Premature thelarche and pesticide exposure: A case-control study in an intensive agricultural area.

The extensive use of pesticides in agriculture significantly enhances crop yields and pest control. However, it also raises concerns regarding environmental and human health impacts. Children are particularly vulnerable to health effects of pesticide exposure, especially for neurological development and reproductive health.

Elucidating emerging signaling pathways driving endothelial dysfunction in cardiovascular aging.

The risk for developing cardiovascular diseases dramatically increases in older individuals, and aging vasculature plays a crucial role in determining their morbidity and mortality. Aging disrupts endothelial balance between vasodilators and vasoconstrictors, impairing function and promoting pathological vascular remodeling. In this Review, we discuss the impact of key and emerging molecular pathways that transduce aberrant inflammatory signals (i.

A Personalized Approach to Vitamin D Supplementation in Cardiovascular Health Beyond the Bone: An Expert Consensus by the Italian National Institute for Cardiovascular Research.

Vitamin D is increasingly recognized for its role in cardiovascular health beyond its well-established effects on bone metabolism. This review synthesizes findings from observational studies, interventional trials, and meta-analyses to clarify the mechanisms through which vitamin D impacts cardiovascular health, including its influence on vascular function, inflammation, and metabolic pathways. Additionally, this review emphasizes the importance of a personalized approach to vitamin D supplementation, integrating individual cardiovascular risk profiles, baseline vitamin D levels, and comorbid conditions, such as hypertension and diabetes.

Whole-Exome Analysis and Osteosarcoma: A Game Still Open.

Osteosarcoma (OS) is the most prevalent malignant bone tumor in adolescents and young adults. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g.

Virtual reality games for spatial hearing training in children and young people with bilateral cochlear implants: the "Both Ears (BEARS)" approach.

Spatial hearing relies on the encoding of perceptual sound location cues in space. It is critical for communicating in background noise, and understanding where sounds are coming from (sound localization). Although there are some monoaural spatial hearing cues (i.

12 real forensic cases solved by the DNA STR-typing of skeletal remains exposed to extreme environment conditions, without the conventional bone pulverization step.

DNA identification of human skeletal remains play a valuable role in the forensic field, especially in missing persons and mass disasters investigation. Hard tissues, such as bones and teeth, represent a very common kind of samples analyzed in forensic laboratories because often they are the only biological materials remaining. However, the major limitation in using these compact samples rely on time consuming and labor-intensive treatment of grinding them into powder before proceeding with the conventional DNA purification and extraction step.

A Population-Wide Exploration of the THAP11 CAG Repeat Size and Structure in the 100,000 Genomes Project and UK Biobank.

Background: A CAG repeat expansion in THAP11 was recently found to be associated with spinocerebellar ataxia in two Chinese families. Expanded repeats ranged from 45 to 100 units, with CAA sequence interruptions in the 5' region and an uninterrupted CAG tract in the 3' tail.

Objective: Here, we assess the population distribution of the THAP11 repeat, and its contribution to neurological diseases.

Memory complaints after COVID-19: a potential indicator of primary cognitive impairment or a correlate of psychiatric symptoms?

Cognitive impairment and symptoms of psychiatric disorders have been reported frequently as features of post-acute sequelae of SARS-CoV-2 infection. This study aims to investigate subjective memory complaints in COVID-19 survivors and determine if these are more strongly associated with objective cognitive impairment related to sequelae of SARS-CoV-2 infection or with symptoms of psychiatric conditions. A total of 608 COVID-19 survivors were evaluated in-person 6-11 months after hospitalization, with 377 patients assigned to a "no subjective memory complaint (SMC)" group and 231 patients assigned to an SMC group based on their Memory Complaint Scale scores.

A recombinant fragment antigen-binding (Fab) of trastuzumab displays low cytotoxic profile in adult human cardiomyocytes: first evidence and the key implication of FcγRIIA receptor.

Fragment crystallizable gamma receptors (FcγRs) mediate various cellular responses with significant cardiovascular implications. They contribute to the anticancer activity of trastuzumab (TRZ), a recombinant humanized monoclonal antibody that interferes with human epidermal growth factor receptor 2 (HER2), thereby blocking its physiological function in cardiac cells. This is responsible for cardiac complications that hamper TRZ clinical application.

Prognostic impact of microscopic residual disease after neoadjuvant chemotherapy in patients undergoing interval debulking surgery for advanced ovarian cancer.

Purpose: To determine the prognostic impact of microscopic residual disease after neoadjuvant chemotherapy (NACT) in patients undergoing interval debulking surgery (IDS) for advanced epithelial ovarian cancer (AEOC).

Methods: Patients affected by FIGO stage IIIC-IV ovarian cancer undergoing IDS between October 2010 and April 2016 were selected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier analysis.

Cohort profile: the ADAPT study, a prospective study of pregnancy preferences, pregnancy, and health and well-being in the southwestern USA.

Purpose: Significant methodological shortcomings limit the validity of prior research on pregnancy decision-making and the effects of 'unintended' pregnancies on people's health and well-being. The Attitudes and Decisions After Pregnancy Testing (ADAPT) study investigates the consequences for individuals unable to attain their pregnancy and childbearing preferences using an innovative nested prospective cohort design and novel conceptualisation and measurement of pregnancy preferences.

Participants: This paper describes the characteristics of the ADAPT Study Cohort, comprised of 2015 individuals aged 15-34 years, assigned female at birth, recruited between 2019 and 2022 from 23 health facilities in the southwestern USA.

A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 associated with intellectual disability.

GC-rich tandem repeat expansions (TREs) are often associated with DNA methylation, gene silencing and folate-sensitive fragile sites, and underlie several congenital and late-onset disorders. Through a combination of DNA-methylation profiling and tandem repeat genotyping, we identified 24 methylated TREs and investigated their effects on human traits using phenome-wide association studies in 168,641 individuals from the UK Biobank, identifying 156 significant TRE-trait associations involving 17 different TREs. Of these, a GCC expansion in the promoter of AFF3 was associated with a 2.

Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals.

variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways.

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify as a new gene implicated in PD and childhood neurodegeneration.

Randomised controlled trial of intermittent calorie restriction in people with multiple sclerosis.

Background: Calorie restriction (CR) ameliorates preclinical models of multiple sclerosis (MS) via multiple mechanisms. These include decreased leptin, a proinflammatory adipokine, but mechanistic studies in humans are lacking. Tests of daily and intermittent CR (iCR) in people with MS (pwMS) showed improvements in fatigue and well-being measures.

Deciphering the role of protein kinase A in the control of FoxP3 expression in regulatory T cells in health and autoimmunity.

The molecular mechanisms that govern differential T cell development from CD4CD25conventional T (Tconv) into CD4CD25 forkhead-box-P3 (FoxP3) inducible regulatory T (iTreg) cells remain unclear. Herein, we investigated the relative contribution of protein kinase A (PKA) in this process. Mechanistically, we found that PKA controlled the efficiency of human iTreg cell generation through the expression of different FoxP3 splicing variants containing or not the exon 2.

Development and validation of an MR-driven dose-of-the-day procedure for online adaptive radiotherapy in upper gastrointestinal cancer patients.

To develop and validate a dose-of-the-day (DOTD) treatment plan verification procedure for liver and pancreas cancer patients treated with an magnetic resonance (MR)-Linac system.DOTD was implemented as an automated process that uses 3D datasets collected during treatment delivery. Particularly, the DOTD pipeline's input included the adapt-to-shape (ATS) plan-i.

Metabolic Plasticity of Regulatory T Cells in Health and Autoimmunity.

Immunometabolism has been demonstrated to control immune tolerance and the pathogenic events leading to autoimmunity. Compelling experimental evidence also suggests that intracellular metabolic programs influence differentiation, phenotype, proliferation, and effector functions of anti-inflammatory CD4+CD25+Foxp3+ regulatory T (Treg) cells. Indeed, alterations in intracellular metabolism associate with quantitative and qualitative impairments of Treg cells in several pathological conditions.