Dysregulation of Nitrosylation Dynamics Promotes Nitrosative Stress and Contributes to Cardiometabolic Heart Failure with Preserved Ejection Fraction.

Background: Recent reports suggest increased myocardial iNOS expression leads to excessive protein -nitrosylation, contributing to the pathophysiology of HFpEF. However, the relationship between NO bioavailability, dynamic regulation of protein -nitrosylation by trans- and de-nitrosylases, and HFpEF pathophysiology has not been elucidated. Here, we provide novel insights into the delicate interplay between NO bioavailability and protein -nitrosylation in HFpEF.

Streamlining segmentation of cryo-electron tomography datasets with Ais.

Segmentation is a critical data processing step in many applications of cryo-electron tomography. Downstream analyses, such as subtomogram averaging, are often based on segmentation results, and are thus critically dependent on the availability of open-source software for accurate as well as high-throughput tomogram segmentation. There is a need for more user-friendly, flexible, and comprehensive segmentation software that offers an insightful overview of all steps involved in preparing automated segmentations.

Editorial Commentary: Clinically Important Outcome Values (Thresholds) Are Specific to the Patient Population Studied.

Patient-reported outcome (PRO) measures are critical toward understanding the influence and benefits of orthopedic surgery. While clinically important outcome values (CIOVs) have been developed to allow clinical interpretation of PRO values, gaps in outcome metrics still remain. The CIOVs can be used to describe specific populations of interest, such as in patients with hip dysplasia undergoing combined hip arthroscopy and periacetabular osteotomy.

Integrated systems biology identifies disruptions in mitochondrial function and metabolism as key contributors to heart failure with preserved ejection fraction (HFpEF).

Background: Heart failure with preserved ejection fraction (HFpEF) accounts for ~50% of HF cases, with no effective treatments. The ZSF1-obese rat model recapitulates numerous clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and LV diastolic dysfunction. Here, we utilized a systems-biology approach to define the early metabolic and transcriptional signatures to gain mechanistic insight into the pathways contributing to HFpEF development.

Systematic review and meta-analysis: do best-evidenced trauma-focused interventions for children and young people with PTSD lead to changes in social and interpersonal domains?

Young people with post-traumatic stress disorder experience difficulties in social and interpersonal domains. We examined whether the best-evidenced treatments of PTSD for children and young people (Trauma-focussed Cognitive Behavioural Therapy or Eye Movement Desensitisation and Reprocessing; aged 5-25) improve social or interpersonal factors in randomised controlled trials, compared to a comparator condition.: The review was preregistered on PROSPERO (CRD42023455615; 18th August 2023).

Cardiomyocyte myofilament function in common animal models of heart failure with preserved ejection fraction.

Human cardiomyocytes from very obese patients with heart failure and preserved ejection fraction (HFpEF) have markedly depressed calcium-activated tension and increased resting stiffness. To test if either are recapitulated by obese-HFpEF animal models, tension‑calcium and tension-sarcomere length relations were measured in myocytes from mice on a high fat diet (HFD) with L-NAME, ZSF1 rats, and Göttingen minipigs on HFD + DOCA (MP). Only MP myocytes displayed reduced Ca-activated tension, and none exhibited increased resting stiffness versus respective controls.

Reduced Hydrogen Sulfide Bioavailability Contributes to Cardiometabolic Heart Failure with Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a significant public health concern with limited treatment options. Dysregulated nitric oxide-mediated signaling has been implicated in HFpEF pathophysiology, however, little is known about the role of endogenous hydrogen sulfide (H2S).

Objectives: This study evaluated H2S bioavailability in patients and two animal models of cardiometabolic HFpEF and assessed the impact of H2S on HFpEF severity through alterations in endogenous H2S production and pharmacological supplementation.

Structural basis for surface activation of the classical complement cascade by the short pentraxin C-reactive protein.

Human C-reactive protein (CRP) is a pentameric complex involved in immune defense and regulation of autoimmunity. CRP is also a therapeutic target, with both administration and depletion of serum CRP being pursued as a possible treatment for autoimmune and cardiovascular diseases, among others. CRP binds to phosphocholine (PC) moieties on membranes to activate the complement system via the C1 complex, but it is unknown how CRP, or any pentraxin, binds to C1.

Women veteran transition mental health and well-being support group programs: A scoping review.

Background: The military is a male-dominated environment and culture in which women veterans can experience significant institutional prejudice. Transition can be confusing and isolating for women veterans. Group programs are an important source of transition support.

The source craters of the martian meteorites: Implications for the igneous evolution of Mars.

Approximately 200 meteorites come from ~10 impact events on the surface of Mars, yet their pre-ejection locations are largely unknown. Here, we combine the results of diverse sets of observations and modeling to constrain the source craters for several groups of martian meteorites. We compute that ejection-paired groups of meteorites are derived from lava flows within the top 26 m of the surface.

Selection and characterization of a peptide-based complement modulator targeting C1 of the innate immune system.

The human complement pathway plays a pivotal role in immune defence, homeostasis, and autoimmunity regulation, and complement-based therapeutics have emerged as promising interventions, with both antagonistic and agonistic approaches being explored. The classical pathway of complement is initiated when the C1 complex binds to hexameric antibody platforms. Recent structural data revealed that C1 binds to small, homogeneous interfaces at the periphery of the antibody platforms.

Solving the High-Intensity Multimodal Training Prescription Puzzle: A Systematic Mapping Review.

Background: High-Intensity Multimodal Training (HIMT) refers to all styles of high-intensity combined aerobic, resistance and/or bodyweight exercise. Previous heterogeneity in exercise prescription and reporting in HIMT reduces the understanding of which factors should be considered when prescribing HIMT (e.g.

A most aggressive bear: Safari videos document sloth bear defense against tiger predation.

Sloth bears are non-carnivorous yet they attack more people than any other bear. They often stand up and charge explosively if a person mistakenly gets too close. Here, we argue that their aggression toward humans is an extension of their behavior toward tigers, which are their only natural predator.

Post-traumatic stress disorder symptoms following exposure to acute psychological trauma in children aged 8-16 years in South Africa: protocol for the Sinethemba longitudinal study.

Introduction: Children exposed to trauma are vulnerable to developing post-traumatic stress disorder (PTSD) and other adverse mental health outcomes. In low-and middle-income countries (LMICs), children are at increased risk of exposure to severe trauma and co-occurring adversities. However, relative to high-income countries, there is limited evidence of the factors that predict good versus poor psychological recovery following trauma exposure in LMIC children, and the role of caregiver support in these high-adversity communities.

Adjunctive therapy with an oral HS donor provides additional therapeutic benefit beyond SGLT2 inhibition in cardiometabolic heart failure with preserved ejection fraction.

Background And Purpose: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a potent therapy for heart failure with preserved ejection fraction (HFpEF). Hydrogen sulphide (HS), a well-studied cardioprotective agent, could be beneficial in HFpEF. SGLT2i monotherapy and combination therapy involving an SGLT2i and HS donor in two preclinical models of cardiometabolic HFpEF was investigated.

Fe-rich X-ray amorphous material records past climate and persistence of water on Mars.

X-ray amorphous material comprises 15-73 wt.% of sedimentary rocks and eolian sediments in Gale crater. This material is variably siliceous and iron rich but aluminum poor.

Short-term effects of kinesiology taping on static and dynamic balance in healthy subjects.

Background: As a therapeutic tool, kinesiology taping (KT) has become increasingly popular for musculoskeletal injuries utilized by physiotherapists. KT has been found to have effects on facilitating muscle strength by generating a concentric pull on the fascia. However, little is known about KT in the improvement of dynamic and static balance.

Engineering Agonistic Bispecifics to Investigate the Influence of Distance on Surface-Mediated Complement Activation.

The development of agonists capable of activating the human complement system by binding to the C1 complex presents a novel approach for targeted cell killing. Bispecific nanobodies and Abs can successfully use C1 for this purpose; however, efficacy varies significantly between epitopes, Ab type, and bispecific design. To address this variability, we investigated monomeric agonists of C1 in the form of bispecific nanobodies, which lack Fc domains that lead to oligomerization in Abs.

Targeted complement inhibition using bispecific antibodies that bind local antigens and endogenous complement regulators.

Complement activation protects against infection but also contributes to pathological mechanisms in a range of clinical conditions such as autoimmune diseases and transplant rejection. Complement-inhibitory drugs, either approved or in development, usually act systemically, thereby increasing the risk for infections. We therefore envisioned a novel class of bispecific antibodies (bsAbs) which are capable of site-directed complement inhibition by bringing endogenous complement regulators in the vicinity of defined cell surface antigens.

Teaching Ultrasound-Guided Venous Cannulation to Newly Qualified Doctors.

Background Venous cannulation is an essential task that allows the intravenous administration of fluids and medications. In the United Kingdom, this task is often performed by newly qualified Foundation Year 1 (FY1) doctors; however, difficulties are commonly encountered. The usage of ultrasound increases the chance of successful cannulation, provided the operator has been trained.