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Fulltext A Systematic Review and Meta-Analysis of Medical Students' Perspectives on the Engagement in Research

Naing C, Wai VN, Durham J, Whittaker MA, Win NN, Aung K, et al.

Medicine (Baltimore), 2015 Jul;94(28):e1089.
PMID: 26181541 DOI: 10.1097/MD.0000000000001089

Engaging students in active learning lies at the center of effective higher education. In medical schools, students' engagement in learning and research has come under increasing attention. The objective of this study was to synthesize evidence on medical students' perspectives on the engagement in research. We performed a systematic review and meta-analysis. Relevant studies were searched in electronic databases. The methodological quality of the included studies was assessed. Overall, 14 observational studies (with 17 data sets) were included. In general, many studies did not use the same questionnaires and the outcome measurements were not consistently reported; these presented some difficulties in pooling the results. Whenever data permitted, we performed pooled analysis for the 4 education outcomes. A Bayesian meta-analytical approach was supplemented as a measure of uncertainty. A pooled analysis showed that 74% (95% confidence interval [CI]: 1.57%-11.07%; I2: 95.2%) of those students who engaged in research (while at the medical school) had positive attitudes toward their research experiences, whereas 49.5% (95% CI: 36.4%-62.7%; I2: 93.4%) had positive attitudes toward the study of medical sciences, 62.3% (95% CI: 46.7%-77.9%; I2: 96.3%) had self-reported changes in their practices, and 64% (95% CI: 30.8%-96.6%; I2: 98.5%) could have published their work. There was substantial heterogeneity among studies. We acknowledged the caveats and the merit of the current review. Findings showed that engagement in research resulted in favorable reactions toward research and academic learning. Future well-designed studies using standardized research tools on how to engage students in research are recommended.
A comparative histopathological study of systemic candidiasis in association with experimentally induced breast cancer

Choo ZW, Chakravarthi S, Wong SF, Nagaraja HS, Thanikachalam PM, Mak JW, et al.

Oncol Lett, 2010 Jan;1(1):215-222.
PMID: 22966285

Systemic candidiasis is a fungal infection which coupled with solid malignancies places patients at high risk of succumbing to the disease. Few studies have shown evidence of the relationship between systemic candidiasis and malignancy-induced immunosuppression disease especially in breast cancer. At present, animal studies that exclusively demonstrate this relationship have yet to be conducted. The exact causative mechanism of systemic candidiasis is currently under much speculation. This study therefore aimed to demonstrate this relationship by observing the histopathological changes of organs harvested from female Balb/c mice which were experimentally induced with breast cancer and inoculated with systemic candidiasis. The mice were randomly assigned to five different groups (n=12). The first group (group 1) was injected with phosphate buffer solution, the second (group 2) with systemic candidiasis, the third (group 3) with breast cancer and the final two groups (groups 4 and 5) had both candidiasis and breast cancer at two different doses of candidiasis, respectively. Inoculation of mice with systemic candidiasis was performed by an intravenous injection of Candida albicans via the tail vein following successful culture methods. Induction of mice with breast cancer occurred via injection of 4T1 cancer cells at the right axillary mammary fatpad after effective culture methods. The prepared slides with organ tissues were stained with hematoxylin and eosin, periodic acidic schiff and gomori methenamine silver stains for a histopathological analysis. Grading of primary tumour and identification of metastatic deposits, as well as scoring of inflammation and congestion in all the respective organs was conducted. Statistical tests performed to compare groups 2 and 4 showed that group 4 exhibited a highly statistically significant increase in organ inflammation and congestion (p<0.01). The median severity of candidiasis in the kidneys and liver also increased in group 4 as compared to group 2. In conclusion, based on the above evidence, systemic candidiasis significantly increased in mice with breast cancer.
A description of adult Wuchereria bancrofti (rural strain) from an experimental infection in the long-tailed macaque, Macaca fascicularis (sny. M. irus)

Dissanaike AS, Mak JW

J Helminthol, 1980 Jun;54(2):117-22.
PMID: 6997363

Adult worms of the rural strain of Wuchereria bancrofti in Peninsular Malaysia obtained from a successful experimental transmission in an immunosuppressed Macaca fascicularis are described for the first time. Although the worms, especially females, were slightly smaller, they were similar in morphology to those of the periodic and non-periodic W. bancrofti previously described.
Fulltext A study of parasitic infections in the luminal contents and tissue sections of appendix specimens

Thanikachalam MP, Kasemsuk Y, Mak JW, Sharifah Emilia TS, Kandasamy P

Trop Biomed, 2008 Aug;25(2):166-72.
PMID: 18948889 MyJurnal

Appendicitis has a worldwide prevalence and affects all age groups. The aetiology of acute appendicitis is still much debated, many factors have been implicated. The pathology is likely to be due to obstruction of the lumen of the appendix. Parasites, both helminths and protozoa have been suggested to be the cause of acute appendicitis. Studies have demonstrated that parasites are present in the appendix specimens removed from surgery methods.
A study of the sensitivity of Plasmodium falciparum to chloroquine and mefloquine using the in vitro microtechnique in Peninsular Malaysia

Ho KB, Mak JW, Ramadas M

Trans R Soc Trop Med Hyg, 1987;81(2):257-9.
PMID: 3303483

Plasmodium falciparum drug sensitivities to chloroquine and mefloquine were assessed with WHO in vitro microtechnique test kits in 5 localities near the border with Thailand in Peninsular Malaysia. 105 of 113 (92.9%) parasite isolates were successfully tested and 103 (98.1%) showed resistance to chloroquine with parasite growth even at greater than or equal to 5.7 pmol of the drug. All these isolates were sensitive to mefloquine, parasite growth being inhibited at less than or equal to 11.3 pmol of the drug.
Fulltext A systematic review of the efficacy of a single dose artemisinin-naphthoquine in treating uncomplicated malaria

Naing C, Whittaker MA, Mak JW, Aung K

Malar J, 2015;14:392.
PMID: 26445424 DOI: 10.1186/s12936-015-0919-5

This study aimed to synthesize the existing evidence on the efficacy and safety of a single dose artemisinin-naphthoquine (ASNQ) for treatment of uncomplicated malaria in endemic countries.
Fulltext Acanthamoeba genotype T4 detected in naturally-infected feline corneas found to be in homology with those causing human keratitis

Ithoi I, Mahmud R, Abdul Basher MH, Jali A, Abdulsalam AM, Ibrahim J, et al.

Trop Biomed, 2013 Mar;30(1):131-40.
PMID: 23665719 MyJurnal

A total of 10 out of 65 cornea swab samples from cats with eye symptoms showed Acanthamoeba-like morphology after cultivation. By PCR and DNA sequencing of Acanthamoeba diagnostic fragment 3 (DF3), all 10 isolates from the positive samples were categorized into two homologous groups of AfC1 (PM1, PM2, PM3, PF6, KM7, KF8, KMK9) and AfC2 (PM4, PM5, KFK10) due to the presence of bases A(354) and G(354), respectively. Furthermore, DF3 of AfC1 and AfC2 showed 100% similarity with Genbank reference isolates with the accession numbers DQ087314, EU146073 and U07401, GU808323, which were Acanthamoeba castellanii strains genotype T4 originating from human keratitis. This finding suggests that A. castellani strains have the capability to infect cats and human under favorable conditions.
Advances in immunology and immunopathology of lymphatic filariasis

Mak JW

Southeast Asian J. Trop. Med. Public Health, 1993;24 Suppl 2:76-81.
PMID: 7973952

The lymphatic filarial parasites which affect about 90 million people worldwide have similar host-parasite relationships in man. They are all able to survive, reproduce and cause chronic infections if they can successfully evade the protective responses of the host. Studies to investigate the wide spectrum of clinical manifestations of the infection even among those living in similar endemic areas and with presumed equal exposure to infective larvae, have been hampered by the lack of animal models showing similar host-parasite responses. The recent use of the nude mouse infected with Brugia spp, and the leaf-monkey (Presbytis spp) infected with B. malayi or Wuchereria spp for the study of immune responses and the associated pathology of these infections, has elucidated some of the host protective immune responses as well as the associated immunopathological reactions. The successfully entrenched parasite elicits minimal reactions and pathology, but with the onset of effective host responses, whether assisted by chemotherapy, development of protective immunity or both, severe inflammatory responses may occur. The role of such immune mediated response in determining subsequent pathology will probably be dependent on the frequency and duration of these episodes, but these have yet to be defined. Prenatal and perinatal sensitization by filarial antigens are postulated to result in tolerance and/or modification of immune responses to subsequent infections. A role for genetic predisposition to certain clinical outcomes, for example, the development of elephantiasis, has been postulated but needs further study. Advances have also been achieved in defining those parasite antigens/products involved in eliciting or suppressing protective and other immune responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Fulltext An outbreak of acute haemorrhagic conjunctivitis in Melaka, Malaysia

Ghazali O, Chua KB, Ng KP, Hooi PS, Pallansch MA, Oberste MS, et al.

Singapore Med J, 2003 Oct;44(10):511-6.
PMID: 15024454

This paper reports a second outbreak of acute haemorrhagic conjunctivitis due to coxsackievirus A24 in peninsular Malaysia. Between June 2002 and early October 2003, 10,327 patients, comprising 3,261 children and 7,066 adults, were treated for acute conjunctivitis in 11 government health clinics in the Melaka Tengah district of the state of Melaka. The figure grossly underestimates the size of the outbreak; as no patients treated in private clinics in the same district were included. Institution and household surveillance showed that the commonest presenting clinical feature of the illness was eye-discharge (91.2%), followed by foreign body sensation (81.8%), pain (78.3%) and subconjunctival haemorrhage (74.4%). The mean duration of illness was 6.5 and five days for patients with and without subconjunctival haemorrhage respectively.
Fulltext Anopheles donaldi incriminated as a vector of periodic Brugia malayi in Grik, Perak, Malaysia

Vythilingam I, Hakim SL, Chan ST, Mak JW

Southeast Asian J. Trop. Med. Public Health, 1996 Sep;27(3):637-41.
PMID: 9185284

Studies were carried out to observe the species composition of mosquitos and to determine the vectors responsible for the transmission of filariasis in Grik, Perak, Malaysia. A total of 2,155 mosquitos belonging to 7 genera and 30 species were collected. Anopheles donaldi comprised 24.1% of the collection. Twelve out of 519 An. donaldi were infected with L3 larvae of Brugia malayi. The peak biting time was around 23.00-24.00 hours. The infective bites per month ranged from 0 to 6.3.
Anopheles flavirostris incriminated as a vector of malaria and Bancroftian filariasis in Banggi Island, Sabah, Malaysia

Hii JL, Kan S, Vun YS, Chin KF, Lye MS, Mak JW, et al.

Trans R Soc Trop Med Hyg, 1985;79(5):677-80.
PMID: 3913069

Seven villages in Banggi Island, Sabah, Malaysia, were surveyed four times to evaluate the roles of local mosquitoes as vectors of malaria and Bancroftian filariasis. 11 species of Anopheles were found biting man. 53.9% of the anophelines caught were An. flavirostris, 27.1% An. balabacensis, 6% An. donaldi and 4.2% An. subpictus. Infective malaria sporozoites, probably of human origin, were found in two of 336 An. flavirostris and 12 of 308 An. balabacensis. Sporozoites, probably of a non-human Plasmodium, were found in An. umbrosus. Nine of 1001 An. flavirostris and four of 365 An. balabacensis harboured L2 or L3 filarial larvae identified as those of Wuchereria bancrofti. This is the first record of An. flavirostris as a natural vector of malaria and W. bancrofti in Sabah.
Antibodies to Plasmodium falciparum in an indigenous population from a malaria endemic area of Malaysia

Archibald CP, Mak JW, Mathias RG, Selvajothi S

Acta Trop, 1990 Dec;48(2):149-57.
PMID: 1980570

Indirect fluorescent antibody (IFA) tests and enzyme-linked immunosorbent assays (ELISA) were used to measure antibodies to Plasmodium falciparum in an indigenous population in an area of Malaysia with high malaria prevalence. The results of three surveys were analyzed to examine the relation of these serologic measures with age, parasite rate, and spleen size. For children 0-4 years old, increasing spleen size was associated with an increasing likelihood of malaria parasitemia, while for 5-9 year olds the two variables were unrelated. Parasite rate declined with age and ELISA titre increased with age in all surveys; IFA titre was consistently high and did not vary with age. Neither antibody measure was significantly correlated with either the presence or the actual density of parasitemia. These antibody measures are most useful as adjuncts to the more traditional techniques of malaria assessment.
Antifilarial activity of CGP 20376 against subperiodic Brugia malayi in the leaf-monkey Presbytis cristata

Mak JW, Suresh K, Lam PL, Choong MF, Striebel HP

Trop. Med. Parasitol., 1990 Mar;41(1):10-2.
PMID: 2339241

CGP 20376, a 5-methoxyl-6-dithiocarbamic-S- (2-carboxy-ethyl) ester derivative of benzothiazole was evaluated for its antifilarial properties and shown to be extremely effective against subperiodic Brugia malayi in the leaf-monkey, Presbytis cristata at oral doses of 20-100 mg/kg. The compound and/or its metabolites had complete micro- and microfilaricidal activities even when given at a single dose of 20 mg/kg. Lower doses had incomplete filaricidal action.
Antifilarial activity of intravenous suramin and oral diethylcarbamazine citrate on subperiodic Brugia malayi in the leaf-monkey, Presbytis cristata

Mak JW, Lam PL, Choong MF, Suresh K

J Helminthol, 1990 Jun;64(2):96-9.
PMID: 2387979

The known filaricides, suramin and diethylcarbamazine citrate, were tested against subperiodic Brugia malayi infection in the leaf-monkey, Presbytis cristata. As expected, intravenous suramin at 10 mg/kg daily x 5 days or 17 mg/kg weekly x 5 weeks, did not show any microfilaricidal activity, but substantially reduced the recovery of live adult worms to 50.6% and 13.6% of controls respectively. Oral diethylcarbamazine citrate at 6 mg/kg daily x 6 or 10 days reduced final microfilarial counts to 30% of initial counts four weeks post-treatment and adult worm recovery was reduced to 4.5% and 0% of controls respectively. Although the antifilarial activity of these drugs against the infection in this non-human primate model appears to be similar to that seen in man, these results have to be confirmed using larger groups of animals.
Fulltext Antifilarial compounds in the treatment and control of lymphatic filariasis

Mak JW

Trop Biomed, 2004 Dec;21(2):27-38.
PMID: 16493396

Diethylcarbamazine citrate (DEC) has been used for treatment and control of lymphatic filariasis since the 1950s. Although this remarkable drug is still useful and modified strategies in its usage have been developed, a number of newer antifilarial compounds are now available. Numerous field trials evaluating their efficacy in the control of lymphatic filariasis have been conducted. In particular, ivermectin (IVM), albendazole (ALB), and DEC have been tested singly and in combinations and the results of such field studies should be evaluated. While most of the studies were based on efficacy in the clearance of microfilaraemia, a few clinical trials evaluated the adulticidal activity of these compounds. Some antibiotics are effective in killing Wolbachia bacteria symbionts of filarial worms, but their role in the chemotherapy of lymphatic filariasis is still undefined. This review of randomised controlled field studies and randomised controlled clinical trials with these compounds will summarise the findings and give recommendations on their appropriate use for the control and treatment of lymphatic filariasis.
Fulltext Antigenic profile of Blomia tropicalis, Aleuroglyphus ovatus and Glycycometus malaysiensis

Tang JC, Wong SF, Mak JW, Ho TM

Trop Biomed, 2011 Aug;28(2):223-36.
PMID: 22041741

House dust mites and storage mites are well-known causes for allergenic diseases. The aim of this study was to investigate the immunogenic sites of Blomia tropicalis, Aleurogyphus ovatus and Glycycometus malaysiensis. The mites were maintained in a culture medium at 25ºC and 75% relative humidity. Mites were harvested either with heat escape or floatation method, purified, homogenized, quantified and used for the production of polyclonal antibody and immunostaining. For each species of mites, five male mice and five male rats were randomly selected and immunized intraperitoneally with respective crude mite extract at two-weekly intervals. Blomia tropicalis, A. ovatus or G. malaysiensis whole mites and paraffin-embedded mite sections were immunostained with the respective polyclonal antibody. The faecal pellets of mites were intensely stained for all the three species in the present study. The legs of sectioned A. ovatus were not immunogenic as compared with those of G. malaysiensis and B. tropicalis. The outer layer (cuticle) of whole mites and the eggs for these species were very immunogenic. Hence, the polyclonal antibodies obtained in this study may serve as potential tools in detecting the eggs and immature mites in environmental samples. Future studies should focus on the antigenic components of eggs since they were relatively abundant in dust and highly antigenic as seen in the present study.
Applications of biotechnology in parasitic diseases in Malaysia

Mak JW, Yong HS, Lim PK, Tan MA

Southeast Asian J. Trop. Med. Public Health, 1988 Mar;19(1):7-9.
PMID: 3406806

Biotechnological tools are being used in malaria, filariasis and dengue research. The main emphasis has been on the production of reagents for immunodiagnosis and research. In this respect monoclonal antibodies (McAbs) against various species and stages of the above pathogens have been produced. It is hoped that these McAbs will be useful not only in immunodiagnosis but also for seroepidemiological applications. A DNA probe against Brugia malayi has been tested in Malaysia and was found to be sensitive and specific.
Armigeres subalbatus incriminated as an important vector of the dog heartworm Dirofilaria immitis and the bird Cardiofilaria in urban Kuala Lumpur

Cheong WH, Mak JW, Naidu S, Mahadevan S

Southeast Asian J. Trop. Med. Public Health, 1981 Dec;12(4):611-2.
PMID: 6124044
Fulltext Association between long-term exposure to ambient air pollution and prevalence of diabetes mellitus among Malaysian adults

Wong SF, Yap PS, Mak JW, Chan WLE, Khor GL, Ambu S, et al.

Environ Health, 2020 04 03;19(1):37.
PMID: 32245482 DOI: 10.1186/s12940-020-00579-w

BACKGROUND: Malaysia has the highest rate of diabetes mellitus (DM) in the Southeast Asian region, and has ongoing air pollution and periodic haze exposure.
METHODS: Diabetes data were derived from the Malaysian National Health and Morbidity Surveys conducted in 2006, 2011 and 2015. The air pollution data (NOx, NO2, SO2, O3 and PM10) were obtained from the Department of Environment Malaysia. Using multiple logistic and linear regression models, the association between long-term exposure to these pollutants and prevalence of diabetes among Malaysian adults was evaluated.
RESULTS: The PM10 concentration decreased from 2006 to 2014, followed by an increase in 2015. Levels of NOx decreased while O3 increased annually. The air pollutant levels based on individual modelled air pollution exposure as measured by the nearest monitoring station were higher than the annual averages of the five pollutants present in the ambient air. The prevalence of overall diabetes increased from 11.4% in 2006 to 21.2% in 2015. The prevalence of known diabetes, underdiagnosed diabetes, overweight and obesity also increased over these years. There were significant positive effect estimates of known diabetes at 1.125 (95% CI, 1.042, 1.213) for PM10, 1.553 (95% CI, 1.328, 1.816) for O3, 1.271 (95% CI, 1.088, 1.486) for SO2, 1.124 (95% CI, 1.048, 1.207) for NO2, and 1.087 (95% CI, 1.024, 1.153) for NOx for NHMS 2006. The adjusted annual average levels of PM10 [1.187 (95% CI, 1.088, 1.294)], O3 [1.701 (95% CI, 1.387, 2.086)], NO2 [1.120 (95% CI, 1.026, 1.222)] and NOx [1.110 (95% CI, 1.028, 1.199)] increased significantly from NHMS 2006 to NHMS 2011 for overall diabetes. This was followed by a significant decreasing trend from NHMS 2011 to 2015 [0.911 for NO2, and 0.910 for NOx].
CONCLUSION: The findings of this study suggest that long-term exposure to O3 is an important associated factor of underdiagnosed DM risk in Malaysia. PM10, NO2 and NOx may have mixed effect estimates towards the risk of DM, and their roles should be further investigated with other interaction models. Policy and intervention measures should be taken to reduce air pollution in Malaysia.
Fulltext Association between telomere length and the risk of colorectal cancer: a meta-analysis of observational studies

Naing C, Aung K, Lai PK, Mak JW

BMC Cancer, 2017 01 05;17(1):24.
PMID: 28056862 DOI: 10.1186/s12885-016-2997-3

BACKGROUND: Human chromosomes are capped and stabilized by telomeres. Telomere length regulates a 'cellular mitotic clock' that defines the number of cell divisions and hence, cellular life span. This study aimed to synthesize the evidence on the association between peripheral blood leucocytes (PBL) telomere length and the risk of colorectal cancer (CRC).
METHODS: We searched relevant studies in electronic databases. When two or more observational studies reported the same outcome measures, we performed pooled analysis. All the analyses were performed on PBL using PCR. The odds ratio (OR) and its 95% confidence interval (CI) were used to assess the strength of association.
RESULTS: Seven studies (with 8 datasets) were included in this meta-analysis; 3 prospective studies, 3 retrospective studies and 1 study with a separate prospective and retrospective designs. The pooled analysis of 4 prospective studies (summary OR 1.01, 95% CI: 0.77-1.34, I (2):30%) and 4 retrospective studies (summary OR 1.65, 95% CI: 0.96-2.83, I (2):96%) showed no relationship between PBL telomere length and the CRC risk. A subgroup analysis of 2 prospective studies exclusively on females also showed no association between PBL telomere length and the CRC risk (summary OR, 1.17, 95% CI:0.72-1.91, I (2):57%).
CONCLUSION: The current analysis is insufficient to provide evidence on the relationship between PBL telomere length and the risk of CRC. Findings suggest that there may be a complex relationship between PBL telomere length and the CRC risk or discrepancy between genetics, age of patients and clinical studies. Future well powered, large prospective studies on the relationship between telomere length and the risk of CRC, and the investigations of the biologic mechanisms are recommended.

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