Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

VDES J2325−5229 a z = 2.7 gravitationally lensed quasar discovered using morphology-independent supervised machine learning

We present the discovery and preliminary characterization of a gravitationally lensed quasar with a source redshift zs = 2.74 and image separation of 2.9 arcsec lensed by a foreground zl = 0.40 elliptical galaxy. Since optical observations of gravitationally lensed quasars showthe lens system as a superposition of multiple point sources and a foreground lensing galaxy, we have developed a morphology-independent multi-wavelength approach to the photometric selection of lensed quasar candidates based on Gaussian Mixture Models (GMM) supervised machine learning. Using this technique and gi multicolour photometric observations from the Dark Energy Survey (DES), near-IR JK photometry from the VISTA Hemisphere Survey (VHS) and WISE mid-IR photometry, we have identified a candidate system with two catalogue components with iAB = 18.61 and iAB = 20.44 comprising an elliptical galaxy and two blue point sources. Spectroscopic follow-up with NTT and the use of an archival AAT spectrum show that the point sources can be identified as a lensed quasar with an emission line redshift of z = 2.739 ± 0.003 and a foreground early-type galaxy with z = 0.400 ± 0.002.We model the system as a single isothermal ellipsoid and find the Einstein radius θE ∼ 1.47 arcsec, enclosed mass Menc ∼ 4 × 1011 M and a time delay of ∼52 d. The relatively wide separation, month scale time delay duration and high redshift make this an ideal system for constraining the expansion rate beyond a redshift of 1

“Microbiota, symbiosis and individuality summer school” meeting report

How does microbiota research impact our understanding of biological individuality? We summarize the interdisciplinary summer school on “Microbiota, symbiosis and individuality: conceptual and philosophical issues” (July 2019), which was supported by a European Research Council starting grant project “Immunity, DEvelopment, and the Microbiota” (IDEM). The summer school centered around interdisciplinary group work on four facets of microbiota research: holobionts, individuality, causation, and human health. The conceptual discussion of cutting-edge empirical research provided new insights into microbiota and highlights the value of incorporating into meetings experts from other disciplines, such as philosophy and history of science

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Production potential of greater duckweed Spirodela polyrhiza (L. Schleiden) and its biochemical composition evaluation

The culture technique of greater duckweed Spirodela polyrhiza (L. Schleiden) was standardized in outdoor tanks using three different manures: manure 1 - cattle manure, poultry droppings and mustard oil cake, manure 2 - urea, potash and triple superphosphate and manure 3 - cattle manure, urea, potash and triple superphosphate. Significantly (p   <  .05) higher production was recorded in manure 1 compared to others. Manure 1 was subsequently selected for pond culture. In ponds, the production of duckweed was 2020 ± 150 kg ha−1 month−1 dry weight basis. Protein content was significantly higher (p  <  .05) in duckweed cultured in manure 1. The amino acid profile study showed the presence of essential (37.4%), non-essential (58.2%) and free (4.5%) amino acids. Leucine, isoleucine and valine contributed 51.4% of total essential amino acids. Duckweed contained 7% lipid and α-linolenic acid (36–37%) was the major fatty acid. The study showed the nutritional value of duckweed as an animal feed ingredient

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society