Comparative Impact of Organic Grass-Fed and Conventional Cattle-Feeding Systems on Beef and Human Postprandial Metabolomics-A Randomized Clinical Trial.

Background/objectives: Cattle-feeding systems may have health implications for consumers of beef products. Organic grass-fed (GRA) and conventional (CON) cattle-feeding systems may result in beef products with differing metabolite profiles and therefore could impact the postprandial metabolomic response of consumers. This study aims to measure whole beef metabolomics and postprandial metabolomic response of consumers between GRA and CON beef to elucidate potential health implications.

Dignity in the Pediatric Population: A Systematic Review.

Context: Children are a uniquely vulnerable patient population with restricted abilities for self-advocacy and autonomy, risking infringement upon their dignity. Yet the concept of dignity in pediatrics remains underexplored relative to the adult literature and other outcome measures.

Objectives: To characterize how dignity is defined, evaluated, and/or measured in pediatrics.

Validation of the Prognostic Performance of Breast Cancer Index in Hormone Receptor-Positive Postmenopausal Breast Cancer Patients in the TEAM Trial.

Purpose: Patients with early-stage hormone receptor-positive (HR+) breast cancer face a prolonged risk of recurrence even after adjuvant endocrine therapy. The Breast Cancer Index (BCI) is significantly prognostic for overall (0-10 years) and late (5-10 years) distant recurrence (DR) risk in N0 and N1 patients. Here, BCI prognostic performance was evaluated in HR+ postmenopausal women from the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial.

Disruption of sugar nucleotide clearance is a therapeutic vulnerability of cancer cells.

Identifying metabolic steps that are specifically required for the survival of cancer cells but are dispensable in normal cells remains a challenge. Here we report a therapeutic vulnerability in a sugar nucleotide biosynthetic pathway that can be exploited in cancer cells with only a limited impact on normal cells. A systematic examination of conditionally essential metabolic enzymes revealed that UXS1, a Golgi enzyme that converts one sugar nucleotide (UDP-glucuronic acid, UDPGA) to another (UDP-xylose), is essential only in cells that express high levels of the enzyme immediately upstream of it, UGDH.

Bacillus Calmette-Guérin vaccination as defense against SARS-CoV-2 (BADAS): a randomized controlled trial to protect healthcare workers in the USA by enhanced trained immune responses.

Background: A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19.

Effect of drysuit seals on intraocular pressure in non-immersed scuba divers.

Objective: This study quantifies the change in intraocular pressure (IOP) secondary to wearing neck seals in scuba diving drysuits. Previous work demonstrates significant pressures exerted by these seals; we hypothesize that they would.

Methods: IOP was measured in 33 divers before and while wearing a drysuit using rebound tonometry.

Cardiovascular Responses During Light-intensity Aerobic Exercise with Varying Levels of Limb Occlusion Pressures.

The study aimed to assess cardiovascular responses to low-intensity aerobic exercise with varying levels of limb occlusion pressures (LOP) in a healthy population of men and women 30 to 60 years. The study was a single-session repeated measures design. Thirty individuals completed the study.

Residual Lung Abnormalities after COVID-19 Hospitalization: Interim Analysis of the UKILD Post-COVID-19 Study.

Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage. The UK Interstitial Lung Disease Consortium (UKILD) post-COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata. The PHOSP-COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge.

De novo sphingolipid biosynthesis necessitates detoxification in cancer cells.

Sphingolipids play important signaling and structural roles in cells. Here, we find that during de novo sphingolipid biosynthesis, a toxic metabolite is formed with critical implications for cancer cell survival. The enzyme catalyzing the first step in this pathway, serine palmitoyltransferase complex (SPT), is upregulated in breast and other cancers.

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial.

Background: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19.

Methods: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days.

Quantifying drysuit seal pressures in non-immersed scuba divers.

Introduction: Drysuits use flexible neck and wrist seals to maintain water-tight seals. However, if the seals exert too much pressure adverse physiological effects are possible, including dizziness, lightheadedness, syncope, and paresthesias in the hands. We aimed to quantify the seal pressures of neck and wrist seals in non-immersed divers.

Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID).

Introduction: The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not.

xCT-Driven Expression of GPX4 Determines Sensitivity of Breast Cancer Cells to Ferroptosis Inducers.

Inducers of ferroptosis such as the glutathione depleting agent Erastin and the GPX4 inhibitor Rsl-3 are being actively explored as potential therapeutics in various cancers, but the factors that determine their sensitivity are poorly understood. Here, we show that expression levels of both subunits of the cystine/glutamate antiporter xCT determine the expression of GPX4 in breast cancer, and that upregulation of the xCT/selenocysteine biosynthesis/GPX4 production axis paradoxically renders the cancer cells more sensitive to certain types of ferroptotic stimuli. We find that GPX4 is strongly upregulated in a subset of breast cancer tissues compared to matched normal samples, and that this is tightly correlated with the increased expression of the xCT subunits SLC7A11 and SLC3A2.

Understanding the impact of professional motivation on the workforce crisis in medicine: a rapid review.

Background: The NHS is facing a workforce crisis. Responses to date have focused on improving recruitment of staff, but less attention has been paid to retention.

Aim: To conduct a rapid review using Rosabeth Moss Kanter's three Ms model of workforce motivation as a sensitising framework to examine the current medical workforce crisis.

Krebs von den Lungen-6 (KL-6) is a pathophysiological biomarker of early-stage acute hypersensitivity pneumonitis among pigeon fanciers.

Background: Identifying early stages of hypersensitivity pneumonitis (HP) is hampered by variable presentation, heterogeneous or undetected causal antigens and lack of gold-standard biomarkers. Krebs von den Lungen (KL)-6 is pathophysiological biomarker of alveolar epithelial damage. Pigeon fanciers, susceptible to HP, provide a model to investigate early HP.

Endogenous toxic metabolites and implications in cancer therapy.

It is well recognized that many metabolic enzymes play essential roles in cancer cells in producing building blocks such as nucleotides, which are required in greater amounts due to their increased proliferation. On the other hand, the significance of enzymes in preventing the accumulation of their substrates is less recognized. Here, we outline the evidence and underlying mechanisms for how many metabolites normally produced in cells are highly toxic, such as metabolites containing reactive groups (e.

Selenium detoxification is required for cancer-cell survival.

The micronutrient selenium is incorporated via the selenocysteine biosynthesis pathway into the rare amino acid selenocysteine, which is required in selenoproteins such as glutathione peroxidases and thioredoxin reductases. Here, we show that selenophosphate synthetase 2 (SEPHS2), an enzyme in the selenocysteine biosynthesis pathway, is essential for survival of cancer, but not normal, cells. SEPHS2 is required in cancer cells to detoxify selenide, an intermediate that is formed during selenocysteine biosynthesis.

A continuously updated, geospatially rectified database of utility-scale wind turbines in the United States.

Over 60,000 utility-scale wind turbines are installed in the United States as of October, 2019, representing over 97 gigawatts of electric power capacity; US wind turbine installations continue to grow at a rapid pace. Yet, until April 2018, no publicly-available, regularly updated data source existed to describe those turbines and their locations. Under a cooperative research and development agreement, analysts from three organizations collaborated to develop and release the United States Wind Turbine Database (USWTDB) - a publicly available, continuously updated, spatially rectified data source of locations and attributes of utility-scale wind turbines in the United States.

Identification of Distinct Prognostic Groups: Implications for Patient Selection to Targeted Therapies Among Anti-Endocrine Therapy-Resistant Early Breast Cancers.

Purpose: Hormone receptor-positive breast cancer remains an ongoing therapeutic challenge, despite optimal anti-endocrine therapies. In this study, we assessed the prognostic ability of genomic signatures to identify patients at risk for recurrence after endocrine therapy. Analysis was performed on the basis of an a priori hypothesis related to molecular pathways, which might predict response to existing targeted therapies.

Benchmarking to the Gold Standard: Hyaluronan-Oxime Hydrogels Recapitulate Xenograft Models with In Vitro Breast Cancer Spheroid Culture.

Many 3D in vitro models induce breast cancer spheroid formation; however, this alone does not recapitulate the complex in vivo phenotype. To effectively screen therapeutics, it is urgently needed to validate in vitro cancer spheroid models against the gold standard of xenografts. A new oxime-crosslinked hyaluronan (HA) hydrogel is designed, manipulating gelation rate and mechanical properties to grow breast cancer spheroids in 3D.

Scottish consensus statement on the role of FeNO in adult asthma.

Fractional exhaled nitric oxide (FeNO) is the only available point of care test to assess type-2 inflammation in asthma. In making a diagnosis of asthma, FeNO should be used together with blood eosinophils and spirometry, alongside a history. Raised FeNO in conjunction with blood eosinophilia are treatable traits of type 2 inflammation in asthma, which in turn may guide personalised management.

Improving the Patient Experience and Decreasing Patient Anxiety With Nursing Bedside Report.

Purpose: The study's purpose was to explore the patient experience in an intervention group participating in nursing bedside report and the control group not participating.

Design: This descriptive, observational study had 3 objectives: (1) to measure baseline anxiety on admission to the hospital using the Beck Anxiety Inventory, (2) to describe patient self-reported anxiety and patient experiences during hospitalization, and (3) to evaluate the opinions by the intervention group about participating in nursing bedside report.

Methods: This mixed-methods study included quantitative and qualitative data.

Reliable consultant level data from an Acute Medical Unit: a powerful tool for improvement.

The development of a novel database interrogating the patient management system in the Acute Medical Unit at Forth Valley Royal Hospital, Scotland, has allowed, for the first time, acquisition of reliable individual consultant-level process and outcome data over a 2-year period. These data have a number of uses, including understanding the level of variation between consultant physicians in AMU across key indicators, such as direct discharge percentage (67.5-44.

What is the optimal systemic treatment of men with metastatic, hormone-naive prostate cancer? A STOPCAP systematic review and network meta-analysis.

Background: Our prior Systemic Treatment Options for Cancer of the Prostate systematic reviews showed improved survival for men with metastatic hormone-naive prostate cancer when abiraterone acetate plus prednisolone/prednisone (AAP) or docetaxel (Doc), but not zoledronic acid (ZA), were added to androgen-deprivation therapy (ADT). Trial evidence also suggests a benefit of combining celecoxib (Cel) with ZA and ADT. To establish the optimal treatments, a network meta-analysis (NMA) was carried out based on aggregate data (AD) from all available studies.