Epigenetic dissection of human blood group genes reveals regulatory elements and detailed characteristics of KEL and four other loci.

Background: Blood typing is essential for safe transfusions and is performed serologically or genetically. Genotyping predominantly focuses on coding regions, but non-coding variants may affect gene regulation, as demonstrated in the ABO, FY and XG systems. To uncover regulatory loci, we expanded a recently developed bioinformatics pipeline for discovery of non-coding variants by including additional epigenetic datasets.

Elucidation of the low-expressing erythroid CR1 phenotype by bioinformatic mining of the GATA1-driven blood-group regulome.

Genetic determinants underlying most human blood groups are now clarified but variation in expression levels remains largely unexplored. By developing a bioinformatics pipeline analyzing GATA1/Chromatin immunoprecipitation followed by sequencing (ChIP-seq) datasets, we identify 193 potential regulatory sites in 33 blood-group genes. As proof-of-concept, we aimed to delineate the low-expressing complement receptor 1 (CR1) Helgeson phenotype on erythrocytes, which is correlated with several diseases and protects against severe malaria.

Development of a dysphagia cup to improve patients' fluid intake and reduce caregiver burden.

Ensuring that the elderly drink adequate fluids to meet their recommended daily allowance is often a challenge, especially among the elderly in hospitals and long-term care settings. The complex interplay of biological, medical and psychosocial factors that cause the elderly to become dehydrated is difficult to tackle especially in care settings where there is a staff shortage and heavy workload. The team realised that 90% of the elderly inpatients in the general ward of a teaching hospital in Singapore were not drinking enough to meet their needs, despite the hot and humid weather.

Evaluation of multi-component interventions for prevention of nosocomial pneumonia in older adults: a randomized, controlled trial.

Aims: To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards.

Methods: A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care.

The Xg blood group system: no longer forgotten.

This update of the Xg blood group system (Johnson NC. XG: The forgotten blood group system. Immunohematology 2011;27:68-71) notes the identification of a cis-regulatory element of both XG and CD99 expression, remarkably by two independent groups during 2018, and confirmed by another in 2019.

A large deletion spanning XG and GYG2 constitutes a genetic basis of the Xg phenotype, underlying anti-Xg production.

Background: The PBDX/XG gene encoding the Xg blood group antigen was described in 1994, but the genetic determinant of XG expression on RBCs was reported only in 2018. However, the frequencies of Xg(a-) individuals could not explain the rarity of anti-Xg makers. We therefore sought to elucidate the molecular basis of the Xg(a-) phenotype in people producing anti-Xg .

Disruption of a GATA1-binding motif upstream of / abolishes Xg expression and resolves the Xg blood group system.

The Xg blood group is differentially expressed on erythrocytes from men and women. The underlying gene, , was identified in 1994, but the molecular background for Xg expression remains undefined. This gene, now designated , partly resides in pseudoautosomal region 1 and encodes a protein of unknown function from the X chromosome.

Screening for Drugs Against the Plasmodium falciparum Digestive Vacuole by Imaging Flow Cytometry.

Phenotypic assays are increasingly employed to provide clues about drug mechanisms. In antimalarial drug screening, however, the majority of assays are designed to only measure parasite-killing activity. We describe here a high-content assay to detect drug-mediated perturbation of the digestive vacuole integrity in the trophozoite stage of Plasmodium falciparum, using the ImageStream imaging flow cytometer.

Imaging flow cytometry for the screening of compounds that disrupt the Plasmodium falciparum digestive vacuole.

Malaria, despite being one of the world's oldest infectious diseases, remains difficult to eradicate because the parasite is rapidly developing resistance to frontline chemotherapies. Previous studies have shown that the parasite exhibits features resembling programmed cell death upon treatment with drugs that disrupt its digestive vacuole (DV), providing a phenotypic readout that can be detected using the imaging flow cytometer. Large compound collections can thus be screened to identify drugs that are able to disrupt the DV of the malaria parasite using this high-content high-throughput screening platform.

Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum.

The mechanism of action of artemisinin and its derivatives, the most potent of the anti-malarial drugs, is not completely understood. Here we present an unbiased chemical proteomics analysis to directly explore this mechanism in Plasmodium falciparum. We use an alkyne-tagged artemisinin analogue coupled with biotin to identify 124 artemisinin covalent binding protein targets, many of which are involved in the essential biological processes of the parasite.

A high-content phenotypic screen reveals the disruptive potency of quinacrine and 3',4'-dichlorobenzamil on the digestive vacuole of Plasmodium falciparum.

Plasmodium falciparum is the etiological agent of malignant malaria and has been shown to exhibit features resembling programmed cell death. This is triggered upon treatment with low micromolar doses of chloroquine or other lysosomotrophic compounds and is associated with leakage of the digestive vacuole contents. In order to exploit this cell death pathway, we developed a high-content screening method to select compounds that can disrupt the parasite vacuole, as measured by the leakage of intravacuolar Ca(2+).

Deep neck abscesses: the Singapore experience.

This study aims to review our experience with deep neck abscesses, identify key trends, and improve the management of this condition. This is a retrospective chart review of patients diagnosed with deep neck abscesses in the Department of ENT (Otorhinolaryngology) at Tan Tock Seng Hospital, Singapore between 2004 and 2009. Patient demographics, etiology, bacteriology, systemic disease, radiology, treatment, complications, duration of hospitalization, and outcomes were reviewed.