Transcription of Brain Natriuretic Peptide and Atria1 Natriuretic Peptide Genes in Human Tissues.

We have compared the expression of atria1 natriuretic peptide (ANP) and brain natriuretic peptide (BNP) genes in various human tissues using a quantitative polymerase chain reaction technique. Tissues of three human subjects, obtained at autopsy, were analyzed. BNP transcripts could be detected in the central nervous system, lung, thyroid, adrenal, kidney, spleen, small intestine, ovary, uterus, and striated muscle. ANP transcripts could also be demonstrated in various human extracardiac tissues including several endocrine organs. In all periphera1 tissues, the level of both natriuretic peptide transcripts was approximately l-2 orders of magnitude lower than in cardiac ventricular tissues. This distribution is in marked contrast to the much lower level of ANP and BNP transcripts present in extracardiac rat tissues (generally less than l/1000 of ventricles). These data suggest differential expression of the two natriuretic peptide genes in cardiac and extracardiac tissues in man. Furthermore, the presence of local synthesis of ANP and BNP in various peripheral organs su gests paracrine and/or autocrine function of these natriuretic peptides

Synthetic Gaia DR3 surveys from the FIRE cosmological simulations of Milky-Way-mass galaxies

The third data release (DR3) of Gaia has provided a five-fold increase in the number of radial velocity measurements of stars, as well as a stark improvement in parallax and proper motion measurements. To help with studies that seek to test models and interpret Gaia DR3, we present nine Gaia synthetic surveys, based on three solar positions in three Milky-Way-mass galaxies of the Latte suite of the Fire-2 cosmological simulations. These synthetic surveys match the selection function, radial velocity measurements, and photometry of Gaia DR3, adapting the code base Ananke, previously used to match the Gaia DR2 release in Sanderson et al. 2020. The synthetic surveys are publicly available and can be found at http://ananke.hub.yt/. Similarly to the previous release of Ananke, these surveys are based on cosmological simulations and thus able to model non-equilibrium dynamical effects, making them a useful tool in testing and interpreting Gaia DR3.Comment: 17 pages, 7 tables, 6 figure

Differential display identifies overexpression of the USP36 gene, encoding a deubiquitinating enzyme, in ovarian cancer

Objectives. To find potential diagnostic markers or therapeutic targets, we used differential display technique to identify genes that are over or under expressed in human ovarian cancer. Methods. Genes were initially identified by differential display between two human ovarian surface epithelium cultures and two ovarian cancer cell lines, A2780 and Caov-3. Genes were validated by relative quantitative RT-PCR and RNA in situ hybridization. Results. Twenty-eight non-redundant sequences were expressed differentially in the normal ovarian epithelium and ovarian cancer cell lines. Seven of the 28 sequences showed differential expression between normal ovary and ovarian cancer tissue by RT-PCR. USP36 was over-expressed in ovarian cancer cell lines and tissues by RT-PCR and RNA in situ hybridization. Northern blot analysis and RT-PCR revealed two transcripts for USP36 in ovarian tissue. The major transcript was more specific for ovarian cancer and was detected by RT-PCR in 9/9 ovarian cancer tissues, 3/3 cancerous ascites, 5/14 (36%) sera from patients with ovarian cancer, and 0/7 sera from women without ovarian cancer. Conclusion. USP36 is overexpressed in ovarian cancer compared to normal ovary and its transcripts were identified in ascites and serum of ovarian cancer patients

Unified treatment of microscopic boundary conditions in computational homogenization method for multiphysics problems

Computational homogenization (so-called FE2) method is an effective tool to model complex behavior of heterogeneous media allowing direct coupling between the structure response and the evolving microstructure not only in purely mechanical problems but also in multiphysics problems [1]. The basic idea of this method is to obtain the macroscopic constitutive relationships from the resolution of the microscopic boundary value problem (BVP) defined on a representative volume element. This method does not requires any constitutive assumption at the macroscopic level, but an appropriate microscopic boundary condition has to be defined. Our work focuses on the unified treatment of the microscopic boundary condition in a multiphysics microscopic BVP. In particular, an efficient way to compute the tangent operator is developed for an arbitrary kind of boundary conditions. When considering the FE2method, the homogenized stresses and homogenized tangents at every macroscopic integration points are required. From the energy consistency condition between macroscopic and microscopic problems, the homogenized stresses can be easily computed by the volumetric averaging integrals of the microscopic counterparts. The required homogenized tangents often follows a stiffness condensation from the microscopic stiffness matrix at the equilibrium state [2]. When using the stiffness condensation, the microscopic stiffness matrix needs to be partitioned, and dense matrices based on Schur complements (under a matrix form ̃ =−−1) have to be estimated. The matrix operations based on Schur complements require a large time consuming and a lot of memory when increasing the number of degrees of freedom of the microscopic BVPs. This work proposes an efficient method allowing to compute the homogenized tangents without significant effort. The microscopic stiffness matrix does not need to be partitioned. The homogenized tangents are computed by solving a linear system, which is based on the linearized system at the converge solution of the microscopic BVP, with multiple right hand sides. With proposed numerical improvements, the FE2 method is used in a fully thermo-mechanically-coupled simulation. The temperature-dependent elastoplastic behavior, thermal conduction as well as the heat conversion from the mechanical deformation are considered in the hyperelastic large strain framework. [1]. Geers, M. G. D., Kouznetsova, V. G., Brekelmans, W. A. M., 2010. J. Comput. Appl. Math. 234 (7), 2175-2182. [2]. Kouznetsova, V., Brekelmans, W. A. M., Baaijens, F. P. T., 2001. Comput. Mech. 27 (1), 37-48.The authors gratefully acknowledge the financial support from F.R.S-F.N.R.S. under the project number PDR T.1015.1

Eligibility for vericiguat in a real-world heart failure population according to trial, guideline and label criteria:Data from the Swedish Heart Failure Registry

Aim: We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. Methods and results: From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration ≥6 months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. Conclusion: In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality.</p

Honey bee predisposition of resistance to ubiquitous mite infestations

Host-parasite co-evolution history is lacking when parasites switch to novel hosts. This was the case for Western honey bees (Apis mellifera) when the ectoparasitic mite, Varroa destructor, switched hosts from Eastern honey bees (Apis cerana). This mite has since become the most severe biological threat to A. mellifera worldwide. However, some A. mellifera populations are known to survive infestations, largely by suppressing mite population growth. One known mechanism is suppressed mite reproduction (SMR), but the underlying genetics are poorly understood. Here, we take advantage of haploid drones, originating from one queen from the Netherlands that developed Varroa-resistance, whole exome sequencing and elastic-net regression to identify genetic variants associated with SMR in resistant honeybees. An eight variants model predicted 88% of the phenotypes correctly and identified six risk and two protective variants. Reproducing and non-reproducing mites could not be distinguished using DNA microsatellites, which is in agreement with the hypothesis that it is not the parasite but the host that adapted itself. Our results suggest that the brood pheromone-dependent mite oogenesis is disrupted in resistant hosts. The identified genetic markers have a considerable potential to contribute to a sustainable global apiculture

Clinical and Cost-Effectiveness of PSYCHOnlineTHERAPY: Study Protocol of a Multicenter Blended Outpatient Psychotherapy Cluster Randomized Controlled Trial for Patients With Depressive and Anxiety Disorders

Introduction: Internet- and mobile-based interventions (IMIs) and their integration into routine psychotherapy (i.e., blended therapy) can offer a means of complementing psychotherapy in a flexible and resource optimized way. Objective: The present study will evaluate the non-inferiority, cost-effectiveness, and safety of two versions of integrated blended psychotherapy for depression and anxiety compared to standard cognitive behavioral therapy (CBT). Methods: A three-armed multicenter cluster-randomized controlled non-inferiority trial will be conducted comparing two implementations of blended psychotherapy (PSYCHOnlineTHERAPYfix/flex) compared to CBT. Seventy-five outpatient psychotherapists with a CBT-license will be randomized in a 1:1:1 ratio. Each of them is asked to include 12 patients on average with depressive or anxiety disorders resulting in a total sample size of N = 900. All patients receive up to a maximum of 16 psychotherapy sessions, either as routine CBT or alternating with Online self-help sessions (fix: 8/8; flex: 0–16). Assessments will be conducted at patient study inclusion (pre-treatment) and 6, 12, 18, and 24 weeks and 12 months post-inclusion. The primary outcome is depression and anxiety severity at 18 weeks post-inclusion (post-treatment) using the Patient Health Questionnaire Anxiety and Depression Scale. Secondary outcomes are depression and anxiety remission, treatment response, health-related quality of life, patient satisfaction, working alliance, psychotherapy adherence, and patient safety. Additionally, several potential moderators and mediators including patient characteristics and attitudes toward the interventions will be examined, complemented by ecological day-to-day digital behavior variables via passive smartphone sensing as part of an integrated smart-sensing sub-study. Data-analysis will be performed on an intention-to-treat basis with additional per-protocol analyses. In addition, cost-effectiveness and cost-utility analyses will be conducted from a societal and a public health care perspective. Additionally, qualitative interviews on acceptance, feasibility, and optimization potential will be conducted and analyzed. Discussion: PSYCHOnlineTHERAPY will provide evidence on blended psychotherapy in one of the largest ever conducted psychotherapy trials. If shown to be non-inferior and cost-effective, PSYCHOnlineTHERAPY has the potential to innovate psychotherapy in the near future by extending the ways of conducting psychotherapy. The rigorous health care services approach will facilitate a timely implementation of blended psychotherapy into standard care

A randomised controlled school-based nutritional intervention in five Middle Eastern countries: Ajyal Salima improved students’ dietary and physical activity habits

Abstract Objective: The purpose of this study was to measure the impact of the Ajyal Salima school intervention on nutrition and physical activity outcomes in children aged 9–11 years. Design: The study was a 1-year cluster-randomised controlled trial. Ajyal Salima used a multi-component approach including classroom activities, family programme and food service adaptation. Outcomes included daily intake of breakfast, frequency of healthy and unhealthy food consumption, frequency of physical activity, knowledge score and self-efficacy score. Intervention and control groups were compared for all main outcomes and a post-intervention qualitative evaluation assessed strengths and limitations of the intervention components. Setting: Schools in five countries – Lebanon, Jordan, Palestine, Saudi Arabia and Bahrain. Participants: Schools were selected by Ministries of Health and Education within their jurisdictions. Forty-five intervention schools (6052 students) and forty-six control schools (6200 students) were included in the analysis. Results: The intervention group had a significantly higher odds of consuming breakfast daily (OR 95 % CI = 1·60, 1·35, 1·90), consuming healthy foods (OR 95 % CI = 1·60, 1·39, 1·84) and a decreased odds of consuming unhealthy foods and sweetened beverages (OR, 95 % CI = 0·70, 0·60, 0·81). Additionally, school children in the intervention group, as compared with the control group, were 47 % more likely to exercise outside school hours (OR 95 % CI = 1·47, 1·23, 1·76). Lastly, children in the intervention group had a significantly improved nutritional knowledge score and improved self-efficacy by 1·3 score unit and 1·1 score unit, respectively. Conclusions: The Ajyal Salima intervention led to significant improvements in dietary and physical activity habits among school children and increased nutritional knowledge scores

Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker

Background We investigated the biomarker potential of growth differentiation factor 15 (GDF-15), a stress response protein highly expressed in placenta, to predict preeclampsia. Methods and Results In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 controls, 41 developed preeclampsia), plasma concentrations of GDF-15 at 36 weeks' gestation were significantly increased among those who developed preeclampsia (P<0.001), area under the receiver operating characteristic curves (AUC) of 0.66 and 0.71, respectively. In cohort 2 a ratio of sFlt-1/PlGF (a clinical biomarker for preeclampsia) had a sensitivity of 61.0% at 83.2% specificity to predict those who will develop preeclampsia (AUC of 0.79). A ratio of GDF-15×sFlt-1/PlGF yielded a sensitivity of 68.3% at 83.2% specificity (AUC of 0.82). GDF-15 was consistently elevated across a number of international cohorts: levels were higher in placenta and blood from women delivering <34 weeks' gestation due to preterm preeclampsia in Melbourne, Australia; and in the blood at 26 to 32 weeks' gestation among 57 women attending the Manchester Antenatal Vascular Service (MAViS, UK) who developed preeclampsia (P=0.0002), compared with 176 controls. In the Preeclampsia Obstetric adVerse Events biobank (PROVE, South Africa), plasma GDF-15 was significantly increased in women with preeclampsia with severe features (P=0.02; n=14) compared to controls (n=14). Conclusions We conclude circulating GDF-15 is elevated among women more likely to develop preeclampsia or diagnosed with the condition. It may have value as a clinical biomarker, including the potential to improve the sensitivity of sFlt-1/PlGF ratio