An ordinary differential equation for velocity distribution and dip-phenomenon in open channel flows

An ordinary differential equation for velocity distribution in open channel flows is presented based on an analysis of the Reynolds-Averaged Navier-Stokes equations and a log-wake modified eddy viscosity distribution. This proposed equation allows to predict the velocity-dip-phenomenon, i.e. the maximum velocity below the free surface. Two different degrees of approximations are presented, a semi-analytical solution of the proposed ordinary differential equation, i.e. the full dip-modified-log-wake law and a simple dip-modified-log-wake law. Velocity profiles of the two laws and the numerical solution of the ordinary differential equation are compared with experimental data. This study shows that the dip correction is not efficient for a small Coles' parameter, accurate predictions require larger values. The simple dip-modified-log-wake law shows reasonable agreement and seems to be an interesting tool of intermediate accuracy. The full dip-modified-log-wake law, with a parameter for dip-correction obtained from an estimation of dip positions, provides accurate velocity profiles

Hypoxia promotes breast cancer cell invasion through HIF-1a-mediated up-regulation of the invadopodial actin bundling protein CSRP2

Hypoxia is a common feature of solid tumours that promotes invasion and metastatic dissemination. Invadopodia are actin-rich membrane protrusions that direct extracellular matrix proteolysis and facilitate tumour cell invasion. Here, we show that CSRP2, an invadopodial actin bundling protein, is upregulated by hypoxia in various breast cancer cell lines, as well as in pre-clinical and clinical breast tumour specimens. We functionally characterized two hypoxia responsive elements within the proximal promoter of CSRP2 gene which are targeted by hypoxia-inducible factor-1 (HIF-1) and required for promoter transactivation in response to hypoxia. Remarkably, CSRP2 knockdown significantly inhibits hypoxia-stimulated invadopodium formation, ECM degradation and invasion in MDA-MB-231 cells, while CSRP2 forced expression was sufficient to enhance the invasive capacity of HIF-1a-depleted cells under hypoxia. In MCF-7 cells, CSRP2 upregulation was required for hypoxia-induced formation of invadopodium precursors that were unable to promote ECM degradation. Collectively, our data support that CSRP2 is a novel and direct cytoskeletal target of HIF-1 which facilitates hypoxia-induced breast cancer cell invasion by promoting invadopodia formation.The authors are grateful to Monika Dieterle, Arnaud Muller, Pter Nazarov and Muhammad Zaeem Noman (Oncology Department, LIH, Luxembourg) for technical assistance, support in statistical analyses and constructive discussions. The authors also warmly thank Sara A. Courtneidge for the gift of the Tks5-GFP construct (Oregon Health and Science University, Portland, USA). This work was mainly supported by a research grant from “Fondation Cancer” Luxembourg (FC/2016/02), and the National Research Fund (C16/ BM/11297905). Joshua Brown Clay is recipient of a Postdoctoral fellowship from “Fonds De La Recherche Scientifque” - FNRS “Télévie” (7.4512.16). Antoun Al Absi and Hannah Wurzer are recipients of PhD fellowships from the National Research Fund, Luxembourg (AFR7892325 and PRIDE15/10675146/CANBIO, respectively)

Herpes Simplex Virus Type 2 Seroprevalence among Different National Populations of Middle East and North African Men

© 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association. Background There are limited data on herpes simplex virus type 2 (HSV-2) seroprevalence in the Middle East and North Africa (MENA). We examined country- and age-specific HSV-2 seroprevalence among select MENA populations residing in Qatar. Methods Sera were collected from male blood donors attending Hamad Medical Corporation between June 2013 and June 2016. Specimens were screened for anti-HSV-2 IgG antibodies following a 2-test algorithm: HerpeSelect 2 ELISA was used to identify HSV-2-positive specimens, and Euroline-WB was used to confirm positive and equivocal specimens for final HSV-2 status. Trends and associations with HSV-2 seropositivity were assessed. Results Of the 2077 tested sera, 61 were found and confirmed positive. The proportion of those confirmed positive increased steadily with HerpeSelect 2 ELISA index value, ranging from 16.3% for index values of 1.101 to 1.999 to 92.9% for index values of 4 or greater. Nationality-specific seroprevalence was 6.0% (95% confidence interval [CI], 4.1%-8.8%) in Qataris, 5.3% (95% CI, 2.5%-11.1%) in Iranians, 4.2% (95% CI, 1.8%-9.5%) in Lebanese, 3.1% (95% CI, 1.2%-7.7%) in Sudanese, 3.0% (95% CI, 1.4%-6.4%) in Palestinians, 2.2% (95% CI, 1.1%-4.3%) in Egyptians, 2.0% (95% CI, 1.0%-5.0%) in Syrians, 1.0% (95% CI, 0.3%-3.6%) in Jordanians, 0.7% (95% CI, 0.1%-3.7%) in Yemenis, and 0.5% (95% CI, 0.1%-2.8%) in Pakistanis. There was evidence for higher seroprevalence in older age groups. Conclusions The seroprevalence of HSV-2 was in the range of few percentage points. There were no major differences in seroprevalence by nationality. These findings add to our understanding of HSV-2 epidemiology in MENA and indicate unmet needs for sexual health and control of sexually transmitted infections.Funding text #1 From the *Infectious Disease Epidemiology Group, Weill Cornell Medicine—Qatar, Cornell University, Qatar Foundation—Education City; †Department of Biomedical Science, College of Health Sciences, and ‡BioMedical Research Center, Qatar University, Doha, Qatar; and §Department of Healthcare Policy and Research, Weill Cornell Medi-cine, Cornell University, Ithaca, NY Acknowledgments: The authors gratefully acknowledge the administrative support of Ms Adona Canlas. They are also grateful to Dr Asmaa Al-Marwani, Ms Maria Samatti, and Ms Sana Abohasera for their work on blood specimen collection. The authors are further grateful for sup-port provided by the Biostatistics, Epidemiology, and Biomathematics Research Core at Weill Cornell Medicine—Qatar. Funding text #2 Funding: Testing kits were provided through pilot funding by the Biomedical Research Program at Weill Cornell Medicine—Qatar. Funding text #3 G.K.N. acknowledges support by Qatar University internal grant No. QUST-CHS-SPR-15/16-7. L.J.A. and S.R.D. acknowledge study conception and design support through NPRP grant number 9-040-3-008 from the Qatar National Research Fund (a member of Qatar Foundation), and G.K.N. acknowledges support from the Qatar National Research Fund UREP grant number UREP18-001-3-001. The findings achieved herein are solely the responsibility of the authors

Performance evaluation of four type-specific commercial assays for detection of herpes simplex virus type 1 antibodies in a Middle East and North Africa population.

The number of diagnostic assays for the detection of herpes simplex virus type 1 (HSV-1) antibodies has increased over the years. However, their performance characteristics could vary among global populations. To investigate performance of two commercial ELISA kits, HerpeSelect1 ELISA and Euroimmun Anti-HSV-1 (gC1) ELISA (IgG); and two commercial immunoblot (IB)/Western blot (WB) assays, HerpeSelect1 and 2 Immunoblot IgG, and Euroimmun Anti-HSV-1/HSV-2 gG2 Euroline-WB (IgG/IgM); in detecting HSV-1 antibodies in a Middle East and North Africa (MENA) population. Blood specimens were collected from blood donors in Doha, Qatar, June 2013-2016. Twenty specimens were randomly selected from 10 MENA nationalities (Egypt, Iran, Jordan, Lebanon, Pakistan, Palestine, Qatar, Sudan, Syria, and Yemen; total = 200), and tested for HSV-1 antibodies. Across all six comparisons between assays, positive percent agreement ranged between 95.7% (95% CI: 91.4-98.3%) and 100.0% (95% CI: 97.8-100.0%). Negative percent agreement ranged between 86.2% (95% CI: 68.3-96.1%) and 96.2% (95% CI: 80.4-99.9%). Overall percent agreement ranged between 95.7% (95% CI: 91.7-97.8%) and 99.4% (95% CI: 96.7-99.9%). Cohen's kappa statistic ranged between 0.84 (95% CI: 0.73-0.95) and 0.98 (95% CI: 0.93-1.00). Compared against IB/WB, HerpeSelectand Euroimmun had sensitivities and specificities >96% and >86%, respectively. Positive and negative predictive values were >97% and >83%, respectively. The assays showed excellent concordance with one another, and with a high kappa statistic. The ELISA kits demonstrated robust diagnostic performance compared to the IB/WB assays. These findings support the assays' utility in clinical diagnosis and research in MENA populations

A Mathematical Model of Liver Cell Aggregation In Vitro

The behavior of mammalian cells within three-dimensional structures is an area of intense biological research and underpins the efforts of tissue engineers to regenerate human tissues for clinical applications. In the particular case of hepatocytes (liver cells), the formation of spheroidal multicellular aggregates has been shown to improve cell viability and functionality compared to traditional monolayer culture techniques. We propose a simple mathematical model for the early stages of this aggregation process, when cell clusters form on the surface of the extracellular matrix (ECM) layer on which they are seeded. We focus on interactions between the cells and the viscoelastic ECM substrate. Governing equations for the cells, culture medium, and ECM are derived using the principles of mass and momentum balance. The model is then reduced to a system of four partial differential equations, which are investigated analytically and numerically. The model predicts that provided cells are seeded at a suitable density, aggregates with clearly defined boundaries and a spatially uniform cell density on the interior will form. While the mechanical properties of the ECM do not appear to have a significant effect, strong cell-ECM interactions can inhibit, or possibly prevent, the formation of aggregates. The paper concludes with a discussion of our key findings and suggestions for future work

Atrioventricular Node Dysfunction and Ion Channel Transcriptome in Pulmonary Hypertension

Background: Heart block is associated with pulmonary hypertension, and the aim of the study was to test the hypothesis that the heart block is the result of a change in the ion channel transcriptome of the atrioventricular (AV) node. Methods and Results: The most commonly used animal model of pulmonary hypertension, the monocrotaline-injected rat, was used. The functional consequences of monocrotaline injection were determined by echocardiography, ECG recording, and electrophysiological experiments on the Langendorff-perfused heart and isolated AV node. The ion channel transcriptome was measured by quantitative PCR, and biophysically detailed computer modeling was used to explore the changes observed. After monocrotaline injection, echocardiography revealed the pattern of pulmonary artery blood flow characteristic of pulmonary hypertension and right-sided hypertrophy and failure; the Langendorff-perfused heart and isolated AV node revealed dysfunction of the AV node (eg, 50% incidence of heart block in isolated AV node); and quantitative PCR revealed a widespread downregulation of ion channel and related genes in the AV node (eg, >50% downregulation of Cav1.2/3 and HCN1/2/4 channels). Computer modeling predicted that the changes in the transcriptome if translated into protein and function would result in heart block. Conclusions: Pulmonary hypertension results in a derangement of the ion channel transcriptome in the AV node, and this is the likely cause of AV node dysfunction in this disease

Low risk of serological cross-reactivity between the dengue virus and SARS-CoV-2 IgG antibodies using advanced detection assays.

Several studies have reported serological cross-reactivity of the immune responses between SARS-CoV-2 and DENV. Most of the available studies are based on the point of care (POC) rapid testing kits. However, some rapid test kits have low specificity and can generate false positives. Hence, we aimed to investigate the potential serological cross-reactivity between SARS-CoV-2 and DENV IgG antibodies using advanced assays including chemiluminescence immunoassay (CLIA) and ELISA test. A total of 90 DENV-IgG-ELISA positive and 90 negative pre-pandemic sera were tested for anti-SARS-CoV-2-IgG using the automated CL-900i CLIA assay. Furthermore, a total of 91 SARS-CoV-2-IgG-CLIA positive and 91 negative post-pandemic sera were tested for anti-DENV-IgG using the Novalisa ELISA assay. The DENV-IgG positive sera resulted in five positives and 85 negatives for SARS-CoV-2-IgG. Similarly, the DENV-IgG negative sera also resulted in five positives and 85 negatives for SARS-CoV-2-IgG. No statistically significant difference in specificity between the DENV-IgG positive and DENV-IgG negative sera was found (p-value=1.00). The SARS-CoV-2-IgG positive sera displayed 43 positives, 47 negatives, and one equivocal for DENV-IgG. Whereas the SARS-CoV-2-IgG negative sera resulted in 50 positives, 40 negatives, and one equivocal for DENV-IgG. No statistically significant difference in the proportion that is DENV-IgG positive between the SARS-CoV-2-IgG positive and SARS-CoV-2-IgG negative sera (p-value=0.58). In conclusion, there is a low risk of serological cross-reactivity between the DENV, and SARS-CoV-2 IgG antibodies when using advanced detection assays.  .L.J.A. acknowledges the support of the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine-Qatar. This work was made possible by Grant Nos. RRC-2-032 and UREP19-013-3-001 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors. In addition, G.K.N. would also like to acknowledge funds from Qatar University’s internal Grant QUERG-CMED-2020-2

Extracorporeal Membrane Oxygenation for Graft Dysfunction Early After Heart Transplantation: A Systematic Review and Meta-analysis

Introduction: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO. Methods and Results: We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%–39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%–57%). Recipient age (odds ratio 1.02, 95% CI 1.01–1.04) and prior sternotomy (OR 1.57, 95% CI 0.99–2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death. Conclusions: One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT

Evaluation of Smear Layer: A Comparison of Automated Image Analysis versus Expert Observers

Consistent and reproducible evaluation techniques of the smear layer in root canals in scanning electron microscopy studies are needed when comparing various instruments and techniques. In this study, the performance of 3 experienced blinded evaluators applying the Hulsmann technique was compared with a digital analysis method. Smear layer in the apical third of root canals of 35 freshly extracted teeth prepared by using nickel-titanium rotary instruments, Er:YAG and Er,Cr:YSGG lasers was scored on coded images. There was good agreement between the digital analysis method and the different evaluators (kappa analysis) across the range of the Hulsmann scores. Image analysis might be useful for evaluating the degree of smear layer removal in endodontic research. © 2008 American Association of Endodontists