Dysbiosis in the Upper Airway and Gut and Altered Urine Metabolome in Malaysian Diabetic Patients.

Gut dysbiosis and an increased risk of respiratory infection in type 2 diabetes have been well recognised. However, the relationship between the gut and respiratory pathobionts carriage rate in the Type 2 diabetic Malaysian population is understudied. To address the knowledge gap, we profiled the gut and upper respiratory tract microbial composition, as well as the urine metabolome of 31 type 2 diabetic adults and 14 non-diabetes adults.

Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.

Background: Polygenic risk scores (PRSs) improve type 2 diabetes (T2D) prediction beyond clinical risk factors but perform poorly in non-European populations, where T2D burden is often higher, undermining their global clinical utility.

Methods: We conducted the largest global effort to date to harmonize T2D genome-wide association study (GWAS) meta-analyses across five ancestries-European (EUR), African/African American (AFR), Admixed American (AMR), South Asian (SAS), and East Asian (EAS)-including 360,000 T2D cases and 1·8 million controls (41% non-EUR). We constructed ancestry-specific and multi-ancestry PRSs in training datasets including 11,000 T2D cases and 32,000 controls, and validated their performance in independent datasets including 39,000 T2D cases and 126,000 controls of diverse ancestries.

Determining the Incidence of Concomitant Traumatic Brain Injury in Patients With Acute Spinal Cord Injury: A 10-Year Cross-sectional Study.

Objective: A concomitant traumatic brain injury is often seen in patients with acute traumatic spinal cord injury. Unfortunately, the exact epidemiology of concomitant traumatic brain injury-traumatic spinal cord injury remains unknown. Our objective was to determine the incidence of concomitant traumatic brain injury-traumatic spinal cord injury and identify clinical factors associated with its occurrence.

Respiratory carriage of hypervirulent Klebsiella pneumoniae by indigenous populations of Malaysia.

Klebsiella pneumoniae is a Gram-negative Enterobacteriaceae that is classified by the World Health Organisation (WHO) as a Priority One ESKAPE pathogen. South and Southeast Asian countries are regions where both healthcare associated infections (HAI) and community acquired infections (CAI) due to extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant K. pneumoniae (CRKp) are of concern.

A virtual library of small molecules mimicking dipeptides.

Virtual combinatorial libraries are prevalent in drug discovery due to improvements in the prediction of synthetic reactions that can be performed. This has gone hand in hand with the development of virtual screening capabilities to effectively screen the large chemical spaces spanned by exhaustive enumeration of reaction products. In this study, we generated a small-molecule dipeptide mimic library to target proteins binding small peptides.

A multicentre study to determine the efficacy of flomoxef against extended-spectrum beta-lactamase producing in Malaysia.

Background: The high burden of extended-spectrum beta-lactamase-producing (ESBL)-producing Enterobacterales worldwide, especially in the densely populated South East Asia poses a significant threat to the global transmission of antibiotic resistance. Molecular surveillance of ESBL-producing pathogens in this region is vital for understanding the local epidemiology, informing treatment choices, and addressing the regional and global implications of antibiotic resistance.

Methods: Therefore, an inventory surveillance of the ESBL- (ESBL-EC) isolates responsible for infections in Malaysian hospitals was conducted.

Differential interaction patterns of opioid analgesics with µ opioid receptors correlate with ligand-specific voltage sensitivity.

The µ opioid receptor (MOR) is the key target for analgesia, but the application of opioids is accompanied by several issues. There is a wide range of opioid analgesics, differing in their chemical structure and their properties of receptor activation and subsequent effects. A better understanding of ligand-receptor interactions and the resulting effects is important.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.

How Carvedilol activates β-adrenoceptors.

Carvedilol is among the most effective β-blockers for improving survival after myocardial infarction. Yet the mechanisms by which carvedilol achieves this superior clinical profile are still unclear. Beyond blockade of β-adrenoceptors, arrestin-biased signalling via β-adrenoceptors is a molecular mechanism proposed to explain the survival benefits.

The Isoleucine at Position 118 in Transmembrane 2 Is Responsible for the Selectivity of Xamoterol, Nebivolol, and ICI89406 for the Human 1-Adrenoceptor.

Known off-target interactions frequently cause predictable drug side-effects (e.g., 1-antagonists used for heart disease, risk 2-mediated bronchospasm).

Does Older Age Affect the Likelihood to Achieve Normal Quality of Life After Traumatic Spinal Cord Injury? A Prospective Observational Cohort Study.

Previous studies suggest that health-related quality of life (HRQoL) is impaired after a traumatic spinal cord injury (TSCI) and may be worse with older age. This study determines whether the expectations to achieve normal HRQoL in Canadians after a TSCI is indeed influenced by older age. A prospective observational study was conducted on adult patients admitted acutely at a single level-1 trauma center after a TSCI.

The Development of a Parental Questionnaire (QQ-MediaSEED) on Bilingual Children's Quantity and Quality of Digital Media Use at Home.

The quantity and quality of children's digital screen media exposure is an emerging area of early childhood studies because of its strong social relevance, and this has been particularly true since the COVID-19 pandemic. The few existing parental questionnaires on children's digital screen media exposure mainly focus on monolingual children's media habits and address either the quantity or quality of children's media exposure. Inspired by the existing instruments, the current study introduces a new parental questionnaire to comprehensively assess the duration, frequency, content, design, and use of bilingual children's digital screen media exposure at home, before and since the COVID-19 pandemic.

Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10), which were delineated to 338 distinct association signals.

Who Recovers Independent Bowel Management During the First Year After a Traumatic Spinal Cord Injury?: A Case-Control Study.

Objectives: The aims of the study were (1) to document the characteristics of patients with impaired bowel functioning during the subacute and chronic phases and (2) to identify factors associated with recovery of independent bowel functioning during the first year after traumatic spinal cord injury in patients who present impaired bowel functioning during the subacute phase, when bowel rehabilitation is completed.

Design: This is a case-control study on 123 adult traumatic spinal cord injury patients. Bowel function assessments using item 7 of the Spinal Cord Independence Measure III were obtained 3 mos after traumatic spinal cord injury and during the early chronic phase.

Carriage of upper respiratory tract pathogens in rural communities of Sarawak, Malaysian Borneo.

Introduction: Pneumonia is a leading cause of death in Malaysia. Whilst many studies have reported the aetiology of pneumonia in Western countries, the epidemiology of pneumonia in Malaysia remains poorly understood. As carriage is a prerequisite for disease, we sought to improve our understanding of the carriage and antimicrobial resistance (AMR) of respiratory tract pathogens in Malaysia.

Clinical Protocol for Identifying and Managing Bladder Dysfunction during Acute Care after Traumatic Spinal Cord Injury.

Bladder dysfunction is widespread following traumatic spinal cord injury (TSCI). Early diagnosis of bladder dysfunction is crucial in preventing complications, determining prognosis, and planning rehabilitation. We aim to suggest the first clinical protocol specifically designed to evaluate and manage bladder dysfunction in TSCI patients during acute care.

Factors associated with discharge destination following inpatient functional rehabilitation in patients with traumatic spinal cord injury.

Study Design: Retrospective review of data from a prospective database of a Level 1 trauma center.

Objectives: This project aims to identify factors collected during the acute and rehabilitative care following a traumatic spinal cord injury (TSCI) associated with success and failure to return home after inpatient intensive functional rehabilitation (IFR).

Setting: Level 1 trauma center specialized in TSCI care in Montreal, Canada.

COVID-19 in adult patients with pre-existing chronic cardiac, respiratory and metabolic disease: a critical literature review with clinical recommendations.

Background: A high burden of severe disease and death from the coronavirus disease 2019 (COVID-19) has been consistently observed in older patients, especially those with pre-existing medical co-morbidities. The global pandemic lockdown has isolated many patients with chronic illnesses from their routine medical care. This narrative review article analyses the multitude of issues faced by individuals with underlying medical conditions during the COVID-19 pandemic.

Identification of type 2 diabetes loci in 433,540 East Asian individuals.

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D); however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D.

Association of variants with hemoglobin A1c and impact on diabetes diagnosis in East Asian individuals.

Objective: Hemoglobin A1c (HbA1c) accuracy is important for diabetes diagnosis and estimation of overall glycemia. The Asahi variant which causes glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to lower HbA1c independently of glycemia in African ancestry populations. As different variants occur in Asian ancestry, we sought to identify Asian-specific variants associated with HbA1c.

A benchmarking study on virtual ligand screening against homology models of human GPCRs.

G-protein-coupled receptor (GPCR) is an important target class of proteins for drug discovery, with over 27% of FDA-approved drugs targeting GPCRs. However, being a membrane protein, it is difficult to obtain the 3D crystal structures of GPCRs for virtual screening of ligands by molecular docking. Thus, we evaluated the virtual screening performance of homology models of human GPCRs with respect to the corresponding crystal structures.