Cost-effectiveness of leveraging existing HIV primary health systems and community health workers for hypertension screening and treatment in Africa: An individual-based modeling study.

Background: Cardiovascular disease (CVD) morbidity and mortality is increasing in Africa, largely due to undiagnosed and untreated hypertension. Approaches that leverage existing primary health systems could improve hypertension treatment and reduce CVD, but cost-effectiveness is unknown. We evaluated the cost-effectiveness of population-level hypertension screening and implementation of chronic care clinics across eastern, southern, central, and western Africa.

Weight trajectories in aging humanized APOE mice with translational validity to human Alzheimer's risk population: A retrospective analysis.

Translational validity of mouse models of Alzheimer's disease (AD) is variable. Because change in weight is a well-documented precursor of AD, we investigated whether diversity of human AD risk weight phenotypes was evident in a longitudinally characterized cohort of 1,196 female and male humanized APOE (hAPOE) mice, monitored up to 28 months of age which is equivalent to 81 human years. Autoregressive Hidden Markov Model (AHMM) incorporating age, sex, and APOE genotype was employed to identify emergent weight trajectories and phenotypes.

Surgical Site Infection after Craniotomy in Neuro-Oncology (SINO): A protocol for an international prospective multicentre service evaluation across the United Kingdom and Ireland.

Introduction: Given its proximity to the central nervous system, surgical site infections (SSIs) after craniotomy (SSI-CRAN) represent a serious adverse event. SSI-CRAN are associated with substantial patient morbidity and mortality. Despite the recognition of SSI in other surgical fields, there is a paucity of evidence in the neurosurgical literature devoted to skin closure, specifically in patients with brain tumors.

Exploiting the similarity of dissimilarities for biomedical applications and enhanced machine learning.

The "similarity of dissimilarities" is an emerging paradigm in biomedical science with significant implications for protein function prediction, machine learning (ML), and personalized medicine. In protein function prediction, recognizing dissimilarities alongside similarities provides a more detailed understanding of evolutionary processes, allowing for a deeper exploration of regions that influence biological functionality. For ML models, incorporating dissimilarity measures helps avoid misleading results caused by highly correlated or similar data, addressing confounding issues like the Doppelgänger Effect.

Transitions in intensive care: Investigating critical slowing down post extubation.

Complex biological systems undergo sudden transitions in their state, which are often preceded by a critical slowing down of dynamics. This results in longer recovery times as systems approach transitions, quantified as an increase in measures such as the autocorrelation and variance. In this study, we analysed paediatric patients in intensive care for whom mechanical ventilation was discontinued through removal of the endotracheal tube (extubation).

Establishment of an Ex Vivo Human Corneal Endothelium Wound Model.

Purpose: A human model able to simulate the manifestation of corneal endothelium decompensation could be advantageous for wound healing and future cell therapy assessment. The study aimed to establish an ex vivo human cornea endothelium wound model where endothelium function can be evaluated by measuring corneal thickness changes.

Methods: The human cornea was maintained in an artificial anterior chamber, with a continuous culture medium infusion system designed to sustain corneal endothelium and epithelium simultaneously.

Associations between the gut microbiome, inflammation and cardiovascular profiles in people with HIV.

Background: Inflammation and innate immune activation are associated with chronic HIV infection, despite effective treatment. Although gut microbiota alterations are linked to systemic inflammation, the relationships between the gut microbiome, inflammation and HIV remain unclear.

Methods: The UPBEAT-CAD sub-study, examining cardiovascular disease (CVD) risk in HIV, enrolled participants matched on HIV status and traditional CVD risk factors.

Factoring fu Variability Into Estimates of Unbound Drug Concentrations Negatively Biases the MIC Versus % Probability of Target Attainment Relationship of Antimicrobial Agents.

The clinical breakpoint for a drug-pathogen combination reflects the drug susceptibility of the pathogen wild-type population, the location of the infection, the integrity of the host immune response, and the drug-pathogen pharmacokinetic (PK)/pharmacodynamic (PD) relationship. That PK/PD relationship, along with the population variability in drug exposure, is used to determine the probability of target attainment (PTA) of the PK/PD index at a specified minimum inhibitory concentration (MIC) for a selected target value. The PTA is used to identify the pharmacodynamic cutoff value (CO), which is one of the three components used to establish the clinical breakpoint.

Penicillin Allergy Management in India and Sri Lanka: Current Challenges.

Data regarding Penicillin allergy labels (PALs) from India and Sri Lanka are sparse. Emerging data suggests that the proportion of patients declaring an unverified PAL in secondary care in India and Sri Lanka (1%-4%) is lesser than that reported in High Income Countries (15%-20%). However, even this relatively small percentage translates into a large absolute number, as this part of the world accounts for approximately 25% of the global population.

Photooxidation Cross-Linked, Glutaraldehyde Cross-Linked, or Enzyme and Hydrostatic Pressure Processed Decellularized Biomaterials for Cardiovascular Repair Do Not Affect Host Response in a Rat Right Ventricular Outflow Flow Tract Reconstruction (RVOT) Model.

Cardiovascular diseases (CVDs) were responsible for approximately 19 million deaths in 2020, marking an increase of 18.7% since 2010. Biological decellularized patches are common therapeutic solutions for CVD such as cardiac and valve defects.

The Songdo consensus: Development of minimum reporting standards for studies of intervention in idiopathic anal fistula using a modified nominal group technique.

Aim: Cryptoglandular anal fistulas carry a substantial burden to quality of life. Surgery is the only effective curative treatment but requires balancing fistula healing against pain, wounds and continence impairment. Sphincter-preserving procedures do exist but demonstrate variable rates of success.

A Parallel Human and Rat Investigation of the Interaction Between Descending and Spinal Modulatory Mechanisms.

Background: Healthy individuals demonstrate considerable heterogeneity upon dynamic quantitative sensory testing assessment of endogenous pain modulatory mechanisms. For those who stratify into a 'pro-nociceptive profile' cohort, consisting of inefficient conditioned pain modulation (CPM) and elevated temporal summation of pain (TSP), the optimal approach for balancing the net output of pain modulatory processes towards anti-nociception remains unresolved. In this translational healthy human and rat study, we examined whether descending modulation countered spinal amplification during concurrent application of a CPM and TSP paradigm alongside pupillometry since pontine activity was previously linked to functionality of endogenous pain modulatory mechanisms and pupil dilation.

Polygenic risk discriminates Lewy body dementia from Alzheimer's disease.

Introduction: Lewy body dementia (LBD) shares genetic risk factors with Alzheimer's disease (AD), including apolipoprotein E (APOE), but is distinguishable at the genome-wide level. Polygenic risk scores (PRS) may therefore improve diagnostic classification.

Methods: We assessed diagnostic classification using AD-PRS excluding APOE (AD-PRS ), APOE risk score (APOE-RS), and plasma phosphorylated tau 181 (p-tau181), in 83 participants with LBD, 27 with positron emission tomography amyloid beta (Aβ)positive mild cognitive impairment or AD (MCI+/AD), and 57 controls.

Reference-Based Multiple Imputation for Longitudinal Binary Data.

Introduction: In clinical trials, a treatment policy strategy is often used to handle treatment nonadherence. However, estimation in this context is complicated when data are missing after treatment deviation. Reference-based multiple imputation has been developed for the analysis of a longitudinal continuous outcome in this setting.

Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum.

Unlabelled: Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.

Objective: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.

Methods: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.

Two London Memorials to "James Parkinson [1755-1824], Esq. Surgeon, Late of Hoxton-Square".

Of all London memorials commemorating historical medical personalities, none perhaps have been so frequented by neurologists as those honoring James Parkinson (1755-1824) of Hoxton square. Situated in the historical London borough of Hackney, there are two well-known memorials to James Parkinson that can still be easily visited: The first, a large, inscribed marble memorial tablet at St Leonard's Church that Parkinson was closely affiliated with throughout life; the second, a historical blue plaque marking the site of Parkinson's birthplace and former home practice at 1 Hoxton Square. Although many contemporary neurologists would freely recall the historical significance of these locations, very few now living can detail the circumstances leading up to these memorials being erected.

Phenotypic variability in progressive encephalopathy with brain atrophy and thin corpus callosum: insights from two families.

The cytoskeleton, composed of microtubules, intermediate filaments and actin filaments is vital for various cellular functions, particularly within the nervous system, where microtubules play a key role in intracellular transport, cell morphology, and synaptic plasticity. Tubulin-specific chaperones, including tubulin folding cofactors (TBCA, TBCB, TBCC, TBCD, TBCE), assist in the proper formation of α/β-tubulin heterodimers, essential for microtubule stability. Pathogenic variants in these chaperone-encoding genes, especially TBCD, have been linked to Progressive Encephalopathy with Brain Atrophy and Thin Corpus Callosum (PEBAT, OMIM #604,649), a severe neurodevelopmental disorder.

Incense Use and the Risk of Chronic Limb-Threatening Ischemia Among Middle-Aged and Older Adults in the Singapore Chinese Health Study.

Background: Epidemiologic studies have shown that daily exposure to incense smoke is associated with greater risk of cardiovascular mortality, which suggests that chronic exposure to incense could be linked to atherosclerosis. We studied the association between home incense use and the risk of chronic limb-threatening ischemia (CLTI), the most severe outcome of peripheral arterial disease.

Methods: We used data from the Singapore Chinese Health Study, which recruited 63,257 Chinese participants 45-74 years old from 1993-1998.

Persistence of the Immune Response to an Intramuscular Bivalent (GI.1/GII.4) Norovirus Vaccine in Adults.

Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine.

Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses to its virus-like particle antigens, GI.1 and GII.

Reactogenicity and Immunogenicity Against MPXV of the Intradermal Administration of Modified Vaccinia Ankara Compared to the Standard Subcutaneous Route.

Background: The recent resurgence of mpox in central Africa has been declared a new public health emergency of international concern (PHEIC) requiring coordinated international responses. Vaccination is a priority to expand protection and enhance control strategies, but the vaccine's need exceeds the currently available doses. Intradermal (ID) administration of one-fifth of the standard modified vaccinia Ankara (MVA-BN) dose was temporarily authorized during the 2022 PHEIC.

Immunobridging Trials: An Important Tool to Protect Vulnerable and Immunocompromised Patients Against Evolving Pathogens.

Safeguarding patients from emerging infectious diseases demands strategies that prioritise patient well-being and protection. Immunobridging is an established trial methodology which has been increasingly employed to ensure patient protection and provide clinicians with swift access to vaccines. It uses immunological markers to infer the effectiveness of a new drug through a surrogate measure of efficacy.

An "Engram-Centric" Approach to Transient Global Amnesia (TGA) and Other Acute-Onset Amnesias.

The differential diagnosis of acute-onset amnesia includes transient global amnesia (TGA), transient epileptic amnesia (TEA), and functional (or psychogenic) amnesia. The most common of these, TGA, is a rare but well-described condition characterised by a self-limited episode of dense anterograde amnesia with variable retrograde amnesia. Although the clinical phenomenology of TGA is well described, its pathogenesis is not currently understood, thus preventing the development of evidence-based therapeutic recommendations.

Reactions of Hydrogen-Passivated Silicon Vacancies in -Quartz with Electron Holes and Hydrogen.

We used density functional theory with a hybrid functional to investigate the structure and properties of [4H] (hydrogarnet) defects in -quartz as well as the reactions of these defects with electron holes and extra hydrogen atoms and ions. The results demonstrate the depassivation mechanisms of hydrogen-passivated silicon vacancies in -quartz, providing a detailed understanding of their stability, electronic properties, and behaviour in different charge states. While fully hydrogen passivated silicon vacancies are electrically inert, the partial removal of hydrogen atoms activates these defects as hole traps, altering the defect states and influencing the electronic properties of the material.

Factors Associated with Adherence to Diabetic Retinopathy Screening Among Patients Attending a Nurse-Led Community Clinic in Australia: A Qualitative Study.

Despite the availability of screening services, the rate of diabetic retinopathy (DR) screening continues to be suboptimal in Australia, necessitating improvement. However, improving DR screening rates requires a more comprehensive understanding of the factors influencing adherence to the screening recommendations. This study aimed to explore the factors that influence adherence to DR screening among people with diabetes attending a community screening clinic in Australia.