High frequency of Polio-like Enterovirus C strains with differential clustering of CVA-13 and EV-C99 subgenotypes in a cohort of Malawian children

Enteroviruses (EVs) are among the most commonly detected viruses infecting humans worldwide. Although the prevalence of EVs is widely studied, the status of EV prevalence in sub-Saharan Africa remains largely unknown. The objective of our present study was therefore to increase our knowledge on EV circulation in sub-Saharan Africa. We obtained 749 fecal samples from a cross-sectional study conducted on Malawian children aged 6 to 60 months. We tested the samples for the presence of EVs using real time PCR, and typed the positive samples based on partial viral protein 1 (VP1) sequences. A large proportion of th

Bronchogenic cyst associated with pericardial defect: Case report and review of the literature

Partial defect of the pericardium combined with bronchogenic cyst is a very rare congenital anomaly. We describe the case of a 32-year-old man with a partial defect of the left pericardium and a bronchogenic cyst arising from the border of the pericardial defect. The cyst was successfully resected with the harmonic scalpel by three-port videothoracoscopic approach

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Rapid Molecular Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review of Diagnostic Accuracy and Clinical Impact Studies

We systematically reviewed available evidence from Embase, Medline, and the Cochrane Library on diagnostic accuracy and clinical impact of commercially available rapid (results <3 hours) molecular diagnostics for respiratory viruses as compared to conventional molecular tests. Quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies criteria for diagnostic test accuracy (DTA) studies, and the Cochrane Risk of Bias Assessment and Risk of Bias in Nonrandomized Studies of Interventions criteria for randomized and observational impact studies, respectively. Sixty-three DTA reports (56 studies) were meta-analyzed with a pooled sensitivity of 90.9% (95% confidence interval [CI], 88.7%-93.1%) and specificity of 96.1% (95% CI, 94.2%-97.9%) for the detection of either influenza virus (n = 29), respiratory syncytial virus (RSV) (n = 1), influenza virus and RSV (n = 19), or a viral panel including influenza virus and RSV (n = 14). The 15 included impact studies (5 randomized) were very heterogeneous and results were therefore inconclusive. However, we suggest that implementation of rapid diagnostics in hospital care settings should be considered

Increased postpartum haemorrhage, the possible relation with serotonergic and other psychopharmacological drugs: a matched cohort study

Postpartum haemorrhage is a major obstetric risk worldwide. Therefore risk factors need to be investigated to control for this serious complication. A recent systematic review and meta-analysis revealed that the use of both serotonergic and non-serotonergic antidepressants in pregnancy are associated with a higher risk of postpartum haemorrhage. However, use of antidepressants in pregnancy is often necessary because untreated depression in pregnancy is associated with adverse maternal and neonatal outcome, such as postpartum depression, preterm birth and dysmaturity. Therefore it is of utmost importance to unravel the possible association between postpartum haemorrhage and the use of serotonergic and other psychopharmacological medication during pregnancy. We performed a matched cohort observational study consecutively including all pregnant women using serotonergic medication (n = 578) or other psychopharmacological medication (n = 50) visiting two teaching hospitals in Amsterdam between 2010 and 2014. The incidence of postpartum haemorrhage in women using serotonergic medication or other psychopharmacological medication was compared with the incidence of postpartum haemorrhage in 641,364 pregnant women not using psychiatric medication selected from the database of the Netherlands Perinatal Registry foundation (Perined). Matching took place 1:5 for nine factors, i.e., parity, maternal age, ethnicity, socioeconomic status, macrosomia, gestational duration, history of postpartum haemorrhage, labour induction and hypertensive disorder. Postpartum haemorrhage occurred in 9.7% of the women using serotonergic medication. In the matched controls this was 6.6% (p = 0.01). The adjusted odds ratio (aOR) before matching was 1.6 (95% CI 1.2-2.1) and after matching 1.5 (95% CI 1.1-2.1). Among the women using other psychopharmacological medication, the incidence of postpartum haemorrhage before matching was 12.0% versus 6.1% (p = 0.08) with OR 2.1 (95% CI 0.9-4.9), and after matching 12.1% versus 4.4% (p = 0.03) with aOR of 3.3 (95% CI 1.1-9.8). Pregnant women using serotonergic medication have an increased risk of postpartum haemorrhage, but this high risk is also seen in pregnant women using other psychopharmacological medication. We suggest that this higher risk of postpartum haemorrhage could not only be explained by serotonin, but also by other mechanisms. An additional explanation could be the underlying psychiatric disorde

Rapid Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review and Meta-analysis

Rapid diagnosis of respiratory virus infections contributes to patient care. This systematic review evaluates the diagnostic accuracy of rapid tests for the detection of respiratory viruses. We searched Medline and EMBASE for studies evaluating these tests against polymerase chain reaction as the reference standard. Of 179 studies included, 134 evaluated rapid tests for influenza viruses, 32 for respiratory syncytial virus (RSV), and 13 for other respiratory viruses. We used the bivariate random effects model for quantitative meta-analysis of the results. Most tests detected only influenza viruses or RSV. Summary sensitivity and specificity estimates of tests for influenza were 61.1% and 98.9%. For RSV, summary sensitivity was 75.3%, and specificity, 98.7%. We assessed the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Because of incomplete reporting, the risk of bias was often unclear. Despite their intended use at the point of care, 26.3% of tests were evaluated in a laboratory setting. Although newly developed tests seem more sensitive, high-quality evaluations of these tests are lackin

Diagnostic performance and clinical feasibility of a point-of-care test for respiratory viral infections in primary health care

Background. Inappropriately high levels of antibiotics are still prescribed in primary health care for respiratory tract infections (RTIs). Access to diagnostic point-of-care tests (POCTs) for RTIs might reduce this over-prescription. Objective. The purpose of our study was to determine the diagnostic performance and clinical feasibility of a recently developed diagnostic POCT for respiratory viruses, the mariPOC (R), in a Dutch primary healthcare setting. Methods. In patients with RTI symptoms presenting to a family practice during the 2015-2016 winter season, we determined the test's sensitivity and specificity relative to polymerase chain reaction (PCR) testing performed in a laboratory. The clinical feasibility of the POCT was evaluated by interviewing general practitioners (GPs). Results. One or more respiratory viruses were detected in 54.9% of the patients (n = 204). For influenza A virus (n = 24), sensitivity of the POCT was 54.2% and specificity was 98.9%; for influenza B virus (n = 18), sensitivity was 72.2% and specificity 99.5%; and for respiratory syncytial virus (RSV) (n = 12), sensitivity was 50.0% and specificity 100%. In samples with higher viral load, sensitivity was 85.7% for influenza A, 78.6% for influenza B and 85.7% for RSV. The availability of a diagnostic test for respiratory viruses was appreciated by both patients and GPs. Conclusions. Our study shows that diagnostic POCTs for respiratory viruses might contribute to a precise and evidence-based diagnosis of RTIs and could positively influence prescription of antibiotics by GPs. However, before implementation in primary healthcare, diagnostic accuracy of the POCT needs improvement and it is impact on clinical decision making should be further assesse

Epidemiology and Etiology of Severe Childhood Encephalitis in The Netherlands

Background: Limited data are available on childhood encephalitis. Our study aimed to increase insight on clinical presentation, etiology, and clinical outcome of children with severe encephalitis in the Netherlands. Methods: We identified patients through the Dutch Pediatric Intensive Care Evaluation database and included children diagnosed with encephalitis <18 years of age admitted to 1 of the 8 pediatric intensive care units (PICU) in the Netherlands between January 2003 and December 2013. We analyzed demographic characteristics, clinical symptoms, neurologic imaging, etiology, treatment and mortality. Results: We included 121 children with a median age of 4.6 years (IQR 1.3-9.8). The most frequently described clinical features were headache (82.1%), decreased consciousness (79.8%) and seizures (69.8%). In 44.6% of the children, no causative agent was identified. Viral-and immune-mediated encephalitis were diagnosed in 33.1% and 10.7% of the patients. A herpes simplex virus infection (13.2%) was mainly seen in children <5 years of age, median age, 1.73 years (IQR 0.77-5.01), while immune-mediated encephalitis mostly affected older children, median age of 10.4 years (IQR, 3.72-14.18). An age of ≥ 5 years at initial presentation was associated with a lower mortality (OR 0.2 [CI 0.08-0.78]). The detection of a bacterial (OR 9.4 [CI 2.18-40.46]) or viral (OR 3.7 [CI 1.16-11.73]) pathogen was associated with a higher mortality. Conclusions: In almost half of the Dutch children presenting with severe encephalitis, a causative pathogen could not be identified, underlining the need for enhancement of microbiologic diagnostics. The detection of a bacterial or viral pathogen was associated with a higher mortality