Loss of Sunda clouded leopards and forest integrity drive potential impacts of mesopredator release on vulnerable avifauna.

Amongst the unintended consequences of anthropogenic landscape conversion is declining apex predator abundance linked to loss of forest integrity, which can potentially re-order trophic networks. One such re-ordering, known as mesopredator release, occurs when medium-sized predators, also called mesopredators, rapidly increase in abundance following the decline in apex predator abundance, consequently reducing the abundance of mesopredator prey, notably including terrestrial avifauna. We examine the cascading impacts of declining Sunda clouded leopard abundance, itself consequent upon a reduction in forest integrity, on the mesopredator community of Sabah, Malaysia, to determine whether the phenomenon of mesopredator release is manifest and specifically whether it impacts the terrestrial avifauna community of pheasants and pittas.

The FAM13A Long Isoform Regulates Cilia Movement and Coordination in Airway Mucociliary Transport.

Single nucelotide polymorphisms (SNPs) at the locus are among the most commonly reported risk alleles associated with chronic obstructive pulmonary disease (COPD) and other respiratory diseases; however, the physiological role of FAM13A is unclear. In humans, two major protein isoforms are expressed at the locus: "long" and "short," but their functions remain unknown, partly because of a lack of isoform conservation in mice. We performed in-depth characterization of organotypic primary human airway epithelial cell subsets and show that multiciliated cells predominantly express the FAM13A long isoform containing a putative N-terminal Rho GTPase-activating protein (RhoGAP) domain.

Airway and Anaesthetic Management of Adult Patients with Mucopolysaccharidoses Undergoing Cardiac Surgery.

Mucopolysaccharidoses (MPSs) are rare congenital lysosomal storage disorders due to a deficiency of enzymes metabolising glycosaminoglycans, leading to their accumulation in tissues. This multisystem disease often requires surgical intervention, including valvular cardiac surgery. Adult MPSs have complex airways making anaesthesia risky.

VRK1 as a synthetic lethal target in VRK2 promoter-methylated cancers of the nervous system.

Collateral lethality occurs when loss of a gene/protein renders cancer cells dependent on its remaining paralog. Combining genome-scale CRISPR/Cas9 loss-of-function screens with RNA sequencing in over 900 cancer cell lines, we found that cancers of nervous system lineage, including adult and pediatric gliomas and neuroblastomas, required the nuclear kinase vaccinia-related kinase 1 (VRK1) for their survival in vivo. VRK1 dependency was inversely correlated with expression of its paralog VRK2.

Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex.

Receptor tyrosine kinase (RTK)-RAS signalling through the downstream mitogen-activated protein kinase (MAPK) cascade regulates cell proliferation and survival. The SHOC2-MRAS-PP1C holophosphatase complex functions as a key regulator of RTK-RAS signalling by removing an inhibitory phosphorylation event on the RAF family of proteins to potentiate MAPK signalling. SHOC2 forms a ternary complex with MRAS and PP1C, and human germline gain-of-function mutations in this complex result in congenital RASopathy syndromes.

CREBBP/EP300 acetyltransferase inhibition disrupts FOXA1-bound enhancers to inhibit the proliferation of ER+ breast cancer cells.

Therapeutic targeting of the estrogen receptor (ER) is a clinically validated approach for estrogen receptor positive breast cancer (ER+ BC), but sustained response is limited by acquired resistance. Targeting the transcriptional coactivators required for estrogen receptor activity represents an alternative approach that is not subject to the same limitations as targeting estrogen receptor itself. In this report we demonstrate that the acetyltransferase activity of coactivator paralogs CREBBP/EP300 represents a promising therapeutic target in ER+ BC.

Exhaled volatile organic compounds and lung microbiome in COPD: a pilot randomised controlled trial.

Background: Breath analysis is a burgeoning field, with interest in volatile organic compounds (VOCs) as a noninvasive diagnostic tool or an outcome measure, but no randomised controlled trials (RCTs) have yet evaluated this technology in a clinical trial longitudinally. In a pilot RCT, our exploratory objectives were feasibility of measuring VOCs multiple techniques, assessing relationships between VOCs and colonisation and whether CXCR2 antagonism with danirixin altered lung microbiome composition in individuals with COPD.

Method: 43 participants had VOCs and sputum biomarkers evaluated.

RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics.

Bladder cancer is a genetically heterogeneous disease, and novel therapeutic strategies are needed to expand treatment options and improve clinical outcomes. Here, we identified a unique subset of urothelial tumors with focal amplification of the RAF1 (CRAF) kinase gene. RAF1-amplified tumors had activation of the RAF/MEK/ERK signaling pathway and exhibited a luminal gene expression pattern.

Why an Increasing Number of Unmatched Residency Positions in Radiation Oncology? A Survey of Fourth-Year Medical Students.

Purpose: The number of US fourth-year medical students applying to radiation oncology has decreased during the past few years. We conducted a survey of fourth-year medical students to examine factors that may be influencing the decision to pursue radiation oncology.

Methods And Materials: An anonymous online survey was sent to medical students at 9 participating US medical schools.

Genomic Amplification and Functional Dependency of the Gamma Actin Gene in Uterine Cancer.

Sarcomere and cytoskeleton genes, or actomyosin genes, regulate cell biology including mechanical stress, cell motility, and cell division. While actomyosin genes are recurrently dysregulated in cancers, their oncogenic roles have not been examined in a lineage-specific fashion. In this report, we investigated dysregulation of nine sarcomeric and cytoskeletal genes across 20 cancer lineages.

Massive atrial myxoma requiring emergency cardiopulmonary bypass in a patient with heparin resistance.

Heparin exhibits complex pharmacology with a wide variation in individual response. Despite this, heparin is the most commonly used anticoagulant during cardiopulmonary bypass. Heparin resistance in the context of a patient with severe cardiovascular compromise presents a potentially life-threatening challenge.

Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients.

In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma.

Activity and Microbiological Efficacy of Gepotidacin from a Phase 2, Randomized, Multicenter, Dose-Ranging Study in Patients with Acute Bacterial Skin and Skin Structure Infections.

A phase 2 study of gepotidacin demonstrated the safety and efficacy of 3 gepotidacin doses (750 mg every 12 h [q12h], 1,000 mg q12h, and 1,000 mg every 8 h [q8h]) in hospitalized patients with suspected/confirmed Gram-positive acute bacterial skin and skin structure infections (ABSSSIs). Evaluating microbiology outcomes and responses were secondary endpoints. Pretreatment isolates recovered from infected lesions underwent susceptibility testing per Clinical and Laboratory Standards Institute guidelines.

A review of ASA physical status - historical perspectives and modern developments.

The American Society of Anesthesiologists (ASA) physical status is a tool commonly used to classify a patient's physical fitness before surgery. Since its introduction in 1941 it has undergone very few modifications to improve its reliability and to eliminate subjectivity, despite vast changes in both surgical and anaesthetic technique. We present the history of the ASA physical status and review the literature on its applicability to contemporary anaesthetic practice.

Implications of deranged activated partial thromboplastin time for anaesthesia and surgery.

Bleeding during and after surgery ranges from trivial to fatal. Bleeding is in part determined by the patient's coagulation status. The UK National Institute for Health and Care Excellence recommends a pre-operative clotting test for patients with a history of abnormal bleeding.

Effectiveness of nonpharmacological interventions to reduce procedural anxiety in children and adolescents undergoing treatment for cancer: A systematic review and meta-analysis.

Objective: Children and young people (CYP) with cancer undergo painful and distressing procedures. We aimed to systematically review the effectiveness of nonpharmacological interventions to reduce procedural anxiety in CYP.

Methods: Extensive literature searches sought randomised controlled trials that quantified the effect of any nonpharmacological intervention for procedural anxiety in CYP with cancer aged 0 to 25.

Human neuromuscular aging: Sex differences revealed at the myocellular level.

Age-related muscle loss (sarcopenia) is a major clinical problem affecting both men and women - accompanied by muscle weakness, dysfunction, disability, and impaired quality of life. Current definitions of sarcopenia do not fully encompass the age-related changes in skeletal muscle. We therefore examined the influence of aging and sex on elements of skeletal muscle health using a thorough histopathological analysis of myocellular aging and assessments of neuromuscular performance.

Analgesic efficacy of bilateral superficial cervical plexus block for thyroid surgery: meta-analysis and systematic review.

Background: Thyroid surgery is moderately painful, but is increasingly being considered as a day-case procedure. Bilateral superficial cervical plexus block (BSCPB) provides an adjuvant technique to facilitate this approach, but there is great evidential heterogeneity in randomised controlled trials (RCTs) about its use.

Methods: A systematic search, critical appraisal, and analysis of RCTs was performed.

Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations.

Background: Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.

Objective: To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.

Methods: We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.

Radiotherapy-induced reactivation of neurotrophic human herpes viruses: Overview and management.

Purpose: Infection by Human Herpes Viruses (HHV) types 1-3, are prevalent throughout the world. It is known that radiotherapy can reactivate HHVs, but it is unclear how and to what extent reactivations can interact with or affect radiotherapeutic efficacy, patient outcomes and mortality risk. Herein, we aim to summarize what is known about Herpes Simplex Virus (HSV)-1,2 and Varicella Zoster Virus (VZV) pathophysiology as it relates to tumor biology, radiotherapy, chemo-radiotherapy, diagnosis and management so as to optimize cancer treatment in the setting of active HHV infection.

Randomized, four-arm, dose-response clinical trial to optimize resistance exercise training for older adults with age-related muscle atrophy.

Purpose: The myriad consequences of age-related muscle atrophy include reduced muscular strength, power, and mobility; increased risk of falls, disability, and metabolic disease; and compromised immune function. At its root, aging muscle atrophy results from a loss of myofibers and atrophy of the remaining type II myofibers. The purpose of this trial (NCT02442479) was to titrate the dose of resistance training (RT) in older adults in an effort to maximize muscle regrowth and gains in muscle function.