Formulas to estimate dietary sodium intake from spot urine lead to misleading associations with cardiovascular disease risk and mortality.

Objectives: To test the hypothesis that the association of formula-estimated sodium intake from spot urine with cardiovascular disease is independent of spot urinary sodium concentration.

Methods: We included 435 336 participants in the UK Biobank whose sodium intake was estimated from spot urine using INTERSALT, Kawasaki, and Tanaka formulas. Hazard ratios for cardiovascular disease (CVD) events and deaths were estimated using Cox proportional-hazard model adjusted for multiple covariates.

Mitochondrial DNA lineages determine tumor progression through T cell reactive oxygen signaling.

Mitochondrial DNA (mtDNA) is highly polymorphic, and host mtDNA variation has been associated with altered cancer severity. To determine the basis of this mtDNA-cancer association, we analyzed conplastic mice with the C57BL/6J (B6) nucleus but two naturally occurring mtDNA lineages, and , where mitochondria generate more oxidative phosphorylation (OXPHOS)-derived reactive oxygen species (mROS). In a cardiac transplant model, Foxp3+ T regulatory (Treg) cells supported long-term allograft survival, whereas Treg cells failed to suppress host T effector (Teff) cells, leading to acute rejection.

Exploring Congruence Between Patient and Clinician Expectations of Benefit in the Non-Surgical Management of Common Musculoskeletal Conditions in Tertiary Care.

Background: Patient and clinician expectations of benefit from recommended management approaches may potentially impact the success of managing musculoskeletal conditions.

Methods: This was a multisite study in an advanced practice musculoskeletal service across Queensland, Australia. Relationships between patient and clinician (advanced physiotherapy practitioner) expectations of benefit, patient characteristics, and clinical outcome recorded 6 months later were explored with regression analysis in 619 patients undergoing non-surgical multidisciplinary care for either knee osteoarthritis (n = 286), low back pain (n = 249) or shoulder impingement syndrome (n = 84).

Generation of an inducible destabilized-domain Cre mouse line to target disease associated microglia.

Unlabelled: The function of microglia during progression of Alzheimer's disease (AD) can be investigated using mouse models that enable genetic manipulation of microglial subpopulations in a temporal manner. We developed a mouse strain that expresses destabilized-domain Cre recombinase (DD-Cre) from the locus ( ) and tested this in 5xFAD amyloidogenic, Ai14 tdTomato cre-reporter line mice. Dietary administration of trimethoprim to induce DD-Cre activity produces long-term labeling in disease associated microglia (DAM) without evidence of leakiness, with tdTomato-expression restricted to cells surrounding plaques.

Formula-led methods using first morning fasting spot urine to assess usual salt intake: a secondary analysis of PURE study data.

Objectives: Observational studies that assess the relationship between salt intake and long-term outcomes require a valid estimate of usual salt intake. The gold-standard measure in individuals is sodium excretion in multiple nonconsecutive 24-h urines. Multiple studies have demonstrated that random spot urine samples are not valid for estimating usual salt intake; however, some researchers believe that fasting morning spot urine samples produce a better measure of usual salt intake than random spot samples.

Blood Pressure-Lowering Medications, Sodium Reduction, and Blood Pressure.

Background: Both blood pressure-lowering medication and sodium reduction are effective in hypertension control, but whether the effect of sodium reduction differ across blood pressure-lowering medications is unclear. This study aims to evaluate the dose-response effect of sodium intake reduction on blood pressure in treated hypertensive individuals and the impact of different classes of blood pressure-lowering drugs.

Methods: We searched multiple databases and reference lists up to July 9, 2024.

How to: assess patient suitability for unlicensed phage therapy in the United Kingdom.

Background: Bacteriophage (phage) therapy is a promising alternative antimicrobial approach that has the potential to transform the way we treat bacterial infections. The antibiotic resistance crisis is driving renewed interest in phage therapy. There are currently no licensed phage therapy medicinal products and phage therapy is used in small but growing patient numbers on an unlicensed basis.

Single-cell spatial transcriptomics reveals distinct patterns of dysregulation in non-neuronal and neuronal cells induced by the Trem2 Alzheimer's risk gene mutation.

The R47H missense mutation of the TREM2 gene is a known risk factor for development of Alzheimer's Disease. In this study, we analyze the impact of the Trem2 mutation on specific cell types in multiple cortical and subcortical brain regions in the context of wild-type and 5xFAD mouse background. We profile 19 mouse brain sections consisting of wild-type, Trem2, 5xFAD and Trem2; 5xFAD genotypes using MERFISH spatial transcriptomics, a technique that enables subcellular profiling of spatial gene expression.

APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology.

Background: Apolipoprotein E ε4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD). A recent case report identified a rare variant in APOE, APOE3-R136S (Christchurch), proposed to confer resistance to autosomal dominant Alzheimer's Disease (AD). However, it remains unclear whether and how this variant exerts its protective effects.

Cystatin F attenuates neuroinflammation and demyelination following murine coronavirus infection of the central nervous system.

Background: Cystatin F is a secreted lysosomal cysteine protease inhibitor that has been implicated in affecting the severity of demyelination and enhancing remyelination in pre-clinical models of immune-mediated demyelination. How cystatin F impacts neurologic disease severity following viral infection of the central nervous system (CNS) has not been well characterized and was the focus of this study. We used cystatin F null-mutant mice (Cst7-/-) with a well-established model of murine coronavirus-induced neurologic disease to evaluate the contributions of cystatin F in host defense, demyelination and remyelination.

Outcomes of sugar reduction policies, United Kingdom of Great Britain and Northern Ireland.

Poor diets are the major cause of death and disease globally, driving high levels of obesity and noncommunicable diseases. Cheap, heavily marketed, ultra-processed, energy-dense and nutrient-poor food and drinks that are high in fat, sugar and salt play a major role. The high-sugar content of these products leads to consumption levels much higher than recommended.

Salt reduction policy for out of home sectors: a supplementary document for the salt reduction strategy to prevent and control non-communicable diseases (NCDS) in Malaysia 2021-2025.

Cardiovascular diseases (CVDs) are the major cause of death among Malaysians. Reduction of salt intake in populations is one of the most cost-effective strategies in the prevention of CVDs. It is very feasible as it requires low cost for implementation and yet could produce a positive impact on health.

Sex-specific associations between AD genotype and the microbiome of human amyloid beta knock-in (hAβ-KI) mice.

Introduction: Emerging evidence links changes in the gut microbiome to late-onset Alzheimer's disease (LOAD), necessitating examination of AD mouse models with consideration of the microbiome.

Methods: We used shotgun metagenomics and untargeted metabolomics to study the human amyloid beta knock-in (hAβ-KI) murine model for LOAD compared to both wild-type (WT) mice and a model for early-onset AD (3xTg-AD).

Results: Eighteen-month female (but not male) hAβ-KI microbiomes were distinct from WT microbiomes, with AD genotype accounting for 18% of the variance by permutational multivariate analysis of variance (PERMANOVA).

The Abca7 variant reduces Aβ generation, plaque load, and neuronal damage.

Background: Variants in ABCA7, a member of the ABC transporter superfamily, have been associated with increased risk for developing late onset Alzheimer's disease (LOAD).

Methods: CRISPR-Cas9 was used to generate an Abca7 variant in mice, modeling the homologous human ABCA7 variant, and extensive characterization was performed.

Results: Abca7 microglia show differential gene expression profiles upon lipopolysaccharide challenge and increased phagocytic capacity.

Patient Opinions and Side Effects Before and After General Anesthesia for Surgery.

As the number of surgical procedures performed the world over continues to increase, so does the number of anesthetic procedures needed for those surgeries to occur. While much thought and research has been focused on the perspective of the anesthesiologist, little has been explored from the perspective of the patient receiving anesthesia. The purpose of this study was to explore the general public's opinions and experiences of general anesthesia, as well as any change in their perception after having undergone a procedure requiring it.

BIN1 suppresses glial response to plaques in mouse model of Alzheimer's disease.

Introduction: The BIN1 coding variant rs138047593 (K358R) is linked to Late-Onset Alzheimer's Disease (LOAD) via targeted exome sequencing.

Methods: To elucidate the functional consequences of this rare coding variant on brain amyloidosis and neuroinflammation, we generated BIN1 knock-in mice using CRISPR/Cas9 technology. These mice were subsequently bred with 5xFAD transgenic mice, which serve as a model for Alzheimer's pathology.

Single cell spatial transcriptomics reveals distinct patterns of dysregulation in non-neuronal and neuronal cells induced by the Alzheimer's risk gene mutation.

Introduction: The R47H missense mutation of the TREM2 gene is a strong risk factor for development of Alzheimer's Disease. We investigate cell-type-specific spatial transcriptomic changes induced by the mutation to determine the impacts of this mutation on transcriptional dysregulation.

Methods: We profiled 15 mouse brain sections consisting of wild-type, , 5xFAD and ; 5xFAD genotypes using MERFISH spatial transcriptomics.

Perceptions, barriers and enablers on salt reduction in the out-of-home sectors in Malaysia (MySaltOH) from the perspective of street food vendors, caterers and consumers.

Objective: To explore the perspectives, barriers and enablers on salt reduction in out-of-home sectors in Malaysia among street food vendors, caterers and consumers.

Design: A qualitative study involving twenty-two focus group discussions and six in-depth interviews was conducted, recorded and transcribed verbatim. An inductive thematic analysis approach was employed to analyse the data.

Dual roles of myocardial mitochondrial AKT on diabetic cardiomyopathy and whole body metabolism.

Background: The PI3K/AKT pathway transduces the majority of the metabolic actions of insulin. In addition to cytosolic targets, insulin-stimulated phospho-AKT also translocates to mitochondria in the myocardium. Mouse models of diabetes exhibit impaired mitochondrial AKT signaling but the implications of this on cardiac structure and function is unknown.