Short-chain fatty acid metabolites propionate and butyrate are unique epigenetic regulatory elements linking diet, metabolism and gene expression.

The short-chain fatty acids (SCFAs) propionate and butyrate have beneficial health effects, are produced in large amounts by microbial metabolism and have been identified as unique acyl lysine histone marks. To better understand the function of these modifications, we used chromatin immunoprecipitation followed by sequencing to map the genome-wide location of four short-chain acyl histone marks, H3K18pr, H3K18bu, H4K12pr and H4K12bu, in treated and untreated colorectal cancer (CRC) and normal cells as well as in mouse intestines in vivo. We correlate these marks with open chromatin regions and gene expression to access the function of the target regions.

"Blindness" is not a contraindication for voretigene neparvovec-rzyl treatment: a review of 9 cases.

Objective: Biallelic RPE65 pathogenic variants may cause Leber congenital amaurosis (LCA). Voretigene neparvovec-rzyl (VN, Luxturna) is the only approved subretinal gene therapy that demonstrated benefit and safety. The eligibility criteria are vague and variable between centres.

Influence of the order of the physical qualities during the microcycle on the weekly external loads and match day's readiness level in highly trained academy soccer players.

Background: Highly trained academy soccer practitioners usually implement an aerobic-oriented session followed by a speed-oriented session during the first and second heavy load session of a training week, respectively. This study aimed to investigate if the order of these physical training sessions would influence the external training loads and the subsequent readiness level on match day.

Methods: Twenty-five highly trained academy soccer players (12 U17 and 13 U19) participated in two experimental weeks randomly presented.

Cardiovascular MRI-derived Right Atrial Strain for Improved Risk Stratification in Patients with Severe Aortic Stenosis.

Purpose To assess the prognostic implications of cardiac MRI-derived imaging markers in individuals with severe aortic stenosis (AS). Materials and Methods This prospective study (German Clinical Trials Register, DRKS00024479) enrolled individuals with severe AS who underwent cardiac MRI before transcatheter aortic valve replacement (TAVR) from January 2017 to March 2022. Image analyses included myocardial volumes, cardiac MRI feature tracking-derived left atrial (LA) and right atrial (RA) as well as left ventricular (LV) and right ventricular (RV) strain, myocardial T1 mapping, and late gadolinium enhancement analyses.

Benzimidazole Derivatives in Breast Cancer: Target-Specific Therapeutic Breakthroughs.

Despite ongoing advancements in drug design and developments, breast cancer remains a serious and devastating disease and is ranked as the second most common illness in women. Breast cancer rates have increased significantly during the last 40 years. This necessitates the development of novel treatment techniques.

Is endometriosis typology a potentially better classification system for assessing risk of female infertility?

Objective: To determine whether endometriosis typology, namely ovarian endometriomas (OE), deep infiltrating endometriosis (DIE), or superficial endometriosis (SE), correlates with fertility history.

Design: Prospective cohort.

Setting: One of fourteen surgical centers in Salt Lake City, Utah (n = 5) or San Francisco, California (n = 9).

Inverted Mattress Knotless Repair of Medial Ulnar Collateral Ligament Avulsion Injury Using Flat Braided Suture Internal Brace.

Direct repair of ulnar collateral ligament (UCL) injuries with suture augmentation has been successful in properly selected patients lacking chronic attritional wear of the medial elbow. Described is a Speed-Fix technique for direct UCL repair using SutureTape, with Brace augmentation. The Speed-Fix repair technique uses an inverted mattress knotless repair with a knotless SwiveLock anchor and FiberTape suture, which allows for theoretical compression at the repair site.

Sleep and circadian disturbances in children with neurodevelopmental disorders.

Sleep is essential for brain development and overall health, particularly in children with neurodevelopmental disorders (NDDs). Sleep disruptions can considerably impact brain structure and function, leading to dysfunction of neurotransmitter systems, metabolism, hormonal balance and inflammatory processes, potentially contributing to the pathophysiology of NDDs. This Review examines the prevalence, types and mechanisms of sleep disturbances in children with NDDs, including autism spectrum disorder, attention-deficit hyperactivity disorder and various genetic syndromes.

Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma.

Background: Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma.

Methods: We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study.

Who will benefit from vorasidenib? Review of data from the literature and open questions.

The clinical efficacy of isocitrate dehydrogenase (IDH) inhibitors in the treatment of patients with grade 2 IDH-mutant (mIDH) gliomas is a significant therapeutic advancement in neuro-oncology. It expands treatment options beyond traditional radiation therapy and cytotoxic chemotherapy, which may lead to significant long-term neurotoxic effects while extending patient survival. The INDIGO study demonstrated that vorasidenib, a pan-mIDH inhibitor, improved progression-free survival for patients with grade 2 mIDH gliomas following surgical resection or biopsy compared to placebo and was well tolerated.

All Suture Biceps Tenodesis Has Greater Biomechanical Strength Than Metal Button Fixation.

Purpose: To evaluate the maximal load to failure, cyclic displacement, stiffness, and modes of failure of onlay subpectoral biceps tenodesis with an intramedullary unicortical metal button (MB) versus an inlay, all-suture Caspari-Weber (CW) technique.

Methods: Sixteen matched paired human cadaveric proximal humeri were randomly allocated for subpectoral BT with either CW or MB using a high-strength suture (N = 16; 8 male, 8 female, mean age = 82.5 years, range 62-99 years).

Rehabilitation at Home Using Mobile Health for Older Adults Hospitalized for Ischemic Heart Disease: The RESILIENT Randomized Clinical Trial.

Importance: Among older adults with ischemic heart disease, participation in traditional ambulatory cardiac rehabilitation (CR) remains low. While mobile health CR (mHealth-CR) provides a novel opportunity to deliver care, age-specific impairments to technology use may limit uptake, and efficacy data are currently lacking.

Objective: To test whether mHealth-CR improves functional capacity in older adults.

Prenatal cfDNA Sequencing and Incidental Detection of Maternal Cancer.

Background: Cell-free DNA (cfDNA) sequence analysis to screen for fetal aneuploidy can incidentally detect maternal cancer. Additional data are needed to identify DNA-sequencing patterns and other biomarkers that can identify pregnant persons who are most likely to have cancer and to determine the best approach for follow-up.

Methods: In this ongoing study we performed cancer screening in pregnant or postpartum persons who did not perceive signs or symptoms of cancer but received unusual clinical cfDNA-sequencing results or results that were nonreportable (i.

Inequities in the Use of Disease-Modifying Therapy Among Adults Living With Multiple Sclerosis in Urban and Rural Areas in Alberta, Canada.

Objectives: To compare disease-modifying therapy (DMT) use between people living with multiple sclerosis (pwMS) who resided in rural vs urban areas.

Methods: This retrospective cohort study used population-level individually linked administrative data to identify pwMS on April 1, 2019 (index date), in Alberta, Canada. DMT use was compared between pwMS who resided in rural vs urban areas during a 1-year postindex period.

A Global Collaborative Comparison of SARS-CoV-2 Antigenicity Across 15 Laboratories.

Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels.

Soil and Site Productivity Effects on Above- and Belowground Radiata Pine Carbon Pools at Harvesting Age.

D. Don is the most widely planted forest species in Chile, making it crucial to understand carbon pools in adult plantations. This study aimed to evaluate the effect of soil type and site productivity on the total carbon stock in adult radiata pine plantations, considering sites with contrasting water and nutrient availability.

N-methyl-D-aspartate Receptors and Depression: Linking Psychopharmacology, Pathology and Physiology in a Unifying Hypothesis for the Epigenetic Code of Neural Plasticity.

Uncompetitive NMDAR (N-methyl-D-aspartate receptor) antagonists restore impaired neural plasticity, reverse depressive-like behavior in animal models, and relieve major depressive disorder (MDD) in humans. This review integrates recent findings from in silico, in vitro, in vivo, and human studies of uncompetitive NMDAR antagonists into the extensive body of knowledge on NMDARs and neural plasticity. Uncompetitive NMDAR antagonists are activity-dependent channel blockers that preferentially target hyperactive GluN2D subtypes because these subtypes are most sensitive to activation by low concentrations of extracellular glutamate and are more likely activated by certain pathological agonists and allosteric modulators.

Anti-Platelet Therapy with Cangrelor in Cardiogenic Shock Patients: A Systematic Review and Single-Arm Meta-Analysis.

Percutaneous coronary intervention (PCI) is a proven therapy for acute myocardial infarction (AMI) cardiogenic shock (CS). Dual anti-platelet therapy (i.e.

Advanced Management of Patients Undergoing Transcatheter Treatment for Pulmonary Embolism: Evidence-Based Strategies for Optimized Patient Care.

Pulmonary embolism (PE) is a life-threatening medical condition caused by the thrombotic occlusion of one or more branches of the lung vasculature, which represents the third most common cause of cardiovascular mortality after myocardial infarction and stroke. PE treatment requires a tailored approach based on accurate risk stratification and personalized treatment decision-making. Anticoagulation is the cornerstone of PE management, yet patients at higher clinical risk may require more rapid reperfusion therapies.

International Nephrology Masterclass in Chronic Kidney Disease: Rationale, Summary, and Future Perspectives.

Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the population worldwide, accounting for more than 843 million (M) individuals. The prevalence of CKD (844 M patients) is higher than that of diabetes mellitus (422 M patients), cancer (42 M patients), and HIV (37 M patients), but people are often less aware of it. Global expert groups predict reductions in the nephrology workforce in the next decade, with a declining interest in nephrology careers.

ALDH Breast Cancer Stem Cells Exhibit a Mesenchymal-Senescent Hybrid Phenotype, with Elevated Metabolic and Migratory Activities.

Cancer stem cells (CSCs) account for 0.01 to 2% of the total tumor mass; however, they play a key role in tumor progression, metastasis and resistance to current cancer therapies. The generation and maintenance of CSCs are usually linked to the epithelial-mesenchymal transition (EMT), a dynamic process involved in reprogramming cancer cells towards a more aggressive and motile phenotype with increased stemness potential.

Choroidal Response to Intravitreal Bevacizumab Injections in Treatment-Naïve Macular Neovascularization Secondary to Chronic Central Serous Chorioretinopathy.

Background/objectives: To evaluate the impact of intravitreal bevacizumab (IVB) therapy on anatomical and visual outcomes in patients with macular neovascularization (MNV) secondary to chronic central serous chorioretinopathy (cCSC).

Methods: This retrospective observational study reviewed the medical records of treatment-naïve patients diagnosed with cCSC complicated by MNV and treated with IVB injections over a 5-year period. The presence of MNV was confirmed using optical coherence tomography angiography (OCTA).

Effects of Different Detraining Periods on the Physical Fitness of Older Adults with Cardiometabolic Risk Factors.

Objective: To verify the effects of two different detraining periods on the physical fitness of older adults with cardiometabolic risk factors.

Methods: This observational study encompassed older individuals with cardiometabolic risk factors, who were assessed after two different detraining periods: 1 month (1DT) and 3 months (3DT). Physical fitness was assessed using the 30-s sit to stand test (STS), 30-s arm curl, chair sit-and-reach, back scratch, timed up and go, and 6-min walk test (6MWT).