Tumor- and host-derived heparanase-2 (Hpa2) attenuates tumorigenicity: role of Hpa2 in macrophage polarization and BRD7 nuclear localization.

Little attention was given to heparanase 2 (Hpa2) over the last two decades, possibly because it lacks a heparan sulfate (HS)-degrading activity typical of heparanase. Emerging results suggest, nonetheless, that Hpa2 plays a role in human pathologies, including cancer progression where it functions as a tumor suppressor. Here, we examined the role of Hpa2 in cervical carcinoma.

Single-cell transcriptomics identifies aberrant glomerular angiogenic signalling in the early stages of WT1 kidney disease.

WT1 encodes a podocyte transcription factor whose variants can cause an untreatable glomerular disease in early childhood. Although WT1 regulates many podocyte genes, it is poorly understood which of them are initiators in disease and how they subsequently influence other cell-types in the glomerulus. We hypothesised that this could be resolved using single-cell RNA sequencing (scRNA-seq) and ligand-receptor analysis to profile glomerular cell-cell communication during the early stages of disease in mice harbouring an orthologous human mutation in WT1 (Wt1).

Assessing the impact of health-care access on the severity of low back pain by country: a case study within the GBD framework.

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is key for policy making. Low back pain is the leading cause of disability in terms of years lived with disability (YLDs). Due to sparse data, a current limitation of GDB is that a uniform severity distribution is presumed based on 12-Item Short Form Health Survey scores derived from US Medical Expenditure Panel Surveys (MEPS).

A targeted gene panel illuminates pathogenesis in young people with unexplained kidney failure.

Background: Kidney failure in young people is often unexplained and a significant proportion will have an underlying genetic diagnosis. National Health Service England pioneered a comprehensive genomic testing service for such circumstances accessible to clinicians working outside of genetics. This is the first review of patients using this novel service since October 2021, following its introduction into clinical practice.

Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation.

An Update on Pediatric Environmental Health Specialty Units: Activities and Impacts, 2015-19.

Objective: Pediatric Environmental Health Specialty Units (PEHSUs) address health concerns impacting children and their families related to environmental hazards by providing consultation and education to families, communities, and health care professionals. This analysis evaluated the productivity of the national PEHSU program.

Methods: PEHSUs reported data on services provided to US communities between October 1, 2014 and September 30, 2019.

Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies.

CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12).

When should we offer antenatal sequencing for urinary tract malformations? A systematic review, cohort study and meta-analysis.

Objective: Determine the incremental yield of prenatal exome sequencing (PES) over chromosome microarray (CMA) and/or karyotype for urinary tract malformations (UTMs).

Method: A prospective cohort study encompassing data from the English Genomic Medicine Service North Thames Laboratory Hub for fetuses with bilateral echogenic kidneys (BEKs) was combined with data from a systematic review. MEDLINE, EMBASE, Web of Science, MedRxiv and GreyLit were searched from 01/2010-02/2023 for studies reporting on the yield of PES over CMA or karyotype in fetuses with UTMs.

Prognostic value of illness perception on changes in knee pain among elderly individuals: Two-year results from the Frederiksberg Cohort study.

Objective: To investigate the prognostic value of illness perception (IP) on knee pain, quality of life (QoL) and functional level in elderly individuals reporting knee pain.

Design: A prospective cohort study of 1552 elderly with knee pain comparing two previously established clusters based on the Brief Illness Perception questionnaire. Cluster 1 ("Concerned optimists" [hypothesized unfavorable profile]; n ​= ​642) perceived their knee pain as a greater threat to them than Cluster 2 ("Unconcerned confident" [hypothesized favorable profile]; n ​= ​910).

Predicting congenital renal tract malformation genes using machine learning.

Congenital renal tract malformations (RTMs) are the major cause of severe kidney failure in children. Studies to date have identified defined genetic causes for only a minority of human RTMs. While some RTMs may be caused by poorly defined environmental perturbations affecting organogenesis, it is likely that numerous causative genetic variants have yet to be identified.

Neurogenic Defects Occur in -Associated Urinary Bladder Disease.

Introduction: Urofacial, or Ochoa, syndrome (UFS) is an autosomal recessive disease featuring a dyssynergic bladder with detrusor smooth muscle contracting against an undilated outflow tract. It also features an abnormal grimace. Half of individuals with UFS carry biallelic variants in , whereas other rare families carry variants in is immunodetected in pelvic ganglia sending autonomic axons into the bladder.

Education on Preventing Early Childhood Injuries Using a Video Game: The VirtualSafeHome Platform.

Poisonings and household injuries are frequent events among toddlers. We developed VirtualSafeHome (VSH)-a novel self-contained, Internet-based home-safety learning tool-to improve awareness of household hazards. Study aims were to investigate VSH usage characteristics.

Drinking Water From Private Wells and Risks to Children.

Drinking water for approximately 23 million US households is obtained from private wells. These wells can become contaminated by pollutant chemicals or pathogenic organisms, leading to significant illness. Although the US Environmental Protection Agency and all states offer guidance for construction, maintenance, and testing of private wells, most states only regulate the construction of new private water wells.

Drinking Water From Private Wells and Risks to Children.

Drinking water for >23 million US households is obtained from private wells. These wells can become contaminated by chemicals, naturally occurring toxic substances, or pathogenic organisms that can cause illness in children. Although the US Environmental Protection Agency and most states offer some guidance for the construction, maintenance, and testing of private wells, most states only regulate the construction of new private water wells.