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Fulltext Embryonic mercury exposure in zebrafish: Alteration of metabolites and gene expression, related to visual and behavioral impairments

Abu Bakar N, Wan Ibrahim WN, Zulkiflli AR, Saleh Hodin NA, Kim TY, Ling YS, et al.

Ecotoxicol Environ Saf, 2023 May;256:114862.
PMID: 37004432 DOI: 10.1016/j.ecoenv.2023.114862

The widespread presence of mercury, a heavy metal found in the environment and used in numerous industries and domestic, raises concerns about its potential impact on human health. Nevertheless, the adverse effects of this environmental toxicant at low concentrations are often underestimated. There are emerging studies showing that accumulation of mercury in the eye may contribute to visual impairment and a comorbidity between autism spectrum disorders (ASD) trait and visual impairment. However, the underlying mechanism of visual impairment in humans and rodents is challenging. In response to this issue, zebrafish larvae with a cone-dominated retinal visual system were exposed to 100 nM mercury chloride (HgCl2), according to our previous study, followed by light-dark stimulation, a social assay, and color preference to examine the functionality of the visual system in relation to ASD-like behavior. Exposure of embryos to HgCl2 from gastrulation to hatching increased locomotor activity in the dark, reduced shoaling and exploratory behavior, and impaired color preference. Defects in microridges as the first barrier may serve as primary tools for HgCl2 toxicity affecting vision. Depletion of polyunsaturated fatty acids (PUFAs), linoleic acid, arachidonic acid (ARA), alpha-linoleic acid, docosahexaenoic acid (DHA), stearic acid, L-phenylalanine, isoleucine, L-lysine, and N-acetylputrescine, along with the increase of gamma-aminobutyric acid (GABA), sphingosine-1-phosphate, and citrulline assayed by liquid chromatography-mass spectrometry (LC-MS) suggest that these metabolites serve as biomarkers of retinal impairments that affect vision and behavior. Although suppression of adsl, shank3a, tsc1b, and nrxn1a gene expression was observed, among these tsc1b showed more positive correlation with ASD. Collectively, these results contribute new insights into the possible mechanism of mercury toxicity give rise to visual, cognitive, and social deficits in zebrafish.
Fulltext Assessing the impact of simplified HCV care on linkage to care amongst high-risk patients at primary healthcare clinics in Malaysia: a prospective observational study

Markby J, Shilton S, Sem X, Chan HK, Md Said R, Siva S, et al.

BMJ Open, 2021 Dec 24;11(12):e055142.
PMID: 34952885 DOI: 10.1136/bmjopen-2021-055142

INTRODUCTION: To achieve the elimination of hepatitis C virus (HCV), substantial scale-up in access to testing and treatment is needed. This will require innovation and simplification of the care pathway, through decentralisation of testing and treatment to primary care settings and task-shifting to non-specialists. The objective of this study was to evaluate the feasibility and effectiveness of decentralisation of HCV testing and treatment using rapid diagnostic tests (RDTs) in primary healthcare clinics (PHCs) among high-risk populations, with referral of seropositive patients for confirmatory viral load testing and treatment.
METHODS: This observational study was conducted between December 2018 and October 2019 at 25 PHCs in three regions in Malaysia. Each PHC was linked to one or more hospitals, for referral of seropositive participants for confirmatory testing and pretreatment evaluation. Treatment was provided in PHCs for non-cirrhotic patients and at hospitals for cirrhotic patients.
RESULTS: During the study period, a total of 15 366 adults were screened at the 25 PHCs, using RDTs for HCV antibodies. Of the 2020 (13.2%) HCV antibody-positive participants, 1481/2020 (73.3%) had a confirmatory viral load test, 1241/1481 (83.8%) were HCV RNA-positive, 991/1241 (79.9%) completed pretreatment assessment, 632/991 (63.8%) initiated treatment, 518/632 (82.0%) completed treatment, 352/518 (68.0%) were eligible for a sustained virological response (SVR) cure assessment, 209/352 (59.4%) had an SVR cure assessment, and SVR was achieved in 202/209 (96.7%) patients. A significantly higher proportion of patients referred to PHCs initiated treatment compared with those who had treatment initiated at hospitals (71.0% vs 48.8%, p<0.001).
CONCLUSIONS: This study demonstrated the effectiveness and feasibility of a simplified decentralised HCV testing and treatment model in primary healthcare settings, targeting high-risk groups in Malaysia. There were good outcomes across most steps of the cascade of care when treatment was provided at PHCs compared with hospitals.
Fulltext Study protocol for a mixed methods approach to optimize colorectal cancer screening in Malaysia: Integrating stakeholders insights and knowledge-to-action framework

Chong DW, Jayaraj VJ, Ab Rahim FI, Syed Soffian SS, Azmi MF, Mohd Yusri MY, et al.

PLoS One, 2024;19(4):e0299659.
PMID: 38593177 DOI: 10.1371/journal.pone.0299659

INTRODUCTION: Colorectal cancer is a growing global health concern and the number of reported cases has increased over the years. Early detection through screening is critical to improve outcomes for patients with colorectal cancer. In Malaysia, there is an urgent need to optimize the colorectal cancer screening program as uptake is limited by multiple challenges. This study aims to systematically identify and address gaps in screening service delivery to optimize the Malaysian colorectal cancer screening program.
METHODS: This study uses a mixed methods design. It focuses primarily on qualitative data to understand processes and strategies and to identify specific areas that can be improved through stakeholder engagement in the screening program. Quantitative data play a dual role in supporting the selection of participants for the qualitative study based on program monitoring data and assessing inequalities in screening and program implementation in healthcare facilities in Malaysia. Meanwhile, literature review identifies existing strategies to improve colorectal cancer screening. Additionally, the knowledge-to-action framework is integrated to ensure that the research findings lead to practical improvements to the colorectal cancer screening program.
DISCUSSION: Through this complex mix of qualitative and quantitative methods, this study will explore the complex interplay of population- and systems-level factors that influence screening rates. It involves identifying barriers to effective colorectal cancer screening in Malaysia, comparing current strategies with international best practices, and providing evidence-based recommendations to improve the local screening program.
Findings from a large Asian chronic hepatitis C real-life study

Lim SG, Phyo WW, Shah SR, Win KM, Hamid S, Piratvisuth T, et al.

J Viral Hepat, 2018 12;25(12):1533-1542.
PMID: 30141214 DOI: 10.1111/jvh.12989

There is a paucity of information on chronic hepatitis C (CHC) patients treated with direct antiviral agents (DAAs) in Asia. We invited Asia-Pacific physicians to collate databases of patients enrolled for CHC treatment, recording baseline clinical, virologic and biochemical characteristics, sustained virologic response at week 12 (SVR12) and virologic failure. SVR12 outcome was based on intention to treat (ITT). Multivariate analysis was used to assess independent risk factors for SVR12 using SPSS version 20. A total of 2171 patients from India (n = 977), Myanmar (n = 552), Pakistan (n = 406), Thailand (n = 139), Singapore (n = 72) and Malaysia (n = 25) were collected. At baseline, mean age was 49 years, 50.2% were males, and 41.8% had cirrhosis. Overall, SVR12 was 89.5% and by genotype (GT) based on ITT and treatment completion, respectively, was 91% and 92% for GT1, 100% and 100% for GT2, 91% and 97% for GT3, 64% and 95% for GT4, 87% and 87% for GT6 and 79% and 91% for GT untested. Patients with cirrhosis had SVR12 of 85% vs 93% for noncirrhosis (P < 0.001) (RR 2.1, 95% CI 1.4-3.1, P = 0.0002). Patients with GT1 and GT3 treated with sofosbuvir/ribavirin (SR) had 88% and 89% SVR12, respectively, but those GT6 treated with sofosbuvir/ledipasvir (SL) had only 77.6% SVR12. Multivariate analysis showed absence of cirrhosis was associated with higher SVR12 (OR 2.0, 95% CI 1.3-3.1, P = 0.002). In conclusion, patients with GT1 and GT3 with/without cirrhosis had surprisingly high efficacy using SR, suggesting that Asians may respond better to some DAAs. However, poor GT6 response to SL suggests this regimen is suboptimal for this genotype.