The effect of generalized seizure activity on ischemia-induced cardiac arrhythmias and myocardial injury with histopathological evaluation in anesthetized rats
Epileptic seizure leads to sudden unexpected death in epilepsy (SUDEP) among affected patients. The causes of SUDEP are still unclear. The aim of this study was to research the effect of epilepsy on myocardial injury and arrhythmias during experimentally induced acute myocardial ischemia. Wistar albino rats were divided into four groups: sham, pentylentetrazole (PTZ) + sham, ischemia, and PTZ + ischemia groups. PTZ (65 mg/kg, ip) was given 2 h before ischemia. Seizure scoring was conducted by evaluating the PTZ-induced behavioral changes in the rats. The left main coronary artery was ligated in anesthetized rats for 30 min. The incidence and the number of ventricular arrhythmias were determined. Histopathological scoring was performed for tissue injury by using a microscope. Seizure scores were not different among the groups (P > 0.05). The incidence and number of ventricular tachycardia (VT) episodes were significantly higher in the PTZ + ischemia group than in the ischemia group (P ˂ 0.05). More prominent myocardial damage was observed in the PTZ + ischemia group than in the other groups (histopathological scores: PTZ + ischemia; 2.5 ± 0.5 versus ischemia; 1.2 ± 0.4, P ˂ 0.05). PTZ-induced seizure in rats increased myocardial injury and the incidence and number of VT episodes in myocardial ischemia. These results reveal that seizure in epilepsy patients may increase ventricular arrhythmia and myocardial injury during heart attack.


Pylorectomy and gastroduodenostomy in the dog: technique and clinical results in 28 cases.
Pylorectomy and end-to-end gastroduodenostomy are surgical procedures that allow excision of abnormal pyloric tissue and provide improved gastric outflow. These techniques were used for the treatment of benign, malignant, and ulcerative conditions that were judged to be not adequately treatable with pyloromyotomies or pyloroplasties. End-to-end gastroduodenostomy was not much more difficult than a standard intestinal anastomosis; however, a thorough knowledge of the pyloric area anatomy was required to avoid serious surgical errors. In addition, gentle tissue manipulation and precise suture placement reduced the chance of iatrogenic pancreatitis, biliary obstruction, tissue ischemia, and/or suture line leakage. The results of surgery depended on the underlying disease process. Dogs with benign lesions such as chronic hypertrophic pyloric gastropathy responded favorably to treatment. Dogs with malignant disease and perforated ulcers had low long-term survival rate. Pyloric adenocarcinoma was not adequately treated with this method alone.


Further studies of Trichomonas Vaginalis with transmission and scanning electron microscopy.
Under the scanning electron microscope, the body surface of trichomonads appears ruffled and creased, with numerous crater-like depressions, which should probably be interpreted as the initial stage in the formation of digestive vacuoles or pinocytotic vesicles. Having contacted epithelial cells, trichomonads engulf them totally or partially. Various micro-organisms also become a prey of the protozoon. The different stages of phagocytosis are illustrated in electron micrographs. Gonococci have been discovered in phagosomes of T. vaginalis. Usually their phagocytosis is not brought to completion and they survive within the trichomonads (endocytobiosis). This suggests that the agent of gonorrhoea may be maintained within trichomonads in cases of mixed infection. In addition to morphological details described earlier, T. vaginalis has lattice-like and lamellar structures of uncertain function. Spherical forms are found usually in an unfavourable environment or as a result of budding.


Assessing the quality of pharmacological treatments from administrative databases: the case of low-molecular-weight heparin after major orthopaedic surgery.
'Real world data' are needed to assess the quality of pharmacological treatments in clinical practice. The aim of this study was to determine whether administrative databases can be used to assess the quality of prophylaxis with low-molecular-weight heparin after major orthopaedic surgery. The study was performed in a Belgian university hospital. Patients undergoing total hip replacement (THR), total knee replacement (TKR) or hip fracture surgery (HFS) were selected retrospectively from the hospital's 2002 and 2003 administrative databases. Readmissions during the same year as the procedure were also analysed. Three quality indicators were assessed: incidence of venous thromboembolism (VTE), major bleeding and death; adherence to guidelines; and the costs of care. Although 70% of data were collected from administrative databases, patients' records also had to be examined. During the period studied, VTE and major bleeding events were rare. Patients undergoing HFS were at greater risk of having a pulmonary embolism [Exact odds ratio (OR)=3.78; 95% confidence interval (CI)=1.13-16.22; P=0.03] or of death from any cause (Exact OR=2.15; 95% CI=1.52-infinity; P<0.01) than patients undergoing THR or TKR. The hospital's prophylaxis protocol was not always followed. Half the patients received higher prophylaxis doses than recommended and 11% received lower doses but no impact on adverse events was demonstrated. Results show that administrative databases contain enough information to measure the frequency of adverse events but complementary data on patient weight and on non-reimbursed drugs must be extracted from the patients' records to evaluate adherence to guidelines. Our findings stress the need for better integration of information systems.


Matrix systems for siRNA delivery.
Over the last decade, considerable effort has been put in the implementation of RNA interference (RNAi) as a treatment for various disorders. As RNAi occurs in the cytoplasm of cells, it is imperative that RNAi mediators such as small interfering RNA (siRNA) cross several extracellular and intracellular barriers to reach this site of action. Among the extensive range of proposed delivery systems for siRNA, matrix systems possess interesting properties to promote the delivery of siRNA to a target tissue. In this review, a number of recently developed matrix and hybrid systems for siRNA delivery are discussed.


A Brief Shared Decision-Making Intervention for Acute Respiratory Infections on Antibiotic Dispensing Rates in Primary Care: A Cluster Randomized Trial.
To determine whether acute respiratory infection (ARI) decision aids and a general practitioner (GP) training package reduces antibiotic dispensing rate and improves GPs' knowledge of antibiotic benefit-harm evidence. A cluster randomized trial of 27 Australian general practices (13 intervention, 14 control) involving 122 GPs. Intervention group GPs were given brief decision aids for 3 ARIs (acute otitis media, acute sore throat, acute bronchitis) and video-delivered training. Primary outcome was dispensing rate of target antibiotic classes (routinely used for ARIs), extracted for 12 months before, and following, randomization. Secondary outcomes were GPs' knowledge of antibiotic benefit-harm evidence; prescribing influences; acceptability, usefulness, and self-reported resource use; and dispensing rate of all antibiotics. The baseline mean dispensing rate of ARI-related antibiotics was 3.5% (intervention GPs) and 3.2% (control GPs) of consultations. After 12 months, mean rates decreased (to 2.9% intervention; 2.6% control): an 18% relative reduction from baseline but similar in both groups (rate ratio 1.01; 95% CI, 0.89-1.15). Greater increases in knowledge were seen in the intervention group than control; a significant increase (average 3.6; 95% CI, 2.4-4.7, P <.001) in the number of correct responses to the 22 knowledge questions. There were no between-group differences for other secondary outcomes. The intervention was well received, perceived as useful, and reported as used by about two-thirds of intervention GPs. A brief shared decision-making intervention provided to GPs did not reduce antibiotic dispensing more than usual care, although GPs' knowledge of relevant benefit-harm evidence increased significantly.


Imaging bodies, imagining relations: narratives of queer women and "assisted conception".
This article is based on ethnographic research conducted between 1998 and 2000 in British Columbia, Canada. In this article Luce brings together the narratives of queer women she interviewed about their experiences of trying to become parents with her own stories about doing the research. Both sets of stories explore the ways in which relationships between people are reproduced and represented through images of sexuality, reproduction, queerness, parents, and families. Shifting between telling about the tensions she experienced while doing ethnographic fieldwork and retelling women's stories about how their relationships to partners, fetuses, babies, and donors were perceived, the article draws attention to both political and methodological questions.


Common and Rare Variants Genetic Association Analysis of Circulating Neutrophil Extracellular Traps.
Neutrophils contribute to host defense through different mechanisms, including the formation of neutrophil extracellular traps (NETs). The genetic background and underlying mechanisms contributing to NET formation remain unclear. We performed a genome-wide association study (GWAS) and exome-sequencing analysis to identify common and rare genetic variants associated with plasma myeloperoxidase (MPO)-DNA complex levels, a biomarker for NETs, in the population-based Rotterdam Study cohort. GWAS was performed using haplotype reference consortium(HRC)-imputed genotypes of common variants in 3,514 individuals from the first and 2,076 individuals from the second cohort of the Rotterdam Study. We additionally performed exome-sequencing analysis in 960 individuals to investigate rare variants in candidate genes. The GWAS yielded suggestive associations (p-value < 5.0 × 10-6) of SNPs annotated to four genes. In the exome-sequencing analysis, a variant in TMPRSS13 gene was significantly associated with MPO-DNA complex levels (p-value < 3.06×10-8). Moreover, gene-based analysis showed ten genes (OR10H1, RP11-461L13.5, RP11-24B19.4, RP11-461L13.3, KHDRBS1, ZNF200, RP11-395I6.1, RP11-696P8.2, RGPD1, AC007036.5) to be associated with MPO-DNA complex levels (p-value between 4.48 × 10-9 and 1.05 × 10-6). Pathway analysis of the identified genes showed their involvement in cellular development, molecular transport, RNA trafficking, cell-to-cell signaling and interaction, cellular growth and proliferation. Cancer was the top disease linked to the NET-associated genes. In this first GWAS and exome-sequencing analysis of NETs levels, we found several genes that were associated with NETs. The precise mechanism of how these genes may contribute to neutrophil function or the formation of NETs remains unclear and should be further investigated in experimental studies.


[Hypophyseal-gonadal and hypophyseal-corticoadrenal system in healthy persons and in patients with ischemic heart disease aged 60-89 years].
Serum basal concentrations of testosterone, estradiol, and androstenedione, FSH, LH, prolactin, ACTH and cortisol were studied in healthy persons, CHD patients aged 60-89, and in healthy persons aged 20-35 (controls). In some persons of each group a study was made of changes in the concentration of blood prolactin. ACTH, cortisol and urinary excretion of free cortisol as a result of bicycle ergometry exercise testing (submaximum in healthy persons and threshold in patients). A conclusion was made that "endocrinological age" of these hormonal systems in CHD patients aged 60-89 was older than in healthy persons of similar age, and hormonal imbalance continued to be a risk factor at late stages of life.


[Hamartoma of the bile duct. Report of a case].
Gallstones and neoplasms generally cause obstructions in the biliary duct. There are some infrequent problems that may lead to obstructions, such as hamartomas of the biliary duct. A 34-year-old diabetic female patient begins with abdominal pain and jaundice. The diagnostic approach initiated with hepatobiliary ultrasound that reported cholelithiasis and enlargement of the biliary ducts. Cholangiopancreatography was subsequently performed and a biliary tree lesion was discovered; the patient underwent cholecystectomy with exploration of the biliary ducts. Clinical evolution was satisfactory. Pathologic findings indicated hamartoma of the biliary duct.


Specific antibodies in oral immunotherapy for cow's milk allergy: kinetics and prediction of clinical outcome.
METHODS for predicting the clinical outcome of specific oral immunotherapy (OIT) would improve the safety of the therapy. We investigated 40 children aged 6-17 years with IgE-mediated cow's milk allergy (CMA) who either successfully completed OIT (n = 32) or discontinued the therapy due to adverse reactions (n = 8). From sera drawn before and after OIT, we analyzed specific IgA, IgG, IgG1 and IgG4 to cow's milk (CM), casein, β-lactoglobulin and ovalbumin (with enzyme-linked immunosorbent assay) and IgE to CM and hen's egg white [with enzymatic fluoroimmunoassay (Phadia ThermoFisher Scientific CAP system)]. As a reference, we also analyzed serum samples from 8- to 9-year-old children who either had no history of CMA (n = 76) or who had spontaneously recovered from IgE-mediated CMA (n = 56). Levels of specific IgA, IgG, IgG1 and IgG4 to CM and casein, and CM-specific IgE prior to OIT were higher in children who discontinued the therapy than in those who achieved desensitization (p < 0.05). Adverse reactions in the entire population were associated with low IgG and IgG4, but high IgG1 levels to ovalbumin (p < 0.05). Specific IgA, IgG, IgG1 and IgG4 to CM proteins significantly increased and IgE to CM decreased during OIT in children who achieved desensitization (p < 0.01). In those who discontinued OIT, only IgG, IgG1 and IgG4 to CM increased significantly (p < 0.03) and CM IgE remained unchanged. High specific IgE, IgA and IgG-class antibodies to CM proteins appear to predict failure to achieve desensitization in CM OIT. Specific IgA and IgG-class antibodies to CM increase and CM IgE decreases during desensitization.


Towards the development of a comprehensive framework: Qualitative systematic survey of definitions of clinical research quality.
To systematically survey existing definitions, concepts, and criteria of clinical research quality, both developed by stakeholder groups as well as in the medical literature. This study serves as a first step in the development of a comprehensive framework for the quality of clinical research. We systematically and in duplicate searched definitions, concepts and criteria of clinical research quality on websites of stakeholders in clinical research until no further insights emerged and in MEDLINE up to February 2015. Stakeholders included governmental bodies, regulatory agencies, the pharmaceutical industry, academic and commercial contract research organizations, initiatives, research ethics committees, patient organizations and funding agencies from 13 countries. Data synthesis involved descriptive and qualitative analyses following the Framework Method on definitions, concepts, and criteria of clinical research quality. Descriptive codes were applied and grouped into clusters to identify common and stakeholder-specific quality themes. Stakeholder concepts on how to assure quality throughout study conduct or articles on quality assessment tools were common, generally with no a priori definition of the term quality itself. We identified a total of 20 explicit definitions of clinical research quality including varying quality dimensions and focusing on different stages in the clinical research process. Encountered quality dimensions include ethical conduct, patient safety/rights/priorities, internal validity, precision of results, generalizability or external validity, scientific and societal relevance, transparency and accessibility of information, research infrastructure and sustainability. None of the definitions appeared to be comprehensive either in terms of quality dimensions, research stages, or stakeholder perspectives. Clinical research quality is often discussed but rarely defined. A framework defining clinical research quality across stakeholders' individual perspectives is desirable to facilitate discussion, assessment, and improvement of quality at all stages of clinical research.


Substance use disorder in adolescence: a review for the pediatric dentist.
Substance use during puberty has become a serious public health issue with significant morbidity and mortality in many countries. Approximately half of American youth have tried an illicit substance by the time they graduate from high school. Drug addiction is defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use. Substance use disorders are maladaptive patterns of use accompanied by clinically significant impairment or distress, causing reduced functioning in major areas of life, risk-taking behavior, exposure to hazardous situations, and an increase in the likelihood of legal problems due to possession. In 2008, there was an annual prevalence of drug use of approximately 7% for eighth graders, 11% for 10th graders, and 18% for 12th graders. The pediatric dentist is in a good position to help prevent and detect suspicious cases of substance use because of the age of patients seen in the pediatric dental practice as well as the many behavioral and oral aspects present in adolescents who use illicit substances.


HistoneHits: a database for histone mutations and their phenotypes.
Histones are the basic protein components of nucleosomes. They are among the most conserved proteins and are subject to a plethora of post-translational modifications. Specific histone residues are important in establishing chromatin structure, regulating gene expression and silencing, and responding to DNA damage. Here we present HistoneHits, a database of phenotypes for systematic collections of histone mutants. This database combines assay results (phenotypes) with information about sequences, structures, post-translational modifications, and evolutionary conservation. The web interface presents the information through dynamic tables and figures. It calculates the availability of data for specific mutants and for nucleosome surfaces. The database currently includes 42 assays on 677 mutants multiply covering 405 of the 498 residues across yeast histones H3, H4, H2A, and H2B. We also provide an interface with an extensible controlled vocabulary for research groups to submit new data. Preliminary analyses confirm that mutations at highly conserved residues and modifiable residues are more likely to generate phenotypes. Buried residues and residues on the lateral surface tend to generate more phenotypes, while tail residues generate significantly fewer phenotypes than other residues. Yeast mutants are cross referenced with known human histone variants, identifying a position where a yeast mutant causes loss of ribosomal silencing and a human variant increases breast cancer susceptibility. All data sets are freely available for download.


Achieving Benchmark Results for Neonatal Palliation of Hypoplastic Left Heart Syndrome and Related Anomalies in an Emerging Program.
Results of surgical management of hypoplastic left heart syndrome (HLHS) and related anomalies are often compared to published benchmark data which reflect the use of a variety of surgical and hybrid protocols. We report encouraging results achieved in an emerging program, despite a learning curve at all care levels. Rather than relying on a single preferred protocol, surgical management was based on matching surgical strategy to individual patient factors. From 2010 to 2014, a total of 47 consecutive patients with HLHS or related anomalies with ductal-dependent systemic circulation underwent initial surgical palliation, including 30 Norwood stage I, 8 hybrid stage I, and 9 salvage-to-Norwood procedures. True hybrid procedures entailed bilateral pulmonary artery banding and ductal stenting. In the salvage-to-Norwood strategy, ductal stenting was withheld in favor of continued prostaglandin infusion in anticipation of a deferred Norwood procedure. Cardiac comorbidities (obstructed pulmonary venous return, poor ventricular function, and atrioventricular valve regurgitation) and noncardiac comorbidities influenced the choice of treatment strategies and were analyzed as potential risk factors for extracorporeal membrane oxygenation (ECMO) support or in-hospital mortality. Overall hospital survival was 81% (Norwood 83.3%, hybrid 88%, "salvage" 67%; P = .4942). Extracorporeal membrane oxygenation support was used for eight (17%) patients with two survivors. For cases with obstructed pulmonary venous return (n = 10, 21%), management choices favored a hybrid or salvage strategy (P = .0026). Aortic atresia (n = 22, 47%) was treated by a Norwood or salvage-to-Norwood. No cardiac, noncardiac, or genetic comorbidities were identified as independent risk factors for ECMO or discharge mortality in a multivariable analysis. Our emerging program achieved outcomes that compare favorably to published benchmark data with respect to hospital survival. These results reflect rigorous interdisciplinary teamwork and a flexible approach to surgical palliation based on matching surgical strategy to patient factors. With major associated cardiac/noncardiac comorbidity and antegrade coronary flow, a true hybrid with ductal stenting was our preferred strategy. For high-risk situations such as aortic atresia with obstructed pulmonary venous return, the salvage hybrid-bridge-to-Norwood strategy may help achieve survival albeit with increased resource utilization.


Treatment of malignant gliomas in the elderly.
The benefit of standard treatment of malignant glioma in older patients is debated. In order to assess the effect of a combination of surgery, radiotherapy and chemotherapy on survival of elderly patients with high grade gliomas, 30 consecutive patients older than 70 years with malignant supratentorial gliomas were studied between 9/93 and 9/96. Median age was 73 years (70-79). The mean Karnofsky performance status (KPS) was 66 (30-100). Patients underwent maximum possible surgery, followed by a course of radiotherapy (45 Gy/25 fractions/5 weeks) with 3 or 4 orthogonal beams and a 2 cm margin around the tumor bed. The administration of chemotherapy was left at the discretion of the responsible physician and 12 patients received reduced dose nitrosourea-based chemotherapy. The overall median survival was 36 weeks. The median time to progression was 26 weeks. Three months after surgery, 26 patients were alive, 5 were in complete response, 2 in partial response and 10 were stabilized. Preradiotherapy KPS was the only significant prognostic factor with a median survival of 40 weeks in patients with KPS > or = 70 and 25 weeks when KPS was < 70 (logrank test, p = 0.05). In responding and stable patients (57% of the group) the median KPS was 68 and 66 at 1 and 3 months after the completion of radiotherapy. There was no case of radiotherapy-induced dementia with this regimen. Four out of 12 patients who received chemotherapy, experienced WHO grade 3/4 hematotoxicity. This study suggest that some patients older than 70 years with KPS > or = 70 may benefit from the treatment of malignant gliomas with surgery followed by reduced dose of limited field radiotherapy. Further studies are needed to define the most appropriate dose of radiotherapy and to evaluate further the risk/benefit ratio of a reduced dose chemotherapy in this population.


Characteristics and outcomes of critically-ill medical patients admitted to a tertiary medical center with restricted ICU bed capacity.
In the emergency department (ED) critically-ill medical patients are treated in the resuscitation room (RR). No studies described the outcomes of critically-ill RR patients admitted to a hospital with low capacity of intensive care unit (ICU) beds. We included all medical patients above 18 who were admitted to a RR of a tertiary hospital during 2011-2012. We conducted multivariate logistic and Cox regressions and propensity score (PS) matched analysis to analyze parameters associated with the study outcomes. In-hospital mortality rate was 32.4% in ICU admitted patients compared to 52.0% of the non-ICU critically-ill patients (p<0.001). Age above 80, female and recent ED encounters were associated with non-ICU admissions (p<0.05 for all). ICU admission had a statistically significant effect on in-hospital mortality in PS matched analysis (OR 0.36, 95% CI 0.21-0.61). A marginal effect was evident in one-year survival in PS matched landmark analysis (HR 0.50 95% CI 0.23-1.06). ED critically-ill medical patients who were treated in the RR had high mortality rates in an institute with restricted ICU beds availability. However, those who were admitted to an ICU showed prolonged short and perhaps long term survival compared to those who were not.


Ventilator-associated pneumonia after pediatric cardiac surgery in southern Taiwan.
To determine the frequency, risk factors, associated pathogens, and outcomes of ventilator-associated pneumonia (VAP) after pediatric cardiac surgery. This was a retrospective review of the medical records of patients younger than 18 years with congenital heart disease (CHD) who underwent cardiac surgery from January 2005 to December 2007. Patients were categorized into 2 groups: with and without VAP. Of 100 patients, 13% acquired VAP. Most patients (85%) who developed VAP were infants younger than 1 year. Patients with complex CHD were more likely to develop VAP than patients with simple CHD (chi(2) = 7.69; p < 0.03). Two independent and modifiable risk factors were identified: prolonged use of mechanical ventilation (adjusted odds ratio [AOR], 15.196; 95% confidence interval [CI], 2.158-107.2) and prolonged use of a central venous catheter (AOR, 7.342; 95% CI, 1.054-51.140). The cardiopulmonary bypass time and duration of chest tube drainage were not risk factors. The development of VAP increased pediatric intensive care unit duration of stay (p < 0.006), duration of hospital stay (p < 0.001), and mortality rate (p < 0.001). Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus were the most common pathogens isolated from endotracheal aspirate. VAP is common after congenital heart surgery. Physicians must pay special attention to infants with complex CHD because they are at high risk for the development of VAP after congenital heart surgery. Shortening the duration of mechanical ventilation and central venous catheter placement are critical factors for reducing the risk for VAP.


Borderline personality disorder classification based on brain network measures during emotion regulation.
Borderline Personality Disorder (BPD) is characterized by an increased emotional sensitivity and dysfunctional capacity to regulate emotions. While amygdala and prefrontal cortex interactions are regarded as the critical neural mechanisms underlying these problems, the empirical evidence hereof is inconsistent. In the current study, we aimed to systematically test different properties of brain connectivity and evaluate the predictive power to detect borderline personality disorder. Patients with borderline personality disorder (n = 51), cluster C personality disorder (n = 26) and non-patient controls (n = 44), performed an fMRI emotion regulation task. Brain network analyses focused on two properties of task-related connectivity: phasic refers to task-event dependent changes in connectivity, while tonic was defined as task-stable background connectivity. Three different network measures were estimated (strength, local efficiency, and participation coefficient) and entered as separate models in a nested cross-validated linear support vector machine classification analysis. Borderline personality disorder vs. non-patient controls classification showed a balanced accuracy of 55%, which was not significant under a permutation null-model, p = 0.23. Exploratory analyses did indicate that the tonic strength model was the highest performing model (balanced accuracy 62%), and the amygdala was one of the most important features. Despite being one of the largest data-sets in the field of BPD fMRI research, the sample size may have been limited for this type of classification analysis. The results and analytic procedures do provide starting points for future research, focusing on network measures of tonic connectivity, and potentially focusing on subgroups of BPD.


Persistence of Enterococcus faecalis in aquatic environments via surface interactions with copepods.
Several human pathogens and fecal-pollution indicators may persist as viable organisms in natural environments, owing to their ability to activate different types of survival strategies. These strategies include adhesion on both abiotic and biotic surfaces and the entrance to the so-called viable but nonculturable (VBNC) state. In an 18-month survey for the detection of enterococci in both lake water and seawater, C. Signoretto et al. (Appl. Environ. Microbiol. 70:6892-6896, 2004) have shown that Enterococcus faecalis was detected mostly bound to plankton and in the VBNC state. In the present study, we show that in vitro adhesion of E. faecalis to copepods accelerated the entry of cells into the VBNC state relative to that of planktonic bacteria. VBNC E. faecalis cells maintained their adhesive properties to copepods and chitin (the main component of the copepod carapace), though to a reduced extent in comparison with growing cells. Sugar competition experiments showed interference with adhesion to both copepods and chitin by GlcNAc and only to copepods by D-mannose. Four enterococcal cell wall proteins present in both growing and VBNC cells and lipoteichoic acid were shown to be capable of binding chitin. The results indicate that copepods may represent an additional environmental reservoir of enterococci, thus suggesting the advisability of redesigning the protocols currently used for microbial detection during the evaluation of the microbiological quality of environmental samples.


Making Waves in the Brain: What Are Oscillations, and Why Modulating Them Makes Sense for Brain Injury.
Traumatic brain injury (TBI) can result in persistent cognitive, behavioral and emotional deficits. However, the vast majority of patients are not chronically hospitalized; rather they have to manage their disabilities once they are discharged to home. Promoting recovery to pre-injury level is important from a patient care as well as a societal perspective. Electrical neuromodulation is one approach that has shown promise in alleviating symptoms associated with neurological disorders such as in Parkinson's disease (PD) and epilepsy. Consistent with this perspective, both animal and clinical studies have revealed that TBI alters physiological oscillatory rhythms. More recently several studies demonstrated that low frequency stimulation improves cognitive outcome in models of TBI. Specifically, stimulation of the septohippocampal circuit in the theta frequency entrained oscillations and improved spatial learning following TBI. In order to evaluate the potential of electrical deep brain stimulation for clinical translation we review the basic neurophysiology of oscillations, their role in cognition and how they are changed post-TBI. Furthermore, we highlight several factors for future pre-clinical and clinical studies to consider, with the hope that it will promote a hypothesis driven approach to subsequent experimental designs and ultimately successful translation to improve outcome in patients with TBI.


A fully Bayesian application of the Copas selection model for publication bias extended to network meta-analysis.
The Copas parametric model is aimed at exploring the potential impact of publication bias via sensitivity analysis, by making assumptions regarding the probability of publication of individual studies related to the standard error of their effect sizes. Reviewers often have prior assumptions about the extent of selection in the set of studies included in a meta-analysis. However, a Bayesian implementation of the Copas model has not been studied yet. We aim to present a Bayesian selection model for publication bias and to extend it to the case of network meta-analysis where each treatment is compared either with placebo or with a reference treatment creating a star-shaped network. We take advantage of the greater flexibility offered in the Bayesian context to incorporate in the model prior information on the extent and strength of selection. To derive prior distributions, we use both external data and an elicitation process of expert opinion.


Evaluation of the effects of stress in cats with idiopathic cystitis.
To determine the effects of stress in cats with feline idiopathic cystitis (FIC) by evaluating bladder permeability, sympathetic nervous system function, and urine cortisol:creatinine (C:Cr) ratios during periods of stress and after environmental enrichment. Prospective study. 13 cats with FIC and 12 healthy cats. Cats subjected to an acute-onset moderate stressor for 8 days received IV injections of fluorescein. Serum fluorescein concentrations were determined and compared with those of controls to evaluate bladder permeability, and urine C:Cr ratios were compared to evaluate function of the hypothalamic-pituitary-adrenal (HPA) axis. Plasma catecholamine concentrations were analyzed in a subset of cats. After 8 days of moderate stress, cats were moved to an enriched environment, and tests were repeated after 21 days. Serum fluorescein concentrations were significantly higher in cats with FIC at all time points. In the cats in which plasma catecholamine concentrations were determined, concentrations of dihydroxyphenylalanine, norepinephrine, and dihyroxyphenylglycol were significantly higher in cats with FIC at all time points, whereas no differences in urine C:Cr ratio between groups were observed. Cats with FIC appeared to have altered bladder permeability, most notably during the period of initial stress. The increase in plasma dihydroxyphenylalanine concentration suggests that there may be stress-induced increase in the activity of tyrosine hydroxylase, which catalyzes the rate-limiting step in catecholamine synthesis. In contrast, no effects of stress on C:Cr ratios were observed, which suggests there was dissociation between the sympathetic nervous system and HPA-axis responses to stress.


The rising global burden of diabetes and its complications: estimates and projections to the year 2010.
Prevention and control programmes are needed to stem the rising epidemic of diabetes and its complications. However, these will not occur unless governments and public health planners are aware of the potential problem. Using published prevalence rates for NIDDM in different populations, and the current and projected age distributions, worldwide prevalence of NIDDM was estimated for 1995 and 1997, and well as projections for 2000 and 2010. Prevalence rates used for projections were chosen to reflect changes in lifestyle with economic development. The global prevalence of IDDM was estimated using published incidence rates and population figures, incorporating the likely survival time from development of IDDM. Data on diabetes complications are also summarised but no attempt has been made to extrapolate to a global estimated. In 1997, an estimated 124 million people worldwide have diabetes, 97% of these having NIDDM. By the year 2010 the total number of people with diabetes is projected to reach 221 million. The regions with the greatest potential increases are Asia and Africa, where diabetes rates could rise to 2 or 3 times those experienced today. With improvements in the treatment of IDDM, the prevalence of this form of diabetes is likely to increase as more people survive for longer after diagnosis. Increases in complications will undoubtedly follow increasing prevalence of diabetes, but population-based studies using standardised methods of diagnosis are required before reliable estimates of the extent of the problem can be made. It is hoped that the information provided in this report, and others like it, will act as an incentive to initiate or improve local diabetes monitoring and prevention strategies.


Glomerular filtration rate estimation using cystatin C alone or combined with creatinine as a confirmatory test.
Glomerular filtration rate (GFR) estimating equations using the combination of creatinine and cystatin C (eGFRcr-cys) are more accurate than equations using either alone (eGFRcr or eGFRcys). New guidelines suggest measuring cystatin C as a confirmatory test when eGFRcr may be inaccurate, but do not specify demographic or clinical conditions in which eGFRcys or eGFRcr-cys are more accurate than eGFRcr nor which estimate to use in such circumstances. We compared the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 1119 subjects in the CKD-EPI cystatin C external validation dataset. Subgroups were defined by eGFRcr, age, sex, diabetes status and body mass index (BMI). The reference test was GFR measured using urinary or plasma clearance of exogenous filtration markers. Cystatin C and creatinine assays were traceable to primary reference materials. Accuracy was defined as the absolute difference in eGFR compared with mGFR. The mean mGFR was 70 ± 41 (SD) mL/min/1.73 m(2). eGFRcys was more accurate than eGFRcr at lower BMI and less accurate at higher BMI, especially at higher levels of eGFRcr. There were small differences in accuracy in people according to the diabetes status. eGFRcr-cys was as accurate or more accurate than eGFRcr or eGFRcys in these and all other subgroups. eGFRcr-cys, but not eGFRcys, is more accurate than eGFRcr in most subgroups we studied, suggesting preferential use of eGFRcr-cys when serum cystatin C is measured as a confirmatory test to obtain more accurate eGFR. Further studies are necessary to evaluate diagnostic strategies for using eGFRcys and eGFRcr-cys.


Interleukin-10 down-regulates voltage gated sodium channels in rat dorsal root ganglion neurons.
The over-expression of voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons following peripheral nerve injury contributes to neuropathic pain by generation of the ectopic discharges of action potentials. However, mechanisms underlying the change in VGSCs' expression are poorly understood. Our previous work has demonstrated that the pro-inflammatory cytokine TNF-α up-regulates VGSCs. In the present work we tested if anti-inflammatory cytokine IL-10, which had been proven to be effective for treating neuropathic pain, had the opposite effect. Western blot and immunofluorescence results showed that IL-10 receptor was localized in DRG neurons. Recombinant rat IL-10 (200 pg/ml) not only reduced the densities of TTX-sensitive and Nav1.8 currents in control DRG neurons, but also reversed the increase of the sodium currents induced by rat recombinant TNF-α (100 pg/ml), as revealed by patch-clamp recordings. Consistent with the electrophysiological results, real-time PCR and western blot revealed that IL-10 (200 pg/ml) down-regulated VGSCs in both mRNA and protein levels and reversed the up-regulation of VGSCs by TNF-α. Moreover, repetitive intrathecal administration of rrIL-10 for 3 days (4 times per day) attenuated mechanical allodynia in L5 spinal nerve ligation model and profoundly inhibited the excitability of DRG neurons. These results suggested that the down-regulation of the sodium channels in DRG neurons might contribute to the therapeutic effect of IL-10 on neuropathic pain.


[Charcot-Marie-Tooth disease. Study of sural nerve biopsy in 41 patients].
We studied the pathological findings of sural nerve biopsy in 41 patients with Charcot-Marie-Tooth (CMT) disease. They were previously classified by the median motor conduction velocity (MCV) in two types. Type I (demyelinating) with 9 patients and type II (axonal) with 32 cases. In type I we found loss of myelinated fibers (unimodal histogram), demyelinated and remyelinated axons with numerous onion bulb formations. In one case there was thickness of myelin with thin axons (axonal atrophy). In type II there were seven patients with normal sural nerve biopsy. In 25 cases there were mild to severe loss of myelinated fibers. In 5 patients the number of myelinated fibers was increased due to the great regeneration of the axons. The electron microscopic studies in type II showed in a few cases small onion bulbs and in one case axonal atrophy. In type I there was no correlation between clinical severity and the loss of myelinated fibers, but there was relationship between the low MCV and the intensity of myelinated fibers. In type II we did not found any correlation between clinical course, MCV and pathological findings.


Intimate partner violence and HIV risk among urban minority women in primary health care settings.
This study describes the associations between intimate partner violence (IPV) and HIV risk among urban, predominantly minority women. Interviews were conducted with 1,590 women, predominantly African American and Latina, attending hospital-based health care clinics. Approximately 1 in 5 women reported experiencing IPV in their current primary heterosexual relationships; about 1 in 8 women reported experiencing IPV in the preceding 6 months. Compared to women who reported no IPV in their primary relationships, women reporting past or current IPV perpetrated by their primary partners were more likely to report having multiple sexual partners, a past or current sexually transmitted infection (STI), inconsistent use or nonuse of condoms, and a partner with known HIV risk factors. These findings indicate that urban minority women experiencing IPV are at elevated risk for HIV infection, results that carry important implications in the efforts to improve HIV and IPV risk assessment protocols and intervention/prevention strategies for women in primary health care settings.


Turbulence phase space in simple magnetized toroidal plasmas.
Plasma turbulence in a simple magnetized torus (SMT) is explored for the first time with three-dimensional global fluid simulations. Three turbulence regimes are described: an ideal interchange mode regime, a previously undiscovered resistive interchange mode regime, and a drift-wave regime. As the pitch of the field lines is decreased, the simulations exhibit a transition from the first regime to the second, while the third--the drift-wave regime--is likely accessible to the experiments only at very low collisionalities.


Models of Shear-Induced Platelet Activation and Numerical Implementation With Computational Fluid Dynamics Approaches.
Shear-induced platelet activation is one of the critical outcomes when blood is exposed to elevated shear stress. Excessively activated platelets in the circulation can lead to thrombus formation and platelet consumption, resulting in serious adverse events such as thromboembolism and bleeding. While experimental observations reveal that it is related to the shear stress level and exposure time, the underlying mechanism of shear-induced platelet activation is not fully understood. Various models have been proposed to relate shear stress levels to platelet activation, yet most are modified from the empirically calibrated power-law model. Newly developed multiscale platelet models are tested as a promising approach to capture a single platelet's dynamic shape during activation, but it would be computationally expensive to employ it for a large-scale analysis. This paper summarizes the current numerical models used to study the shear-induced platelet activation and their computational applications in the risk assessment of a particular flow pattern and clot formation prediction.


Purification and properties of a cephalosporinase from Enterobacter cloacae.
A cephalosporin beta-lactamase (cephalosporinase) was extracted from Enterobacter cloacae GN7471 and purified by means of column chromatography. The resulting preparation gave a single protein band upon polyacrylamide gel electrophoresis. The enzyme's isoelectric point was 8.4, and its molecular weight was 44,000. The optimal pH was 8.5, and the optimal temperature was 40 degrees C. The enzyme hydrolyzed cephalosporins much more readily than penicillins. The enzyme activity was inhibited by iodine, semisynthetic penicillins, cefuroxime-type cephalosporins, and cephamycin derivatives. The enzymological properties of the purified enzyme were compared with those of beta-lactamases derived from other gram-negative enteric bacteria.


Laryngeal Mask Airway for neonatal resuscitation in a developing country: evaluation of an educational intervention. Neonatal LMA: an educational intervention in DRC.
Studies carried out in developing countries have indicated that training courses in newborn resuscitation are efficacious in teaching local birth attendants how to properly utilize simple resuscitation devices. The aim of this study was to assess the knowledge and expertise gained by physicians and midwifes who participated in a Neonatal Resuscitation Course and workshop organized in a Third World Country on the use of Laryngeal Mask Airway (LMA). A 28-item questionnaire, derived from the standard test contained in the American Heart Association and the American Academy of Pediatrics Neonatal Resuscitation Manual, was administered to 21 physicians and 7 midwifes before and after a course, which included a practical, hands-on workshop focusing on LMA positioning and bag-ventilation in a neonatal manikin. The knowledge gained by the physicians was superior to that demonstrated by the midwifes. The physicians, in fact, demonstrated a significant improvement with respect to their pre-course knowledge. Both the physicians and the midwives showed a good level of expertise in manipulating the manipulating the manikin during the practical trial session. The midwifes and physicians almost unanimously manifested a high degree of approval of neonatal resuscitation by LMA, as they defined it a sustainable and cost-effective method requiring minimal expertise. Further studies are warranted to test the advantages and limits of the neonatal LMA training courses in developing countries.


CEBPG Exhibits Allele-Specific Expression in Human Bronchial Epithelial Cells.
Inter-individual variation in CCAAT/enhancer binding protein gamma (CEBPG) transcript expression in normal human bronchial epithelial cells (NBEC) is associated with predisposition to lung cancer. We hypothesize that this inter-individual variation is in part explained by cis-acting genetic variation in CEBPG. To test this hypothesis we measured transcript expression derived from each parental copy of CEBPG (ie, allele-specific expression; ASE). There was a significant 2.9-fold higher cell cycle-specific variation in ASE of CEBPG rs2772 A compared to C allele (P < 0.001). In 20% of NBEC samples, CEBPG rs2772 A allele was expressed on average 2.10 fold greater than rs2772 C allele. These data support the hypothesis that genetic variation in linkage disequilibrium with rs2772 influences regulation of CEBPG transcript expression through a trans-effect downstream of RNA polymerase II transcription and confirm that cis-acting genetic variation contributes to inter-individual variation in CEBPG transcript expression in NBEC, which is associated with variation in lung cancer risk.


Organization of the nigrothalamocortical system in the rhesus monkey.
The nigrothalamocortical connections and their topography were analyzed by autoradiography and double or triple retrograde labeling with the fluorescent dyes Fast Blue, Diamidino Yellow, and Propidium Iodide. Injections of tritiated leucine into different parts of the substantia nigra (SN) revealed that the medial SN projects to the medial magnocellular subdivisions of the ventral anterior (VAmc) and mediodorsal (MDmc) nuclei of the thalamus while the lateral SN projects to the more lateral and more posterior part of the VAmc, and the paralaminar, parvicellular, and densocellular subdivisions of the mediodorsal nucleus (MDmf, MDpc, and MDdc). With the exception of the MDmf, terminal areas observed in the mediodorsal nucleus were in the form of scattered clusters of grains. Analysis of the thalamus in cases with fluorescent dye injections into the lateral orbital gyrus (Walker's area 11), principal sulcus (area 46), anterior bank of the arcuate gyrus (areas 8 and 45), supplementary motor area (area 6), and motor cortex (area 4) revealed topographic organization of the nigrothalamocortical projection system. The parts of the VAmc and MDmc which receive afferents from the medial part of the SN in turn project to the most anterior regions of the frontal lobe including principal sulcus and orbital cortex. The lateral posterior VAmc, MDmf, MDpc, and MDdc, all of which receive afferents from the lateral part of the SN; project to more posterior regions of the frontal lobe including, in addition to the principal sulcus, the frontal eye field and also areas of the premotor cortex. These findings indicate that the SN has preferential targets in the thalamus and cerebral cortex which are segregated from those of the globus pallidus and cerebellum. Whereas the motor cortex is the primary target of cerebellar output (Asanuma et al., '83b), and the premotor cortex is the target of pallidal output (Schell and Strick, '84), the SN output appears to be directed more anteriorally--to the prefrontal cortex.


Seminar: Extracellular Vesicles as Mediators of Environmental Stress in Human Disease.
Extracellular vesicles (EVs), membrane-bound particles containing a variety of RNA types, DNA, proteins, and other macromolecules, are now appreciated as an important means of communication between cells and tissues, both in normal cellular physiology and as a potential indicator of cellular stress, environmental exposures, and early disease pathogenesis. Extracellular signaling through EVs is a growing field of research for understanding fundamental mechanisms of health and disease and for the potential for biomarker discovery and therapy development. EVs are also known to play important roles in mediating the effects of exposure to environmental stress. This seminar addresses the application of new tools and approaches for EV research, developed in part through the National Institutes of Health (NIH) Extracellular RNA Communication Program, and reflects presentations and discussions from a workshop held 27-28 September 2021 by the National Institute of Environmental Health Sciences (NIEHS) and the National Center for Advancing Translational Sciences (NCATS) on "Extracellular Vesicles, Exosomes, and Cell-Cell Signaling in Response to Environmental Stress." The panel of experts discussed current research on EVs and environmental exposures, highlighted recent advances in EV isolation and characterization, and considered research gaps and opportunities toward identifying and characterizing the roles for EVs in environmentally related diseases, as well as the current challenges and opportunities in this field. The authors discuss the application of new experimental models, particularly organ-on-chip (OOC) systems and in vitro approaches and how these have the potential to extend findings in population-based studies of EVs in exposure-related diseases. Given the complex challenges of identifying cell-specific EVs related to environmental exposures, as well as the general heterogeneity and variability in EVs in blood and other accessible biological samples, there is a critical need for rigorous reporting of experimental methods and validation studies. The authors note that these efforts, combined with cross-disciplinary approaches, would ensure that future research efforts in environmental health studies on EV biomarkers are rigorous and reproducible. https://doi.org/10.1289/EHP12980.


Synthesis of dinucleoside phosphorodithioates from nucleoside phosphonodithioates.
The conversion, in good yield, of 5'-O-(9-phenylxanthen-9-yl) thymidine (1) into the triethylammonium salt of its 3'-phosphonodithioate (2a) is described. The latter compound (2a) is converted into a dinucleoside phosphonothioate (4a), and thence into a corresponding dinucleoside phosphorodithioate (6a) and phosphorothioate (6;X = 0).


[Non-myeloablative stem cell transplant].
Myeloablation and immunosuppression were considered to be the two major roles of the conditioning regimens for allogeneic stem cell transplantation to facilitate engraftment. It has turned out, however, that immunosuppression is more important and myeloablation is not necessary for engraftment. At the same time, it is considered that the major anti-tumor effect of allogeneic stem cell transplantation depends on the graft-versus-leukemia effect, not on the conditioning regimen itself. In patients with CML who relapsed after allogeneic transplantation, for example, infusion of donor lymphocytes can induce a second complete remission. Non-myeloablative stem cell transplantation (NST) was developed in the late 90s based on these theories. Low-dose, less toxic, so-called "non-myeloablative" preparative regimens have been designed not to eradicate the malignancies, but to provide sufficient immunosuppression to allow donor cells to engraft, while the graft-versus-malignancy effects eradicate the tumor. This strategy permits allogeneic transplantation to be used in patients who are not eligible for conventional, often myeloablative, transplantation because of advanced age or organ dysfunction. Non-myeloablative preparative regimens contain purine analogs, such as fludarabine or cladribine. The NST regimen being used at the National Cancer Center Hospital, Tokyo, Japan, consists of cladribine (0.11 mg/kg x 6 days), busulfan (4 mg/kg x 2 days) and rabbit anti-thymocyte globulin (2.5 mg/kg x 4 days). We enrolled 6 patients in this NST protocol so far: 1 with severe aplastic anemia (sibling-PBSCT), 2 with MDS-RA (1 for sibling-PBSCT and 1 for matched uBMT), 1 with AML-CR2 (matched uBMT), 1 with AML-CR3 (sibling-PBSCT), and 1 with relapsed AML (mismatched related PBSCT). All patients achieved engraftment within 14 days with complete donor chimerism. In addition to leukemias, a graft-versus-malignancy effect was also reported in allogeneic NST of solid tumors, such as renal cell carcinoma and malignant melanoma. The long-term efficacy of NST remains to be determined, and further clinical trials are warranted.


Ultra-Early Angiographic Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.
After aneurysmal subarachnoid hemorrhage (aSAH), prognosis is affected heavily by the presence of delayed cerebral ischemia (DCI). There is growing recognition of ultra-early angiographic vasospasm (UEAV) occurring within 48 hours of aSAH; however, its relationship with DCI and ultimately prognosis remains unclear. Various databases limited to the English language through September 2016 were searched systematically. Eligible studies were those comparing UEAV with control non-UEAV outcomes and follow-up. Two independent reviewers evaluated the quality of studies and abstracted the data, with discrepancies resolved by a third. We calculated odds ratios (ORs) and 95% confidence intervals for all outcomes by using random-effects meta-analyses and performed a heterogeneity analysis. Four comparative studies were selected for analysis. Pooled analysis demonstrated that UEAV compared with no-UEAV was associated with greater proportion of rupture aneurysms sized greater than 12 mm (38.3% vs. 24.3%, P < 0.00001). A significantly greater number of patients with UEAV had ruptured MCA aneurysms compared with patients without UEAV (29.7% vs. 19.9%, P = 0.005). Compared with no-UEAV, patients with UEAV were significantly associated with symptomatic cerebral vasospasm (OR 2.07, P = 0.05) and DCI/infarction (OR 2.52, P = 0.02). A significant association also was found between UEAV and an unfavorable outcome at follow-up (OR 1.64, P = 0.03) and greater mortality (OR 2.65, P < 0.00001). UEAV was significantly associated with symptomatic cerebral vasospasm, DCI/infarction, unfavorable outcome at follow-up, and greater mortality. Patients with intracerebral hematoma, intraventricular hemorrhage (Fisher Grade IV), larger ruptured aneurysms >12 mm, and an MCA location were more likely to have UEAV.


p16(INK4a) protects against dysfunctional telomere-induced ATR-dependent DNA damage responses.
Dysfunctional telomeres limit cellular proliferative capacity by activating the p53-p21- and p16(INK4a)-Rb-dependent DNA damage responses (DDRs). The p16(INK4a) tumor suppressor accumulates in aging tissues, is a biomarker for cellular senescence, and limits stem cell function in vivo. While the activation of a p53-dependent DDR by dysfunctional telomeres has been well documented in human cells and mouse models, the role for p16(INK4a) in response to telomere dysfunction remains unclear. Here, we generated protection of telomeres 1b p16-/- mice (Pot1bΔ/Δ;p16-/-) to address the function of p16(INK4a) in the setting of telomere dysfunction in vivo. We found that deletion of p16(INK4a) accelerated organ impairment and observed functional defects in highly proliferative organs, including the hematopoietic system, small intestine, and testes. Pot1bΔ/Δ;p16-/- hematopoietic cells exhibited increased telomere loss, increased chromosomal fusions, and telomere replication defects. p16(INK4a) deletion enhanced the activation of the ATR-dependent DDR in Pot1bΔ/Δ hematopoietic cells, leading to p53 stabilization, increased p21-dependent cell cycle arrest, and elevated p53-dependent apoptosis. In contrast to p16(INK4a), deletion of p21 did not activate ATR, rescued proliferative defects in Pot1bΔ/Δ hematopoietic cells, and significantly increased organismal lifespan. Our results provide experimental evidence that p16(INK4a) exerts protective functions in proliferative cells bearing dysfunctional telomeres.


[Surgery without donor's blood].
Complex program "Surgery without blood" was developed and introduced into a broad clinical practice. The main elements of this program are stimulation of erythropoesis, preparing in autoserum and autoblood before surgery with acute normovolemic hemodilution method, precise surgical technique, reinfusion of blood from wound and drainages, adequate anesthesia and correction of hemostasis system. This program permits one to minimize infusion of donor's blood components (DBC) in elective surgery (cardiosurgery, orthopedic surgery, neurosurgery, oncology, general surgery) and reduce significantly transfusion of DBC in urgent surgery. Rejection of DBC transfusion decreases number of postoperative complications and hospital stay, improves results of treatment and is cost-effective.


Risk of chronic ankle instability: A reliability study on radiographic assessment of the ankle joint geometry.
Chronic ankle instability (CAI) is a multifactorial disabling condition. Ideally all factors contributing to CAI are identified and implemented in a risk assessment model. However, they need to meet strict reliability requirements. To assess usability of radiographic factors for this risk assessment model and future clinical practice, the objective of the current study was to assess the intra and inter observer reliability of three radiographic measurements. The radiographs of 39 consecutive patients, at least 16years, who visited the Emergency Department after sustaining a lateral ankle sprain (LAS), were assessed by four observers. The radiographic measurements included absolute and relative ankle alignment, sagittal fibular position and ankle joint congruency (talar radius and height, and tibiotalar sector), performed twice by all observers independently. Reliability was assessed by calculating the Intraclass Correlation Coefficient (ICC) which was considered good when ICC>0.70. The intra observer reliability of the absolute and relative fibular position, and talar height were good to excellent, (ICC 0.84-0.98, 0.85-0.98, and 0.79-0.93, respectively). The talar radius (ICC 0.69-0.89) was moderate to good. The overall inter observer reliability was good for the absolute and relative fibular position, and talar radius (ICC 0.84, 0.86, and 0.79, respectively). Other measurements had ICC values of <0.70. In an effort to identify the multifactorial nature of CAI, both the fibular position and the talar radius measurements showed good observer reliability, and will be implemented in a future risk assessment models. The other measurements are too prone for measurement errors, for future reference. IV Case Series.


Dietary choline and betaine intake and risk of hypertension development: a 7.4-year follow-up.
The evidence for a linkage between dietary intake of choline and betaine, a choline metabolism product, and the risk of hypertension (HTN) is limited. The current population-based cohort study was designed to investigate the possible association between dietary intake of choline and betaine with the risk of HTN in adults. This cohort study was conducted on the participants of the Tehran Lipid and Glucose Study (TLGS). Dietary intake of choline and betaine was calculated using the United States Department of Agriculture (USDA) database. Hypertension was diagnosed as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or used drugs to treat hypotension. In this study, 2865 subjects participated and followed-up for a median of 7.4 years. During the follow-up period, 623 patients with hypertension (22.1%) were detected. Our results revealed per every 100 mg increased dietary intake of choline, the risk of developing HTN decreased by 16% (0.84; 95% CI: 0.74 to 0.96, P for trend = 0.009). No significant association was observed between habitual dietary intake of betaine and the risk of HTN (1.10; 95% CI: 0.88 to 1.38, P for trend = 0.21). After stratification based on age, sex, and BMI, each 100 mg per d increase in dietary choline decreased the risk of HTN occurrence in subjects younger than 55 years old by 17% (0.83; 95% CI: 0.71 to 0.96) and men by 21% (0.79; 95% CI: 0.66 to 0.95). The current study's findings provide further support to confirm the protective properties of choline and choline-rich foods against HTN.


Differential Allele-Specific Expression Uncovers Breast Cancer Genes Dysregulated by Cis Noncoding Mutations.
Identifying cancer-relevant mutations in noncoding regions is challenging due to the large numbers of such mutations, their low levels of recurrence, and difficulties in interpreting their functional impact. To uncover genes that are dysregulated due to somatic mutations in cis, we build upon the concept of differential allele-specific expression (ASE) and introduce methods to identify genes within an individual's cancer whose ASE differs from what is found in matched normal tissue. When applied to breast cancer tumor samples, our methods detect the known allele-specific effects of copy number variation and nonsense-mediated decay. Further, genes that are found to recurrently exhibit differential ASE across samples are cancer relevant. Genes with cis mutations are enriched for differential ASE, and we find 147 potentially functional noncoding mutations cis to genes that exhibit significant differential ASE. We conclude that differential ASE is a promising means for discovering gene dysregulation due to cis noncoding mutations.


Perspectives of community pharmacists in Pakistan about practice change and implementation of extended pharmacy services: a mixed method study.
Background Community pharmacists' role in the primary health care, patient-centered services, beyond traditional dispensing services is well established in the developed world. However, this role is not fully established in low-middle-income countries including Pakistan. Objective To explore community pharmacists' perspectives and preparedness about practice change and associated facilitators and barriers to extended services. Setting A study was conducted involving community pharmacists of Lahore, Pakistan. Method Two phased studies were conducted using mixed-method sequential design. The first phase involved qualitative semi-structured face-to-face interviews with the community pharmacists, while the second phase constituted a questionnaire-based cross-sectional study. Main outcome measure Pharmacists' perspectives about extended pharmacy services, facilitators, barriers and preparedness for the practice change. Results For the first phase, pharmacists were purposively sampled and the saturation yielded a final sample size of fifteen pharmacists (N = 15). The thematic content analysis yielded four distinct themes; (1) current practices and familiarity with extended pharmacy services (2) practice gap between Pakistan and the developed countries (3) facilitators and the preparedness, and (4) barriers towards its implementation and provision. The second part was a questionnaire-based cross-sectional phase, where a total of 348 community pharmacists were approached, while only 242 responded, yielding a response rate of 69.5%. The triangulation of qualitative and quantitative data identified several barriers such as; shortage of pharmacists, lack of knowledge and skills, poor collaboration with general practitioners, failure of customers to pay for extended services. Facilitators and preparedness for the provision of extended pharmacy services were; access to patient notes, follow-up, separate counselling areas, accreditation of specific services and sufficient resources. Conclusion This study's findings call for the implementation and enforcement of Punjab Drug Sale Rules 2007 to facilitate the practice change and provision of comprehensive pharmacy services in Punjab, Pakistan. There is a need for additional laws to define community pharmacists' roles, uniform job description, training, new funding model, separate area, and accreditation of extended pharmacy services in Pakistan.


Hibernation triggers and myocardial protection.
Hypothermic cardioplegia provides myocellular protection, yet postischemic dysfunction remains a significant problem. Interestingly, the subcellular changes in hibernation parallel the altered biology of induced cardiac ischemia but are well tolerated by hibernated mammalian myocardium. An uncharacterized factor derived from hibernating animals, hibernation induction trigger (HIT), has been shown to induce hibernation in active animals and afford myocardial protection after ischemia-reperfusion injury. Therefore, it was of interest to further characterize the cardioprotective effects of HIT in the setting of ischemia-reperfusion injury. To determine whether HIT could improve myocardial recovery after global ischemia, isolated rabbit hearts received either standard cardioplegia or HIT in the cardioplegia or underwent preperfusion with HIT before cardioplegia. Alternatively, to determine whether HIT requires metabolic alteration, additional rabbits had in vivo pretreatment with HIT from 15 minutes to 5 days before ischemia. All hearts underwent 2 hours of global ischemia at 34 degrees C. Recovery of postischemic isovolumic developed pressure, coronary flows, and MVO2 were compared. Compared with vehicle pretreatment, HIT pretreatment (1 hour) significantly enhanced indexes of functional recovery, including developed pressure (38 +/- 3 versus 69 +/- 7 mm Hg) and coronary flow (46 +/- 2 versus 82 +/- 11 mL/min). In addition, ultrastructural morphology was preserved but only with in vivo pretreatment. Liver protein content was not increased in rabbits treated from 12 hours to 5 days with HIT versus controls, belying a protein neosynthesis mechanism. However, the temporal sequences suggested conversion of an inactive HIT profactor to an active form. Administration of serum derived from hibernating black bears to rabbits affords protection against ischemia-reperfusion injury compared with vehicle (saline)-treated animals in a rabbit isolated heart preparation. It is apparent that HIT deserves further identification and mechanistic study in the setting of ischemia-reperfusion injury.


Testing protocol and recruitment in the genes in myopia twin study.
The genes in myopia twin study were established to assess the relative genetic contribution of spherical equivalent using a classical twin model. This manuscript will provide a detailed outline of the methodological design, twin recruitment, and the prevalence of myopia in the genes in myopia twin study. All Victorian-based twins registered with the Australian Twin Registry aged 18 years or older were invited to participate genes in myopia twin study. Each subject underwent a general questionnaire, comprehensive eye examination, and a blood sample was collected. Myopia was defined as worse than or equal to -0.50 diopters sphere (in at least one eye). A total of 627 twin pairs out of 4,158 twin pairs consented to participate in the genes in myopia twin study. A total of 345 monozygotic and 267 dizygotic twin pairs aged between 18 and 86 years were examined. The response rate for monozygotic twins (19.8%) was almost double that of dizygotic twins (11.7%). The overall prevalence of myopia was 29.7% for all twins. The genes in myopia twin study is the first Australian-based twin study to assess refraction in an adult twin population and the largest of its kind in the world. The comprehensive testing protocol used in the in the genes in myopia twin study has provided an extensive twin database for genetic analysis. Participation rate was found to vary according to zygosity, gender, and age.


Prognostic Scoring Models for Patients Undergoing Sorafenib Treatment for Advanced Stage Hepatocellular Carcinoma in Real-Life Practice.
The purpose of this study was to build prognostic models capable of estimating the outcomes of individual sorafenib-treated advanced stage hepatocellular carcinoma (HCC) patients based on specific patient and tumor factors. A parametric model for time-to-event data was used to construct scoring systems based on the intent-to-treat data set from 480 sorafenib-treated patients with advanced stage HCC: 356 for derivation and 124 for validation. Clinical parameters included in the models were based on importance variable scores generated by a random forest approach and bootstrap resampling. The model's accuracy was internally and externally assessed using the time-dependent C-index of discrimination and a Hosmer-Lemeshow type test for calibration. The models generated for time-to-progression and overall survival based on Child-Pugh score, serum α-fetoprotein, tumor morphology, and vascular invasion and/or extrahepatic involvement had good calibration and discrimination abilities, with C-indexes of 0.669 (3 mo progression) and 0.809 (6 mo survival), respectively. External validation results also showed that these models performed well in terms of goodness-of-fit and discrimination (C-index: 0.746 for 3 mo progression and 0.875 for 6 mo survival). Receiver operating characteristic curve analysis in the validation patients indicated that these models have better predictive power than Child-Pugh scores (C-index: 0.686 for 3 mo progression and 0.777 for 6 mo survival). The prognostic tools developed to quantify the potential outcomes for progression and survival expected from sorafenib treatment can serve as useful clinical aids in personalized decision making regarding treatment in advanced stage HCC patients.


Relationship between blood peroxidases activity and visfatin levels in metabolic syndrome patients.
The observed relationships between visfatin, peroxidases activity, and metabolic syndrome (MetS) are inconsistent; therefore, this study was undertaken to understand these relationships. This cross-sectional study was conducted as a part of the Isfahan Healthy Heart Program, Iran. A blood sample of 90 MetS and non-MetS patients were used to estimate total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), fasting blood glucose (FBG), waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP), visfatin and peroxidases activity. Data analysis for MetS group was carried out in two ways. (1) MetS with three components and with > 3 components. (2) MetS with hyperglycemia and without hyperglycemia. SBP, DBP, WC, FBG, TC, TG, LDL-C, and were higher and HDL-C levels was lower in MetS patients. There was a significant correlation between visfatin levels and peroxidases activity in MetS patients with three components. Levels of visfatin were significantly higher in male as compared to female subjects in the MetS with three components group. There was a significant decrease in peroxidases activity in > 45 years old subjects in the MetS with > 3 components group. A significant correlation was observed between serum visfatin levels and FBG in the MetS without hyperglycemia group. Peroxidases activities in MetS patients can be related to visfatin levels. Gender influences on peroxidases activity probably and was lower in female patients with MetS. Hyperglycemia does not influence peroxidases activities and visfatin levels.


Triply Periodic Minimal Surfaces Sheet Scaffolds for Tissue Engineering Applications: An Optimization Approach toward Biomimetic Scaffold Design.
Biomimetic scaffold design is gaining attention in the field of tissue engineering lately. Recently, triply periodic minimal surfaces (TPMSs) have attracted the attention of tissue engineering scientists for fabrication of biomimetic porous scaffolds. TPMS scaffolds offer several advantages, which include a high surface area to volume ratio, less stress concentration, and increased permeability compared to the traditional lattice structures, thereby aiding in better cell adhesion, migration, and proliferation. In literature, several design methods for TPMS scaffolds have been developed, which considered some of the important tissue-specific requirements, such as porosity, Young's modulus, and pore size. However, only one of the requirements of a tissue engineering scaffold was investigated in these studies, and not all of the requirements were satisfied simultaneously. In this work, we develop a design method for TPMS sheet scaffolds, which is able to satisfy multiple requirements including the porosity, Young's modulus, and pore size, based on a parametric optimization approach. Three TPMSs, namely, the primitive (P), gyroid (G), and diamond (D) surfaces, with cubic symmetry are considered. The versatility of the proposed design method is demonstrated by three different applications, namely, tissue-specific scaffolds, scaffolds for stem cell differentiation, and functionally graded scaffolds with biomimetic functional gradients.


Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus.
Relatively little is understood about the dynamics of global host-pathogen transcriptome changes that occur during bacterial infection of mucosal surfaces. To test the hypothesis that group A Streptococcus (GAS) infection of the oropharynx provokes a distinct host transcriptome response, we performed genome-wide transcriptome analysis using a nonhuman primate model of experimental pharyngitis. We also identified host and pathogen biological processes and individual host and pathogen gene pairs with correlated patterns of expression, suggesting interaction. For this study, 509 host genes and seven biological pathways were differentially expressed throughout the entire 32-day infection cycle. GAS infection produced an initial widespread significant decrease in expression of many host genes, including those involved in cytokine production, vesicle formation, metabolism, and signal transduction. This repression lasted until day 4, at which time a large increase in expression of host genes was observed, including those involved in protein translation, antigen presentation, and GTP-mediated signaling. The interactome analysis identified 73 host and pathogen gene pairs with correlated expression levels. We discovered significant correlations between transcripts of GAS genes involved in hyaluronic capsule production and host endocytic vesicle formation, GAS GTPases and host fibrinolytic genes, and GAS response to interaction with neutrophils. We also identified a strong signal, suggesting interaction between host gammadelta T cells and genes in the GAS mevalonic acid synthesis pathway responsible for production of isopentenyl-pyrophosphate, a short-chain phospholipid that stimulates these T cells. Taken together, our results are unique in providing a comprehensive understanding of the host-pathogen interactome during mucosal infection by a bacterial pathogen.


Progress towards the 'Golden Age' of biotechnology.
Biotechnology uses substances, materials or extracts derived from living cells, employing 22 million Europeans in a € 1.5 Tn endeavour, being the premier global economic growth opportunity this century. Significant advances have been made in red biotechnology using pharmaceutically and medically relevant applications, green biotechnology developing agricultural and environmental tools and white biotechnology serving industrial scale uses, frequently as process feedstocks. Red biotechnology has delivered dramatic improvements in controlling human disease, from antibiotics to overcome bacterial infections to anti-HIV/AIDS pharmaceuticals such as azidothymidine (AZT), anti-malarial compounds and novel vaccines saving millions of lives. Green biotechnology has dramatically increased food production through Agrobacterium and biolistic genetic modifications for the development of 'Golden Rice', pathogen resistant crops expressing crystal toxin genes, drought resistance and cold tolerance to extend growth range. The burgeoning area of white biotechnology has delivered bio-plastics, low temperature enzyme detergents and a host of feedstock materials for industrial processes such as modified starches, without which our everyday lives would be much more complex. Biotechnological applications can bridge these categories, by modifying energy crops properties, or analysing circulating nucleic acid elements, bringing benefits for all, through increased food production, supporting climate change adaptation and the low carbon economy, or novel diagnostics impacting on personalized medicine and genetic disease. Cross-cutting technologies such as PCR, novel sequencing tools, bioinformatics, transcriptomics and epigenetics are in the vanguard of biotechnological progress leading to an ever-increasing breadth of applications. Biotechnology will deliver solutions to unimagined problems, providing food security, health and well-being to mankind for centuries to come.


Systemic multimodal approach to speech therapy treatment in autistic children.
Conditions in which speech therapy treatment is applied in autistic children are often not in accordance with characteristics of opinions and learning of people with autism. A systemic multimodal approach means motivating autistic people to develop their language speech skill through the procedure which allows reliving of their personal experience according to the contents that are presented in the their natural social environment. This research was aimed at evaluating the efficiency of speech treatment based on the systemic multimodal approach to the work with autistic children. The study sample consisted of 34 children, aged from 8 to 16 years, diagnosed to have different autistic disorders, whose results showed a moderate and severe clinical picture of autism on the Childhood Autism Rating Scale. The applied instruments for the evaluation of ability were the Childhood Autism Rating Scale and Ganzberg II test. The study subjects were divided into two groups according to the type of treatment: children who were covered by the continuing treatment and systemic multimodal approach in the treatment, and children who were covered by classical speech treatment. It is shown that the systemic multimodal approach in teaching autistic children affects the stimulation of communication, socialization, self-service and work as well as that the progress achieved in these areas of functioning was retainable after long time, too. By applying the systemic multimodal approach when dealing with autistic children and by comparing their achievements on tests applied before, during and after the application of this mode, it has been concluded that certain improvement has been achieved in the functionality within the diagnosed category. The results point to a possible direction in the creation of new methods, plans and programs in dealing with autistic children based on empirical and interactive learning.


Effect of enteric flora on inflammatory and angiogenic mechanisms in human intestinal microvascular endothelial cells.
The intestine is a highly vascularized organ, and the splanchnic microcirculation is now appreciated to play a key role in immune and inflammatory responses in the gut. Emerging evidence demonstrates that the enteric flora not only exerts an important effect on innate immunity and the mucosal immune system, but will also affect inflammatory and angiogenic mechanisms involving the gut microcirculation. In response to bacterial lipopolysaccharide, the intestinal microcirculation and its endothelial lining will undergo activation, which will contribute to cell adhesion molecule expression and the recruitment of leukocytes into the gut wall, an early and rate limiting step in the inflammatory process. This is balanced by the fact that human intestinal microvascular endothelial cells possess specific mechanisms of endotoxin tolerance, which will diminish inflammatory activation in response to repeated bacterial activation. Likewise, the process of angiogenesis, or new blood vessel growth is influenced by the presence of bacteria, which stimulate the release of angiogenic factors from innate immune mechanisms. Conversely, bacterial derived products of dietary carbohydrate fermentation, the short chain fatty acids, will decrease angiogenic mechanisms in human intestinal microvascular endothelial cells. In this review we summarize our present state of knowledge regarding the interplay between enteric flora and inflammatory and angiogenic activation of the intestinal microcirculation its microvascular endothelium.


Percutaneous nucleotomy in the treatment of cervical disc herniation: report of three cases and review.
We describe here three patients with cervical disc herniation who were treated at our department with manual percutaneous nucleotomy. These patients had suffered from cervical pain radiating into an upper extremity, with the duration of the conservative treatment varying between three and six months before the operation. After a follow-up of three years, radiating pain into the upper extremity was totally recovered in one patient, markedly diminished in one and remained unchanged in one. All patients were continuously working. The outcome of patients who underwent percutaneous nucleotomy for cervical disc herniation has been evaluated in only three previous papers, all focusing on automated cervical nucleotomy. We review the literature on cervical percutaneous nucleotomy and discuss the usefulness of this methodology.


Recent clinical developments in pathophysiology, epidemiology, diagnosis and treatment of intra-abdominal adhesions.
Postsurgical intra-abdominal adhesions pose a significant medical problem in the Western world, and in the past decade progress has been made in understanding their pathophysiology. The early balance between fibrin formation and degradation in the peritoneal cavity during and after surgery seems to be a major determinant of adhesion formation. Postsurgical inhibition of fibrinolytic activity severely impairs fibrin breakdown. Adhesive small-bowel obstruction, inadvertent enterotomy at reoperation, prolonged operative time dividing adhesions, increased clinical workload and high financial costs are important adhesion-related problems discussed in this review. The cumulative risk of adhesive small-bowel obstruction after (sub)total colectomy is 11% within 1 year, increasing to 30% at 10 years. One of five patients undergoing reoperation suffers from inadvertent enterotomy, resulting in significant postoperative morbidity and mortality. Roughly 3% of all surgical admissions are associated with intra-abdominal adhesions. Clinical prospective trials have recently been designed to investigate the efficacy of barrier membranes and gels in the reduction of abdominal and pelvic adhesions and prevention of long-term morbidity, e.g., adhesive bowel obstruction and infertility in women. Early results are promising and contribute to the increased interest among clinicians in postsurgical adhesion formation and its consequences.


A Decision Aid to Promote Appropriate Colorectal Cancer Screening among Older Adults: A Randomized Controlled Trial.
Concerns have been raised about both over- and underutilization of colorectal cancer (CRC) screening in older patients and the need to align screening behavior with likelihood of net benefit. The purpose of this study was to test a novel use of a patient decision aid (PtDA) to promote appropriate CRC screening in older adults. A total of 424 patients ages 70 to 84 y who were not up to date with CRC screening participated in a double-blinded randomized controlled trial of a PtDA targeted to older adults making decisions about whether to undergo CRC screening from March 2012 to February 2015. Patients were randomized to a targeted PtDA or an attention control. The PtDA was designed to facilitate individualized decision making-helping patients understand the potential risks, benefits, and uncertainties of CRC screening given advanced age, health state, preferences, and values. Two composite outcomes, appropriate CRC screening behavior 6 mo after the index visit and appropriate screening intent immediately after the visit, were defined as completed screening or intent for patients in good health, discussion about screening with their provider for patients in intermediate health, and no screening or intent for patients in poor health. Health state was determined by age and Charlson Comorbidity Index. Four hundred twelve (97%) and 421 (99%) patients were analyzed for the primary and secondary outcomes, respectively. Appropriate screening behavior at 6 mo was higher in the intervention group (55% v. 45%, P = 0.023) as was appropriate screening intent following the provider visit (61% v. 47%, P = 0.003). The study took place in a single geographic region. The appropriate CRC screening classification system used in this study has not been formally validated. A PtDA for older adults promoted appropriate CRC screening behavior and intent. Clinicaltrials.gov, registration number NCT01575990. https://clinicaltrials.gov/ct2/show/NCT01575990?term=epic-d&rank=1.


Effects of chronic kidney disease on blood cells membrane properties.
Chronic kidney disease (CKD) is progressive loss of renal function associated among others with increased intracellular calcium concentration. The purpose of this study was to identify the effects of CKD on cell membrane properties such as human red blood cell Ca(2+) ATPase activity, lymphocyte plasma membrane P2X(7) receptor expression and function. This could help us in elucidating the origin of increased calcium concentration in blood cells. We found out Ca(2+) ATPase activity is decreased in early stage CKD patients resulting in altered calcium removal from cytoplasm. By means of flow cytometry we assessed that P2X(7) receptor expression on lymphocyte membrane is 1.5 fold increased for CKD patients. Moreover, we detected an increased uptake of ethidium bromide through this receptor in CKD at basal conditions. It means CKD lymphocyte membranes contain more receptors which are more permeable thus allowing increased calcium influx from extracellular milieu. Finally, we can state alterations in blood cell membranes are closely linked to CKD and may be responsible for intracellular calcium accumulation.


On the stability of the Bayenv method in assessing human SNP-environment associations.
Phenotypic variation along environmental gradients has been documented among and within many species, and in some cases, genetic variation has been shown to be associated with these gradients. Bayenv is a relatively new method developed to detect patterns of polymorphisms associated with environmental gradients. Using a Bayesian Markov Chain Monte Carlo (MCMC) approach, Bayenv evaluates whether a linear model relating population allele frequencies to environmental variables is more probable than a null model based on observed frequencies of neutral markers. Although this method has been used to detect environmental adaptation in a number of species, including humans, plants, fish, and mosquitoes, stability between independent runs of this MCMC algorithm has not been characterized. In this paper, we explore the variability of results between runs and the factors contributing to it. Independent runs of the Bayenv program were carried out using genome-wide single-nucleotide polymorphism (SNP) data from samples from 60 worldwide human populations following previous applications of the Bayenv method. To assess factors contributing to the method's stability, we used varying numbers of MCMC iterations and also analyzed a second modified data set that excluded two Siberian populations with extreme climate variables. Between any two runs, correlations between Bayes factors and the overlap of SNPs in the empirical p value tails were surprisingly low. Enrichments of genic versus non-genic SNPs in the empirical tails were more robust than the empirical p values; however, the significance of the enrichments for some environmental variables still varied among runs, contradicting previously published conclusions. Runs with a greater number of MCMC iterations slightly reduced run-to-run variability, and excluding the Siberian populations did not have a large effect on the stability of the runs. Because of high run-to-run variability, we advise against making conclusions about genome-wide patterns of adaptation based on only one run of the Bayenv algorithm and recommend caution in interpreting previous studies that have used only one run. Moving forward, we suggest carrying out multiple independent runs of Bayenv and averaging Bayes factors between runs to produce more stable and reliable results. With these modifications, future discoveries of environmental adaptation within species using the Bayenv method will be more accurate, interpretable, and easily compared between studies.


The molecular level degradation state of drift plastics in the Sea of Japan coastline.
Polyethylene (PE) and polyethylene terephthalate (PET) are among the most abundant plastics polluting the oceans. However, their environmental fate depends on how they have been weathered. Due to its unique geography, the Sea of Japan is a pollution hotspot where plastics accumulate. In this study, the structures of plastics, having drifted into the Sea of Japan coastline environment, were analyzed with a particular focus on examining polymer crystallization and carbonyl formation; two factors which influence microplastic formation and the adsorption of contaminants onto plastic surfaces. PE in the coastal environment did not show evidence of crystallization, although carbonyl formation did increase. By contrast, PET bottles were shown to not be uniform in structure, with unaged bottles being less crystalline in the neck component compared to the body. Because of this difference, in environmental PET bottles, it was the bottle neck that showed increases in crystallization and carbonyl group formation.


Red herrings in crossmatching kidneys for transplant.
Crossmatching of prospective renal transplant donors against recipients is a mandatory component of the transplant workup, being performed for over 40 years now. Allografting patients with human leukocyte antigens which are recognized by preformed antibodies constitutes the main cause of hyperacute or acute rejections. The existence of these donor-specific anti-human leukocyte antigen antibodies (DSAs) is regarded as a contraindication for graft trans-plantation, both cadaveric and live kidney. We present two unusual cases in which both complement-dependent cytotoxicity crossmatch and DSA by Luminex were falsely positive due to autoimmune and infectious causes, but single-antigen bead assay showed these antibodies to be against nondonor antigens. After treating their basic disease, thought to be responsible for false-positive DSA, these patients became DSA negative and underwent transplantation with an uneventful posttransplant period. Our aim through these examples is to highlight the problem of false-positive crossmatch in potential renal allograft transplant recipients. Further, we propose antigenic determination of donor-specific antibodies in such patients where we suspect the immune system to be chronically activated to pick up false-positive cases and therefore increase the donor pool without compromising the transplant outcome.


Toxicity and Repellency Efficacy of Benzyl Alcohol and Benzyl Benzoate as Eco-Friendly Choices to Control the Red Flour Beetle Tribolium castaneum (Herbst. 1797).
Tribolium castaneum is a damaging pest of stored grains, causing significant losses and secreting lethal quinones, which render the grains unfit for human consumption. Chemical insecticides are the most commonly used approach for control; however, they create insecticide resistance and affect the health of humans, animals, and the environment. As a result, it is critical to find an environmentally friendly pest-management strategy. In this study, two naturally occurring chemicals, benzyl alcohol (BA) and benzoyl benzoate (BB), were investigated for insecticidal activity against T. castaneum using different assays (impregnated-paper, contact toxicity, fumigant, and repellency assays). The results showed that BA had a significant insecticidal effect, with the LC50 achieved at a lower concentration in the direct-contact toxicity test (1.77%) than in the impregnated-paper assay (2.63%). BB showed significant effects in the direct-contact toxicity test, with an LC50 of 3.114%, and a lower toxicity in the impregnated-paper assay, with an LC50 of 11.75%. Furthermore, BA exhibited significant fumigant toxicity against T. castaneum, with an LC50 of 6.72 µL/L, whereas BB exhibited modest fumigant toxicity, with an LC50 of 464 µL/L. Additionally, at different concentrations (0.18, 0.09, 0.045, and 0.0225 µL/cm2), BA and BB both showed a notable and potent repelling effect. BA and BB significantly inhibited acetylcholinesterase, reduced glutathione (GSH), and increased malondialdehyde (MDA) in treated T. castaneum. This is the first report of BA insecticidal activity against the red flour beetle. Also, the outcomes of various assays demonstrated that the application of BA induces a potent bio-insecticidal effect. BA may be a promising eco-friendly alternative to control T. castaneum due to its safety and authorization by the EFSA (European Food Safety Authority).


Fetal cardiac cine imaging using highly accelerated dynamic MRI with retrospective motion correction and outlier rejection.
Development of a MRI acquisition and reconstruction strategy to depict fetal cardiac anatomy in the presence of maternal and fetal motion. The proposed strategy involves i) acquisition and reconstruction of highly accelerated dynamic MRI, followed by image-based ii) cardiac synchronization, iii) motion correction, iv) outlier rejection, and finally v) cardiac cine reconstruction. Postprocessing entirely was automated, aside from a user-defined region of interest delineating the fetal heart. The method was evaluated in 30 mid- to late gestational age singleton pregnancies scanned without maternal breath-hold. The combination of complementary acquisition/reconstruction and correction/rejection steps in the pipeline served to improve the quality of the reconstructed 2D cine images, resulting in increased visibility of small, dynamic anatomical features. Artifact-free cine images successfully were produced in 36 of 39 acquired data sets; prolonged general fetal movements precluded processing of the remaining three data sets. The proposed method shows promise as a motion-tolerant framework to enable further detail in MRI studies of the fetal heart and great vessels. Processing data in image-space allowed for spatial and temporal operations to be applied to the fetal heart in isolation, separate from extraneous changes elsewhere in the field of view. Magn Reson Med 79:327-338, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.