Behavior of mice aboard the International Space Station.

Interest in space habitation has grown dramatically with planning underway for the first human transit to Mars. Despite a robust history of domestic and international spaceflight research, understanding behavioral adaptation to the space environment for extended durations is scant. Here we report the first detailed behavioral analysis of mice flown in the NASA Rodent Habitat on the International Space Station (ISS).

Insulin resistance: Genetic associations with depression and cognition in population based cohorts.

Insulin resistance, broadly defined as the reduced ability of insulin to exert its biological action, has been associated with depression and cognitive dysfunction in observational studies. However, it is unclear whether these associations are causal and whether they might be underpinned by other shared factors. To address this knowledge gap, we capitalized on the stability of genetic biomarkers through the lifetime, and on their unidirectional relationship with depression and cognition.

Design, Synthesis, and Pharmacokinetic Evaluation of Phosphate and Amino Acid Ester Prodrugs for Improving the Oral Bioavailability of the HIV-1 Protease Inhibitor Atazanavir.

Phosphate and amino acid prodrugs of the HIV-1 protease inhibitor (PI) atazanavir (1) were prepared and evaluated to address solubility and absorption limitations. While the phosphate prodrug failed to release 1 in rats, the introduction of a methylene spacer facilitated prodrug activation, but parent exposure was lower than that following direct administration of 1. Val amino acid and Val-Val dipeptides imparted low plasma exposure of the parent, although the exposure of the prodrugs was high, reflecting good absorption.

The accuracy of date of death recording in the Clinical Practice Research Datalink GOLD database in England compared with the Office for National Statistics death registrations.

Purpose: It is not clear whether all deaths are recorded in the Clinical Practice Research Datalink (CPRD) or how accurate a recorded date of death is. Individual-level linkage with national data from the Office for National Statistics (ONS) and Hospital Episode Statistics (HES) in England offers the opportunity to compare death information across different data sources.

Methods: Age-standardised mortality rates (ASMRs) standardised to the European Standard Population (ESP) 2013 for CPRD were compared with figures published by the ONS, and crude mortality rates were calculated for a sample population with individual linkage between CPRD, ONS, and HES data.

Gene and environmental interactions according to the components of lifestyle modifications in hypertension guidelines.

Risk factors for hypertension consist of lifestyle and genetic factors. Family history and twin studies have yielded heritability estimates of BP in the range of 34-67%. The most recent paper of BP GWAS has explained about 20% of the population variation of BP.

B-based photoreceptors: from structure and function to applications in optogenetics and synthetic biology.

Vitamin B-based photoreceptor proteins sense ultraviolet (UV), blue or green light using 5'-deoxyadenosylcobalamin (AdoCbl). The prototype of this widespread bacterial photoreceptor family, CarH, controls light-dependent gene expression in photoprotective cellular responses. It represses transcription in the dark by binding to operator DNA as an AdoCbl-bound tetramer, whose disruption by light relieves operator binding to allow transcription.

Microalbuminuria as an early predictor of preeclampsia in the pre-gestational diabetic population: A prospective cohort study.

Objectives: To determine if microalbuminuria can be used as a predictive marker of preeclampsia and adverse pregnancy and neonatal outcomes in women with pre-existing diabetes and to compare the prognostic utility of urinary albumin to creatinine ratio (uACR) and urinary protein to creatinine ratio (uPCR).

Study Design: Multicentre prospective cohort study. Antenatal Diabetes in Pregnancy clinics at three tertiary referral hospitals in Western Sydney, Australia.

Genetic and environmental determinants of stressful life events and their overlap with depression and neuroticism.

Stressful life events (SLEs) and neuroticism are risk factors for major depressive disorder (MDD). However, SLEs and neuroticism are heritable and genetic risk for SLEs is associated with risk for MDD. We sought to investigate the genetic and environmental contributions to SLEs in a family-based sample, and quantify genetic overlap with MDD and neuroticism.

Genome-wide association study of antidepressant treatment resistance in a population-based cohort using health service prescription data and meta-analysis with GENDEP.

Antidepressants demonstrate modest response rates in the treatment of major depressive disorder (MDD). Despite previous genome-wide association studies (GWAS) of antidepressant treatment response, the underlying genetic factors are unknown. Using prescription data in a population and family-based cohort (Generation Scotland: Scottish Family Health Study; GS:SFHS), we sought to define a measure of (a) antidepressant treatment resistance and (b) stages of antidepressant resistance by inferring antidepressant switching as non-response to treatment.

Rationale and design of the Coronary Microvascular Angina Cardiac Magnetic Resonance Imaging (CorCMR) diagnostic study: the CorMicA CMR sub-study.

Introduction: Angina with no obstructive coronary artery disease (ANOCA) is a common syndrome with unmet clinical needs. Microvascular and vasospastic angina are relevant but may not be diagnosed without measuring coronary vascular function. The relationship between cardiovascular magnetic resonance (CMR)-derived myocardial blood flow (MBF) and reference invasive coronary function tests is uncertain.

Causes of stillbirths in diabetic and gestational diabetes pregnancies at a NSW tertiary referral hospital.

Background: Diabetes in pregnancy may result in stillbirth or neonatal death.

Aim: This audit examined stillbirths of mothers with pre-existing diabetes in pregnancy (DIP) and gestational diabetes (GDM) to determine maternal and diabetic characteristics implicated in these deaths.

Materials And Methods: A retrospective cohort study was conducted to identify stillbirths occurring in diabetic pregnancies at Westmead Hospital during 2006-2017.

Exploring the context of diacidic motif DE as a signal for unconventional protein secretion in eukaryotic proteins.

Unconventional protein secretion (UPS) is an important phenomenon with fundamental implications to cargo export. How eukaryotic proteins transported by UPS are recognized without a conventional signal peptide has been an open question. It was recently observed that a diacidic amino acid motif (ASP-GLU or DE) is necessary for the secretion of superoxide dismutase 1 (SOD1) from yeast under nutrient starvation.

Extended-spectrum Beta-lactamase-producing Community-acquired Urinary Tract Infections in Children: Chart Review of Risk Factors.

Background: Community acquired urinary tract infections (CA-UTI) caused by extended spectrum beta lactamase (ESBL) producing organisms is on the rise throughout the world. There are known risk factors such as age <1 year, children on uroprophylaxis, recurrent UTI, recent antibiotic usage etc which can predict the occurrence of these ESBL producers.

Objectives: To correlate known risk factors with occurrence of ESBL UTI and antibiotic susceptibility of uropathogens isolated.

Necessity of Preventing Cardiovascular Disease by Smoke-Free Policies.

See Article by Mayne et al.

Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.

Folate/Vitamin B12 Supplementation Combats Oxidative Stress-Associated Carcinogenesis in a Rat Model of Colon Cancer.

Folate and vitamin B12 deficiency is associated with depletion of the major intracellular antioxidant glutathione, and oxidative stress is emerging as an etiological mechanism for colon cancer. Azoxymethane (AOM), a potent carcinogen, induces colon cancer in rats by causing pathophysiological changes and oxidative stress. We investigated the synergistic effect of folate and vitamin B12 supplementation against AOM-induced carcinogenesis and oxidative stress in rat colon.

Comparative Evaluation of Antimicrobial Efficacy of Platelet-rich Plasma, Platelet-rich Fibrin, and Injectable Platelet-rich Fibrin on the Standard Strains of and .

Context: Platelet concentrates are commonly used to promote periodontal soft- and hard-tissue regeneration. Recently, their antimicrobial efficacy is also explored. Various platelet concentrates have evolved which differ in the centrifugation protocols.

Plasticity in oligomerization, operator architecture, and DNA binding in the mode of action of a bacterial B-based photoreceptor.

Newly discovered bacterial photoreceptors called CarH sense light by using 5'-deoxyadenosylcobalamin (AdoCbl). They repress their own expression and that of genes for carotenoid synthesis by binding in the dark to operator DNA as AdoCbl-bound tetramers, whose light-induced disassembly relieves repression. High-resolution structures of CarH have provided snapshots of the dark and light states and have revealed a unique DNA-binding mode whereby only three of four DNA-binding domains contact an operator comprising three tandem direct repeats.

Approach to record linkage of primary care data from Clinical Practice Research Datalink to other health-related patient data: overview and implications.

Record linkage is increasingly used to expand the information available for public health research. An understanding of record linkage methods and the relevant strengths and limitations is important for robust analysis and interpretation of linked data. Here, we describe the approach used by Clinical Practice Research Datalink (CPRD) to link primary care data to other patient level datasets, and the potential implications of this approach for CPRD data analysis.

Salt stress in the renal tubules is linked to TAL-specific expression of uromodulin and an upregulation of heat shock genes.

Previously, our comprehensive cardiovascular characterization study validated Uromodulin as a blood pressure gene. Uromodulin is a glycoprotein exclusively synthesized at the thick ascending limb of the loop of Henle and is encoded by the Umod gene. Umod mice have significantly lower blood pressure than Umod mice, are resistant to salt-induced changes in blood pressure, and show a leftward shift in pressure-natriuresis curves reflecting changes of sodium reabsorption.

MIP-1α and MCP-1 as salivary biomarkers in periodontal disease.

Aim: Chemokines released by different host cells when exposed to the components of periodontopathic bacteria induce and maintain an inflammatory response in the periodontium. The aim of the study was to estimate the salivary levels of two chemokines, macrophage inflammatory protein-1 alpha (MIP-1α) and monocyte chemo attractant protein-1 (MCP-1) in health, gingivitis and periodontitis and to evaluate their role as reliable salivary biomarkers in discriminating gingivitis and periodontitis from health.

Methods: A cross sectional study was designed to estimate the levels of MIP-1α and MCP-1 in whole unstimulated saliva from 75 patients who were divided into healthy (Group 1, n = 25), gingivitis (Group 2, n = 25) and chronic generalized periodontitis (Group 3, n = 25).

Novel properties of recombinant Sso7d-Taq DNA polymerase purified using aqueous two-phase extraction: Utilities of the enzyme in viral diagnosis.

Using Sso7d from as the DNA binding protein fused to Taq DNA polymerase at its amino terminus, we report the hyper-expression and a novel purification methodology of Sso7d-Taq polymerase (S-Taq) using aqueous two-phase extraction system followed by Ni-affinity chromatography. The utility of such a fusion enzyme in carrying out PCR of human genes from whole blood directly and in detecting hepatitis B virus from clinical samples is demonstrated in this article. We present data on the enhanced thermo-stability of S-Taq DNA polymerase over Taq DNA polymerase and also provide evidence of its higher stability with detergents in comparison to Taq polymerase.

Lipopolysaccharide-induced inflammation does not alter muscle spindle afferent mechanosensation or sensory integration in the spinal cord of adult mice.

Inflammation is known to alter nervous system function, but its effect on muscle spindle afferent mechanosensation and sensory integration in the spinal cord has not been well studied. We tested the hypothesis that systemic inflammation induced by an intraperitoneal injection of the endotoxin lipopolysaccharide (LPS; 7.5 × 10 endotoxin units/kg 18 h before experiment) would alter muscle spindle afferent mechanosensation and spinal cord excitability to Group Ia input in male and female adult C57Bl/6 mice.

Use of coagulation factor XIII (F13) gene as an internal control for normalization of genomic DNA's for HLA typing.

Genomic DNA (gDNA) obtained from whole blood samples is a critical element for genomic research and clinical diagnosis. PCR efficiencies of the targeted genes like HLA-A, -B, -C, DPB1 and DRB1 using such isolated gDNAs were variable in spite of having similar amounts of gDNA taken for PCR. We addressed such PCR variabilities by normalizing the gDNA's using an internal control of human coagulation factor XIII that was found to be variable with all samples and did not correlate with the observed A nm readings.