Displaying publications 21 - 40 of 77 in total

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  1. Liu C, Zhang F, Wang X, Chan NW, Rahman HA, Yang S, et al.
    PMID: 34993791 DOI: 10.1007/s11356-021-17886-5
    Surface water quality deterioration is commonly associated with environmental changes and human activities. Although some research has been carried out to evaluate the relationship between various influencing factors and water quality, there is still very little scientific understanding on how to accurately define the key factors of water quality deterioration. This study aims to quantify the impact of environmental factors and land use land cover (LULC) changes on water quality in the Ebinur Lake Watershed, Xinjiang, China. A total of 20 water parameters were used to calculate the Environment Water Quality Index (CWQI). Meanwhile, the partial least squares-structural equation model (PLS-SEM) was used to quantify the impact of eleven factors influencing water quality in the watershed. About 33.3% of the monitoring points that located mostly in the downstream region with dominant anthropogenic activities were detected as poor quality. There were no obvious temporal changes in water quality from 2016 to 2019. The PLS-SEM simulation shows that the latent variable "land use/cover types" (path coefficient =  - 0.600) and "Environmental factor" (path coefficient =  - 0.313) are two major factors affected water quality in the Ebinur Lake Watershed, with a strong explanatory power to water quality change (R2 = 0.727). In the latent variable "Environmental factors", the "NDVI" and "night light brightness value" have a great influence on water quality, with the weights of 0.451 and 0.427, respectively. Correspondingly, the "farmland" and "forest land" within the latent variable of "Land use/cover type" have a considerable impact water quality, with the weights of 0.361 and - 0.340, respectively. In conclusion, the influence of anthropogenic activities on surface water quality of the Ebinur Lake Watershed is greater than that of environmental factors. Compared with the traditional multivariate statistical method, PLS-SEM provides a new insight for quantifying the complex relationship between different influencing factors and water quality.
  2. Tan ML, Gassman PW, Liang J, Haywood JM
    Sci Total Environ, 2021 Nov 15;795:148915.
    PMID: 34328938 DOI: 10.1016/j.scitotenv.2021.148915
    Alternative climate products, such as gauge-based gridded data, ground-based weather radar, satellite precipitation and climate reanalysis products, are being increasingly applied for hydrological modelling. This review aims to summarize the studies that have evaluated alternative climate products within Soil and Water Assessment Tool (SWAT) applications and to propose future research directions, primarily for modelers who wish to study limited gauge, ungauged or transnational river basins. A total of 126 articles have been identified since 2004, the majority of which have been published within the last five years. About 58% of the studies were conducted in Asia, mostly in China and India, while another 14% were reported for United States studies. CFSR and TRMM are the most popular applied products in SWAT modelling, followed by PERSIANN, CMADS, APHRODITE, CHIRPS and NEXRAD. Generally, the performance of climate products is region-dependent; e.g., CFSR typically performs well in the United States and South America, but performs more poorly for Asia, Africa and mountainous basin conditions, as compared to other products. In contrast, the CMADS, TRMM, APRHODITE and NEXRAD have shown the strongest capability for supporting SWAT modelling in these regions. However, most of the evaluated products contain only precipitation input; therefore, merging reliable precipitation with CFSR-temperature is recommended for hydro-climatic modelling. Future research directions include: (1) examination of optimal combinations; e.g. CHIRPS-precipitation and CFSR-temperature, for simulating streamflow in different types of river basins; (2) development of a standardized validation scheme which incorporates the commonly accepted products, statistical approaches and temperature variables; (3) further evaluation of existing climate data products to accurately capture extreme events, pattern and indices as well as WGEN statistics; (4) improvement of climate data in terms of averaging approach, bias correction and additional factors or indices integration; and (5) bias correction of CMIP6 climate projections using the optimal climate data combinations.
  3. Zhang H, Zhang F, Song J, Tan ML, Kung HT, Johnson VC
    Environ Res, 2021 11;202:111702.
    PMID: 34284019 DOI: 10.1016/j.envres.2021.111702
    This study aims to analyze the pollution characteristics and sources of heavy metal elements for the first time in the Zhundong mining area in Xinjiang using the linear regression model. Additionaly, the health risks with their probability and infleuencing factors on different groups of people's were also evaluated using Monte Carlo (MC) simulation approach. The results shows that 89.28% of Hg was from coal combustion, 40.28% of Pb was from transportation, and 19.54% of As was from atmospheric dust. The main source of Cu and Cr was coal dust, Hg has the greatest impact on potential ecological risks. which accounted for 60.2% and 81.46% of the Cu and Cr content in soil, respectively. The all samples taken from Pb have been Extremely polluted (100%). 93.3% samples taken from As have been Extremely polluted. The overall potential ecological risk was moderate. Adults experienced higher non-carcinogenic risks of heavy metals from their diets than children. Interestingly, body weight was the main factor affecting the adult's health risks. This research provides more comprehensive information for better soil management, soil remediation, and soil pollution control in the Xinjiang mining areas.
  4. Foong SC, Hwang YC, Foong WC, Tan ML
    Med J Malaysia, 2021 Nov;76(6):924-926.
    PMID: 34806687
    Methaemoglobinaemia occurs when there is >1% methaemoglobin in erythrocytes. In an infant, they can present either congenitally or in an acquired form. We present a rare case of methaemoglobinaemia presenting simultaneously in a mother and infant pair. The mother and infant were discharged well on Day-4 post-delivery with both mother and baby recording oxygen saturation levels of 100%. On Day-7, during a routine clinic visit, they were incidentally found to be centrally cyanosed. There were no other abnormalities. On investigation, the methaemoglobin levels were elevated in the infant (23.9%) and mother (14.3%). Treatment with ascorbic acid normalised mother's methaemoglobin levels; but baby's levels remained high until the administration of oral methylene blue. Both baby and mother remained well and pink at last follow-up at 2 years 8 months of age. This case illustrates difficulties in ascertaining the cause of methaemoglobinaemia. Postdelivery, the mother-neonate pair were pink, and their haemoglobin electrophoresis were normal, hence it was unlikely to be congenital methaemoglobinaemia. The team could not identify any triggering factors for acquired methaemoglobinaemia. There was also the uncertainty of the necessity to treat the baby. This is because treatment is not without harmful effects and despite the high methaemoglobin levels, the infant was otherwise well. Only a single published paper recommended that high methaemoglobin levels must be treated, and the recommendation was not supported by evidence. Lessons learnt from our case are that neonates with methaemoglobinaemia can be safely treated with oral methylene blue, but more research is needed on the benefitrisk profile of treatment.
  5. Ooi KL, Zakaria R, Tan ML, Sulaiman SF
    J Ethnopharmacol, 2021 Oct 05;278:114294.
    PMID: 34090914 DOI: 10.1016/j.jep.2021.114294
    ETHNOPHARMACOLOGICAL RELEVANCE: Anti-hyperuricemic plant parts that were selected for this study, are traditionally used to treat gout in Malaysia. Caffeic acid (a hydroxycinnamic acid), apigenin (a flavone), myricetin, quercetin and kaempferol (flavonols), were reported to act as potent xanthine oxidase inhibitors. These compounds can be found in some of the selected ethnomedicinal plants. However, there is still lack of published research works on the quantification of these inhibitors from these urate-lowering phytotherapies.

    AIMS OF THE STUDY: The compounds were quantified from 21 hydrolyzed extracts of the phytotherapies for gout. The activity-content contributions of the compounds to the potent extracts were determined.

    MATERIALS AND METHODS: The anti-hyperuricemic activities of the extracts and the compounds were determined using a xanthine oxidase inhibitory assay. Ultra-Performance Liquid Chromatography (UPLC) coupled with Photodiode Array Detector (PDA) was used to quantify the compounds in the extracts.

    RESULTS: The results revealed higher activity of the hydrolyzed extracts. The hydrolyzed extract of the flower bud of Syzygium aromaticum Merr. & L.M.Perry exhibited the highest activity (EC50 = 39.58 ± 0.10 μg/mL) due to the highest content of myricetin (42,297.55 ± 159.47 μg/g). The activity-content contribution of myricetin was 7.69%. Due to the highest activity of apigenin (EC50 = 3.27 ± 0.09 μg/mL), the highest contribution of this flavone (29.96%) to the hydrolyzed extract of Orthosiphon aristatus (Blume) Miq. was observed.

    CONCLUSION: The results revealed different contents and activities of xanthine oxidase inhibitors in the hydrolyzed extracts of anti-hyperuricemic plants can play a major role to influence the activity.

  6. Tiyasha T, Tung TM, Bhagat SK, Tan ML, Jawad AH, Mohtar WHMW, et al.
    Mar Pollut Bull, 2021 Sep;170:112639.
    PMID: 34273614 DOI: 10.1016/j.marpolbul.2021.112639
    Dissolved oxygen (DO) is an important indicator of river health for environmental engineers and ecological scientists to understand the state of river health. This study aims to evaluate the reliability of four feature selector algorithms i.e., Boruta, genetic algorithm (GA), multivariate adaptive regression splines (MARS), and extreme gradient boosting (XGBoost) to select the best suited predictor of the applied water quality (WQ) parameters; and compare four tree-based predictive models, namely, random forest (RF), conditional random forests (cForest), RANdom forest GEneRator (Ranger), and XGBoost to predict the changes of dissolved oxygen (DO) in the Klang River, Malaysia. The total features including 15 WQ parameters from monitoring site data and 7 hydrological components from remote sensing data. All predictive models performed well as per the features selected by the algorithms XGBoost and MARS in terms applied statistical evaluators. Besides, the best performance noted in case of XGBoost predictive model among all applied predictive models when the feature selected by MARS and XGBoost algorithms, with the coefficient of determination (R2) values of 0.84 and 0.85, respectively, nonetheless the marginal performance came up by Boruta-XGBoost model on in this scenario.
  7. Mohtar N, Parumasivam T, Gazzali AM, Tan CS, Tan ML, Othman R, et al.
    Cancers (Basel), 2021 Jul 15;13(14).
    PMID: 34298753 DOI: 10.3390/cancers13143539
    Lung cancers, the number one cancer killer, can be broadly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC being the most commonly diagnosed type. Anticancer agents for NSCLC suffer from various limitations that can be partly overcome by the application of nanomedicines. Nanoparticles is a branch within nanomedicine that can improve the delivery of anticancer drugs, whilst ensuring the stability and sufficient bioavailability following administration. There are many publications available in the literature exploring different types of nanoparticles from different materials. The effectiveness of a treatment option needs to be validated in suitable in vitro and/or in vivo models. This includes the developed nanoparticles, to prove their safety and efficacy. Many researchers have turned towards in vitro models that use normal cells or specific cells from diseased tissues. However, in cellular works, the physiological dynamics that is available in the body could not be mimicked entirely, and hence, there is still possible development of false positive or false negative results from the in vitro models. This article provides an overview of NSCLC, the different nanoparticles available to date, and in vitro evaluation of the nanoparticles. Different types of cells suitable for in vitro study and the important precautions to limit the development of false results are also extensively discussed.
  8. Tan ML, Hamid SBS
    J Cancer Prev, 2021 Mar 30;26(1):1-17.
    PMID: 33842401 DOI: 10.15430/JCP.2021.26.1.1
    Patients with cancer are prone to several debilitating side effects including fatigue, insomnia, depression and cognitive disturbances. Beetroot (Beta vulgaris L.) as a health promoting functional food may be potentially beneficial in cancer. As a source of polyphenols, flavonoids, dietary nitrates and other useful nutrients, beetroot supplementation may provide a holistic means to prevent cancer and manage undesired effects associated with chemotherapy. The main aim of this narrative review is to discuss beetroot's nutrient composition, current studies on its potential utility in chemoprevention and cancer-related fatigue or treatment-related side effects such as cardiotoxicity. This review aims to provide the current status of knowledge and to identify the related research gaps in this area. The flavonoids and polyphenolic components present in abundance in beetroot support its significant antioxidant and anti-inflammatory capacities. Most in vitro and in vivo studies have shown promising results; however, the molecular mechanisms underlying chemopreventive and chemoprotective effects of beetroot have not been completely elucidated. Although recent clinical trials have shown that beetroot supplementation improves human performance, translational studies on beetroot and its functional benefits in managing fatigue or other symptoms in patients with cancer are still lacking.
  9. Tan ML, Parkinson EK, Yap LF, Paterson IC
    Sci Rep, 2021 01 12;11(1):584.
    PMID: 33436723 DOI: 10.1038/s41598-020-79789-8
    Many of the characteristics ascribed to cancer-associated fibroblasts (CAFs) are shared by activated, autophagic and senescent fibroblasts. Whilst most oral squamous cell carcinomas (OSCCs) are genetically unstable (GU-OSCC), genetically stable variants (GS-OSCC) have been described and, notably, CAF activation (myofibroblast differentiation) and senescence are characteristics particularly associated with GU-OSCCs. However, it is not known whether autophagy is disrupted in these cells or whether autophagy regulates the development of the myofibroblast and senescent phenotypes. In this study, we show that senescent CAFs from GU-OSCCs contained more autophagosomes than normal human oral fibroblasts (NHOFs) and CAFs from GS-OSCCs possibly due to autophagic impairment. Further, we show that deregulation of autophagy in normal fibroblasts, either by inhibition with autophagy inhibitor, SAR405, or activation with TGF-β1, induced fibroblast activation and senescence: In response to TGF-β1, autophagy was induced prior to the development of the activated and senescent phenotypes. Lastly, we show that both SAR405- and TGF-β1-treated NHOFs enhance OSCC cell migration but only TGF-β1-treated cells increase OSCC invasion through Matrigel, indicating that TGF-β1 has additional effects that are independent of fibroblast activation/senescence. These results suggest a functional role for autophagy in the development of myofibroblast and CAF phenotypes.
  10. Foong SC, Tan ML, Foong WC, Ho JJ, Rahim FF
    Int Breastfeed J, 2021 01 06;16(1):4.
    PMID: 33407645 DOI: 10.1186/s13006-020-00353-1
    BACKGROUND: Ethnic Chinese mothers in Malaysia adhere to 30 days of traditional postpartum practices (the "confinement period") aimed at recuperation after delivery. Recently there has been an emergence of confinement centres (CCs) where mothers stay and receive traditional confinement care. Ethnic Chinese mothers have low breastfeeding rates. There are concerns that practices in CCs could contribute to this but no data exists. We described mothers' breastfeeding experiences at CCs and identified areas for potential improvement in breastfeeding support.

    METHODS: Ethnic Chinese mothers intending to breastfeed their healthy infants were recruited post-delivery between August and October 2017 then, at 1 and 6 months, they were telephone interviewed about their experience. For every participant going to a CC after the birth, another mother going home ("home") for her confinement was recruited. Chi-square test was used to compare groups and multiple logistic regression was used to assess the effect of confinement place on exclusive breastfeeding.

    RESULTS: Of 187 mothers, 88 (47%) went to CCs. Significantly more were primipara and fewer had previous breastfeeding experience. Response rates for the 1- and 6- month interviews were 88% (CC) versus 97% (home); and 77% (CC) versus 87% (home) respectively. Exclusive breastfeeding rates were similar between the groups: 62% (CC) versus 56% (home) at 1 month (p = 0.4); and 37% (CC) versus 42% (home) at 6 months (p = 0.5). Multiple logistic regression did not show that CCs were a factor affecting exclusive breastfeeding rates at 1 month, (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 0.9, 3.3), or 6 months (aOR 0.9, 95% CI 0.4, 1.7). However, significantly more CC participants only fed expressed breast milk. Despite 66% of CC participants reporting that their centre supported breastfeeding, only 6 (8%) CC participants compared to 66 (69%) of home participants roomed-in with their baby (p 

  11. Shaharudin SM, Ismail S, Hassan NA, Tan ML, Sulaiman NAF
    Front Public Health, 2021;9:604093.
    PMID: 34195166 DOI: 10.3389/fpubh.2021.604093
    Novel coronavirus (COVID-19) was discovered in Wuhan, China in December 2019, and has affected millions of lives worldwide. On 29th April 2020, Malaysia reported more than 5,000 COVID-19 cases; the second highest in the Southeast Asian region after Singapore. Recently, a forecasting model was developed to measure and predict COVID-19 cases in Malaysia on daily basis for the next 10 days using previously-confirmed cases. A Recurrent Forecasting-Singular Spectrum Analysis (RF-SSA) is proposed by establishing L and ET parameters via several tests. The advantage of using this forecasting model is it would discriminate noise in a time series trend and produce significant forecasting results. The RF-SSA model assessment was based on the official COVID-19 data released by the World Health Organization (WHO) to predict daily confirmed cases between 30th April and 31st May, 2020. These results revealed that parameter L = 5 (T/20) for the RF-SSA model was indeed suitable for short-time series outbreak data, while the appropriate number of eigentriples was integral as it influenced the forecasting results. Evidently, the RF-SSA had over-forecasted the cases by 0.36%. This signifies the competence of RF-SSA in predicting the impending number of COVID-19 cases. Nonetheless, an enhanced RF-SSA algorithm should be developed for higher effectivity of capturing any extreme data changes.
  12. Abduraman MA, Azizan NA, Teoh SH, Tan ML
    Obes Res Clin Pract, 2020 12 25;15(1):10-18.
    PMID: 33371997 DOI: 10.1016/j.orcp.2020.12.001
    Obesity is a serious chronic disease and a public health concern in both developing and developed countries. Managing obesity has been a great challenge for both health care professionals and patients alike. Among the various diet programs aimed at promoting weight loss, the ketogenic diet, a diet high in fat and low in carbohydrates, has been at the forefront recently and its mechanism in weight loss is much debated. Activation of Sirtuin 1 or SIRT1 is able to circumvent various diseases, including metabolic syndrome and obesity and is thought to be a potentially reliable treatment target for both of them. Augmentation of SIRT1 may be carried out using dietary means such as nicotinamide adenine dinucleotide (NAD) supplementation and/or ketogenic diet. Although ketogenic diet may augment SIRT1 activation in people affected by obesity, recent studies have indicated that the relationship between SIRT1 and ketogenesis is unpredictable. The exact circumstances and mechanisms of SIRT1, NAD and ketogenesis in the clinical setting as an intervention tool in managing obesity remained uncertain. Although several recent literatures have documented significant weight-loss following ketogenic diet interventions, there were limitations with regards to duration of trial, choice and the number of trial subjects. Studies investigating the safety of ketogenic diet in the long term, beyond 46 weeks and related mechanism and pathways are still lacking and the sustainability of this diet remains to be determined. This review explores the recent progress on ketogenic diet and its relationships with SIRT1 as a tool in managing obesity and relevant clinical implications.
  13. Tan ML, Abrams SA, Osborn DA
    Cochrane Database Syst Rev, 2020 Dec 11;12(12):CD013046.
    PMID: 33305822 DOI: 10.1002/14651858.CD013046.pub2
    BACKGROUND: Vitamin D deficiency is common worldwide, contributing to nutritional rickets and osteomalacia which have a major impact on health, growth, and development of infants, children and adolescents. Vitamin D levels are low in breast milk and exclusively breastfed infants are at risk of vitamin D insufficiency or deficiency.

    OBJECTIVES: To determine the effect of vitamin D supplementation given to infants, or lactating mothers, on vitamin D deficiency, bone density and growth in healthy term breastfed infants.

    SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to 29 May 2020 supplemented by searches of clinical trials databases, conference proceedings, and citations.

    SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in breastfeeding mother-infant pairs comparing vitamin D supplementation given to infants or lactating mothers compared to placebo or no intervention, or sunlight, or that compare vitamin D supplementation of infants to supplementation of mothers.

    DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We used the GRADE approach to assess the certainty of evidence.

    MAIN RESULTS: We included 19 studies with 2837 mother-infant pairs assessing vitamin D given to infants (nine studies), to lactating mothers (eight studies), and to infants versus lactating mothers (six studies). No studies compared vitamin D given to infants versus periods of infant sun exposure. Vitamin D supplementation given to infants: vitamin D at 400 IU/day may increase 25-OH vitamin D levels (MD 22.63 nmol/L, 95% CI 17.05 to 28.21; participants = 334; studies = 6; low-certainty) and may reduce the incidence of vitamin D insufficiency (25-OH vitamin D < 50 nmol/L) (RR 0.57, 95% CI 0.41 to 0.80; participants = 274; studies = 4; low-certainty). However, there was insufficient evidence to determine if vitamin D given to the infant reduces the risk of vitamin D deficiency (25-OH vitamin D < 30 nmol/L) up till six months of age (RR 0.41, 95% CI 0.16 to 1.05; participants = 122; studies = 2), affects bone mineral content (BMC), or the incidence of biochemical or radiological rickets (all very-low certainty). We are uncertain about adverse effects including hypercalcaemia. There were no studies of higher doses of infant vitamin D (> 400 IU/day) compared to placebo. Vitamin D supplementation given to lactating mothers: vitamin D supplementation given to lactating mothers may increase infant 25-OH vitamin D levels (MD 24.60 nmol/L, 95% CI 21.59 to 27.60; participants = 597; studies = 7; low-certainty), may reduce the incidences of vitamin D insufficiency (RR 0.47, 95% CI 0.39 to 0.57; participants = 512; studies = 5; low-certainty), vitamin D deficiency (RR 0.15, 95% CI 0.09 to 0.24; participants = 512; studies = 5; low-certainty) and biochemical rickets (RR 0.06, 95% CI 0.01 to 0.44; participants = 229; studies = 2; low-certainty). The two studies that reported biochemical rickets used maternal dosages of oral D3 60,000 IU/day for 10 days and oral D3 60,000 IU postpartum and at 6, 10, and 14 weeks. However, infant BMC was not reported and there was insufficient evidence to determine if maternal supplementation has an effect on radiological rickets (RR 0.76, 95% CI 0.18 to 3.31; participants = 536; studies = 3; very low-certainty). All studies of maternal supplementation enrolled populations at high risk of vitamin D deficiency. We are uncertain of the effects of maternal supplementation on infant growth and adverse effects including hypercalcaemia. Vitamin D supplementation given to infants compared with supplementation given to lactating mothers: infant vitamin D supplementation compared to lactating mother supplementation may increase infant 25-OH vitamin D levels (MD 14.35 nmol/L, 95% CI 9.64 to 19.06; participants = 269; studies = 4; low-certainty). Infant vitamin D supplementation may reduce the incidence of vitamin D insufficiency (RR 0.61, 95% CI 0.40 to 0.94; participants = 334; studies = 4) and may reduce vitamin D deficiency (RR 0.35, 95% CI 0.17 to 0.72; participants = 334; studies = 4) but the evidence is very uncertain. Infant BMC and radiological rickets were not reported and there was insufficient evidence to determine if maternal supplementation has an effect on infant biochemical rickets. All studies enrolled patient populations at high risk of vitamin D deficiency. Studies compared an infant dose of vitamin D 400 IU/day with varying maternal vitamin D doses from 400 IU/day to > 4000 IU/day. We are uncertain about adverse effects including hypercalcaemia.

    AUTHORS' CONCLUSIONS: For breastfed infants, vitamin D supplementation 400 IU/day for up to six months increases 25-OH vitamin D levels and reduces vitamin D insufficiency, but there was insufficient evidence to assess its effect on vitamin D deficiency and bone health. For higher-risk infants who are breastfeeding, maternal vitamin D supplementation reduces vitamin D insufficiency and vitamin D deficiency, but there was insufficient evidence to determine an effect on bone health. In populations at higher risk of vitamin D deficiency, vitamin D supplementation of infants led to greater increases in infant 25-OH vitamin D levels, reductions in vitamin D insufficiency and vitamin D deficiency compared to supplementation of lactating mothers. However, the evidence is very uncertain for markers of bone health. Maternal higher dose supplementation (≥ 4000 IU/day) produced similar infant 25-OH vitamin D levels as infant supplementation of 400 IU/day. The certainty of evidence was graded as low to very low for all outcomes.

  14. Foong SC, Tan ML, Foong WC, Ho JJ
    Arch Dis Child Educ Pract Ed, 2020 12;105(6):372-373.
    PMID: 31073039 DOI: 10.1136/archdischild-2018-316682
  15. Brindha K, Paul R, Walter J, Tan ML, Singh MK
    Environ Geochem Health, 2020 Nov;42(11):3819-3839.
    PMID: 32601907 DOI: 10.1007/s10653-020-00637-9
    Monitoring the groundwater chemical composition and identifying the presence of pollutants is an integral part of any comprehensive groundwater management strategy. The present study was conducted in a part of West Tripura, northeast India, to investigate the presence and sources of trace metals in groundwater and the risk to human health due to direct ingestion of groundwater. Samples were collected from 68 locations twice a year from 2016 to 2018. Mixed Ca-Mg-HCO3, Ca-Cl and Ca-Mg-Cl were the main groundwater types. Hydrogeochemical methods showed groundwater mineralization due to (1) carbonate dissolution, (2) silicate weathering, (3) cation exchange processes and (4) anthropogenic sources. Occurrence of faecal coliforms increased in groundwater after monsoons. Nitrate and microbial contamination from wastewater infiltration were apparent. Iron, manganese, lead, cadmium and arsenic were above the drinking water limits prescribed by the Bureau of Indian Standards. Water quality index indicated 1.5% had poor, 8.7% had marginal, 16.2% had fair, 66.2% had good and 7.4% had excellent water quality. Correlation and principal component analysis reiterated the sources of major ions and trace metals identified from hydrogeochemical methods. Human exposure assessment suggests health risk due to high iron in groundwater. The presence of unsafe levels of trace metals in groundwater requires proper treatment measures before domestic use.
  16. Tan ML, Foong SC, Ho JJ, Foong WC, Mohd R, Harun Z
    Int Breastfeed J, 2020 10 14;15(1):85.
    PMID: 33054789 DOI: 10.1186/s13006-020-00328-2
    BACKGROUND: Antenatal breastfeeding education (ANBE) is provided to all pregnant women attending Ministry of Health (MOH) clinics and some private health facilities in Malaysia, in line with the WHO/UNICEF Baby-Friendly Hospital Initiative (BFHI). However, the 6 month exclusive breastfeeding prevalence remains relatively low in Malaysia, suggesting that there may be a gap between what is currently taught and what is received by the women.

    OBJECTIVES: To determine how women perceived their ANBE experience in the first 8 weeks postpartum including what was useful and what they would like to have been included, sources of ANBE and infant feeding practices at the time of survey.

    METHODS: Women during their first 8 weeks postpartum who attended MOH clinics in Penang State, Malaysia were surveyed using a self-administered questionnaire in April and May 2015. Categorical responses were presented as numbers and proportions while free text responses were compiled verbatim and categorised into themes. The perceptions of primiparous and multiparous women were compared. Multivariate logistic regression adjusted to known confounders was used to determine if ANBE was associated with exclusive breastfeeding at the time of survey.

    RESULTS: A total of 421 women completed the 15-item questionnaire (84% response rate) of which 282 were complete and available for analysis. Of these, 95% had received ANBE, majority (88%) from MOH clinics. Almost all women found it useful. However, there were areas both in the delivery (e.g. too short) and the content (e.g. nothing new) that were described as not useful; and areas they would like more coverage (e.g. milk expression, storage and overcoming low milk supply). The exclusive breastfeeding prevalence at the time of survey was 61%. ANBE was significantly associated with exclusive breastfeeding even after adjusting for confounders (adjusted odds ratio [aOR] 8.1, 95% confidence interval 1.7, 38.3).

    CONCLUSIONS: ANBE is widely implemented and perceived as useful and may be associated with exclusive breastfeeding. Our findings give insight into content that women would like more of and how delivery of ANBE could be improved, including individualized sessions and communicating at a suitable level and language. Future studies could focus on the quality of ANBE delivery.

  17. Foong SC, Tan ML, Foong WC, Marasco LA, Ho JJ, Ong JH
    Cochrane Database Syst Rev, 2020 May 18;5(5):CD011505.
    PMID: 32421208 DOI: 10.1002/14651858.CD011505.pub2
    BACKGROUND: Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use.

    OBJECTIVES: To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs.

    SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019).

    SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials.

    DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification.

    MAIN RESULTS: Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I2 = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I2 = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome.

    AUTHORS' CONCLUSIONS: Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used.

  18. Abdul Rahman M, Tan ML, Johnson SP, Hollows RJ, Chai WL, Mansell JP, et al.
    PeerJ, 2020;8:e10328.
    PMID: 33240646 DOI: 10.7717/peerj.10328
    Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and accounts for 300,000 new cases yearly. The five-year survival rate is approximately 50% and the major challenges to improving patient prognosis include late presentation, treatment resistance, second primary tumours and the lack of targeted therapies. Therefore, there is a compelling need to develop novel therapeutic strategies. In this study, we have examined the effect of lysophosphatidic acid (LPA) on OSCC cell migration, invasion and response to radiation, and investigated the contribution of cyclooxygenase-2 (COX-2) in mediating the tumour promoting effects of LPA. Using the TCGA data set, we show that the expression of the lipid phosphate phosphatases (LPP), LPP1 and LPP3, was significantly down-regulated in OSCC tissues. There was no significant difference in the expression of the ENPP2 gene, which encodes for the enzyme autotaxin (ATX) that produces LPA, between OSCCs and control tissues but ENPP2 levels were elevated in a subgroup of OSCCs. To explore the phenotypic effects of LPA, we treated OSCC cell lines with LPA and showed that the lipid enhanced migration and invasion as well as suppressed the response of the cells to irradiation. We also show that LPA increased COX-2 mRNA and protein levels in OSCC cell lines and inhibition of COX-2 activity with the COX-2 inhibitor, NS398, attenuated LPA-induced OSCC cell migration. Collectively, our data show for the first time that COX-2 mediates some of the pro-tumorigenic effects of LPA in OSCC and identifies the ATX-LPP-LPA-COX-2 pathway as a potential therapeutic target for this disease.
  19. Tay YL, Amanah A, Adenan MI, Wahab HA, Tan ML
    Sci Rep, 2019 12 24;9(1):19757.
    PMID: 31874991 DOI: 10.1038/s41598-019-56106-6
    Mitragyna speciosa Korth (M. speciosa) has been widely used as a recreational product, however, there are growing concerns on the abuse potentials and toxicity of the plant. Several poisoning and fatal cases involving kratom and mitragynine have been reported but the underlying causes remain unclear. The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit underlying cardiac rapidly delayed rectifier potassium current (IKr). Pharmacological blockade of the IKr can cause acquired long QT syndrome, leading to lethal cardiac arrhythmias. This study aims to elucidate the mechanisms of mitragynine-induced inhibition on hERG1a/1b current. Electrophysiology experiments were carried out using Port-a-Patch system. Quantitative RT-PCR, Western blot analysis, immunofluorescence and co-immunoprecipitation methods were used to determine the effects of mitragynine on hERG1a/1b expression and hERG1-cytosolic chaperones interaction. Mitragynine was found to inhibit the IKr current with an IC50 value of 332.70 nM. It causes a significant reduction of the fully-glycosylated (fg) hERG1a protein expression but upregulates both core-glycosylated (cg) expression and hERG1a-Hsp90 complexes, suggesting possible impaired hERG1a trafficking. In conclusion, mitragynine inhibits hERG1a/1b current through direct channel blockade at lower concentration, but at higher concentration, it upregulates the complexation of hERG1a-Hsp90 which may be inhibitory towards channel trafficking.
  20. Lai SL, Tan ML, Hollows RJ, Robinson M, Ibrahim M, Margielewska S, et al.
    Cancers (Basel), 2019 Nov 09;11(11).
    PMID: 31717573 DOI: 10.3390/cancers11111766
    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and includes squamous cell carcinomas of the oropharynx and oral cavity. Patient prognosis has remained poor for decades and molecular targeted therapies are not in routine use. Here we showed that the overall expression of collagen subunit genes was higher in cancer-associated fibroblasts (CAFs) than normal fibroblasts. Focusing on collagen8A1 and collagen11A1, we showed that collagen is produced by both CAFs and tumour cells, indicating that HNSCCs are collagen-rich environments. We then focused on discoidin domain receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase, and showed that it is over-expressed in HNSCC tissues. Further, we demonstrated that collagen promoted the proliferation and migration of HNSCC cells and attenuated the apoptotic response to cisplatin. Knockdown of DDR1 in HNSCC cells demonstrated that these tumour-promoting effects of collagen are mediated by DDR1. Our data suggest that specific inhibitors of DDR1 might provide novel therapeutic opportunities to treat HNSCC.
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