Management of prediabetes in Malaysian population: An experts' opinion.

INTRODUCTION: Prediabetes, typically defined as blood glucose levels above normal but below diabetes thresholds, denotes a risk state that confers a high chance of developing diabetes. Asians, particularly the Southeast Asian population, may have a higher genetic predisposition to diabetes and increased exposure to environmental and social risk factors. Malaysia alone was home to 3.4 million people with diabetes in 2017; the figure is estimated to reach 6.1 million by 2045. Developing strategies for early interventions to treat prediabetes and preventing the development of overt diabetes and subsequent cardiovascular and microvascular complications are therefore important. METHODS: An expert panel comprising regional experts was convened in Kuala Lumpur, for a one-day meeting, to develop a document on prediabetes management in Malaysia. The expert panel comprised renowned subject-matter experts and specialists in diabetes and endocrinology, primary-care physicians, as well as academicians with relevant expertise. RESULTS: Fifteen key clinical statements were proposed. The expert panel reached agreements on several important issues related to the management of prediabetes providing recommendations on the screening, diagnosis, lifestyle and pharmacological management of prediabetes. The expert panel also proposed changes in forthcoming clinical practice guidelines and suggested that the government should advocate early screening, detection, and intensive management of prediabetes. CONCLUSION: This document provides a comprehensive approach to the management of prediabetes in Malaysia in their daily activities and offer help in improving government policies and the decision-making process.

Length of stay and odds of MRSA acquisition: a dose-response relationship?

The association between methicillin-resistant Staphylococcus aureus (MRSA) colonisation and/or infection with increased morbidity and mortality among hospital patients has long been recognised. We sought to build on previous studies to identify modifiable risk factors associated with the acquisition of MRSA colonisation and infection by conducting a retrospective cohort study on patients admitted through the Emergency Department of an acute tertiary-care general hospital in Singapore which implemented universal on-admission MRSA screening. Patients were assigned to the acquisition or non-acquisition group depending on whether they acquired MRSA during their admission. We used logistic regression models with a patient being in the acquisition group as the binary outcome to identify factors associated with MRSA acquisition. A total of 1302 acquisition and 37 949 non-acquisition group patients were analysed. Fifteen variables were included in the multivariate model. A dose-response relationship between length of stay and odds of MRSA acquisition was observed, with a length of stay 3 weeks or more (Adj OR 11.78-57.36, all P < 0.001) being the single biggest predictor of MRSA acquisition. Other variables significantly associated with MRSA acquisition were: male gender, age 65 or greater, previous MRSA colonisation or infection, exposure to certain antibiotics and surgery, and history of diabetes.

Positive replication and linkage disequilibrium mapping of the chromosome 21q22.1 malaria susceptibility locus.

Four cytokine receptor genes are located on Chr21q22.11, encoding the alpha and beta subunits of the interferon-alpha receptor (IFNAR1 and IFNAR2), the beta subunit of the interleukin 10 receptor (IL10RB) and the second subunit of the interferon-gamma receptor (IFNGR2). We previously reported that two variants in IFNAR1 were associated with susceptibility to malaria in Gambians. We now present an extensive fine-scale mapping of the associated region utilizing 45 additional genetic markers obtained from public databases and by sequencing a 44 kb region in and around the IFNAR1 gene in 24 Gambian children (12 cases/12 controls). Within the IFNAR1 gene, a newly studied C --> G single-nucleotide polymorphism (IFNAR1 272354c-g) at position -576 relative to the transcription start was found to be more strongly associated with susceptibility to severe malaria. Association was observed in three populations: in Gambian (P=0.002), Kenyan (P=0.022) and Vietnamese (P=0.005) case-control studies. When all three studies were combined, using the Mantel-Haenszel test, the presence of IFNAR1 -576G was associated with a substantially elevated risk of severe malaria (N=2444, OR=1.38, 95% CI: 1.17-1.64; P=1.7 x 10(-4)). This study builds on previous work to further highlight the importance of the type-I interferon pathway in malaria susceptibility and illustrates the utility of typing SNPs within regions of high linkage disequilibrium in multiple populations to confirm initial positive associations.

Strong HLA class I--restricted T cell responses in dengue hemorrhagic fever: a double-edged sword?

Dengue is an increasingly important cause of morbidity and mortality in the tropics, but vaccine development has been impeded by a poor understanding of disease pathogenesis and, in particular, of immunologic enhancement. In a large case-control study of Vietnamese patients with dengue hemorrhagic fever (DHF), variation at the HLA-A locus was significantly associated with susceptibility to DHF (P=.02), and specific HLA-A susceptibility and resistance alleles were identified. HLA-A-specific epitopes were predicted from binding motifs, and ELISPOT analyses of patients with DHF revealed high frequencies of circulating CD8 T lymphocytes that recognized both serotype-specific and -cross-reactive dengue virus epitopes. Thus, strong CD8 T cell responses are induced by natural dengue virus infection, and HLA class I genetic variation is a risk factor for DHF. These genetic and immunologic data support both protective and pathogenic roles for dengue virus-specific CD8 T cell responses in severe disease. The potentially pathogenic role of serotype-cross-reactive CD8 T cells poses yet another obstacle to successful dengue vaccine development.

Active acetyl-CoA synthase from Clostridium thermoaceticum obtained by cloning and heterologous expression of acsAB in Escherichia coli.

Acetyl-CoA synthase from Clostridium thermoaceticum (ACS(Ct)) is an alpha(2)beta(2) tetramer containing two novel Ni-X-Fe(4)S(4) active sites (the A and C clusters) and a standard Fe(4)S(4) cluster (the B cluster). The acsA and acsB genes encoding the enzyme were cloned into Escherichia coli strain JM109 and overexpressed at 37(o)C under anaerobic conditions with Ni supplementation. The isolated recombinant His-tagged protein (AcsAB) exhibited characteristics essentially indistinguishable from those of ACS(Ct), from which Ni had been removed from the A cluster. AcsAB migrated through nondenaturing electrophoretic gels as a single band and contained a 1:1 molar ratio of subunits and 1.0-1.6 Ni/alphabeta and 14-22 Fe/alphabeta. AcsAB exhibited 100-250 units/mg CO oxidation activity but no CO/acetyl-CoA exchange activity. Electronic absorption spectra of thionin-oxidized and CO-reduced AcsAB were similar to those of ACS(Ct), with features typical of redox-active Fe(4)S(4) clusters. Partially oxidized and CO-reduced AcsAB exhibited EPR signals with g values and low spin intensities indistinguishable from those of the B(red) state of the B cluster and the C(red1) and C(red2) states of the C cluster of ACS(Ct). Upon overnight exposure to NiCl(2), the resulting recombinant enzyme (ACS(Ec)) developed 0. 06-0.25 units/mg exchange activity. The highest of these values is typical of fully active ACS(Ct). When reduced with CO, ACS(Ec) exhibited an EPR signal indistinguishable from the NiFeC signal of Ni-replete ACS(Ct). Variability of activities and signal intensities were observed among different preparations. Issues involving the assembly of these metal centers in E. coli are discussed.

The 'TRAP' sequence--life threatening consequences to the pump twin.

The acardius foetal malformation is a rare abnormality occurring in monozygotic multiple pregnancies. This is a case report of a pair of twins with the "twin reversed arterial perfusion (TRAP)" sequence and its complications. The recipient twin was born acardius acephalus. The pump twin had problems of prematurity, disseminated intravascular coagulation, sclerema and right ventricular hypertrophy. On follow-up at seven months he has failure to thrive, spastic quadriplegia and developmental delay. An awareness of the TRAP sequence may lead to better antenatal diagnosis and optimal management of the twin pregnancy.

Accuracy and reliability of two methods of screening for hypoglycemia in neonates.

Two hundred and six neonates were screened for hypoglycemia using two glucose test strips and their results compared with a simultaneous blood sugar obtained from the Beckman's glucose analyser. Both test strips, Reflotest hypoglycemia and the Reflolux (BM test glycemia 20-800) gave rapid estimates of blood sugar readings. In this study, these two strips were assessed in their accuracy and reliability to detect neonatal hypoglycaemia (blood sugar levels less than 2.2 mmol/L). The sensitivity and specificity of the two test strips are 0.82 and 0.90 for Reflotest, and 0.88 and 0.81 for Reflolux respectively. Hence we conclude that both Reflotest and Reflolux are sensitive in detecting blood sugar levels at or below 2.2 mmol/L (40 mg/dl) although Reflolux is less specific. A laboratory result is mandatory before the diagnosis and prognosis of hypoglycemia is made.

Systemic candidiasis and pneumonia in preterm infants.

Twenty-two preterm infants with systemic candidiasis are reported, of which seven cases were presumed to be antenatally acquired and 15 postnatally acquired. All except one were of very low birthweight. Fifteen infants had positive cultures of blood, cerebrospinal fluid or urine and seven had candida pneumonia only. Clinical features included general instability, respiratory deterioration and a necrotizing enterocolitis-like presentation. The incidence of leukocytosis, shift to the left, eosinophilia and thrombocytopenia were not different from those with bacterial infection. The diagnosis was made after death in two infants. In the remaining 20 infants, treatment was initiated between 5 and 97 days of age, with a median delay of 4 days after the first positive cultures were taken. Complications of amphotericin and 5-flucytosine therapy which developed in five infants resolved on cessation of treatment. The mortality rate was 18% and impairment rate among the 17 very low birthweight survivors was 18%. A high index of suspicion is required for systemic candidiasis, especially in infants of less than 1000 g birthweight. If recognized early, effective and safe antifungal therapy is possible with favourable short- and long-term outcome.

Outcome of singleton infants delivered vaginally or by caesarean section at 23 to 28 weeks' gestation.

The survival and impairment rates of 276 inborn singleton infants of 23-28 weeks' gestation were reported according to route of delivery and mode of presentation. The Caesarean section rate was 29% overall, ranging from 13% at 25 weeks to 46% at 28 weeks. In the vertex group, no significant difference in survival or impairment rate was found between Caesarean and vaginal births. In the non-vertex group, Caesarean births had a similar survival rate but a significantly lower impairment rate compared to vaginal births. For Caesarean births, no significant difference in survival or impairment rate was found between vertex and non-vertex groups. In contrast, for vaginal births, the mode of presentation was important: the non-vertex group had a significantly lower survival rate and higher impairment rate compared to the vertex group. We found no evidence to support the use of Caesarean section in extremely preterm infants with vertex presentation, except for recognized maternal or fetal indications. The findings in the non-vertex group indicated that there is a definite need for a randomized clinical trial to investigate the possible benefits of Caesarean section in extremely preterm infants with non-vertex presentation.

Prognosis for infants born at 23 to 28 weeks' gestation.

The survival and neurodevelopmental outcome of 356 extremely preterm infants born at 23 to 28 weeks' gestation were reported by week of gestation. Their corrected 1 year survival improved from 7% at 23 weeks to 75% at 28 weeks. The overall incidence of impairment was 19% and of major disability 12%. Boys had a significantly lower normal survival than girls. Multiple births had a significantly lower survival and higher incidence of impairment than singleton births. Predictions of outcome were made before delivery, after resuscitation, and at 1 week to aid the development of guidelines on when perinatal intensive care is justified, whether obstetric intervention for fetal reasons is warranted, and what initial and ongoing prognoses to give to parents. Intensive care for progressively smaller and more immature infants, many of whom were previously considered non-viable, needs to be carefully monitored by every perinatal centre.