Nutrition and Feeding Behavior of Goats and Sheep Grazing Deciduous Shrub-Woodland in Northeastern Brazil

Production of sheep and goats in the Brazilian Northeast is important for the livelihood of both subsistence and market-oriented producers. Seasonal nutritional stress oh animals in the caatinga vegetational zone of this region causes periodic high mortality and chronically low productivity. Under such conditions, the survivability of goats has been higher than for other domestic livestock. Possible reasons for this include unique aspects of dietary selection and goat feeding behavior. The objectives of this research were to seasonally determine the botanical and nutritive content of goat and sheep diets, to determine forage intake by grazing goats and sheep, and to compare their feeding behavior. Dietary selections by sheep and goats were similar during the dry season, but diverged markedly during the wet season. Leaf litter from the deciduous trees was the major dietary component for both species during the dry season, and provided the bulk of dry season forage. Current hypotheses predict that goats select diets of higher nutritional quality and have a greater forage intake than do sheep. Goats selected diets significantly (P.05) in cell wall content, and lower (P This study confirmed the vertical stratification of foraging by goats and sheep. Sheep foraged more in lower vertical strata than did goats. Goats spent about 4% of their grazing time in a bipedal stance, while sheep virtually never used a bipedal stance to feed. In addition, no nutritional advantage was found for goats over sheep through use of a bipedal stance. This latter finding is constrained by the deciduous nature of the caatinga woodland during the dry season

Human papillomavirus mediated inhibition of DNA damage sensing and repair drives skin carcinogenesis

Background: The failure to mount an effective DNA damage response to repair UV induced cyclobutane pyrimidine dimers (CPDs) results in an increased propensity to develop cutaneous squamous cell carcinoma (cSCC). High-risk patient groups, such as organ transplant recipients (OTRs) frequently exhibit field cancerization at UV exposed body sites from which multiple human papillomavirus (HPV)-associated cSCCs develop rapidly, leading to profound morbidity and increased mortality. In vitro molecular evidence indicates that HPV of genus beta-papillomavirus (β-PV) play an important role in accelerating the early stages of skin tumorigenesis. Methods: We investigated the effects of UV induced DNA damage in murine models of β-PV E6 oncoprotein driven skin tumorigenesis by crossing K14-HPV8-E6wt mice (developing skin tumors after UV treatment) with K14-CPD-photolyase animals and by generating the K14-HPV8-E6-K136N mutant mouse strain. Thymine dimers (marker for CPDs) and γH2AX (a marker for DNA double strand breaks) levels were determined in the murine skin and organotypic skin cultures of E6 expressing primary human keratinocytes after UV-irradiation by immunohistochemistry and in cell lines by In Cell Western blotting. Phosphorylation of ATR/Chk1 and ATM were assessed in cell lines and organotypic skin cultures by Western blots and immunohistochemistry. Results: Skin tumor development after UV-irradiation in K14-HPV8-E6wt mice could completely be blocked through expression of CPD-photolyase. Through quantification of thymine dimers after UV irradiation in cells expressing E6 proteins with point mutations at conserved residues we identified a critical lysine in the

Maximizing Adherence and Gaining New Information For Your Chronic Obstructive Pulmonary Disease (MAGNIFY COPD):Study Protocol for the Pragmatic, Cluster Randomized Trial Evaluating the Impact of Dual Bronchodilator with Add-On Sensor and Electronic Monitoring on Clinical Outcomes

Background: Poor treatment adherence in COPD patients is associated with poor clinical outcomes and increased healthcare burden. Personalized approaches for adherence management, supported with technology-based interventions, may offer benefits to patients and providers but are currently unproven in terms of clinical outcomes as opposed to adherence outcomes. Methods: Maximizing Adherence and Gaining New Information For Your COPD (MAGNIFY COPD study), a pragmatic cluster randomized trial, aims to evaluate the impact of an adherence technology package (interventional package), comprising an adherence review, ongoing provision of a dual bronchodilator but with an add-on inhaler sensor device and a connected mobile application. This will compare time to treatment failure and other clinical outcomes in patients identified at high risk of exacerbations with historic poor treatment adherence as measured by prescription collection to mono/dual therapy over one year (1312 patients) versus usual care. Treatment failure is defined as the first occurrence of one of the following: (1) moderate/severe COPD exacerbation, (2) prescription of triple therapy (inhaled corticosteroid/long-acting β2-agonist/long-acting muscarinic antagonist [ICS/LABA/LAMA]), (3) prescription of additional chronic therapy for COPD, or (4) respiratory-related death. Adherence, moderate/severe exacerbations, respiratory-related healthcare resource utilization and costs, and intervention package acceptance rate will also be assessed. Eligible primary care practices (N=176) participating in the Optimum Patient Care Quality Improvement Program will be randomized (1:1) to either adherence support cluster arm (suitable patients already receiving or initiated Ultibro® Breezhaler® [indacaterol/glycopyrronium] will be offered interventional package) or the control cluster arm (suitable patients continue to receive usual clinical care). Patients will be identified and outcomes collected from anonymized electronic medical records within the Optimum Patient Care Research Database. On study completion, electronic medical record data will be re-extracted to analyze outcomes in both study groups. Registration Number: ISRCTN10567920. Conclusion: MAGNIFY will explore patient benefits of technology-based interventions for electronic adherence monitoring

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Conditioning and aversion to toxic Solanum bonariense ("naranjillo") leaves in calves

ABSTRACT: Solanum bonariense is a perennial poisonous shrub that induces cerebellar cortical degeneration when eaten by cattle. The aim of this research was to outline a protocol to induce a conditioned aversion to this plant. During the pre-conditioning period ten calves (126±12kg BW) were maintained at half of their normal energy intake with lucerne hay and water ad libitum, to stimulate consumption of S. bonariense. Every two days they were offered 100g ofS. bonariense leaves for 5 minutes. Calves began eating the target plant on day 10 and consumed all the plant material on day 12. The conditioning period began after each calf consumed the entire amount of S. bonariense for three consecutive sessions. Five animals were randomly selected for conditioning, and after ingestion ofS. bonariense they were dosed by oral gavage with lithium chloride (LiCl) at 200mg kg-1 BW (treated group), while the other five received a similar volume of water by oral gavage (control group). After 2 doses of LiCl the treated group ate no S. bonariense while the control group consumed the entire 100g. We confirmed that LiCl is a powerful tool to induce conditioned aversions against S. bonariense in calves, which persists for at least 3 months

Effect of Dietary Protein Level and Quebracho Tannin on Consumption of Pine Needles (Pinus Ponderosa) by Beef Cows

Ponderosa pine trees occupy over 15 million hectares of rangeland in western North America. Pregnant cows often consume pine needles (PN), and subsequently abort. The protein-to-energy ratio may be important in the ability of cattle to tolerate dietary terpenes. Tannins often co-occur with terpenes and may also influence diet selection. The objective of this experiment was to determine if the protein-to-energy ratio or the addition of quebracho tannin to cattle diets would influence PN consumption. In trial 1, 15 cows in moderate body condition were assigned to high (15.4% CP), medium (10.2% CP), or low (4.9% CP) dietary protein treatments for 12 d. In trial 2, 15 cows were assigned to high (5%), medium (2.5%), or no (0%) quebracho tannin diets for 8 d. In both trials, green PN were offered at 0930 h for 90 min. There was a treatment effect (P = 0.05) and a treatment × day interaction (P = 0.01) for PN consumption, as cattle on the high CP treatment consumed more PN than cattle on the medium and low CP diets for 4 and 6 d, respectively. Initially, treatments did not differ (P \u3e 0.09), but from d 3 to 9 cattle on the high CP treatment ate more PN than the other treatments. There was a day × treatment interaction (P = 0.002) for PN consumption; cattle on the 2.5% tannin treatment consumed less PN than did animals on the other treatments. Cattle are apparently unable to tolerate high quantities of PN terpenes on a low-protein diet. Tannins may influence PN consumption, but the mechanism is unknown