ABSTRACT:The uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene encodes the enzyme responsible for bilirubin glucuronidation. To evaluate the contribution of UGT1A1 promoter mutations to neonatal jaundice, we determined the genotypes of c.-3279TϾG, c.-3156GϾA, and A(TA)7TAA in Malay infants with neonatal jaundice (patients) and in infants without neonatal jaundice (controls). In our population study, only c.-3279TϾG was associated with neonatal jaundice. The genotype distributions between both groups were significantly different (p ϭ 0.003): the frequency of homozygosity for c.-3279G was much higher in patients than those in controls. Allele frequency of c.-3279G was significantly higher in patients than those in controls (p ϭ 0.006). We then investigated changes in transcriptional activity because of c.-3279TϾG. Luciferase reporter assay in HepG2 cells demonstrated that transcriptional activity of the c.-3279G allele was significantly lower than that of the c.-3279T allele in both the absence and presence of bilirubin. Luciferase reporter assay in COS-7 cells elucidated that c.-3279TϾG modified the synergistic effects of the nuclear factors associated with transcriptional machinery. In conclusion, the c.-3279TϾG mutation in the UGT1A1 promoter is a genetic risk factor for neonatal jaundice. T he uridine diphospho (UDP)-glucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene encodes bilirubin UDPglucuronosyltransferase (UGT1A1), which is the enzyme responsible for bilirubin glucuronidation. A decrease in UGT1A1 activity leads to unconjugated hyperbilirubinemia. Inherited UGT1A1 deficiencies because of UGT1A1 mutations are classified into three forms based on clinical severity: Crigler-Najjar syndrome type 1 (CN-1, a severe form), Crigler-Najjar syndrome type 2 (CN-2, an intermediate form), and Gilbert's syndrome (GS, a mild form) (1,2). Such inherited UGT1A1 deficiencies may cause neonatal jaundice.A mutant TATA box with an additional TA insertion, A(TA)7TAA, was first found in patients with CN-1, CN-2, and GS (3-5). GS with homozygosity for A(TA)7TAA accelerates or prolongs neonatal jaundice (6). This mutation is frequently observed in whites and Africans (7). Another GScausing gene mutation, c.211GϾA, is frequent in the East Asian population (8). The c.211GϾA mutation causes an amino acid change, glycine to arginine at codon 71.Recently, polymorphic mutations, c.-3279TϾG and c.-3156GϾA, were identified in the UGT1A1 promoter region (9,10). The c.-3279TϾG mutation is located in the phenobarbital responsive enhancer module (gtPBREM), which is activated by a nuclear receptor, constitutive androstane receptor (CAR) (11). Sugatani et al. (9) showed using luciferase reporter assay that mutant gtPBREM with c.-3279TϾG decreases the transcriptional activity of the UGT1A1 promoter by 60%. The c.-3156GϾA mutation is located between the gtPBREM and TATA box. A haplotype analysis showed that there is a high extent of linkage disequilibrium between c.-3156GϾA and A(TA)7TAA (10,12). However, it is unknown ...

IntroductionThe hepatitis B virus (HBV) is a blood-borne virus that can be transmitted by percutaneous and mucocutaneous contact with infected bodily fluid. Healthcare workers (HCWs) are more exposed to HBV infection. They must have a thorough understanding of HBV infection since they can contract and spread the virus. In this study, we systematically reviewed all published evidence on the seroprevalence of Hepatitis B virus (HBV) infection among HCWs. and synthesize evidence on the association between knowledge and awareness with HBV infection.MethodsWe searched PubMed, EMBASE, Cochrane Library and Scopus for studies reporting on HBV seroprevalence from January 1997 to September 2021 among healthcare workers. We used random-effects meta-analyses to estimate the pool prevalence of HBV infection.ResultsWe identified 25 studies that met our inclusion criteria, with data on 10,043 adults from 11 countries and two regions: Africa and Asia. The overall seroprevalence of HBV was 5.0% (95% confidence interval [CI] 3.6%), with Africa reporting higher estimates (5.0%, 95% CI 3.7%) than Asia population (4.0%, 95% CI 1.9%). The highest pooled prevalence estimate in African countries came from studies published in the Cameroon region (8.0%, 95% CI 5–10%) while the lowest came from Ethiopia (4.0%, 95% CI 2.6%). The overall seroprevalence estimates in the African population were significantly higher than those in the Asian group. Studies in Africa found that the average knowledge and seroprevalence were 1.4% and 11.0%, respectively where, eight studies (53.3%) reported good knowledge and seven studies (46.7%) reported average knowledge. In Asia, two studies (40.0%) reported good knowledge, one study (20.0%) reporting average knowledge, and two studies (40.0%) reporting poor knowledge. African studies demonstrated good knowledge despite the fact that their HBV infection rate was higher than 6.7%.ConclusionAfrica and Asia have the highest seroprevalence of HBV infection. Improving the comparability of epidemiological and clinical studies constitutes an important step forward. More high-quality data is needed to improve the precision of burden estimates.Systematic Review RegistrationPROSPERO CRD42021279905.

AIM: To derive a Malaysia guideline and consensus as part of the Malaysia Retina Group’s efforts for diagnosis, treatment, and best practices of diabetic macular edema (DME). The experts’ panel suggests that the treatment algorithm to be divided into groups according to involvement the central macula. The purpose of DME therapy is to improve edema and achieve the best visual results with the least amount of treatment load. METHODS: On two different occasions, a panel of 14 retinal specialists from Malaysia, together with an external expert, responded to a questionnaire on management of DME. A consensus was sought by voting after compiling, analyzing and discussion on first-phase replies on the round table discussion. A recommendation was deemed to have attained consensus when 12 out of the 14 panellists (85%) agreed with it. RESULTS: The terms target response, adequate response, nonresponse, and inadequate response were developed when the DME patients’ treatment responses were first characterized. The panelists reached agreement on a number of DME treatment-related issues, including the need to classify patients prior to treatment, first-line treatment options, the right time to switch between treatment modalities, and side effects associated with steroids. From this agreement, recommendations were derived and a treatment algorithm was created. CONCLUSION: A detail and comprehensive treatment algorithm by Malaysia Retina Group for the Malaysian population provides guidance for treatment allocation of patients with DME.

Introduction Despite the burden of cardiovascular disease (CVD) continuing to increase globally, no comprehensive meta-analyses have been conducted quantifying premature CVD mortality. This paper reports the protocol for a systematic review and meta-analysis to derive updated estimates of premature CVD mortality. Methods and expected outputs This review will include the studies that reported premature CVD mortality based on standard premature mortality indicators, including years of life lost (YLL), age standardized mortality rate (ASMR) or standardised mortality ratio (SMR). PUBMED, Scopus, Web of Science (WoS), CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL) will be used as the literature databases. The study selection as well as the evaluation of the quality of the included articles will be done independently by two reviewers. Pooled estimates of YLL, ASMR, and SMR will be computed by applying random-effects meta-analysis. Heterogeneity among selected studies will be assessed using the I2 statistic and Q statistic with associated p-values. A funnel plot analysis and Egger’s test will be conducted to assess the potential impact of publication bias. Depending on data availability, we propose to conduct subgroup analyses by sex, geographic location, main CVD types, and study time. Reporting of our findings will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Conclusion Our meta-analysis will provide a comprehensive synthesis of the available evidence on premature CVD mortality, which is a major public health concern worldwide. The results of this meta-analysis will have important implications for clinical practice and public health policy, providing insights into strategies to prevent and manage premature CVD mortality. Trial registration Systematic review registration: PROSPERO CRD42021288415. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021288415.

Background Cardiovascular disease (CVD) is a significant cause of premature mortality worldwide, with a growing burden in recent years. Despite this, there is a lack of comprehensive meta-analyses that quantify the extent of premature CVD mortality. Study addressed this gap by estimating the pooled age-standardized mortality rate (ASMR) of premature CVD mortality. Methods We conducted a systematic review of published CVD mortality studies that reported ASMR as an indicator for premature mortality measurement. All English articles published as of October 2022 were searched in four electronic databases: PubMed, Scopus, Web of Science (WoS), and the Cochrane Central Register of Controlled Trials (CENTRAL). We computed pooled estimates of ASMR using random-effects meta-analysis. We assessed heterogeneity from the selected studies using the I2 statistic. Subgroup analyses and meta regression analysis was performed based on sex, main CVD types, income country level, study time and age group. The analysis was performed using R software with the “meta” and “metafor” packages. Results A total of 15 studies met the inclusion criteria. The estimated global ASMR for premature mortality from total CVD was 96.04 per 100,000 people (95% CI: 67.18, 137.31). Subgroup analysis by specific CVD types revealed a higher ASMR for ischemic heart disease (ASMR = 15.57, 95% CI: 11.27, 21.5) compared to stroke (ASMR = 12.36, 95% CI: 8.09, 18.91). Sex-specific differences were also observed, with higher ASMRs for males (37.50, 95% CI: 23.69, 59.37) than females (15.75, 95% CI: 9.61, 25.81). Middle-income countries had a significantly higher ASMR (90.58, 95% CI: 56.40, 145.48) compared to high-income countries (21.42, 95% CI: 15.63, 29.37). Stratifying by age group indicated that the age groups of 20–64 years and 30–74 years had a higher ASMR than the age group of 0–74 years. Our multivariable meta-regression model suggested significant differences in the adjusted ASMR estimates for all covariates except study time. Conclusions This meta-analysis synthesized a comprehensive estimate of the worldwide burden of premature CVD mortality. Our findings underscore the continued burden of premature CVD mortality, particularly in middle-income countries. Addressing this issue requires targeted interventions to mitigate the high risk of premature CVD mortality in these vulnerable populations.