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Biodegradation of a medium-chain-length polyhydroxyalkanoate in tropical river water

Ho YH, Gan SN, Tan IK

Appl Biochem Biotechnol, 2002 10 25;102-103(1-6):337-47.
PMID: 12396135

The medium-chain-length polyhydroxyalkanoate (PHA(MCL)) produced by Pseudomonas putida PGA1 using saponified palm kernel oil as the carbon source could degrade readily in water taken from Kayu Ara River in Selangor, Malaysia. A weight loss of 71.3% of the PHA film occurred in 86 d. The pH of the river water medium fell from 7.5 (at d 0) to 4.7 (at d 86), and there was a net release of CO2. In sterilized river water, the PHA film also lost weight and the pH of the water fell, but to lesser extents. The C8 monomer of the PHA was completely removed after 6 d of immersion in the river water, while the proportions of the other monomers (C10, C12, and C14) were reversed from that of the undegraded PHA. By contrast, the monomer composition of the PHA immersed in sterilized river water did not change significantly from that of the undegraded PHA. Scanning electron microscopy showed physical signs of degradation on the PHA film immersed in the river water, but the film immersed in sterilized river water was relatively unblemished. The results thus indicate that the PHA(MCL) was degraded in tropical river water by biologic as well as nonbiologic means. A significant finding is that shorter-chain monomers were selectively removed throughout the entire PHA molecule, and this suggests enzymatic action.
Characteristics of patients with tuberculosis and the associated factors with TB-related mortality in a rural setting in Sarawak, Malaysia: A single-centre study

Ho YH, Lim CT, Albart SA, Schee JP, Yong MC, Looi I

Med J Malaysia, 2023 Jan;78(1):1-6.
PMID: 36715183

INTRODUCTION: Tuberculosis (TB) in Malaysia has estimated incidence and mortality rates of 81 cases per 100,000 people-year and 4.9 per 100,000 populations, respectively. This study aimed to study the characteristics of rural TB patients and their mortality outcomes.
MATERIALS AND METHODS: This is a retrospective observational study involving real-world data analysis, looking into TB patients in Lubok Antu Health Clinic by obtaining data through clinic cards, from 1 January 2019 till 31 December 2020. Statistical significance was p < 0.05.
RESULTS: Eighty-four patients were included. Fifty-two (61.9%) were male. Median age was 58.5 (39-67). Forty-six (54.8%) had smear-positive TB. Seventy-eight (92.9%) were alive at treatment completion. Fifteen (17.9%) experienced adverse drug reactions. Estimated prevalence and mortality rate were 7.1% and 10.7 per 100,000 populations, respectively. Regression analyses revealed that drug reaction was significantly associated with compliance [OR = 8.38 (95% CI: 1.26, 55.53), p = 0.029]. Patients compliant with treatment were more likely to survive [OR = 12.5 (95% CI: 1.61, 97.34), p = 0.028].
CONCLUSION: Compliance with TB treatment should be emphasised to reduce TB-related mortality.
Fulltext Pseudo-infarction electrocardiographic changes in delayed onset hypoparathyroidism: A case report

Chow HB, Lim CT, Ho YH, Cham YL, Fong AYY, Said A, et al.

Clin Case Rep, 2023 Jun;11(6):e7580.
PMID: 37351358 DOI: 10.1002/ccr3.7580

KEY CLINICAL MESSAGE: The high-risk "Shark Fin" electrocardiogram (ECG) pattern has been associated with transmural ischemia but can also result from electrolyte anomalies. Therefore, the decision for invasive coronary catheterization requires a detailed history and dedicated biochemical tests.
ABSTRACT: Pseudo-infarction ECG pattern resembling "Shark Fin" was demonstrated in a 76-year-old lady with a previous total thyroidectomy who presented with unspecific symptoms. An incidental finding of hypokalemia and hypocalcemia was thought to be related to delayed onset hypoparathyroidism. Potential etiologies like coronary vasospasm and catecholamine-associated myocardial injury were suggested.
Factors associated with in-hospital mortality among infective endocarditis patients

Ho YH, Lim CT, Chua CZF, Chow HB, Chua HH, Fong AYY

Med J Malaysia, 2023 Nov;78(6):743-750.
PMID: 38031215

INTRODUCTION: Despite recent advancements in the diagnosis and management of infective endocarditis (IE), it is associated with substantial morbidity and mortality. Our study objective is to determine the factors associated with in-hospital mortality in IE patients among the local population.
MATERIALS AND METHODS: All IE patients who were diagnosed with definite or possible IE and were treated at Sarawak Heart Centre from 1st January 2020 to 31st December 2022 were recruited. We examined the demographic features of the subjects and the factors that contributed to in-hospital mortality. Multivariate logistic regression was used to analyse the associated factors and in-hospital mortality.
RESULTS: Our study population comprised a total of 37 patients with a mean age of 46.4 years and male predominance. The in-hospital mortality rate of IE in this study was 44.4%. Haemodynamic instability and anaemia were found to be strong predictors of IE survival outcome, with an odds ratio of 51.5 and 35.7 respectively. Patients with vascular phenomenon and heart failure were at 10.5- and 6.0-times higher odds of dying, however, these two associations were found to be not statistically significant.
CONCLUSION: The in-hospital mortality due to IE in our study was among the highest in developing countries. Factors of hypotension and optimal response to individual hemodynamic parameters may confer lower mortality. While anaemia is demonstrable as a risk factor for inpatient mortality, a target has yet to be reasonably established.
A clinical audit on the diagnosis and management of infective endocarditis in a tertiary heart centre in Malaysia

Ho YH, Lim CT, Chua CZF, Chua HH, Ong TK

Med J Malaysia, 2024 Jul;79(4):388-392.
PMID: 39086334

INTRODUCTION: Infective endocarditis (IE) has a high mortality rate in developing countries including Malaysia. This clinical audit aims to identify the shortcomings in the diagnosis and management of IE patients in a local tertiary centre to implement changes for improvement.
MATERIALS AND METHODS: This retrospective audit had two cycles - the first includes all IE patients in Sarawak Heart Centre, Malaysia from January 2020 to December 2022 with different parameters (blood culture, echocardiogram, the appropriateness of antibiotics and surgery) assessed against Malaysian Clinical Practice Guideline (CPG); and reaudit from July 2023 to December 2023. Interventions before re-audit include presentation at different hospital levels and continuing medical education.
RESULTS: Fifty patients were recruited (37 in the first cycle, 13 in the second cycle). The median age was 48.5 years with male predominance. Valve prosthesis (12.0%) and rheumatic heart disease (10.0%) were the commonest predisposing factors. Native mitral (44.0%) and aortic valves (28.0%) were most commonly involved. Twenty-eight (56.0%) patients were culture-positive. In the first cycle, most parameters (culture technique 0.0%, vegetation measured 54.1%, empirical 5.4%, culture-guided 29.7% antibiotics therapy, indicated surgery 0.0%) did not achieve the expected standard except timeliness of echocardiograms and blood culture incubation period. After initial interventions, all parameters showed statistically significant improvement (culture technique p<0.001, echocardiography p<0.001, empirical p<0.001, culture-guided p=0.021, surgery p<0.001) during the re-audit.
CONCLUSION: Compliance with clinical practice guidelines (CPG) on IE management was suboptimal during the first audit but improved after interventions. Hence, regular continuing medical education (CME) is essential, and a written hospital protocol may be useful. Regular audits alongside multidisciplinary teamwork are crucial efforts.
Fulltext Tissue-Specific microRNA Expression Profiling to Derive Novel Biomarkers for the Diagnosis and Subtyping of Small B-Cell Lymphomas

Hue SS, Jin Y, Cheng H, Bin Masroni MS, Tang LWT, Ho YH, et al.

Cancers (Basel), 2023 Jan 10;15(2).
PMID: 36672402 DOI: 10.3390/cancers15020453

Accurate diagnosis of the most common histological subtypes of small B-cell lymphomas is challenging due to overlapping morphological features and limitations of ancillary testing, which involves a large number of immunostains and molecular investigations. In addition, a common diagnostic challenge is to distinguish reactive lymphoid hyperplasia that do not require additional stains from such lymphomas that need ancillary investigations. We investigated if tissue-specific microRNA (miRNA) expression may provide potential biomarkers to improve the pathology diagnostic workflow. This study seeks to distinguish reactive lymphoid proliferation (RL) from small B-cell lymphomas, and to further distinguish the four main subtypes of small B-cell lymphomas. Two datasets were included: a discovery cohort (n = 100) to screen for differentially expressed miRNAs and a validation cohort (n = 282) to develop classification models. The models were evaluated for accuracy in subtype prediction. MiRNA gene set enrichment was also performed to identify differentially regulated pathways. 306 miRNAs were detected and quantified, resulting in 90-miRNA classification models from which smaller panels of miRNAs biomarkers with good accuracy were derived. Bioinformatic analysis revealed the upregulation of known and other potentially relevant signaling pathways in such lymphomas. In conclusion, this study suggests that miRNA expression profiling may serve as a promising tool to aid the diagnosis of common lymphoid lesions.
Fulltext JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

Nairismägi ML, Tan J, Lim JQ, Nagarajan S, Ng CC, Rajasegaran V, et al.

Leukemia, 2016 06;30(6):1311-9.
PMID: 26854024 DOI: 10.1038/leu.2016.13

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.