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Fulltext Bone Health and Its Positive Relationships with Body Composition in Malaysian Schoolchildren: Findings from a Cross-Sectional Study

Koo HC, Lim GP, Kaur S, Chan KQ, Chan KE, Chung C, et al.

Children (Basel), 2021 Jul 02;8(7).
PMID: 34356548 DOI: 10.3390/children8070569

BACKGROUND: Optimal bone health is vital in children to prevent osteoporosis later in life, and body composition plays a crucial role in it. However, the literature reports contradictory results when considering the relationship between body composition and bone health in children. This study aimed to examine the bone health and its relationship with body composition in Malaysian schoolchildren.
METHODS: In this cross sectional study, body composition data (weight, height, body fat percentage [% fat], fat mass, fat free mass, visceral fat, waist circumference [WC] and body mass index-for-age [BMI z-score]) and bone health data (Z-score and broadband ultrasound attenuation [BUA]) were collected from 415 schoolchildren aged 9-12 years, cluster sampled from randomly selected primary schools in Kuala Lumpur, Malaysia.
RESULTS: Girls generally had significantly higher height, body fat percentage, fat mass, visceral fat and Z-score as compared to boys. A steady increase of the mean BUA value was observed with increasing age in both sexes. The mean BUA value of the present study across the population was significantly higher than that of schoolchildren from Nigeria (p < 0.001), Colombia (p < 0.001) and Spain (p = 0.002). Significant positive correlations were found between all the body composition variables and bone outcome variables across the population. Further, BUA was significantly correlated with weight (β = 0.172; p = 0.001), height (β = 0.299; p < 0.001), % fat (β = 0.131; p = 0.007), fat mass (β = 0.130; p = 0.007), fat free mass (β = 0.209; p < 0.001), visceral fat (β = 0.127, p = 0.008), WC (β = 0.165; p = 0.001) and BMI z-score (β = 0.162; p = 0.001), after controlling for sex, age and ethnicity. Similarly, after confounders adjusted, Z-score was significantly predicted by weight (β = 0.160; p = 0.001), height (β = 0.310; p < 0.001), % fat (β = 0.104; p = 0.032), fat mass (β = 0.107; p = 0.026), fat free mass (β = 0.218; p < 0.001), visceral fat (β = 0.107, p = 0.026), WC (β = 0.145; p = 0.002) and BMI z-score (β = 0.150; p = 0.002).
CONCLUSIONS: Our findings have revealed that body composition variables were positive correlated with bone outcome variables, suggesting that adipose tissue acts to stimulate bone growth. Further clinical and molecular studies in the future is recommended to fully illustrate the complex interactions between adiposity and bone health.
Fulltext Experimental Phage Therapy for Burkholderia pseudomallei Infection

Guang-Han O, Leang-Chung C, Vellasamy KM, Mariappan V, Li-Yen C, Vadivelu J

PLoS One, 2016;11(7):e0158213.
PMID: 27387381 DOI: 10.1371/journal.pone.0158213

Burkholderia pseudomallei is an intracellular Gram-negative bacterial pathogen intrinsically resistant to a variety of antibiotics. Phages have been developed for use as an alternative treatment therapy, particularly for bacterial infections that do not respond to conventional antibiotics. In this study, we investigated the use of phages to treat cells infected with B. pseudomallei. Phage C34 isolated from seawater was purified and characterised on the basis of its host range and morphology using transmission electron microscopy (TEM). Phage C34 was able to lyse 39.5% of B. pseudomallei clinical strains. Due to the presence of contractile tail, phage C34 is classified as a member of the family Myoviridae, a tailed double-stranded DNA virus. When 2 × 105 A549 cells were exposed to 2 × 107 PFU of phage C34, 24 hours prior to infection with 2 × 106 CFU of B. pseudomallei, it was found that the survivability of the cells increased to 41.6 ± 6.8% as compared to 22.8 ± 6.0% in untreated control. Additionally, application of phage successfully rescued 33.3% of mice infected with B. pseudomallei and significantly reduced the bacterial load in the spleen of the phage-treated mice. These findings indicate that phage can be a potential antimicrobial agent for B. pseudomallei infections.
Fulltext The SAD-MEN questionnaire: a new and reliable questionnaire for assessing sexual dysfunction in Asians with diabetes

Chung CM, Lu MZ, Wong CY, Goh SG, Azhar MI, Lim YM, et al.

Diabet Med, 2016 May;33(5):674-80.
PMID: 26202696 DOI: 10.1111/dme.12864

AIM: The aim of this study is to construct a new tool for the assessment of sexual dysfunction among men with diabetes that is valid and reliable across different ethnicities, languages and socio-economic backgrounds in South East Asia.
METHODS: Focus group interviews were conducted to determine the construct of the questionnaire. Content and face validity were assessed by a panel of experts. A pilot study was conducted to validate the Sexual Dysfunction in Asian Men with Diabetes (SAD-MEN) questionnaire in English and Malay. The International Index of Erectile Function-5 (IIEF-5) was used for comparison. Construct validity was assessed using exploratory factor analysis, reliability was determined using Cronbach's α (> 0.700), and test-retest reliability using Spearman's rank correlation coefficient.
RESULTS: The SAD-MEN questionnaire yielded moderate face and content validity, with high reliability as shown by Cronbach's α values of 0.949 for sexual performance and 0.775 for sexual desire for the English version. The Malay language questionnaire had a Cronbach's α value of 0.945 for sexual performance and 0.750 for sexual desire. Test-retest reliability using Spearman's test gave correlation coefficients of r = 0.853, P = 0.000 for the English language questionnaire and r = 0.908, P = 0.000 for the Malay language questionnaire.
CONCLUSION: The SAD-MEN questionnaire is a valid and reliable tool by which to assess sexual dysfunction in English- and Malay-speaking Malaysian and South East Asian men with diabetes.
Rapamycin synergizes cisplatin sensitivity in basal-like breast cancer cells through up-regulation of p73

Wong SW, Tiong KH, Kong WY, Yue YC, Chua CH, Lim JY, et al.

Breast Cancer Res Treat, 2011 Jul;128(2):301-13.
PMID: 20686837 DOI: 10.1007/s10549-010-1055-0

Recent gene expression profiling studies have identified five breast cancer subtypes, of which the basal-like subtype is the most aggressive. Basal-like breast cancer poses serious clinical challenges as there are currently no targeted therapies available to treat it. Although there is increasing evidence that these tumors possess specific sensitivity to cisplatin, its success is often compromised due to its dose-limiting nephrotoxicity and the development of drug resistance. To overcome this limitation, our goal was to maximize the benefits associated with cisplatin therapy through drug combination strategies. Using a validated kinase inhibitor library, we showed that inhibition of the mTOR, TGFβRI, NFκB, PI3K/AKT, and MAPK pathways sensitized basal-like MDA-MB-468 cells to cisplatin treatment. Further analysis demonstrated that the combination of the mTOR inhibitor rapamycin and cisplatin generated significant drug synergism in basal-like MDA-MB-468, MDA-MB-231, and HCC1937 cells but not in luminal-like T47D or MCF-7 cells. We further showed that the synergistic effect of rapamycin plus cisplatin on basal-like breast cancer cells was mediated through the induction of p73. Depletion of endogenous p73 in basal-like cells abolished these synergistic effects. In conclusion, combination therapy with mTOR inhibitors and cisplatin may be a useful therapeutic strategy in the treatment of basal-like breast cancers.
Donor Diabetes and Steatosis Affects Recipient Survival Following Liver Transplantation Based on Etiology of Liver Cirrhosis

Lim WH, Ng CH, Tan DJH, Xiao J, Fu CE, Ong C, et al.

Transplantation, 2024 Feb 01;108(2):473-482.
PMID: 37439778 DOI: 10.1097/TP.0000000000004718

BACKGROUND: Liver transplantation (LT) offers patients with decompensated cirrhosis the best chance at long-term survival. With the rising prevalence of diabetes, further clarity is needed on the impact of receiving a liver allograft from a donor with diabetes on post-LT outcomes. This study aims to evaluate the impact of donor diabetes on clinical outcomes after LT.
METHODS: This is a retrospective analysis of the United Network for Organ Sharing registry data of LT recipients from January 1, 2000, to December 31, 2021. Outcomes analysis was performed using Cox proportional model for all-cause mortality and graft failure. Confounding was reduced by coarsened exact matching causal inference analysis.
RESULTS: Of 66 960 donors identified, 7178 (10.7%) had diabetes. Trend analysis revealed a longitudinal increase in the prevalence of donor diabetes ( P
Higher risk of adverse cardiovascular outcomes in females with type 2 diabetes Mellitus: an Umbrella review of systematic reviews

Yaow CYL, Chong B, Chin YH, Kueh MTW, Ng CH, Chan KE, et al.

Eur J Prev Cardiol, 2023 Sep 06;30(12):1227-1235.
PMID: 37185913 DOI: 10.1093/eurjpc/zwad133

BACKGROUND: Previous studies have shown that females with type 2 diabetes mellitus (T2DM) may have excess mortality risk compared to their male counterparts. An important next step to address the high global burden of T2DM and cardiovascular disease (CVD) is an umbrella review to summarize data on sex differences in cardiovascular outcomes for patients with T2DM and assess the strength of the evidence observed.
METHODS AND RESULTS: Medline and Embase were searched from inception till 7 August 2022 for systematic reviews and meta-analyses studying the effects of sex on cardiovascular outcomes in T2DM patients. Results from reviews were synthesized with a narrative synthesis, with a tabular presentation of findings and forest plots for reviews that performed a meta-analysis. 27 review articles evaluating sex differences in cardiovascular outcomes were included. Females with T2DM had a higher risk of developing coronary heart disease (CHD; RRR: 1.52, 95%CI: 1.32-1.76, P < 0.001), acute coronary syndrome (ACS; RRR: 1.38, 95%CI: 1.25-1.52, P < 0.001), heart failure (RRR: 1.09, 95%CI: 1.05-1.13, P < 0.001) than males. Females had a higher risk of all-cause mortality (RRR: 1.13, 95%CI: 1.07-1.19, P < 0.001), cardiac mortality (RRR: 1.49, 95%CI: 1.11-2.00, P = 0.009) and CHD mortality (RRR: 1.44, 95%CI: 1.20-1.73, P < 0.001) as compared to males.
CONCLUSIONS: This umbrella review demonstrates that females with T2DM have a higher risk of cardiovascular outcomes than their male counterparts. Future research should address the basis of this heterogeneity and epidemiological factors for better quality of evidence, and identify actionable interventions that will narrow these sex disparities.