core-shell nanospheres with tunable drug release profiles from calixarene-cyclodextrin heterodimers. Stable core-shell nanospheres self-assemble in water from heterodimers combining a hydrophobic calix[4]arene moiety and a hydrophilic β-cyclodextrin head; their potential to encapsulate and provide sustained release of the anticancer drug docetaxel and undergo surface post-modification with glycoligands targeting the macrophage mannose receptor is discussed.

Effect of thiamine concentration on animal health, feedlot performance, carcass characteristics, and ruminal hydrogen sulfide concentrations in lambs fed diets based on 60% distillers dried grains plus solubles. Limited data are available regarding the influence of thiamine supplementation on the incidence of polioencephalomalacia (PEM) in lambs fed diets containing increased concentrations of S in the diet (>0.7%). Therefore, our objective was to evaluate the influence of thiamine supplementation on feedlot performance, carcass quality, ruminal hydrogen sulfide gas concentrations, and incidence of PEM in lambs fed a finishing diet containing 60% distillers dried grains with solubles (DDGS; DM basis). Two studies were conducted using completely randomized designs to evaluate the influence of concentration of thiamine supplementation. Study 1 used 240 lambs fed in 16 pens, whereas study 2 used 55 individually fed lambs. Lamb finishing diets contained 60% DDGS, which resulted in a dietary S concentration of 0.73% (DM basis). Treatments diets were based on the amount of supplemental thiamine provided: 1) no supplemental thiamine (CON), 2) 50 mg/animal per day (LO), 3) 100 mg/animal per day (MED), or 4) 150 mg/animal per day (HI). Additionally, in study 2, a fifth treatment was included, which contained 0.87% S (DM basis; increased S provided by addition of dilute sulfuric acid) and provided 150 mg of thiamine/animal per day (HI+S). In study 1, ADG decreased quadratically (P = 0.04), with lambs fed the CON, LO, and MED diets gaining BW at a greater rate than lambs fed the HI diet. In study 1, DMI responded quadratically (P < 0.01), whereas G:F tended to differ linearly (P = 0.08) to concentration of thiamine supplementation, with MED lambs having greater DMI and decreased G:F. No differences (P > or = 0.17) in lamb performance were observed in study 2. In both studies, most carcass characteristics were unaffected, with the exception of a tendency for decreased carcass conformation (study 1; P = 0.09) and greater flank streaking (study 2; P = 0.03). No differences in ruminal hydrogen sulfide concentration (P > 0.05) among treatments were apparent until d 10, at which point lambs fed the LO diet had less hydrogen sulfide concentrations than all other treatments. Lambs fed HI had the greatest concentrations of hydrogen sulfide on d 31 (1.07 g of hydrogen sulfide /m(3); P < 0.009). Ruminal pH did not differ (P = 0.13) and averaged 5.6 +/- 0.06. No clinical cases of PEM were observed during the course of either study. The use of thiamine as a dietary additive to aid in the prevention of PEM in finishing lambs does not appear to be necessary under the conditions of this study.

Neutrophil responses to aspergillosis: new roles for old players. Neutrophils are professional phagocytic cells that play a crucial role in innate immunity. Through an assortment of antifungal effector mechanisms, neutrophils are essential in controlling the early stages of fungal infection. These mechanisms range from the production of reactive oxygen intermediates and release of antimicrobial enzymes to the formation of complex extracellular traps that aid in the elimination of the fungus. Their importance in antifungal immunity is supported by the extreme susceptibility to infection of patients with primary (e.g., chronic granulomatous disease) or acquired (e.g., undergoing immunosuppressive therapy) neutrophil deficiency. More recently, common genetic variants affecting neutrophil antifungal capacity have also been disclosed as major risk factors for aspergillosis in conditions of generalized immune deficiency. The present review revisits the role of neutrophils in the host response against Aspergillus and highlights the consequences of their deficiency in susceptibility to aspergillosis.

Sulfonato-imino copper(ii) complexes: fast and general Chan-Evans-Lam coupling of amines and anilines. Sulfonato-imine copper complexes with either chloride or triflate counteranions were prepared in a one-step reaction followed by anion-exchange. They are highly active in Chan-Evans-Lam couplings under mild conditions with a variety of amines or anilines, in particular with sterically hindered substrates. No optimization of reaction conditions other than time and/or temperature is required.

Profiling and characterization of miRNAs associated with intramuscular fat content in Yorkshire pigs. miRNAs are short noncoding RNAs that post-transcriptionally regulate gene expression by binding to complementary regions of the target mRNA. The miRNAs associated with the deposition of intramuscular fat (IMF) content in pigs, which is an important meat quality trait, still remain to be investigated. In this study, the longissimus dorsi muscles (LDMs) from 234 individuals were collected from Yorkshire pigs at 90 kg body weight and the miRNA deep sequencing was conducted by using two tailed groups which were taken five individuals each from high (2.94 ± 0.04%) and low (1.62 ± 0.02%) IMF samples. The results showed that total 268 mature miRNAs were identified, of which 70 were previously known, 162 were conserved among species and 36 were identified specifically in pigs. Moreover, 28 miRNAs involved in adipogenesis were differentially expressed in the two groups, and five out of 16 miRNAs were validated by quantitative PCR (qPCR) using stem loop primers. Our results may serve as a fundamental basis for understanding the roles of miRNA in IMF development in pigs. The miRNAs identified in our study can be utilized for research IMF trait in pig population and will provide further clues to the study of meat quality regulatory mechanisms.

Localized glenoid hypoplasia. An anatomic variation of possible clinical significance. Examinations were done on 1150 scapular bone specimens from museum collections. A localized hypoplasia of the posteroinferior glenoid was found in significant numbers (20%-35%) depending on the population group studied. Criteria were established for the identification of this variant in computed tomography and magnetic resonance studies. Localized hypoplasia of the posteroinferior glenoid was detected as an incidental finding in 54 (18%) of 300 such studies. Using these same imaging criteria in a prospective manner, 9 of 12 patients seen for voluntary multidirectional instability of the shoulder displayed a localized posteroinferior glenoid hypoplasia. This phenomenon also may add to the picture of extreme posterior glenoid wear that sometimes is seen in association with osteoarthritis of the shoulder.

A modular computer system for the nuclear medicine/ultrasound laboratory. Computer-controlled graphic displays are a necessity in many nuclear medicine studies. The authors propose using a set-up consisting of three modules: (a) a display system based on television technology; (b) an instrument interface employing list mode and having a low information loss rate; and (c) flexible modular software which can easily be tailored to the needs of both radiologists and technicians. The authors consider a mini-computer system with broad, flexible applications to be a valuable tool, particularly for those function studies which can only be done by means of nuclear medicine techniques.

The toxic effects and fate of intravenously administered zearalenone in goats. To clarify the toxic effects and fate of zearalenone (ZEA) in ruminants, we studied histopathological changes and toxicokinetic profiles in goats administered with a single intravenous (iv) injection of ZEA at doses of 2.4 mg/kg bw and 1.2 mg/kg bw, respectively. The expression of the mRNA of estrogen receptor (ER) alpha and beta in tissues was also investigated. The histopathological study revealed that ZEA caused hepatocellular swelling and lymphocytic infiltration in the liver, kidney, and uterus. The expression of ERalpha mRNA was enhanced by ZEA in association with the histopathological changes, indicating the possible involvement of ERalpha in the toxic effects of ZEA. For toxicokinetic profiles, blood plasma, urine, and feces were collected consecutively after iv injection of ZEA and analyzed for ZEA and its metabolites with high performance liquid chromatography (HPLC). alpha-Zearalenol (ZOL) and beta-ZOL were detected with ZEA, but alpha-zearalanol (ZAL), beta-ZAL, and zearalanone were below the detection limits. The distribution half-life (t(1/2alpha)) and elimination half-life (t(1/2beta)) of ZEA were 3.15 and 28.58h, respectively. ZEA, alpha-ZOL, and beta-ZOL were excreted in urine and feces, with beta-ZOL being the predominant metabolite. The ZEA and ZOL in urine were largely in their glucuronide and/or sulphate conjugated forms, while those in feces were largely in their free forms. This study showed the toxic effect of zearalenone and its metabolites, and their pharmacokinetic characteristics in goats.

Unexpected double-primary aortoenteric fistula resulting in massive bleeding after induction of anesthesia. We report a case of a patient with a double-primary aortoenteric fistula with an abdominal aortic aneurysm. A 75-year-old man was taken to the operating room for the repair of an abdominal aortic aneurysm and a suspected aortoenteric fistula between the aorta and sigmoid colon. Sudden onset of massive bleeding through the nasogastric tube occurred after the induction of anesthesia. Surgical exploration confirmed an unexpected aortoduodenal fistula. Primary aortoenteric fistula is extremely rare and difficult to diagnose, and may cause fatal bleeding. The possibility of the presence of aortoenteric fistula, including multiple types, should be considered in the anesthetic management of abdominal aortic aneurysm.

Immunoglobulin synthesis after HLA-identical marrow grafting. V. The role of peripheral blood monocytes in the regulation of in vitro immunoglobulin secretion stimulated by pokeweed mitogen. The ability of purified monocytes to regulate in vitro immunoglobulin (Ig) production was examined in 12 patients after HLA-identical marrow grafting. Five patients were studied less than 3 mo after grafting and seven more than 1 yr after grafting. One of the former had acute graft-vs-host disease and five of the latter had chronic graft-vs-host disease. Ficoll-Hypaque-separated peripheral blood mononuclear cells from patients, normal marrow donors, or healthy unrelated individuals were separated into T and non-T cells by sheep erythrocyte rosetting. Highly enriched monocyte and B cell subpopulations were obtained by placing the non-T cells over discontinuous Percoll gradients. Co-cultures of patient or normal monocyte populations with either normal or patient T and B cells with pokeweed mitogen were performed. A hemolytic plaque assay was used to assess Ig secretion after 6 days of culture. Co-culture of T and non-T cells from 10 of 12 patients failed to produce Ig. Monocyte-enriched fractions from all patients provided normal accessory cell functions when co-cultured with normal T and B cells. Two of five patients with chronic graft-vs-host disease had monocytes that suppressed Ig synthesis at high ratios of monocytes to normal T and B cells. Normal monocyte-enriched fractions did not restore Ig production to T and B cells of patients whose T and non-T cells failed to produce Ig. These data indicate that the observed defects in pokeweed mitogen-driven Ig secretion after marrow grafting are due primarily to defective T and B cell functions and that the monocyte accessory function is intact in most patients studied.

Use of a puncture needle for recanalization of an occluded right subclavian vein. We report a patient in whom we used a puncture needle to initiate percutaneous recanalization of a chronic occlusion of the junction between the right subclavian vein and the right brachiocephalic vein. Under fluoroscopic guidance, an 18-gauge needle was used to puncture the right subclavian vein. When contrast material injected through the needle confirmed intravascular location, the needle was advanced until it deflected and perforated an occlusion balloon target positioned within the right brachiocephalic vein. This technique may be useful in patients with central venous occlusions that are refractory to traversal using traditional catheter and guidewire techniques.

Crystal structure of the mosquito-larvicidal toxin Cry4Ba and its biological implications. Cry4Ba, isolated from Bacillus thuringiensis subsp. israelensis, is specifically toxic to the larvae of Aedes and Anopheles mosquitoes. The structure of activated Cry4Ba toxin has been determined by multiple isomorphous replacement with anomalous scattering and refined to R(cryst) = 20.5% and R(free)= 21.8% at 1.75 Angstroms resolution. It resembles previously reported Cry toxin structures but shows the following distinctions. In domain I the helix bundle contains only the long and amphipathic helices alpha3-alpha7. The N-terminal helices alpha1-alpha2b, absent due to proteolysis during crystallisation, appear inessential to toxicity. In domain II the beta-sheet prism presents short apical loops without the beta-ribbon extension of inner strands, thus placing the receptor combining sites close to the sheets. In domain III the beta-sandwich contains a helical extension from the C-terminal strand beta23, which interacts with a beta-hairpin excursion from the edge of the outer sheet. The structure provides a rational explanation of recent mutagenesis and biophysical data on this toxin. Furthermore, added to earlier structures from the Cry toxin family, Cry4Ba completes a minimal structural database covering the Coleoptera, Lepidoptera, Diptera and Lepidoptera/Diptera specificity classes. A multiple structure alignment found that the Diptera-specific Cry4Ba is structurally more closely similar to the Lepidoptera-specific Cry1Aa than the Coleoptera-specific Cry3Aa, but most distantly related to Lepidoptera/Diptera-specific Cry2Aa. The structures are most divergent in domain II, supporting the suggestion that this domain has a major role in specificity determination. They are most similar in the alpha3-alpha7 major fragment of domain I, which contains the alpha4-alpha5 hairpin crucial to pore formation. The collective knowledge of Cry toxin structure and mutagenesis data will lead to a more critical understanding of the structural basis for receptor binding and pore formation, as well as allowing the scope of diversity to be better appreciated.

Mitochondrial DNA mutations at nucleotide 8993 show a lack of tissue- or age-related variation. Two pathogenic mitochondrial DNA mutations, a T-to-G substitution (8993T > G) and a T-to-C substitution (8993T > C), at nucleotide 8993 have been reported. We describe 13 pedigrees with mitochondrial DNA mutations at nucleotide 8993; 10 pedigrees with the 8993T > G mutation and three with the 8993T > C mutation. Prenatal diagnosis of the nucleotide 8993 mutations is technically possible. However, there are three major concerns: (i) that there is variation in mutant loads among tissues; (ii) that the mutant load in a tissue may change over time; and (iii) that the genotype-phenotype correlation is not clearly understood. We have used the 13 pedigrees to determine specifically the extent of tissue- and age-related variation of the two mutations at nucleotide 8993 in the mitochondrial DNA. The tissue variation was investigated by analysing two or more different tissues from a total of 18 individuals. The age-related variation of the mutation was investigated by comparing the amount of both mutations in blood taken at birth and at a later age. No substantial tissue variation was found, nor was there any substantial change in the proportion of either mutation over periods of 8-23 years in the four individuals studied. In addition, we noted that two features were remarkably common in families with nucleotide 8993 mutations, namely (i) unexplained infant death (8 cases in 13 pedigrees); and (ii) de novo mutations (5 of the 10 8993T > G pedigrees).

Optimization of donkey sperm vitrification: Effect of sucrose, sperm concentration, volume and package (0.25 and 0.5 mL straws). The aim of this study was to assess the effect of different factors affecting vitrification success of donkey sperm: extender, sperm concentration, volume and storage vessel type. In Experiment 1, sucrose supplementations at 0.25 and 0.1 M were compared using two base extenders (containing or not egg-yolk); in Experiment 2, three sperm concentrations were assessed: 100, 200 or 300 million sperm/mL; and in Experiment 3, three different sperm volumes (100, 160 and 200 μL) and two different storage vessels (0.25 and 0.5 mL straws) were assessed. Sperm motility variables (CASA), plasma membrane and acrosome (evaluated under fluorescence microscopy) and sperm DNA integrity (flow cytometry) were evaluated after warming with comparisons of protocols. There was a greater total (55.7 ± 16.4%) and progressive (44.0 ± 11.5%) motility using the extender with egg-yolk and 0.1 M sucrose. There were no effects of sperm concentrations on vitrification results (P > 0.05). The 0.25 mL covered straw showed higher values than the 0.5 mL straw for total (50.0 ± 17.3% vs 2.0 ± 6.7%) and progressive (40.5 ± 14.9% vs 0.9 ± 1.5%) motility, plasma membrane (43.9 ± 14.4% vs 14.0 ± 16.4%) and acrosome integrity (51.5 ± 13.6% vs 28.0 ± 14.7%), respectively. In conclusion, values for donkey sperm quality variables after vitrification were greater using an extender containing egg-yolk and 0.1 M sucrose, at 300 million sperm/mL in 0.25 mL straws with outer covers.

A comparison of river water quality sampling methodologies under highly variable load conditions. When river water quality fluctuates over relatively short periods of time with respect to the sampling frequency, the collection of grab samples may be inappropriate for characterising average water quality. This paper presents the results of a water quality monitoring study carried out on a stretch of the river Lambro (northern Italy) dominated by a periodically overloaded sewage treatment works (STW) located near its upstream end. Water quality was strongly influenced by a pronounced diurnal cycle in pollutant loads caused by the regular emission of untreated waste water during periods of high domestic flow (daytime). Two different sampling techniques were employed: grab sampling and 24-h composite sampling using automatic samplers. Samples were collected at the plant overflow and at several sites along the river and analysed for two common ingredients of household detergents, linear alkylbenzene sulphonate (LAS) and boron (B) and for routine water quality variables. The results obtained show that: (1) The diurnal variability of point-source-derived chemical concentrations in the river downstream of the undersized STW increased with increasing removal efficiency in sewage treatment. (2) The shape of the diurnal concentration signal remained relatively intact for a considerable distance downstream of the STW for several water quality variables, suggesting that hydrodynamic dispersion plays a relatively minor role in controlling concentration patterns in this river. (3) In-stream degradation of LAS was consistent with first order kinetics with a rate constant of 0.05-0.06 h(-1). (4) Grab sampling is a relatively inefficient methodology for capturing mean concentrations for rivers subjected to highly variable loads, especially when it is restricted to office hours. The inefficiency of grab sampling is more marked for substances (e.g. LAS) which are effectively removed during sewage treatment than for substances which are not. (5) For LAS, diurnal variability in the concentration signal decreases with distance downstream, making grab sampling an increasingly reliable methodology for estimating mean concentrations. (6) 24-h composite sampling is an efficient way of eliminating the effect of diurnal variations in load strength.

Using algorithms and computerized decision support systems to treat major depression. The American Psychiatric Association practice guidelines for treating major depressive disorder advocate using measurement-based care and treatment algorithms, which have been shown to be effective strategies in improving patient outcomes. However, in practice, clinicians may avoid using algorithms and guidelines due to barriers such as lack of time, lack of staff support, and the perceived inflexibility of algorithms. Computerized decision support systems (CDSS) are one approach to increasing guideline adherence. A CDSS can make measurement-based care strategies accessible and user-friendly for physicians and staff, individualize treatment options according to each patient's circumstances, and provide guideline information at the point of care. In addition, a CDSS can be merged with electronic health record systems, which should simplify implementation and increase guideline adherence.

Effects of peritonsillar infiltration on post-tonsillectomy pain. A double-blind study. The concept that local infiltration of the operative area with a local anesthetic when using general anesthesia could alleviate postoperative pain is well known. We tested this concept on 129 patients scheduled for elective tonsillectomy. The patients were investigated in a double-blind, randomized study, and the operation was carried out via the standard technique of infiltrating the peritonsillar area preoperatively. The results indicated that preincisional infiltration of the tonsils with bupivacaine hydrochloride markedly decreased the intensity of pain following tonsillectomy, well beyond the immediate postoperative period.

Shoulder-arm pain from cervical bands and scalene muscle anomalies. Fourteen patients were identified with (1) pain and sensory changes in a brachial plexus distribution, (2) aggravation of pain with use of the affected extremity, and (3) pain on palpation over the brachial plexus. All patients had minimal or no intrinsic hand muscle atrophy. Only one patient had cervical ribs. Nerve conduction studies were normal, and electromyography (EMG) showed mild chronic neuropathic changes in 2 patients. None of the patients responded to conservative therapy over a prolonged period (7-12 months). A compressive brachial plexopathy from abnormally attached or enlarged scalene muscles that affected both upper and lower trunks of the brachial plexus was found at surgery in all patients. In 13 patients, at least one fibrous band compressed the lower trunk of the brachial plexus. Therefore, neurogenic thoracic outlet syndrome can occur from cervical bands and scalene muscle anomalies without intrinsic hand muscle atrophy, cervical ribs, enlarged C7 transverse processes, or EMG abnormalities.

Rational Design of UCST-type Ureido Copolymers Based on a Hydrophobic Parameter. Thermoresponsive polymers exhibiting upper critical solution temperature (UCST)-type behavior under physiologically relevant conditions have potential as biomaterials. The phase separation temperature ( Tp) of the UCST-type polymers can be increased by copolymerization with hydrophobic comonomers. Quantitative index parameters that could be used to rationally tune the Tp are lacking, however. We have reported that ureido copolymers such as poly(allylamine- co-allylurea) (AM-PU) and poly(l-ornithine- co-citrulline) exhibit UCST-type solution behavior under physiologically relevant conditions. In this study, AM-PU was hydrophobized by acylation. Tp of AM-PU can be regulated in a wide temperature range from about 20 to 80 °C or even higher by 20 mol % acylation with acetyl, propionyl, isobutanoyl, or pivaloyl groups, implying considerable impacts of hydrophobic groups on UCST phase separation. We observed a liner relationship between Tp and the hydrophobic parameter, log P, of the acyl groups. Furthermore, the acylation significantly reduced the influence of serum components on Tp by eliminating interactions of copolymers with serum components such as proteins and lipids. Acylation also abolished pH dependence of Tp which had been observed for unmodified AM-PU. Owing to the simple relationship between log P and Tp and the inertness of the acylated copolymer to serum components and pH changes, it is possible to rationally design copolymers exhibiting UCST-type behavior at a desired temperature under biological conditions.

Plant regeneration by organogenesis in Vitis rootstock species. A procedure for the regeneration of Vitis rootstocks plantlets by organogenesis from foliar tissues is described. Leaves from mature plants grown in growth chambers or from plantlets grown in tubes were wounded with a scalpel and cultured on a modified Murashige and Skoog liquid medium containing different concentrations of benzyl-aminopurine. The presence of benzyl-aminopurine is required for shoot formation. The age of the source explant, the composition of the culture medium and the culture temperature are important parameters of the regeneration process.

Transseptal approach for stent implantation in right internal carotid artery stenosis. Carotid artery stenting is emerging as an effective measure to prevent strokes in patients with significant carotid artery stenosis. We report a case of right internal carotid artery stenosis in which we used a transseptal approach for successful carotid artery stenting. This patient had concomitant stenosis at all three coronary arteries, including the left main coronary artery. A transseptal approach was adopted due to the sharply angled take-off of the right brachiocephalic artery from the tortuous aortic arch, where advancement of an extra-stiff wire into the right common carotid artery was not possible by a femoral artery approach.

Incomplete nuclear transformation of human spermatozoa in oligo-astheno-teratospermia: characterization by indirect immunofluorescence of chromatin and thiol status. BACKGROUND Sperm heterogeneity in the human, as observed in oligo-astheno-teratozoospermia (OAT), is associated with hypospermatogenesis. METHODS The chromatin of sperm from OAT and normospermic males was characterized with antibodies specific for nucleosomes, the histone H3.1/H3.2 isoform, histone TH2B, apoptosis-associated H4 acetylation (KM-2) and protamines. Subsequently, sperm samples were stained with the thiol-specific fluorochrome monobromobimane (mBBr) before and after reduction with dithiotreitol (DTT) as most thiol groups reside in the cysteine-rich protamines. We also used fluorescence-activated cell sorter (FACS) for sperm histograms and sorting for high or low free and total thiol levels. These fractions were further analysed for DNA damage with the TdT-UTP nick end-labelling (TUNEL) assay. RESULTS OAT sperm nuclei stained higher for nucleosomes and KM2-epitopes, and lower for TH2B. For free, and total, thiol groups, OAT sperm were characterized by biphasic distributions, reflecting incomplete thiol oxidation as well as overoxidation, and possibly reduced protamine contents. The TUNEL assay on sperm subfractions, for both control and OAT sperm, revealed that a lower level of free thiol groups is associated with a higher TUNEL incidence, and this relationship was also found for total thiol levels. Hence, both overoxidation and a low total number of thiol groups predestine for sperm apoptosis. CONCLUSIONS Chromatin characteristics reflecting an incomplete nucleosome to protamine remodelling were found in subfertile males. Sperm apoptosis is related to both incomplete remodelling and protamine overoxidation.

DNA damage in dihydroartemisinin-resistant Molt-4 cells. Artemisinin generates carbon-based free radicals when it reacts with iron, and induces molecular damage and apoptosis. Its toxicity is more selective toward cancer cells because cancer cells contain a higher level of intracellular free iron. Dihydroartemisinin (DHA), an analog of artemisinin, has selective cytotoxicity toward Molt-4 human lymphoblastoid cells. A major concern is whether cancer cells could develop resistance to DHA, thus limiting its therapeutic efficacy. We have developed a DHA-resistant Molt-4 cell line (RTN) and found out that these cells exhibited resistance to DHA but no significant cross- resistance to artemisinin-tagged holotransferrin (ART-TF), a synthetic artemisinin compound. In the present study, we investigated DNA damage induced by DHA and ART-TF in both Molt-4 and RTN cells using the comet assay. RTN cells exhibited a significantly lower level of basal and X-ray-induced DNA damage compared to Molt-4 cells. Both DHA and ART-TF induced DNA damage in Molt-4 cells, whereas DNA damage was induced in RTN cells by ART-TF, and not DHA. The result of this study shows that by the cell selection method, it is possible to generate a Molt-4 cell line which is not sensitive to DHA, but sensitive to ART-TF, as measured by DNA damage.

Characteristics of coherent lidar returns from calibration targets and aerosols. A CO(2) heterodyne lidar system and high speed digitizer were used to examine properties of returns from disk and belt-type calibration targets and atmospheric aerosols. Amplitude statistics of the returns from the targets examined corresponded to those of the Rayleigh phasor predicted by theory. Returns from a belt sander fluctuated at a much slower rate than those from the disks or aerosols, requiring longer averaging times for accurate power measurement. At very close focal lengths returns from single large particles often domier nated the backscattered aerosol signal.

Introducing the concept of modern depression in Japan; an international case vignette survey. Japanese psychiatrists have increasingly reported patients with depression that does not seem to fit the criteria of the ICD-10 and the DSM-IV, and which has recently been called modern type depression (MTD). We explored whether MTD is frequently seen in Japan and also in other countries, and if so, how patients with MTD are diagnosed and treated. The questionnaires, with two case vignettes (traditional type depression (TTD) and MTD), were sent to psychiatrists in Australia, Bangladesh, India, Iran, Japan, Korea, Taiwan, Thailand and the USA. Participants rated their opinions about each case's prevalence in their country, etiology, diagnosis, suicide risk, and treatment using Likert scales. Out of 247 responses (123 from Japan and 124 from other countries), two hundred thirty-nine valid responses were received. MTD was recognized in all participating countries, and especially in urban areas. Generally, the factor of personality was regarded as the most probable cause of MTD. Whereas about 90% of Japanese psychiatrists applied the ICD/DSM criteria to TTD, only about 60% applied the criteria to MTD. Our results indicate that Japan's MTD seems to be occurring in many other countries, and that the present ICD/DSM criteria may not be sufficient to diagnose MTD. Therefore, it could be an important candidate for a new international diagnostic criterion as a subtype of depression. A clear diagnostic framework and consensus on the interventions to treat MTD would be valuable. Further clinical, psychopathological and international epidemiological studies are needed to confirm our preliminary findings of MTD.

An interactive computer program for recording and analysing longitudinal cephalometric growth material. An interactive suite of chained programs is described for recording, measuring, and analysing a large number of longitudinal cephalometric records. The programs are arranged in a logical sequence, and integrated with the hardware, to ensure a smooth and automatic running of the system from data collection to data analysis. The results of the analysis can be presented in suitable numerical and/or graphical forms to show individual as well as mean growth profiles.

Writing to get published. Writing for publication is an important way to contribute to the knowledge base for professional nurses. This paper reviews the process of writing a professional paper from identification of a topic to the time the paper appears in print. Web-based resources to facilitate the writing process are highlighted.

Discovery of potent and selective phenylalanine derived CCR3 receptor antagonists. Part 2. Highly potent CCR3 antagonists have been developed from a previously reported series of phenylalanine ester-based leads. Solution-phase, parallel synthesis optimization was utilized to identify highly potent, functional CCR3 antagonists.

Enzymatic inactivation of major circulating forms of atrial and brain natriuretic peptides. We compared the enzymatic inactivation of major circulating forms of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Both ANP and BNP induced a significant increase in cyclic GMP (cGMP) formation in cultured epithelial cell line derived from porcine kidney, LLC-PK1. The cGMP formation stimulated by ANP in LLC-PK1 cells was significantly decreased by pre-treatment of the peptide with rat renal brush-border membranes, and the inactivation of ANP was inhibited by neutral endopeptidase inhibitors, phosphoramidon and S-thiorphan. BNP exhibited greater resistance to enzymatic inactivation than did ANP. In addition, phosphoramidon potentiated the natriuresis with a low dose (7.5 pmol min(-1) kg(-1)) of ANP but not of BNP in rats. These results suggest that enzymatic degradation of natriuretic peptides is highly dependent on peptide structure, and that the affinity of BNP to neutral endopeptidase is less than that of ANP.

Activation by stress of the habenulo-interpeduncular substance P neurons in the rat. Substance P levels were significantly decreased in the ventro-tegmental area and the interpeduncular nucleus of rats submitted for 20 min to electric foot-shocks. Substance P levels in the substantia nigra and in the prefrontal cortex were not affected. These results are discussed in light of the selective activation of the mesocortico-prefrontal dopaminergic neurons induced by this stress situation.

Intramolecular electrophilic aromatic substitution in gas-phase-protonated difunctional compounds containing one or two arylmethyl groups. A variety of dibenzyl esters and ethers undergo a rearrangement process upon isobutane chemical ionization and collision-induced dissociation of their MH(+) ions, whereby a new bond is formed between the two benzyl groups, giving rise to abundant [C(14)H(13)](+) (m/z 181) ions. This rearrangement has been explained as an intramolecular electrophilic substitution in the gas phase occurring in an ion-neutral complex formed by the cleavage of one of the benzyl-oxygen bonds. A similar highly efficient intramolecular electrophilic substitution takes place in di-alpha- and beta-naphthylmethyl adipates affording m/z 281 [C(22)H(17)](+) ions, but not in the sterically hindered di-9-anthracylmethyl adipate. An analogous efficient rearrangement occurs in benzyl alpha- and beta-naphthylmethylcyclohexane-1,4-dicarboxylates and in benzyl alpha- and beta-phenylethylcyclohexane-1,4-dimethanol ethers. The analogous rearrangement is much less efficient in benzylallyl, benzylpropargyl and benzyl-9-anthracylmethyl derivatives, even less in benzylisopropyl and benzylacetyl analogs, and it is absent in benzyltetrahydropyranyl derivatives. The distinctive behavior of the protonated difunctional benzyl derivatives is interpreted in terms of the energy requirements of the O-R bond heterolysis of the protonated functionalities, the ability of the neutral R' groups (non-dissociated from the oxygen atom) to play the role of the nucleophile in the intramolecular electrophilic substitution processes and the electrophilicity of the R(+) ions.

Reduction of osteopontin in vivo inhibits tubular epithelial to mesenchymal transition in rats with chronic allograft nephropathy. Chronic allograft nephropathy (CAN) is an important etiological factor causing graft loss. However, the mechanism of CAN is unclear. Osteopontin (OPN), a proinflammatory and profibrosis molecule, plays a key role in late stages of renal diseases. We investigated the potential role of OPN in the pathogenesis of CAN. Using a F344 to Lewis rat CAN model, we injected short hairpin RNA (shRNA) constructs targeting OPN or negative control plasmids through the renal vein following electroporation. At 12 weeks after the transplantation, we determined interstitial fibrosis (IF) and tubular atrophy (TA) of the tubular epithelial cells (TECs). OPN expression was examined using Western blots and immunohistochemistry (IHC). Molecules involved in epithelial to mesenchymal transition (EMT) of TECs were examined using IHC and Western blots. OPN expression in kidney grafts was decreased by the RNA interference (RNAi) group. Histology observations showed IF and TA to be mild with stable renal function in the RNAi-treated group. EMT of TECs was significantly lessened after reducing OPN. Reduction of OPN in vivo inhibited progression of CAN. OPN may be of therapeutic value in transplantation settings.

Role of the ghrelin system in alcoholism: Acting on the growth hormone secretagogue receptor to treat alcohol-related diseases. There exists a substantial need to identify new neuropharmacological targets to treat alcohol-dependent individuals. Ghrelin represents a gut-brain peptide, initially discovered as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The existing literature clearly demonstrates that ghrelin affects appetite and food intake. Both animal and human studies provide evidence that ghrelin not only influences hunger but also has a role in the search for rewarding substances, such as alcohol. Animal studies provide evidence that ghrelin stimulates the reward system, acting on specific brain reward nodes, and that ghrelin signaling is required for stimulation of the reward system by alcohol. Human studies show that ethanol acutely affects ghrelin levels. Interestingly, human studies with alcohol-dependent individuals suggest that higher ghrelin levels are associated with higher self-reported measurements of alcohol craving. Altogether, these findings suggest that the ghrelin system plays a role in alcohol dependence. Ghrelin antagonists (i.e., GHS-R1a antagonists and/or inverse agonists) might affect alcohol-seeking behavior, thus having therapeutic potential in alcohol use disorders. Future laboratory and clinical studies testing this hypothesis are warranted.

Probing the mechanistic principles of bacterial cell division with super-resolution microscopy. Bacterial cell division takes place almost entirely below the diffraction limit of light microscopy, making super-resolution microscopy ideally suited to interrogating this process. I review how super-resolution microscopy has advanced our understanding of bacterial cell division. I discuss the mechanistic implications of these findings, propose physical models for cell division compatible with recent data, and discuss key outstanding questions and future research directions.

Macrophage colony-stimulating activity is produced by three different EBV-transformed lymphoblastoid cell lines. The lymphoblastoid cell lines BLY 9.84, Gl, and Pl constitutively release a colony-stimulating activity (CSA) which specifically stimulates murine macrophage progenitor cells in vitro. The biochemical characterization of BLY 9.84-derived CSA exhibits a molecular size of apparently 150-200 kDa even under dissociating conditions with 6 M guanidine hydrochloride or inhibition of glycosylation. Production of this CSA is inhibited by cycloheximide and its activity is destroyed by reduction with dithiothreitol. Replating experiments give evidence for a functional similarity with CSF-1 (macrophage colony-stimulating factor).

Prevention of in vitro low-density lipoprotein oxidation by an albumin-containing Lp A-I subfraction. High-density lipoprotein (HDL) and two lipoprotein particles, those containing apo A-I and apo A-II (LpA-I:A-II) and those containing only apo A-I (LpA-I) were examined for their effect on Cu(2+)-catalyzed oxidation of human low-density lipoprotein (LDL). Lipoproteins and lipoprotein particles were prepared from plasma samples of five healthy subjects. LDL and HDL were purified by ultracentrifugation, LpA-I and LpA-I:A-II were isolated by an immunoaffinity chromatography procedure. The contaminating albumin often linked to the LpA-I affinity purified particles was eliminated by selected affinity immunosorption. The presence of HDL, LpA-I or LpA-I:A-II, at an apo A-I-containing lipoproteins/LDL ratio of 1, did not prevent LDL oxidation when assessed by oxidation kinetics, electrophoretic mobility, amounts of thiobarbituric acid-reactive products and fragmentation of apo B-100. On the other hand, when the albumin removing step was omitted, the subfraction of albumin-containing LpA-I particles impeded and even inhibited the oxidation of LDL in an albumin dose-dependent manner.

Antimicrobial activity and resistance selection of different bioglass S53P4 formulations against multidrug resistant strains. This study aimed to evaluate the antimicrobial activity of two different formulations of bioglass BAG-S53P4 against multiresistant microorganisms involved in bone infections, and the capability of bioglass to select for resistance. Antibacterial activity was evaluated by means of killing curves. The ability to select for resistant bacteria was evaluated by subculturing microorganisms in serial dilutions of bioglass. Scanning electron microscope acquisitions were conducted to evaluate bioglass-induced morphology changes. BAG-S53P4 formulations display a high antimicrobial activity and do not seem to select for resistance. Scanning electron microscopy analysis showed cell shrinkage and membrane damage after exposure to bioglass. BAG-S53P4 has a significant potential as bone substitute for the treatment of infections caused by multiresistant microorganisms.

Comparison between off-resonance and electron Bernstein waves heating regime in a microwave discharge ion source. A microwave discharge ion source (MDIS) operating at the Laboratori Nazionali del Sud of INFN, Catania has been used to compare the traditional electron cyclotron resonance (ECR) heating with an innovative mechanisms of plasma ignition based on the electrostatic Bernstein waves (EBW). EBW are obtained via the inner plasma electromagnetic-to-electrostatic wave conversion and they are absorbed by the plasma at cyclotron resonance harmonics. The heating of plasma by means of EBW at particular frequencies enabled us to reach densities much larger than the cutoff ones. Evidences of EBW generation and absorption together with X-ray emissions due to high energy electrons will be shown. A characterization of the discharge heating process in MDISs as a generalization of the ECR heating mechanism by means of ray tracing will be shown in order to highlight the fundamental physical differences between ECR and EBW heating.

Clergy knowledge and attitudes concerning faith community nursing: toward a three-dimensional scale. Research has described faith community nursing practice, including positive aspects and barriers to practice. Barriers to faith community nursing practice must be identified and addressed to facilitate faith community nursing programs. The primary purpose of this study was to pilot test a newly developed instrument to measure knowledge and attitudes concerning faith community nursing. A survey design was used. The sample included clergy in the United Church of Christ (n=34). An investigator developed survey entitled Knowledge, Attitudes, and Opinions Concerning Faith Community Nursing was administered. Psychometric evaluation of the survey included content validity and internal consistency reliability for each of 3 scales. Coefficient alpha was high, ranging from .88 to .95. The results of the survey indicate that clergy, within the selected Christian denomination, generally have adequate knowledge and positive attitudes about faith community nursing. Knowledge scores on one item indicated some uncertainty among clergy about spiritual counseling as a nursing intervention. A major limitation to this study was the small, homogeneous sample. Future research should include further psychometric evaluation of validity and reliability in a larger, diverse sample. The results of this study indicate that, with further testing, the Knowledge, Attitudes, and Opinions Concerning Faith Community Nursing Survey has the potential to expand assessment of barriers to faith community nursing.

Inhibition of glutamine synthetase in rabbit pneumococcal meningitis is associated with neuronal apoptosis in the dentate gyrus. Apoptosis of dentate granular cells in the hippocampal formation during bacterial meningitis may be mediated by glutamate toxicity. For this reason, we studied the relationship between glutamine synthetase activity and regional neuronal apoptosis in rabbits with experimental pneumococcal meningitis. The duration of meningitis was 24 h, and the treatment was started 16 h after infection. Significant increases of glutamine synthetase protein concentration (P < 0.05) were found in the frontal cortex of rabbits with meningitis (n = 7) and rabbits with meningitis receiving ceftriaxone treatment (n = 12) as compared to the control animals (n = 14). No significant differences were seen in the hippocampal formation. The enzymatic activity of glutamine synthetase also was elevated in the frontal cortex (P < 0.05), but not in the hippocampal formation of rabbits with meningitis. After intravenous administration of L-methionine sulfoximine (specific inhibitor of glutamine synthetase) in rabbits with meningitis treated with ceftriaxone (n = 10), the concentration of neuron-specific enolase in CSF (P = 0.025) and the density of apoptotic neurons in the dentate gyrus quantified with the in-situ tailing reaction (P = 0.043) were higher than in meningitic animals receiving only ceftriaxone (n = 10). In conclusion, the inability of hippocampal glutamine synthetase to metabolize excess amounts of glutamate may contribute to neuronal apoptosis in the hippocampal formation during meningitis.

Renal tubular transport and nephrotoxicity of beta lactam antibiotics: structure-activity relationships. Several of the cephalosporin and carbapenem antibiotics produce acute renal failure when given in large single doses. Antibiotic concentrations in the tubular cell, determined by the net effects of contraluminal secretory transport and subsequent movement across the luminal membrane, make the proximal tubule the sole target of injury, and are important determinants of the nephrotoxic potentials of different beta-lactams in different animal species. At least three molecular mechanisms of injury have been shown with cephaloridine, the most widely studied nephrotoxic beta-lactam: (1) lipid peroxidation, (2) competitive inhibition of mitochondrial carnitine (zwitterionic) transport and fatty acid oxidation, and (3) acylation and inactivation of tubular cell proteins, most thoroughly evaluated with mitochondrial anionic substrate transporters. The first two of these injuries are dependent upon one or both of cephaloridine's side group substituents, which are not present on the other nephrotoxic cephalosporins or carbapenems. It is not surprising, therefore, that only toxicity to mitochondrial anionic substrate carriers has been found in studies of the other beta-lactams. However, the several effects of cephaloridine on the tubular cell indicate a potential for different mechanisms of attack on different molecular targets. Continuing studies of the effects of existing and newly developed beta-lactams are likely to identify further nephrotoxic mechanisms of this complex and rapidly growing group of antimicrobials.

Novel optineurin mutations in patients with familial and sporadic amyotrophic lateral sclerosis. Optineurin (OPTN), a causative gene of hereditary primary open-angle glaucoma, has been recently associated with amyotrophic lateral sclerosis (ALS) with mainly autosomal recessive, but also dominant, traits. To further define the contribution of OPTN gene in ALS, we performed a mutational screening in a large cohort of Italian patients. A group of 274 ALS patients, including 161 familial (FALS) and 113 sporadic (SALS) cases, were screened for OPTN mutations by direct sequencing of its coding sequence. All patients fulfilled the El Escorial criteria for probable or definite ALS and were negative for mutations in SOD1, ANG, TARDBP and FUS/TLS genes. The genetic analysis revealed six novel variants in both FALS and SALS patients, all occurring in an heterozygous state. We identified three missense (c.844A→C p.T282P, c.941A→T p.Q314L, c.1670A→C p.K557T), one nonsense (c.67G→T p.G23X) and two intronic mutations (c.552+1delG, c.1401+4A→G). The intronic c.552+1delG variant determined a splicing defect as demonstrated by mRNA analysis. All mutations were absent in 280 Italian controls and over 6800 worldwide glaucoma patients and controls screened so far. The clinical phenotype of OPTN-mutated patients was heterogeneous for both age of onset and disease duration but characterised by lower-limb onset and prevalence of upper motor neuron signs. In this cohort, OPTN mutations were present both in FALS (2/161), accounting for 1.2% cases, and in SALS patients (4/113), thereby extending the spectrum of OPTN mutations associated with ALS. The study further supports the possible pathological role of optineurin protein in motor neuron disease.

Acute and persistent protein synthesis inhibition following cerebral reperfusion. Lack of recovery from protein synthesis inhibition (PSI) closely correlates with neuronal death following brain ischemia and reperfusion. It has therefore been suggested that understanding the mechanisms of PSI will shed light on the mechanisms of selective neuronal death following ischemia and reperfusion. It is now known that the PKR-like ER kinase (PERK)-mediated phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) causes translation inhibition at initial reperfusion. Activation of PERK, in turn, indicates endoplasmic reticulum stress and activation of the unfolded protein response. However, phosphorylation of eIF2alpha is a transient event and can account for PSI only in the initial hours of reperfusion. Although a number of other regulators of protein synthesis, such as eIF4F, 4EBP-1, eEF-2, and S6 kinase, have been assessed following cerebral ischemia and reperfusion, the causes of prolonged PSI have yet to be fully elucidated. The purpose of the present article is to bring together the evidence indicating that, at minimum, postischemic PSI should be conceptualized as consisting of two components: an acute, transient component mediated by unfolded protein response-induced eIF2alpha phosphorylation and a longer term component that correlates with neuronal death. Ischemic tolerance appears to separate the acute and persistent components of reperfusion-induced translation inhibition. Specific models of the relationship among acute PSI, persistent PSI, and neuronal death are presented to clarify issues that have emerged from ongoing work in this area.

Parathyroid hormone regulates the expression of rat osteoblast and osteosarcoma nuclear matrix proteins. Parathyroid hormone (PTH) alters osteoblast morphology. How these changes in cell shape modify nuclear structure and ultimately gene expression is not known. Chronic exposure to rat PTH (1-34) [10 nM] attenuated the expression of 200, 190, and 160 kD proteins in the nuclear matrix-intermediate filament subfraction of the rat osteosarcoma cells, ROS 17/2.8 [Bidwell et al. (1994b): Endocrinology 134:1738-1744]. Here, we determined that these same PTH-responsive proteins were expressed in rat metaphyseal osteoblasts. We identified the 200 kD protein as a non-muscle myosin. Although the molecular weights, subcellular distribution, and half-lives of the 190 and 160 kD proteins were similar to topoisomerase II-alpha and -beta, nuclear matrix enzymes that mediate DNA topology, the 190 and 160 kD proteins did not interact with topoisomerase antibodies. Nevertheless, the expression of topoisomerase II-alpha, and NuMA, a component of the nuclear core filaments, was also regulated by PTH in the osteosarcoma cells. The 190 kD protein was selectively expressed in bone cells as it was not observed in OK opossum kidney cells, H4 hepatoma cells, or NIH3T3 cells. PTH attenuated mRNA expression of the PTH receptor in our cell preparations. These results demonstrate that PTH selectively alters the expression of osteoblast membrane, cytoskeletal, and nucleoskeletal proteins. Topoisomerase II-alpha, NuMA, and the 190 and 160 kD proteins may direct the nuclear PTH signalling pathways to the target genes and play a structural role in osteoblast gene expression.

[Mechanism of synergism of the sympathetic and parasympathetic nervous system in regulating cardiac and gastric activity]. The authors studied the mechanism of the higher vagus suppression of cardiac performance, which occurs when irritation of the sympathetic nerve is added to that of the vagus and when gastric motility occurring with the irritation of the sympathetic trunk is stimulated. Preganglionic serotonic fibers synaptically connected with serotoninergic intramural neurons are involved in showing these mechanisms.

Taste and odor compounds associated with aquatic plants in Taihu Lake: distribution and producing potential. The odor problem caused by the decay of aquatic plants is widespread in many freshwater lakes. In this study, the spatial distributions of seven taste and odor (T&O) compounds (dimethyl sulfide, dimethyl disulfide, dimethyl trisulfide, 2-methylisoborneol, geosmin, β-cyclocitral, and β-ionone) in the sediments and overlying water of the east of Taihu Lake were investigated. The effects of plant and physico-chemical parameters on the release of T&O compounds were also analyzed. The results showed that high concentrations of T&O compounds were detected in the area where Eichhornia crassipes was flourishing. Volatile organic sulfur compounds were not found in the water source area, which was not covered by aquatic plants. High plant biomass and aquiculture activities might increase the release of the taste and odor compounds. The correlation between the concentrations of odorous compounds and nutrients in the sediment was also analyzed. The production of odorants was positively correlated with the nitrogen, and they may migrate from sediment to overlying water. The result suggested that controlling the plant density and aquaculture activities could reduce the release of odorous compounds.

The natriuretic peptides. The natriuretic peptides are a family of widely distributed, but evolutionarily conserved, polypeptide mediators that exert a range of actions throughout the body. In cardiovascular homeostasis, the endocrine roles of the cardiac-derived atrial and B-type natriuretic peptide (ANP and BNP) in regulating central fluid volume and blood pressure have been recognised for two decades. However, there is a growing realisation that natriuretic peptide actions go far beyond their volume regulating effects. These pleiotropic actions include local (autocrine/paracrine) regulatory actions of ANP and BNP within the heart, and of another natriuretic peptide, CNP, within the vessel wall. Effects on function and growth of the local tissue environment are likely to be of great importance, especially in disease states where tissue and circulating levels of ANP and BNP rise markedly. At present, the relevance of other natriuretic peptides (notably uroguanylin and DNP) to human physiology and pathology remain uncertain. Other articles in this issue of Basic Research in Cardiology review the molecular physiology of natriuretic peptide signalling, with a particular emphasis on the lessons from genetically targetted mice; the vascular activity of natriuretic peptides; the regulation and roles of natriuretic peptides in ischaemic myocardium; and the diagnostic, prognostic and therapeutic roles of natriuretic peptides in heart failure.

The Use of Propensity Scores for Nonrandomized Designs With Clustered Data. In this article we propose several modeling choices to extend propensity score analysis to clustered data. We describe different possible model specifications for estimation of the propensity score: single-level model, fixed effects model, and two random effects models. We also consider both conditioning within clusters and conditioning across clusters. We examine the underlying assumptions of these modeling choices and the type of randomized experiment approximated by each approach. Using a simulation study, we compare the relative performance of these modeling and conditioning choices in reducing bias due to confounding variables at both the person and cluster levels. An applied example based on a study by Hughes, Chen, Thoemmes, and Kwok (2010) is provided in which the effect of retention in Grade 1 on passing an achievement test in Grade 3 is evaluated. We find that models that consider the clustered nature of the data both in estimation of the propensity score and conditioning on the propensity score performed best in our simulation study; however, other modeling choices also performed well. The applied example illustrates practical limitations of these models when cluster sizes are small.

[Mirizzi syndrome with cholecystoduodenal fistula--a rare complication of cholecyctolithiasis]. Mirizzi syndrome is a rare complication of the long-term gallbladder stone disease. It's caused by a gallbladder stone impression to the common bile duct wall. The clinical appearance is an obstructive jaundice, pain in right subchondrium and dyspepsia. Higher pressure in the extrahepatal bile ducts leads to biliobiliary or enterobiliary fistula formation. In the described case a cholecystoduodenal fistula was found. Preoperative diagnosis of MS is a medical challenge, and majority of the diagnosis is set introperatively. Surgery is the treatment of first choice. Ignoring the possibility of MS can seriously damage patient's health by injuring bile ducts during the surgery.

Brief Report: Modest but Clinically Meaningful Effects of Early Behavioral Intervention in Twins with Rett Syndrome-A Case Study. A growing evidence base supports early intensive behavioral intervention (EIBI) for young children with autism spectrum disorder. We have found only one study exploring the outcome of EIBI for children with Rett syndrome, which reported little effect. It suggested that future studies should employ more fine-grained outcome measures. We provided EIBI for twin 3-year-old girls with Rett syndrome for a period of 3 years. We analyzed raw scores and standard scores from a measure of adaptive behavior and a detailed assessment of skills across 25 areas. We detected moderate but clinically meaningful gains in areas such as communication and self-help. Gains are discussed from a quality of life perspective and whether the moderate effects can justify the resources required in EIBI.

Full steam ahead on the SS "external regulator"? Mandatory reporting, professional independence, self-regulation and patient harm. Mandatory reporting by medical practitioners of their colleagues who demonstrate poor clinical performance, are intoxicated while working or have sexual relations with patients, has been recently legislated for in New South Wales, and is likely to become law in Queensland. Somewhat similar legislation was introduced in New Zealand in relation to most health practitioners, but resistance, particularly from the New Zealand Medical Association, resulted in discretionary, as opposed to mandatory, reporting. The National Registration and Accreditation Scheme for the Health Professions in Australia is also canvassing mandatory reporting for 10 major health profession registrants, as part of its processes for dealing with performance, health and conduct matters. Mandatory reporting is an important incursion on the self-regulation functions and privileges of the health professions. The medical profession, in particular, has resisted mandatory reporting provisions, but appears not to discern that its allegiance to a model of traditional rather than transparent self-regulation may be self-defeating.

Analysis of a new technique to stabilize the chronic peritoneal dialysis catheter. A significant cause of morbidity for peritoneal dialysis patients is catheter dysfunction. In our experience, the most common cause of catheter dysfunction was cephalad migration of the catheter tip out of the true pelvis. A new technique for catheter placement that reduces catheter migration from 35% to 6% (P less than .01 chi 2) is described. Our results demonstrate that peritoneal catheters which dysfunction because of catheter flip generally do so in the first 3 months.

Associated reactions after stroke: a randomized controlled trial of the effect of botulinum toxin type A. To measure the impact of botulinum toxin A on associated reactions in patients following stroke. Randomized placebo-controlled trial. Forty patients with spasticity in their paretic arm (median time since stroke: 2.7 years) were randomized to botulinum toxin A (Dysport; 1000 mouse units (MU) divided between elbow, wrist and finger flexors) or placebo. Associated reactions were measured using hand dynamometry. The effort used was measured using maximum voluntary grip in the unaffected arm. Measurements were recorded at 2 pre-treatment and 3 post-intervention times. Activities that patients felt caused associated reactions and activities that were affected by associated reactions were recorded. Peak associated reactions force was reduced at week 6 with botulinum toxin A compared with placebo (mean group difference 19.0 N; 95% confidence interval (CI): 7.2, 30.9; p < 0.01) and week 2 (p = 0.005), with the effect wearing off by week 12 (p = 0.09). Thirty-one patients noted associated reactions on a regular basis and 24 said that these movements interfered with daily activities. Ten of 12 patients receiving botulinum toxin A and 2 of 12 receiving placebo reported reduction in interference with daily activities (p = 0.02). Botulinum toxin A reduces associated reactions and may be a useful adjunct to other rehabilitation interventions. The impact of associated reactions on daily activities may also be reduced.

Delayed cord clamping in preterm dichorionic twin gestations. To examine the practice of delayed cord clamping and associated neonatal outcomes in preterm dichorionic twin gestations. This is a retrospective cohort study of women delivering dichorionic-diamniotic twin gestations between 23 and 32 weeks of gestation at a single large academic center between 2013 and 2015. Neonatal outcomes of twins receiving delayed cord clamping were compared to those who did not. Of 58 eligible women delivering dichorionic twins, eight (13.8%) had both neonates receive delayed cord clamping, resulting in 16 neonates who received delayed cord clamping and 100 who did not. Neonates who received delayed cord clamping had no difference in umbilical artery pH, 5 min Apgar score, NICU length of stay, need for pressors, neonatal death, or other adverse outcomes. Delayed cord clamping in dichorionic twin gestations born at 32 weeks or less is feasible and in this small cohort does not appear to be associated with worse neonatal outcomes.

Describing different brain computer interface systems through a unique model: a UML implementation. All the protocols currently implemented in brain computer interface (BCI) experiments are characterized by different structural and temporal entities. Moreover, due to the lack of a unique descriptive model for BCI systems, there is not a standard way to define the structure and the timing of a BCI experimental session among different research groups and there is also great discordance on the meaning of the most common terms dealing with BCI, such as trial, run and session. The aim of this paper is to provide a unified modeling language (UML) implementation of BCI systems through a unique dynamic model which is able to describe the main protocols defined in the literature (P300, mu-rhythms, SCP, SSVEP, fMRI) and demonstrates to be reasonable and adjustable according to different requirements. This model includes a set of definitions of the typical entities encountered in a BCI, diagrams which explain the structural correlations among them and a detailed description of the timing of a trial. This last represents an innovation with respect to the models already proposed in the literature. The UML documentation and the possibility of adapting this model to the different BCI systems built to date, make it a basis for the implementation of new systems and a mean for the unification and dissemination of resources. The model with all the diagrams and definitions reported in the paper are the core of the body language framework, a free set of routines and tools for the implementation, optimization and delivery of cross-platform BCI systems.

Effect of Bacoside A on growth and biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa. The goal of this study was to evaluate the antibiofilm and antimicrobial activities of Bacoside A, a formulation of phytochemicals from Bacopa monnieri, against Staphylococcus aureus and Pseudomonas aeruginosa, which are known to form biofilms as one of their virulence traits. The antimicrobial effects of Bacoside A were tested using the minimum inhibitory concentration and minimum bactericidal concentration assays. A cell membrane disruption assay was performed to find its possible target site. MTT assay, crystal violet assay, and microscopic studies were performed to assess the antibiofilm activity. Bacoside A showed antimicrobial activity against both test organisms in their planktonic and biofilm states. At a subminimum inhibitory concentration of 200 μg·mL-1, Bacoside A significantly removed ∼88%-93% of bacterial biofilm developed on microtiter plates. Biochemical and microscopic studies suggested that the eradication of biofilm might be due to the loss of extracellular polymeric substances and to a change in cell membrane integrity of the selected bacterial strains treated with Bacoside A. These results indicate that Bacoside A might be considered as an antimicrobial having the ability to disrupt biofilms. Thus, either alone or in combination with other therapeutics, Bacoside A could be useful to treat biofilm-related infections caused by opportunistic bacterial pathogens.

Enhancement of the complement activating capacity of 17-1A mAb to overcome the effect of membrane-bound complement regulatory proteins on colorectal carcinoma. Adjuvant immunotherapy with 17-1A mAb directed against colorectal carcinoma is found to be effective in patients. However, 52 % of the patients treated with mAb 17-1A showed recurrence within 7 years. This high recurrence rate might be due to inhibition of complement activation by membrane-bound complement regulatory proteins (mCRP). The effect of these complement regulatory proteins might be reduced by blocking mCRP, or be overcome by activating more complement at the tumor cell membrane. In this study the complement-activating capacity of the 17-1A mAb was enlarged by conjugating it to cobra venom factor (CVF) or C3b. The most important C3 regulatory protein, CD55, was blocked using a bispecific mAb directed against the 17-1A / Ep-CAM antigen and CD55. Up to a 13-fold increase in C3 deposition was observed due to 17-1A-CVF and 17-1A-C3b, as compared to 17-1A. CD55 was shown to partly inhibit complement activation by these conjugates. The effect of the bispecific anti-17-1A / Ep-CAM*anti-CD55 mAb was compared with 17-1A conjugates with CVF or C3, and bispecific mAb were shown to be equally or more efficient in complement activation than the 17-1A-CVF or 17-1A-C3b conjugates. Therefore, 17-1A conjugates and anti-17-1A / EpCAM*anti-CD55 bispecific mAb may be promising immunotherapeutic agents for patients with colorectal cancer.

Reduced frequency of wheezing respiratory illness in infants with perinatal human immunodeficiency virus-type 1 infection: a model for immunologic and inflammatory mechanisms of airway obstruction? A multivariate analysis using a logistic regression model evaluated odds ratio (OR) and 95% confidence limits (95% CL) of pediatrician-diagnosed wheezing respiratory illness in 75 infants with perinatal human immunodeficiency virus-type 1 (HIV-1) infection, 205 uninfected infants of HIV-1 infected mothers, and 1780 infants of HIV-1 uninfected mothers. Infants were prospectively followed-up for the first 2 years of life. Covariates were risk factors for wheezing respiratory illness (preterm delivery, low birth weight, maternal smoking, formula feeding, and neonatal respiratory disorders). Maternal use of illicit drugs in pregnancy, antiretroviral treatment in pregnancy, maternal HIV-1-related clinical condition at the time of delivery were also included in the models when infants of HIV-1 infected mothers were taken into account. Although the frequency of risk factors for wheezing respiratory illness was higher in infants of HIV-1 infected than in those of uninfected mothers, HIV-1 infection emerged as a protective factor [OR: 0.001 (95% CL: 0.0001-0.01); p < 0.001]. The frequency of risk factors was similarly high among infants of infected mothers, but OR was lower in HIV-1 infected than in uninfected infants of infected mothers (0.005; 95% CL: 0.0004-0.06; p < 0.001). Finally, OR was higher in uninfected infants of HIV-1 infected mothers (who evidenced a higher frequency of risk factors) than in infants of HIV-1 uninfected mothers (9.97; 95% CL: 4.87-20.40; p < 0.001). Understanding the reason why HIV-1 protects against wheezing respiratory illness could shed light on the immunologic and inflammatory mechanisms of airway obstruction.