Extra-osseous Roles of the RANK-RANKL-OPG Axis with a Focus on Skeletal Muscle.

Purpose Of Review: This review aims to consolidate recent observations regarding extra-osseous roles of the RANK-RANKL-OPG axis, primarily within skeletal muscle.

Recent Findings: Preclinical efforts to decipher a common signalling pathway that links the synchronous decline in bone and muscle health in ageing and disease disclosed a potential role of the RANK-RANKL-OPG axis in skeletal muscle. Evidence suggests RANKL inhibition benefits skeletal muscle function, mass, fibre-type switching, calcium homeostasis and reduces fall incidence.

Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD).

Neoadjuvant immunotherapy for dMMR and pMMR colorectal cancers: therapeutic strategies and putative biomarkers of response.

Approximately 15% of locally advanced colorectal cancers (CRC) have DNA mismatch repair deficiency (dMMR), resulting in high microsatellite instability and a high tumour mutational burden. These cancers are frequently sensitive to therapy with immune-checkpoint inhibitors (ICIs) in the metastatic setting. This sensitivity seems to be even more pronounced in locally advanced disease, and organ preservation has become a realistic aim in ongoing clinical trials involving patients with dMMR rectal cancer.

Ex Vivo Machine Perfusion as a Platform for Lentiviral Gene Delivery in Rat Livers.

Developing new strategies for local monitoring and delivery of immunosuppression is critical to making allografts safer and more accessible. Ex vivo genetic modification of grafts using machine perfusion presents a promising approach to improve graft function and modulate immune responses while minimizing risks of off-target effects and systemic immunogenicity in vivo. This proof-of-concept study demonstrates the feasibility of using normothermic machine perfusion (NMP) to mimic in vitro conditions for effective gene delivery.

Pregnancy-Associated Plasma Protein-A and Free β-Human Chorionic Gonadotrophin in Relation with Oxidative Stress in Obese Pregnant Women: A Clinical Cross-Sectional Study.

: The pathophysiological mechanism underlying pregnancy complications is not entirely known. Although it is currently impossible to predict the occurrence of redox imbalance, it is possible to identify women with a high or medium risk of developing this disease prior to a negative outcome by non-invasive diagnostic methods. : This study aimed to examine the possible role of the parameter of oxidative stress (OS) measured in early pregnancy in the screening/treatment of obesity and its complications during pregnancy.

Determinants of Engagement in Leisure-Time Physical Activity and Club Sports among University Students: A Large-Scale Study.

Various socio-demographic, environmental, and lifestyle-related factors have been reported to be associated with physical activity (PA) habits. However, there exist insufficient data comparing different forms of engagement in PA, sports, and exercise. This study aimed to investigate potential factors associated with the engagement in leisure-time PA (LPA) and club sports (CSs) in a large sample of college/university students.

DNA Methylation Age Mediates Effect of Metabolic Profile on Cardiovascular and General Aging.

Background: Alterations in lipid metabolism and DNA methylation are 2 hallmarks of aging. Connecting metabolomic, epigenomic, and aging outcomes help unravel the complex mechanisms underlying aging. We aimed to assess whether DNA methylation clocks mediate the association of circulating metabolites with incident atherosclerotic cardiovascular disease (ASCVD) and frailty.

Integrated multi-omics analysis of zinc-finger proteins uncovers roles in RNA regulation.

RNA interactome studies have revealed that hundreds of zinc-finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), yet their RNA substrates and functional significance remain largely uncharacterized. Here, we present a systematic multi-omics analysis of the DNA- and RNA-binding targets and regulatory roles of more than 100 ZFPs representing 37 zinc-finger families. We show that multiple ZFPs are previously unknown regulators of RNA splicing, alternative polyadenylation, stability, or translation.

Large-scale map of RNA-binding protein interactomes across the mRNA life cycle.

mRNAs interact with RNA-binding proteins (RBPs) throughout their processing and maturation. While efforts have assigned RBPs to RNA substrates, less exploration has leveraged protein-protein interactions (PPIs) to study proteins in mRNA life-cycle stages. We generated an RNA-aware, RBP-centric PPI map across the mRNA life cycle in human cells by immunopurification-mass spectrometry (IP-MS) of ∼100 endogenous RBPs with and without RNase, augmented by size exclusion chromatography-mass spectrometry (SEC-MS).

Phase-change VO-based thermochromic smart windows.

Thermochromic coatings hold promise in reducing building energy consumption by dynamically regulating the heat gain of windows, which are often regarded as less energy-efficient components, across different seasons. Vanadium dioxide (VO) stands out as a versatile thermochromic material for smart windows owing to its reversible metal-to-insulator transition (MIT) alongside correlated structural and optical properties. In this review, we delve into recent advancements in the phase-change VO-based thermochromic coatings for smart windows, spanning from the macroscopic crystal level to the microscopic structural level (including elemental doping and micro/nano-engineering), as well as advances in controllable fabrication.

Moving from psychiatric practice in the UK to Australia: some personal reflections.

In this article, we reflect on factors which may tempt psychiatrists to move from working in the UK to Australia. A comparison between the UK and Australian healthcare systems is presented. Following this, G.

Evolved cytidine and adenine base editors with high precision and minimized off-target activity by a continuous directed evolution system in mammalian cells.

Continuous directed evolution of base editors (BEs) has been successful in bacteria cells, but not yet in mammalian cells. Here, we report the development of a Continuous Directed Evolution system in Mammalian cells (CDEM). CDEM enables the BE evolution in a full-length manner with Cas9 nickase.

Sensory-Motor Neuropathy in Mfn2 T105M Knock-in Mice and Its Reversal by a Novel Piperine-Derived Mitofusin Activator.

Mitochondrial dysfunction is a hallmark of many genetic neurodegenerative diseases, but therapeutic options to reverse mitochondrial dysfunction are limited. While recent studies support the possibility of improving mitochondrial fusion/fission dynamics and motility to correct mitochondrial dysfunction and resulting neurodegeneration in Charcot-Marie-Tooth disease (CMT) and other neuropathies, the clinical utility of reported compounds and relevance of preclinical models are uncertain. Here, we describe motor and sensory neuron dysfunction characteristic of clinical CMT type 2 A in a CRISPR/Casp-engineered Mfn2 Thr105Met (T105M) mutant knock-in mouse.

Ameliorated cellular hallmarks of myotonic dystrophy in hybrid myotubes from patient and unaffected donor cells.

Background: Cell-based strategies are being explored as a therapeutic option for muscular dystrophies, using a variety of cell types from different origin and with different characteristics. Primary pericytes are multifunctional cells found in the capillary bed that exhibit stem cell-like and myogenic regenerative properties. This unique combination allows them to be applied systemically, presenting a promising opportunity for body-wide muscle regeneration.

Association between Flexibility, Measured with the Back-Scratch Test, and the Odds of Oxytocin Administration during Labour and Caesarean Section.

This study explored whether assessing flexibility levels in clinical settings might predict the odds of oxytocin administration and caesarean section to stimulate labour. Pregnant women from the GESTAFIT Project (n = 157), participated in this longitudinal study. Maternal upper-body flexibility was assessed at 16 gestational weeks (g.

The Role of Physical Fitness in Emotional Well-Being and Distress during Pregnancy: The GESTAFIT Project.

Pregnancy involves various physiological, physical, and social changes that can impact the mental health of the woman, causing her to have a stressful experience. Physical fitness (PF) is postulated as a powerful marker of health in this population. Therefore, this longitudinal study examined the association of PF with maternal emotional well-being and ill-being outcomes at 16th and 34th gestational weeks (g.

Impact of Cryopreserved Placental Allografts on Biochemical Recurrence in Prostate Cancer.

Background: Human placental allografts are widely used to promote wound healing. Placental (or amniotic membrane/umbilical cord) allografts are placed along the neurovascular bundles during radical prostatectomy to improve continence and erectile function recovery. It is unknown whether placental allografts impact biochemical recurrence (BCR).

Surprising sounds influence risky decision making.

Adaptive behavior depends on appropriate responses to environmental uncertainty. Incidental sensory events might simply be distracting and increase errors, but alternatively can lead to stereotyped responses despite their irrelevance. To evaluate these possibilities, we test whether task-irrelevant sensory prediction errors influence risky decision making in humans across seven experiments (total n = 1600).

Striving for Stability in Patients with COPD: A New Way Forward?

This article summarises key themes from a symposium held during the recent European Respiratory Society congress, which took place in Vienna, Austria, 7-11 September 2024. The symposium was sponsored by GSK and entitled 'Striving for disease stability in COPD: Giving patients more of their best days'. During the session, the speakers (MeiLan Han, Lowie Vanfleteren and Dave Singh) highlighted the specific challenges of chronic obstructive pulmonary disease (COPD), such as its unpredictable and unstable nature, with additional insights provided from patients with COPD in the form of video interviews.