Phenotypic variability and the gender paradox in the R363C variant of Fabry disease.

Fabry disease is an X-linked lysosomal disease caused by variants in the gene. Although Fabry disease is X-linked, gene variants in females can exhibit a wide range of symptoms, challenging the traditional view of Fabry as an X-linked recessive disease. A family is presented here with a 36-year-old female who is symptomatic with chronic kidney disease and her oligosymptomatic 70-year-old father, both of whom have a heterozygous and hemizygous GLA pathogenic variant, respectively, c.

Optimizing data collection for obstetrical ultrasound research at the primary health care level in rural Uganda.

Background: Neonatal and maternal mortality remains high in low- and middle-income countries (LMIC), especially in sub-Saharan Africa. Quality data collection is crucial to understand the magnitude of these problems and to measure the impact of interventions aimed at improving neonatal and maternal mortality. However, data collection in the low-income country setting, especially in rural areas, has been a challenge for researchers, policy makers, and public health officials.

Using a novel smartphone app to track noise and vibration exposure during neonatal ambulance transport.

Objective: To assess the utility of a bespoke smartphone app to map noise and vibration exposure across neonatal road ambulance journeys.

Design And Setting: Prospective observational study of ambulance journeys across a large UK neonatal transport service. Smartphones, with an in-house developed app, were secured to incubator trolleys to collect vibration and noise data for comparison with international standards.

Charting the course: a scoping review on telehealth research trends in Australia.

This review of telehealth research describes the landscape of Australian digital health and telehealth research from 1999 to 2022, focusing on outlining past, present and future trends. A scoping review was conducted using the Joanna Briggs Institute methodology and PRISMA extension for scoping reviews framework, which identified 495 primary research studies of digital or telehealth interventions aimed at improving health outcomes. Data were charted according to technological modality, health focus, professional representation, participant location, year and size.

Immunopathology in human tuberculosis.

() is a bacterial pathogen that has evolved in humans, and its interactions with the host are complex and best studied in humans. Myriad immune pathways are involved in infection control, granuloma formation, and progression to tuberculosis (TB) disease. Inflammatory cells, such as macrophages, neutrophils, conventional and unconventional T cells, B cells, NK cells, and innate lymphoid cells, interact via cytokines, cell-cell communication, and eicosanoid signaling to contain or eliminate infection but can alternatively mediate pathological changes required for pathogen transmission.

Unpacking the COVID-19 roadway fatality paradox: an analysis of motor vehicle crashes in Michigan 2019-2022.

Objectives: Motor vehicle travel shifts during the COVID-19 pandemic resulted in fewer vehicle miles traveled yet paradoxically higher fatality rates. Anecdotally, the paradox was blamed on increases in risky behavior in the absence of regular traffic and enforcement. We examined three hypotheses to explain the fatality paradox using Michigan crash data: (1) lack of congestion led to higher-speed impacts; (2) increased risky driver/driving; and (3) low-risk driving miles decreased.

Longitudinal mitochondrial bioenergetic signatures of blood monocytes and lymphocytes improve during treatment of drug-susceptible pulmonary tuberculosis patients Monocyte/lymphocyte bioenergetic signatures post-TB treatment.

The impact of human pulmonary tuberculosis (TB) on the bioenergetic metabolism of circulating immune cells remains elusive, as does the resolution of these effects with TB treatment. In this study, the rates of oxidative phosphorylation (OXPHOS) and glycolysis in circulating lymphocytes and monocytes of patients with drug-susceptible TB at diagnosis, 2 months, and 6 months during treatment, and 12 months after diagnosis were investigated using extracellular flux analysis. At diagnosis, the bioenergetic parameters of both blood lymphocytes and monocytes of TB patients were severely impaired in comparison to non-TB and non-HIV-infected controls.

PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells.

Olaparib, a PARP inhibitor, is effective against various cancers, including prostate cancer. However, resistance to olaparib poses a significant challenge. This study uncovers that mitochondrial alterations and PINK1 gene overexpression contribute to this resistance in prostate cancer cells.

To be or not to be on: aspirin and coronary artery bypass graft surgery.

Aspirin's role in secondary prevention for patients with known coronary artery disease (CAD) is well established, validated by numerous landmark trials over the past several decades. However, its perioperative use in coronary artery bypass graft (CABG) surgery remains contentious due to the delicate balance between the risks of thrombosis and bleeding. While continuation of aspirin in patients undergoing CABG following acute coronary syndrome is widely supported due to the high risk of re-infarction, the evidence is less definitive for elective CABG procedures.

Push or pull? Digital notification platform implementation reduces dysglycaemia.

Pushing selected information to clinicians, as opposed to the traditional method of clinicians pulling information from an electronic medical record, has the potential to improve care. A digital notification platform was designed by clinicians and implemented in a tertiary hospital to flag dysglycaemia. There were 112 patients included in the study, and the post-implementation group demonstrated lower rates of dysglycaemia (2.

Genomic analysis of five antibiotic-resistant bacteria isolated from the environment.

Our study presents the whole-genome sequences and annotation of five bacteria isolates, each demonstrating distinct antibiotic resistance. These isolates include RIT 841, RIT 842, RIT 844, RIT 845, and RIT 846, underscoring the importance of understanding antimicrobial resistance.

LX1 Dual Targets AR Variants and AKR1C3 in Advanced Prostate Cancer Therapy.

The development of resistance to current standard-of-care treatments, such as androgen receptor (AR) targeting therapies, remains a major challenge in the management of advanced prostate cancer. There is an urgent need for new therapeutic strategies targeting key resistant drivers, such as AR variants like AR-V7, and steroidogenic enzymes, such as aldo-keto reductase 1C3 (AKR1C3), to overcome drug resistance and improve outcomes for patients with advanced prostate cancer. Here, we have designed, synthesized, and characterized a novel class of LX compounds targeting both the AR/AR variants and AKR1C3 pathways.

Bedaquiline: what might the future hold?

Tuberculosis drug development has stagnated for decades, so the recent availability of bedaquiline is welcome. Bedaquiline-containing regimens, now the first-line therapy recommended by WHO, have transformed the treatment of drug-resistant tuberculosis, offering safer and more effective oral treatment options. However, key obstacles need to be overcome to ensure global access and prevent the rapid development of resistance against this promising class of drugs.

Detailed phenotyping reveals diverse and highly skewed neutrophil subsets in both the blood and airways during active tuberculosis infection.

Introduction: Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of immunopathology if infection progresses to active disease. Neutrophils are now recognized to exist in functionally diverse states, but little work has been done on how neutrophil states or subsets are skewed in TB disease.

Sex and intelligence quotient differences in age of diagnosis among youth with attention-deficit hyperactivity disorder.

Objectives: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental condition and is characterized by inattention, hyperactivity, and impulsivity. Research suggests that some populations, such as females and individuals with high intelligence quotients may be a risk for late ADHD diagnosis and subsequent treatment. Our goal is to advance our understanding of ADHD diagnosis, by examining (1) how child sex and cognitive abilities together are related to the age of diagnosis and (2) whether symptom presentation, current internalizing and externalizing symptoms, and demographic factors are related to age of diagnosis.

Translational artificial intelligence-led optimization and realization of estimated discharge with a supportive weekend interprofessional flow team (TAILORED-SWIFT).

Weekend discharges occur less frequently than discharges on weekdays, contributing to hospital congestion. Artificial intelligence algorithms have previously been derived to predict which patients are nearing discharge based upon ward round notes. In this implementation study, such an artificial intelligence algorithm was coupled with a multidisciplinary discharge facilitation team on weekend shifts.

Identifying neonatal transport research priorities: a modified Delphi consensus.

Objectives: With increasing advances in neonatal transport, a focused research strategy is required to increase the evidence base towards providing optimal care. We aimed to identify the most important neonatal transport research questions as prioritised by parents and healthcare professionals (HCPs).

Design: Key stakeholders participated in a modified three-stage Delphi consensus process.

On the road to retirement: Predicting nighttime driving difficulty and cessation using self-reported health factors.

Introduction: Older drivers now expect to drive longer than previous cohorts and will make up about 25% of licensed U.S. drivers by 2050.

B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles.

B cells are important in tuberculosis (TB) immunity, but their role in the human lung is understudied. Here, we characterize B cells from lung tissue and matched blood of patients with TB and found they are decreased in the blood and increased in the lungs, consistent with recruitment to infected tissue, where they are located in granuloma associated lymphoid tissue. Flow cytometry and transcriptomics identify multiple B cell populations in the lung, including those associated with tissue resident memory, germinal centers, antibody secretion, proinflammatory atypical B cells, and regulatory B cells, some of which are expanded in TB disease.

Disparities in Mammography Screening: Analyzing Barriers to Access Using Individual Patient Perspectives and the Health Belief Model.

Objective: The objective of our study is to explore Nepali women's beliefs about access to mammography screening, and motivations to get screened or not. This work was intended to be hypothesis generating for subsequent quantitative analysis and to inform policy and decision-making to improve access.

Methods: We conducted structured qualitative interviews among nine Nepali women in the Northeast of the United States receiving care at a local community health center and among nine white women receiving mammography care at a large academic medical center in the Northeast.

Myeloid cell expression of CD200R is modulated in active TB disease and regulates infection in a biomimetic model.

A robust immune response is required for resistance to pulmonary tuberculosis (TB), the primary disease caused by (). However, pharmaceutical inhibition of T cell immune checkpoint molecules can result in the rapid development of active disease in latently infected individuals, indicating the importance of T cell immune regulation. In this study, we investigated the potential role of CD200R during infection, a key immune checkpoint for myeloid cells.