The APOE-R136S mutation protects against APOE4-driven Tau pathology, neurodegeneration and neuroinflammation.

Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD), leading to earlier age of clinical onset and exacerbating pathologies. There is a critical need to identify protective targets. Recently, a rare APOE variant, APOE3-R136S (Christchurch), was found to protect against early-onset AD in a PSEN1-E280A carrier.

APOE4-promoted gliosis and degeneration in tauopathy are ameliorated by pharmacological inhibition of HMGB1 release.

Apolipoprotein E4 (APOE4) is an important driver of Tau pathology, gliosis, and degeneration in Alzheimer's disease (AD). Still, the mechanisms underlying these APOE4-driven pathological effects remain elusive. Here, we report in a tauopathy mouse model that APOE4 promoted the nucleocytoplasmic translocation and release of high-mobility group box 1 (HMGB1) from hippocampal neurons, which correlated with the severity of hippocampal microgliosis and degeneration.

Neuronal APOE4 removal protects against tau-mediated gliosis, neurodegeneration and myelin deficits.

Apolipoprotein E4 (APOE4) is the strongest known genetic risk factor for late-onset Alzheimer's disease (AD). Conditions of stress or injury induce APOE expression within neurons, but the role of neuronal APOE4 in AD pathogenesis is still unclear. Here we report the characterization of neuronal APOE4 effects on AD-related pathologies in an APOE4-expressing tauopathy mouse model.

Sex-heterogeneous SNPs disproportionately influence gene expression and health.

Phenotypic differences across sexes are pervasive, but the genetic architecture of sex differences within and across phenotypes is mostly unknown. In this study, we aimed to improve detection power for sex-differentially contributing SNPs previously demonstrated to be enriched in disease association, and we investigate their functions in health, pathophysiology, and genetic function. We leveraged GIANT and UK Biobank summary statistics and defined a set of 2,320 independent SNPs having sexually dimorphic effects within and across biometric traits (MAF > 0.

Open partial horizontal laryngectomy for T2-T3-T4a laryngeal cancer: oncological outcomes and prognostic factors of two Italian hospitals.

Purpose: The purpose of this study was to analyse the oncologic results of open partial horizontal laryngectomy (OPHL) and to assess the prognostic factors that could affect the survival of patients affected by T2, T3 and T4a laryngeal cancer. Using this data, we aim to identify clinical criteria to select patients amenable to conservative surgery, and to facilitate a more targeted approach in the management of advanced laryngeal cancer.

Methods: A retrospective study was performed in patients who underwent OPHL type II for laryngeal squamous cell carcinoma from January 2005 to December 2018.

A profile and review of findings from the Early Markers for Autism study: unique contributions from a population-based case-control study in California.

Background: The Early Markers for Autism (EMA) study is a population-based case-control study designed to learn more about early biologic processes involved in ASD.

Methods: Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n = 629) and intellectual disability without ASD (ID, n = 230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records.

Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits.

Background: The origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations, we tested for a sex-differentiated genetic architecture within and between traits.

Methods: Using European ancestry genome-wide association summary statistics for 20 neuropsychiatric and behavioral traits, we tested for sex differences in single nucleotide polymorphism (SNP)-based heritability and genetic correlation (r < 1).

New statistical RI index allow to better track the dynamics of COVID-19 outbreak in Italy.

COVID-19 pandemic in Italy displayed a spatial distribution that made the tracking of its time course quite difficult. The most relevant anomaly was the marked spatial heterogeneity of COVID-19 diffusion. Lombardia region accounted for around 60% of fatal cases (while hosting 15% of Italian population).

Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes.

Mutations in gene regulatory elements have been associated with a wide range of complex neuropsychiatric disorders. However, due to their cell-type specificity and difficulties in characterizing their regulatory targets, the ability to identify causal genetic variants has remained limited. To address these constraints, we perform an integrative analysis of chromatin interactions, open chromatin regions and transcriptomes using promoter capture Hi-C, assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing, respectively, in four functionally distinct neural cell types: induced pluripotent stem cell (iPSC)-induced excitatory neurons and lower motor neurons, iPSC-derived hippocampal dentate gyrus-like neurons and primary astrocytes.

Validation of the objective assessment of facial movement with a new software-based system.

Background: Most used subjective Unilateral Peripheral Facial Palsy (UPFP) grading systems are characterized by high variability and low reproducibility and doesn't allow a separate evaluation of single facial regions.

Objective: To assess the reliability of a new objective method for classification of UPFP, comparing it with House-Brackmann (HB) and Sunnybrook facial grading (SFGS) systems.

Method: Forty-seven patients affected by UPFP of different HB grade were included.

Ultra-trace determination of total mercury in Italian bottled waters.

Mercury (Hg) is a widespread, highly toxic persistent pollutant with adverse health effects on humans. So far, concentrations below the method detection limit have always been reported by studies on the concentration of mercury in bottled water when determined using instrumental analytical methods. These are often very expensive and are unaffordable for many laboratories.

Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.

Author Correction: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps.

In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs.

Cross-genetic determination of maternal and neonatal immune mediators during pregnancy.

Background: The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control.

Bold personality makes domestic dogs entering a shelter less vulnerable to diseases.

It is widely recognised that for vertebrate species, personalities vary along an axis with extremes represented by 'proactive' and 'reactive' individuals. The aim of this study was to verify whether there is a relationship between personality and disease vulnerability in domestic dogs (Canis familiaris) exposed to an intensely stressful situation such as entering a shelter. Twenty-eight shelter dogs participated in the study.

Quality of Life in Workers and Stress: Gender Differences in Exposure to Psychosocial Risks and Perceived Well-Being.

Background: Quality of working life is the result of many factors inherent in the workplace environment, especially in terms of exposure to psychosocial risks.

Objectives: The purpose of this study is to assess the quality of life with special attention to gender differences.

Methods: The HSE-IT questionnaire and the WHO-5 Well-Being Index were administered to a group of workers (74 males and 33 females).

Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.

Magnesium (Mg) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg, which is crucial for Mg homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg homeostasis.

Prenatal Serum Concentrations of Brominated Flame Retardants and Autism Spectrum Disorder and Intellectual Disability in the Early Markers of Autism Study: A Population-Based Case-Control Study in California.

Background: Prior studies suggest neurodevelopmental impacts of polybrominated diphenyl ethers (PBDEs), but few have examined diagnosed developmental disorders.

Objectives: Our aim was to determine whether prenatal exposure to brominated flame retardants (BFRs) is associated with autism spectrum disorder (ASD) or intellectual disability without autism (ID).

Methods: We conducted a population-based case-control study including children with ASD (n=545) and ID (n=181) identified from the California Department of Developmental Services and general population (GP) controls (n=418) from state birth certificates.