Diabetes and infection: review of the epidemiology, mechanisms and principles of treatment.

An association between diabetes and infection has been recognised for many years, with infection being an important cause of death and morbidity in people with diabetes. The COVID-19 pandemic has re-kindled an interest in the complex relationship between diabetes and infection. Some infections occur almost exclusively in people with diabetes, often with high mortality rates without early diagnosis and treatment.

Transcription-induced domains form the elementary constraining building blocks of bacterial chromosomes.

Transcription generates local topological and mechanical constraints on the DNA fiber, leading to the generation of supercoiled chromosome domains in bacteria. However, the global impact of transcription on chromosome organization remains elusive, as the scale of genes and operons in bacteria remains well below the resolution of chromosomal contact maps generated using Hi-C (~5-10 kb). Here we combined sub-kb Hi-C contact maps and chromosome engineering to visualize individual transcriptional units.

Design, construction, and functional characterization of a tRNA neochromosome in yeast.

Here, we report the design, construction, and characterization of a tRNA neochromosome, a designer chromosome that functions as an additional, de novo counterpart to the native complement of Saccharomyces cerevisiae. Intending to address one of the central design principles of the Sc2.0 project, the ∼190-kb tRNA neochromosome houses all 275 relocated nuclear tRNA genes.

Extended sister-chromosome catenation leads to massive reorganization of the E. coli genome.

In bacteria, chromosome segregation occurs progressively from the origin to terminus within minutes of replication of each locus. Between replication and segregation, sister loci are held in an apparent cohesive state by topological links. The decatenation activity of topoisomerase IV (Topo IV) is required for segregation of replicated loci, yet little is known about the structuring of the chromosome maintained in a cohesive state.

Distribution of Holliday junctions and repair forks during Escherichia coli DNA double-strand break repair.

Accurate repair of DNA double-strand breaks (DSBs) is crucial for cell survival and genome integrity. In Escherichia coli, DSBs are repaired by homologous recombination (HR), using an undamaged sister chromosome as template. The DNA intermediates of this pathway are expected to be branched molecules that may include 4-way structures termed Holliday junctions (HJs), and 3-way structures such as D-loops and repair forks.

Generating High-Resolution Hi-C Contact Maps of Bacteria.

During the past decade, Chromosome Conformation Capture (3C/Hi-C)-based methods have been used to probe the 3D structure and organization of bacterial genomes, revealing fundamental aspects of chromosome dynamics. However, the current protocols are expensive, inefficient, and limited in their resolution. Here we present a simple, cost-effective Hi-C approach that is readily applicable to a range of Gram-positive and Gram-negative bacteria.

Kinetics of the Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Response and Serological Estimation of Time Since Infection.

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time.

Methods: We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms.

Generation of gene-level resolution chromosome contact maps in bacteria and archaea.

Chromosome conformation capture (Hi-C) has become a routine method for probing the 3D organization of genomes. However, when applied to bacteria and archaea, current protocols are expensive and limited in their resolution. By dissecting the different steps of published eukaryotic and prokaryotic Hi-C protocols, we have developed a cost- and time-effective approach to generate high-resolution (down to 500 bp - 1 kb) contact matrices of both bacteria and archaea genomes.

Multiplex assays for the identification of serological signatures of SARS-CoV-2 infection: an antibody-based diagnostic and machine learning study.

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces an antibody response targeting multiple antigens that changes over time. This study aims to take advantage of this complexity to develop more accurate serological diagnostics.

Methods: A multiplex serological assay was developed to measure IgG and IgM antibody responses to seven SARS-CoV-2 spike or nucleoprotein antigens, two antigens for the nucleoproteins of the 229E and NL63 seasonal coronaviruses, and three non-coronavirus antigens.

Euryarchaeal genomes are folded into SMC-dependent loops and domains, but lack transcription-mediated compartmentalization.

Hi-C has become a routine method for probing the 3D organization of genomes. However, when applied to prokaryotes and archaea, the current protocols are expensive and limited in their resolution. We develop a cost-effective Hi-C protocol to explore chromosome conformations of these two kingdoms at the gene or operon level.

Management of E. coli sister chromatid cohesion in response to genotoxic stress.

Aberrant DNA replication is a major source of the mutations and chromosomal rearrangements associated with pathological disorders. In bacteria, several different DNA lesions are repaired by homologous recombination, a process that involves sister chromatid pairing. Previous work in Escherichia coli has demonstrated that sister chromatid interactions (SCIs) mediated by topological links termed precatenanes, are controlled by topoisomerase IV.

RecG Directs DNA Synthesis during Double-Strand Break Repair.

Homologous recombination provides a mechanism of DNA double-strand break repair (DSBR) that requires an intact, homologous template for DNA synthesis. When DNA synthesis associated with DSBR is convergent, the broken DNA strands are replaced and repair is accurate. However, if divergent DNA synthesis is established, over-replication of flanking DNA may occur with deleterious consequences.

Quantitative genomic analysis of RecA protein binding during DNA double-strand break repair reveals RecBCD action in vivo.

Understanding molecular mechanisms in the context of living cells requires the development of new methods of in vivo biochemical analysis to complement established in vitro biochemistry. A critically important molecular mechanism is genetic recombination, required for the beneficial reassortment of genetic information and for DNA double-strand break repair (DSBR). Central to recombination is the RecA (Rad51) protein that assembles into a spiral filament on DNA and mediates genetic exchange.

Influenza virus load in hospitalised patients.

1. Hospitalised patients with severe influenza have persistently high viral loads, for whom a different therapeutic approach may be needed. 2.

Prediction of women's long-term cardiometabolic risks using glycemic indices during pregnancy.

Aims: To study the prediction of abnormal glucose tolerance (AGT), diabetes mellitus (DM), hypertension (HT) and metabolic syndrome (MetS) among Chinese women using glycemic indices in the mid-trimester of pregnancy.

Methods: A cohort of Chinese women who had had either normal glucose tolerance or gestational diabetes mellitus (GDM) during a pregnancy were assessed at a median of 8 and 15 years post-delivery. All women underwent a 50-g glucose challenge test (GCT) and a 75-g oral glucose tolerance test in the mid-trimester of the index pregnancy.

The GIANT study, a cluster-randomised controlled trial of efficacy of education of doctors about type 2 diabetes mellitus management guidelines in primary care practice.

Objectives: Primary aim: does general practitioner (GP) education on type 2 diabetes treatment improve HbA1c? Secondary aim: cardiovascular risk factors, hypoglycaemia, treatment intensification, health service utilisation, treatment barriers.

Methods: 99 Asia-Pacific GPs were cluster-randomised to be educated on regional diabetes management guidelines (intervention) or continue standard care (control). The intervention employed meetings, reminders, medical record summary sheets and patient result cards.

Cardiometabolic risk in Chinese women with prior gestational diabetes: a 15-year follow-up study.

Aims: The progression to type 2 diabetes mellitus (DM) and other long-term cardiometabolic risks in Chinese women with prior history of gestational diabetes (GD) was studied at 15 years postpartum.

Methods: 139 Chinese women (45 with GD and 94 with normal glucose tolerance (NGT) at the index pregnancy) who had their insulin sensitivity and β-cell functions examined at 8 years postpartum were again followed up at 15 years for the investigation of the rate of type 2 DM, hypertension and metabolic syndrome.

Results: Women with prior history of GD had a significantly higher rate of hypertension (35.

Interferon gamma release assay for differentiating tuberculosis among pneumonia cases in acute healthcare setting.

Objectives: Early diagnosis of smear-negative tuberculosis remains challenging. The role of an interferon-gamma release assay (IGRA) in discriminating active pulmonary tuberculosis (PTB) among cases of 'pneumonia' was investigated.

Methods: Consecutive patients admitted to an acute hospital in Hong Kong (intermediate TB burden) during 2006-2008 because of pneumonia and suspected PTB were recruited for IGRA (Quantiferon-TB Gold, QFN-G) study.

Evaluation of functional and malignant adrenal incidentalomas.

Background: Adrenal incidentalomas are adrenal masses discovered inadvertently. We undertook this study to review the clinical characteristics of patients with adrenal incidentalomas who presented to a tertiary endocrine center in Hong Kong.

Methods: Retrospective review of all 139 cases of adrenal incidentalomas that were referred to the Endocrine Centre of the Prince of Wales Hospital between June 1, 2000, and May 31, 2007.

Glucose intolerance and cardiovascular risk factors in Hong Kong: data from two occupation-based cross-sectional surveys.

Aims: To examine the distribution of plasma glucose and related cardiovascular risk factors in two occupation-based cross-sectional surveys in a Chinese ethnic population.

Methods: Two cross-sectional surveys in a Hong Kong working population. In 1990, 1496 participants aged 18-66 years underwent an OGTT, anthropometric, and other biochemical measures.

A simple risk score to identify Southern Chinese at high risk for diabetes.

Aims: To develop a simple scoring system for identifying Southern Chinese at risk of diabetes.

Methods: The score was derived from a risk factor matching cohort for Type 2 diabetes in Hong Kong Chinese (cohort 1, 2448 subjects without a history of diabetes; age, mean +/- sd 37.2 +/- 8.

Outcomes of adults hospitalised with severe influenza.

Background: The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza.

Methods: A prospective, observational cohort study was conducted over 24 months (2007-2008) in two acute, general hospitals. Consecutive, hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established (based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol).