Cerebral perfusion alterations in healthy young adults due to two genetic risk factors of Alzheimer's disease: APOE and MAPT.

Functional brain changes such as altered cerebral blood flow occur long before the onset of clinical symptoms in Alzheimer's disease (AD) and other neurodegenerative disorders. While cerebral hypoperfusion occurs in established AD, middle-aged carriers of genetic risk factors for AD, including APOE ε4, display regional hyperperfusion due to hypothesised pleiotropic or compensatory effects, representing a possible early biomarker of AD and facilitating earlier AD diagnosis. However, it is not clear whether hyperperfusion already exists even earlier in life.

ADME, Toxicity, Molecular Docking, Molecular Dynamics, Glucokinase activation, DPP-IV, α-amylase, and α-glucosidase Inhibition Assays of Mangiferin and Friedelin for Antidiabetic Potential.

Today the alarming situation of diabetes seeks innovative antidiabetic medications, especially those derived from natural sources, as natural substances are safer than manufactured pharmaceuticals. Therefore, this study investigated the inhibitory properties of mangiferin and friedelin against glucokinase (GK), dipeptidyl peptidase-IV (DPP-IV), α-amylase, and α-glucosidase using computational methods, in vitro enzyme assays, and in-depth ADMET analysis. The study utilized a computer-aided drug design approach to assess the potential therapeutic properties of mangiferin and friedelin as Type 2 diabetes mellitus (T2DM) therapeutic agents.

Remote ischaemic conditioning for neurological disorders-a systematic review and narrative synthesis.

Introduction: Remote ischaemic conditioning (RIC) refers to the use of controlled transient ischemic and reperfusion cycles, commonly of the upper or lower limb, to mitigate cellular damage from ischaemic injury. Preclinical studies demonstrate that RIC may have a neuroprotective effect and therefore could represent a novel therapeutic option in the management of neurological disorders. The aim of this review is to comprehensively describe the current clinical evidence of RIC in neurological disorders.

Clinical and genetic characterization of a progressive RBL2-associated neurodevelopmental disorder.

Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants.

An international Delphi consensus on patient preparation for metabolic and bariatric surgery.

Global obesity rates have risen dramatically, now exceeding deaths from starvation. Metabolic and bariatric surgery (MBS), initially for severe obesity (BMI ≥35 kg/m), is performed globally over 500 000 times annually, offering significant metabolic benefits beyond weight loss. However, varying eligibility criteria globally impact patient care and healthcare resources.

Optimizing non-invasive vagus nerve stimulation for treatment in stroke.

Stroke remains a leading cause of long-term disability worldwide. There is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological recovery. Transcutaneous vagus nerve stimulation has been demonstrated to show potential therapeutic effects in both acute and chronic stroke.

A novel (-)-(2S)-7,4'-dihydroxyflavanone compound for treating age-related diabetes mellitus through immunoinformatics-guided activation of CISD3.

The iron-sulfur domain (CISD) proteins of CDGSH are classified into three classes: CISD1, CISD2, and CISD3. During premature ageing, mutations that affect these proteins, namely their binding sites, could result in reduced protein production and an inability to preserve cellular integrity. Consequently, this leads to the development of conditions such as diabetes.

Rare homozygous cilia gene variants identified in consanguineous congenital heart disease patients.

Congenital heart defects (CHD) appear in almost one percent of live births. Asian countries have the highest birth prevalence of CHD in the world. Recessive genotypes may represent a CHD risk factor in Asian populations with a high degree of consanguineous marriages.

Synonymous variant of TLR7 at restriction site rs864058 identified in Covid 19 Pakistani patients.

Background: TLR7, the receptor accountable for immune response to RNA viruses, has been studied extensively to identify its variants related to the severity of Covid-19 in different populations worldwide. However, the genotype of Pakistani population is still unknown. This study aimed to determine the TLR7 genotypes and their relation with severity in our population.

Biallelic EPB41L3 variants underlie a developmental disorder with seizures and myelination defects.

Erythrocyte membrane protein band 4.1 like 3 (EPB41L3: NM_012307.5), also known as DAL1, encodes the ubiquitously expressed, neuronally enriched 4.

Segmentation of pre- and posttreatment diffuse glioma tissue subregions including resection cavities.

Background: Evaluating longitudinal changes in gliomas is a time-intensive process with significant interrater variability. Automated segmentation could reduce interrater variability and increase workflow efficiency for assessment of treatment response. We sought to evaluate whether neural networks would be comparable to expert assessment of pre- and posttreatment diffuse gliomas tissue subregions including resection cavities.

Immunoinformatic-based drug design utilizing hesperetin to target CISD2 activation for liver aging in humans.

The CISD protein family, consisting of CISD1, CISD2, and CISD3, encodes proteins that feature CDGSH iron-sulfur domains crucial for cellular functions and share a common 2Fe-2S domain. CISD2, which is pivotal in cells, regulates intracellular calcium levels, maintains the endoplasmic reticulum and mitochondrial function, and is associated with longevity and overall health, with exercise stimulating CISD2 production. However, CISD2 expression decreases with age, impacting age-related processes.

MDR TB-The Lethal Sound of Silent Mutations.

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Exploring the Perceptions and Behaviours of UK Prescribers Concerning Novel Lipid-Lowering Agent Prescriptions: A Qualitative Study.

Reducing low-density lipoprotein cholesterol levels lowers the risk of atherosclerotic cardiovascular disease. With the current and future portfolios of emerging lipid-lowering therapies included in various national and international guidelines, the objectives of this study were (i) to investigate the perceptions of UK prescribers', including doctors, pharmacists, and nurses, on current lipid management for cardiovascular diseases and prescriptions of novel lipid-lowering therapies, and (ii) to explore the challenges and facilitating factors of prescribing novel lipid-lowering therapies through qualitative interviews. Qualitative semi-structured interviews with twelve medical and non-medical prescribers were conducted, around 20-30 min in length.

30-day morbidity and mortality of revisional bariatric surgery - An international multi-centre collaborative (BROAD) study.

Introduction: Revisional bariatric surgery (RBS) for insufficient weight loss/weight regain or metabolic relapse is increasing worldwide. There is currently no large multinational, prospective data on 30-day morbidity and mortality of RBS. In this study, we aimed to evaluate the 30-day morbidity and mortality of RBS at participating centres.

Molecular genetics, neuroimaging outcomes, and structural analyses of novel and recurrent variants of WDR62 gene in two consanguineous Pakistani families with autosomal recessive primary microcephaly.

Background: Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental and genetically heterogeneous disorder, characterized by small cranium size (> - 3 SD below mean) and often results in varying degree of intellectual disability. Thirty genes have been identified for the etiology of this disorder due to its clinical and genetic heterogeneity.

Methods And Results: Here, we report two consanguineous Pakistani families affected with MCPH exhibiting mutation in WDR62 gene.

Bacterial contamination in contact lens training area in private optical clinics.

Background: Contamination in the contact lens training area could be due to bacteria, which can lead to the major consequence of ocular infections. We aimed to investigate the contamination caused by bacteria in the contact lens training area in private optical clinics of the Udupi district, India.

Methods: A cross-sectional study evaluated the swabs from the contact lens container, contact lens solution tip, washing area and lens fitting area for bacterial contamination.

Defining the cardiovascular phenotype of adults with Alström syndrome.

Background: >40% of infants with Alström Syndrome (AS) present with a transient, severe cardiomyopathy in the first months of life, with apparent recovery in survivors. One in five individuals then develop a later-onset cardiomyopathy but wide clinical variability is observed, even within the same family. The rationale for this study is to provide a comprehensive evaluation of the cardiovascular phenotype in adults with AS.

Sub-50 nm patterning of alloy thin films nanophase separation for hydrogen gas sensing.

A novel patterning method achieves two-dimensional nano-patterning of metal nanofibers by depositing a platinum-cerium alloy film on a silicon wafer and inducing phase separation in an oxygen-carbon monoxide atmosphere. The resulting nano-patterned thin film, Pt#CeO/Si, consists of platinum and cerium oxide with an average pattern width of 50 nm and exhibits potential as a hydrogen sensor with sensitive electrical responses to hydrogen ad/desorption. The patterning method introduced herein addresses the challenge of wavelength limitations in traditional optical lithography, offering a scalable approach for sub-50 nm patterns, which are crucial for advanced sensor and electronic applications.