How aging influences the gut-bone marrow axis and alters hematopoietic stem cell regulation.

The gut microbiome has come to prominence across research disciplines, due to its influence on major biological systems within humans. Recently, a relationship between the gut microbiome and hematopoietic system has been identified and coined the gut-bone marrow axis. It is well established that the hematopoietic system and gut microbiome separately alter with age; however, the relationship between these changes and how these systems influence each other demands investigation.

UK endoscopy trainer survey: perspectives on current endoscopy training delivery, experience, barriers and opportunities.

Objective: UK endoscopy training is delivered by trainers possessing well developed endoscopy and teaching skills to help learners perform high-quality endoscopy. Train The Trainer (TTT) courses are effective, but additional trainer support is variable with little formal quality assurance. We performed a survey to map UK endoscopy training, assess trainer perspectives on training delivery and identify factors that would enhance training.

Significant human health co-benefits of mitigating African emissions.

Future African aerosol emissions, and therefore air pollution levels and health outcomes, are uncertain and understudied. Understanding the future health impacts of pollutant emissions from this region is crucial. Here, this research gap is addressed by studying the range in the future health impacts of aerosol emissions from Africa in the Shared Socioeconomic Pathway (SSP) scenarios, using the UK Earth System Model version 1 (UKESM1), along with human health concentration-response functions.

CDC COVID-19 vaccination program: Healthcare provider compliance with COVID-19 vaccine requirements and recommendations.

The COVID-19 Vaccination Provider Oversight (CVPO) program was implemented by the Centers for Disease Control and Prevention (CDC) to ensure the proper management and administration of COVID-19 vaccines by healthcare providers participating in the CDC COVID-19 Vaccination Program. As part of the CVPO program, the 64 CDC-funded immunization program awardees conducted site visits with participating healthcare providers. We evaluated healthcare provider adherence to CVPO program requirements between May 2021 and May 2023.

JAG consensus statements for training and certification in flexible sigmoidoscopy.

Introduction: Joint Advisory Group (JAG) certification in endoscopy is awarded when trainees attain minimum competency standards for independent practice. A national evidence-based review was undertaken to update standards for training and certification in flexible sigmoidoscopy (FS).

Methods: A modified Delphi process was conducted between 2019 and 2020 with multisociety representation from experts and trainees.

JAG consensus statements for training and certification in colonoscopy.

Introduction: In the UK, endoscopy certification is awarded when trainees attain minimum competency standards for independent practice. A national evidence-based review was undertaken to update and develop standards and recommendations for colonoscopy training and certification.

Methods: Under the oversight of the Joint Advisory Group (JAG), a modified Delphi process was conducted between 2019 and 2020 with multisociety expert representation.

Chaperone-mediated autophagy promotes PCa survival during ARPI through selective proteome remodeling.

The androgen receptor (AR) plays an important role in PCa metabolism, with androgen receptor pathway inhibition (ARPI) subjecting PCa cells to acute metabolic stress caused by reduced biosynthesis and energy production. Defining acute stress response mechanisms that alleviate ARPI stress and therefore mediate prostate cancer (PCa) treatment resistance will help improve therapeutic outcomes of patients treated with ARPI. We identified the up-regulation of chaperone-mediated autophagy (CMA) in response to acute ARPI stress, which persisted in castration-resistant PCa (CRPC); previously undefined in PCa.

Dynamic phase separation of the androgen receptor and its coactivators key to regulate gene expression.

Numerous cancers, including prostate cancer (PCa), are addicted to transcription programs driven by specific genomic regions known as super-enhancers (SEs). The robust transcription of genes at such SEs is enabled by the formation of phase-separated condensates by transcription factors and coactivators with intrinsically disordered regions. The androgen receptor (AR), the main oncogenic driver in PCa, contains large disordered regions and is co-recruited with the transcriptional coactivator mediator complex subunit 1 (MED1) to SEs in androgen-dependent PCa cells, thereby promoting oncogenic transcriptional programs.

Endoscopy training in the UK pre-COVID-19 environment: a multidisciplinary survey of endoscopy training and the experience of reciprocal feedback.

Objective: Training in gastrointestinal endoscopy in the UK occurs predominantly in a real world one-to-one trainer to trainee interaction. Previous surveys have shown surgical and gastroenterology trainees have had mixed experiences of supervision and training, and no surveys have explored specifically the role of trainee to trainer feedback. This study aimed to explore the experience of training and of providing trainer feedback for all disciplines of endoscopy trainees.

The integration of personalized medicine into health systems: progress and a path forward.

Tweetable abstract Fueled by technological advancements and the integration efforts of many pioneer health systems, personalized medicine is now being clinically implemented at measurable but incomplete levels system-wide.

Projected shifts in coral size structure in the Anthropocene.

Changes in the size structure of coral populations have major consequences for population dynamics and community function, yet many coral reef monitoring projects do not record this critical feature. Consequently, our understanding of current and future trajectories in coral size structure, and the demographic processes underlying these changes, is still emerging. Here, we provide a conceptual summary of the benefits to be gained from more comprehensive attention to the size of coral colonies in reef monitoring projects, and we support our argument through the use of case-history examples and a simplified ecological model.

Healthcare Resources Utilization and Costs of Patients with Non-IPF Progressive Fibrosing Interstitial Lung Disease Based on Insurance Claims in the USA.

Introduction: Idiopathic pulmonary fibrosis (IPF) is the classic progressive fibrosing interstitial lung disease (ILD), but some patients with ILDs other than IPF also develop a progressive fibrosing phenotype (PF-ILD). Information on use and cost of healthcare resources in patients with PF-ILD is limited.

Methods: We used USA-based medical insurance claims (2014-2016) to assess use and cost of healthcare resources in PF-ILD.

Alternative transcription cycle for bacterial RNA polymerase.

RNA polymerases (RNAPs) transcribe genes through a cycle of recruitment to promoter DNA, initiation, elongation, and termination. After termination, RNAP is thought to initiate the next round of transcription by detaching from DNA and rebinding a new promoter. Here we use single-molecule fluorescence microscopy to observe individual RNAP molecules after transcript release at a terminator.

Out of the Blue: The Failure of the Introduced Sea Anemone (Dalyell, 1848) in Salem Harbor, Massachusetts.

Failed invasions can be a key component for understanding and controlling introduced populations because understanding mechanisms behind failures can improve effective controls. In 2000, the non-native sea anemone was first found in Salem, Massachusetts, and it recolonized each summer. No individuals of have been found after 2010, despite intensive search efforts.

Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management.

Some patients with interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) develop a progressive fibrosing phenotype. We investigated the diagnosis and management of non-IPF ILDs using data from a survey of physicians and from US insurance claims. Pulmonologists, rheumatologists and internists in France, Germany, Italy, Japan, Spain, UK and US who had managed ≥10 patients with non-IPF ILDs in the past year, including those with progressive fibrosing ILDs, completed an online survey.

Certification of UK gastrointestinal endoscopists and variations between trainee specialties: results from the JETS e-portfolio.

In the UK, endoscopy certification is administered by the Joint Advisory Group on Gastrointestinal Endoscopy (JAG). Since 2011, certification for upper and lower gastrointestinal endoscopy has been awarded via a national (JETS) e-portfolio to the main training specialties of: gastroenterology, gastrointestinal surgeons (GS) and non-medical endoscopists (NME). Trends in endoscopy certification and differences between trainee specialties were analyzed.

The Facility-Level HIV Treatment Cascade: Using a Population Health Tool in Health Care Facilities to End the Epidemic in New York State.

Background: The HIV treatment cascade is a tool for characterizing population-level gaps in HIV care, yet most adaptations of the cascade rely on surveillance data that are ill-suited to drive quality improvement (QI) activities at the facility level. We describe the adaptation of the cascade in health care organizations and report its use by HIV medical providers in New York State (NYS).

Methods: As part of data submissions to the NYS Department of Health, sites that provide HIV medical care in NYS developed cascades using facility-generated data.

Changes in scoring of Direct Observation of Procedural Skills (DOPS) forms and the impact on competence assessment.

Background: Direct Observation of Procedural Skills (DOPS) is an established competence assessment tool in endoscopy. In July 2016, the DOPS scoring format changed from a performance-based scale to a supervision-based scale. We aimed to evaluate the impact of changes to the DOPS scale format on the distribution of scores in novice trainees and on competence assessment.

The N54- Mutant Has Decreased Affinity for and Suggests a Mechanism for Coupling Heterotrimeric G Protein Nucleotide Exchange with Subunit Dissociation.

Ser54 of G binds guanine nucleotide and Mg as part of a conserved sequence motif in GTP binding proteins. Mutating the homologous residue in small and heterotrimeric G proteins generates dominant-negative proteins, but by protein-specific mechanisms. For , this results from persistent binding of to , whereas for small GTP binding proteins and this results from persistent binding to guanine nucleotide exchange factor or receptor.

Individual marking of soft-bodied subtidal invertebrates in situ - A novel staining technique applied to the giant plumose anemone Metridium farcimen (Tilesius, 1809).

The ability to recognize individuals and track growth over time is crucial to population dynamics research as well as studies of animal behavior. Invertebrates are particularly difficult to track as they often molt, have regenerative capabilities, or lack hard parts to attach markers. We tested, in laboratory and field studies, a new way of marking sea anemones (order Actiniaria) by injection of three vital stains (i.

Gβγ directly modulates vesicle fusion by competing with synaptotagmin for binding to neuronal SNARE proteins embedded in membranes.

G-coupled G protein-coupled receptors can inhibit neurotransmitter release at synapses via multiple mechanisms. In addition to Gβγ-mediated modulation of voltage-gated calcium channels (VGCC), inhibition can also be mediated through the direct interaction of Gβγ subunits with the soluble -ethylmaleimide attachment protein receptor (SNARE) complex of the vesicle fusion apparatus. Binding studies with soluble SNARE complexes have shown that Gβγ binds to both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs, competing with synaptotagmin 1(syt1) for binding sites on t-SNARE.

The Unintended Consequences of Over-Reducing Cardiopulmonary Bypass Circuit Prime Volume.

Background: The Society of Thoracic Surgeon blood conservation guidelines recommend minimizing cardiopulmonary bypass circuit prime volume (PV) as an integral, evidence-based (Class I, Level A) blood conservation strategy. We used a large, multiinstitutional registry to evaluate the effectiveness of restricting cardiopulmonary bypass PV on intraoperative red blood cell (RBC) transfusion.

Methods: We reviewed 47,273 isolated coronary artery bypass graft procedures performed among 189 institutions between April 2012 and May 2015.

Promiscuous targeting of bromodomains by bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia.

Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET (bromo and extra-terminal) inhibitors and their significant activity in diverse tumor models have rapidly translated into clinical studies and have motivated drug development efforts targeting non-BET BRDs. However, the complex multidomain/subunit architecture of BRD protein complexes complicates predictions of the consequences of their pharmacological targeting.