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The Daturas of Malaya

Gimlette JD

Ind Med Gaz, 1906 Jun;41(6):236.
PMID: 29006038
Fulltext Lessons learned from the COVID-19 pandemic

Khoo EJ, Lantos JD

Acta Paediatr, 2020 07;109(7):1323-1325.
PMID: 32289175 DOI: 10.1111/apa.15307
Inverse frequency weighting of fragments for similarity-based virtual screening

Arif SM, Holliday JD, Willett P

J Chem Inf Model, 2010 Aug 23;50(8):1340-9.
PMID: 20672867 DOI: 10.1021/ci1001235

This paper discusses the weighting of two-dimensional fingerprints for similarity-based virtual screening, specifically the use of weights that assign greatest importance to the substructural fragments that occur least frequently in the database that is being screened. Virtual screening experiments using the MDL Drug Data Report and World of Molecular Bioactivity databases show that the use of such inverse frequency weighting schemes can result, in some circumstances, in marked increases in screening effectiveness when compared with the use of conventional, unweighted fingerprints. Analysis of the characteristics of the various schemes demonstrates that such weights are best used to weight the fingerprint of the reference structure in a similarity search, with the database structures' fingerprints unweighted. However, the increases in performance resulting from such weights are only observed with structurally homogeneous sets of active molecules; when the actives are diverse, the best results are obtained using conventional, unweighted fingerprints for both the reference structure and the database structures.
Fulltext Targeting the intrinsic apoptosis pathway as a strategy for melanoma therapy

Mohana-Kumaran N, Hill DS, Allen JD, Haass NK

Pigment Cell Melanoma Res, 2014 Jul;27(4):525-39.
PMID: 24655414 DOI: 10.1111/pcmr.12242

Melanoma drug resistance is often attributed to abrogation of the intrinsic apoptosis pathway. Targeting regulators of apoptosis is thus considered a promising approach to sensitizing melanomas to treatment. The development of small-molecule inhibitors that mimic natural antagonists of either antiapoptotic members of the BCL-2 family or the inhibitor of apoptosis proteins (IAPs), known as BH3- or SMAC-mimetics, respectively, are helping us to understand the mechanisms behind apoptotic resistance. Studies using BH3-mimetics indicate that the antiapoptotic BCL-2 protein MCL-1 and its antagonist NOXA are particularly important regulators of BCL-2 family signaling, while SMAC-mimetic studies show that both XIAP and the cIAPs must be targeted to effectively induce apoptosis of cancer cells. Although most solid tumors, including melanoma, are insensitive to these mimetic drugs as single agents, combinations with other therapeutics have yielded promising results, and tests combining them with BRAF-inhibitors, which have already revolutionized melanoma treatment, are a clear priority.
Fulltext Asia Cohort Consortium: challenges for collaborative research

Song M, Rolland B, Potter JD, Kang D

J Epidemiol, 2012;22(4):287-90.
PMID: 22672913 DOI: 10.2188/jea.je20120024

In this era of chronic diseases, large studies are essential in investigating genes, environment, and gene-environment interactions as disease causes, particularly when associations are important but not strong. Moreover, to allow expansion and generalization of the results, studies should be conducted in populations outside Western countries. Here, we briefly describe the Asia Cohort Consortium (ACC), a collaborative cancer cohort research project that was first proposed in 2004 and now involves more than 1 million healthy individuals across Asia. There are approximately 50 active members from Bangladesh, China, India, Japan, Korea, Malaysia, Singapore, Taiwan, Thailand, the United States, and elsewhere. To date, the work of the ACC includes 3 articles published in 2011 on the roles of body mass index, tobacco smoking, and alcohol consumption in mortality, diabetes, and cancer of the small intestine. Many challenges remain, including data harmonization, resolution of ethical and legal issues, establishment of protocols for biologic samples and transfer agreements, and funding procurement.
Ethical Concerns When Minors Act as Standardized Patients

Khoo EJ, Schremmer RD, Diekema DS, Lantos JD

Pediatrics, 2017 Mar;139(3).
PMID: 28174202 DOI: 10.1542/peds.2016-2795

When minors are asked to assist medical educators by acting as standardized patients (SPs), there is a potential for the minors to be exploited. Minors deserve protection from exploitation. Such protection has been written into regulations governing medical research and into child labor laws. But there are no similar guidelines for minors' work in medical education. This article addresses the question of whether there should be rules. Should minors be required to give their informed consent or assent? Are there certain practices that could cause harm for the children who become SPs? We present a controversial case and ask a number of experts to consider the ethical issues that arise when minors are asked to act as SPs in medical education.
Fulltext Equitable Access to State-of-the-Art Medical Technology-a Malaysian Mini-Public-Private Partnership Case Study

Waran V, Thillainathan R, Karuppiah R, Pickard JD

World Neurosurg, 2022 01;157:135-142.
PMID: 34687934 DOI: 10.1016/j.wneu.2021.10.112

BACKGROUND: The provision of equitable and affordable health care has become increasingly challenging as advanced technology is introduced, particularly in developing countries. We explored the hypothesis that focused, small-scale mini-public-private partnerships have a potential role in providing equitable and affordable access to advanced technology for the benefit of all patients in developing nations, particularly middle-income countries.
METHODS: A clinician-led financial plan was developed at the University of Malaya to create the Centre for Image Guidance and Minimally Invasive Therapy (CIGMIT) to provide an integrated platform for high-end care for Malaysian patients of all ages, both public and private, requiring complex neurosurgical and spinal procedures and stereotactic and intensity-modulated radiotherapy. The challenges faced during development of the plan were documented together with an audit of patient throughput and analyses of financial risk and return.
RESULTS: CIGMIT opened in 2015. Patient throughput, both public and private, progressively increased in all facilities. In 2015-2019, 37,724 patients used the Centre's facilities. CIGMIT has become progressively more profitable for the University of Malaya, the public and private hospitals, and the investor. CIGMIT has weathered the challenges posed by coronavirus disease 19.
CONCLUSIONS: Focused, small-scale mini-public-private partnerships have a potential role in providing advanced technology for the benefit of patients in developing nations, particularly middle-income countries, subject to an approach that balances equity of access between public and private health care systems with fair reward.
Changes in balance function with chronic antiepileptic drug therapy: A twin and sibling study

Shiek Ahmad B, Wark JD, Petty SJ, O'Brien TJ, Gorelik A, Sambrook PN, et al.

Epilepsia, 2015 Nov;56(11):1714-22.
PMID: 26513212 DOI: 10.1111/epi.13136

To investigate cross-sectional and longitudinal differences in static and dynamic standing balance measures and lower limb muscle strength in patients who are treated chronically with antiepileptic drugs (AEDs).
Rights of patients: comparative perspectives from five countries

Blum JD, Talib N, Carstens P, Nasser M, Tomkin D, McAuley A

Med Law, 2003;22(3):451-71.
PMID: 14626880

Recognition and articulation of patient rights are core issues in the medical jurisprudence of most nations. While the nature of rights in medical care may vary from country to country, reflecting the idiosyncrasies of domestic law and health delivery, there are commonalities in this area of law that cut across borders. This paper presents five case studies in the patient rights area from Malaysia, Ireland, South Africa, Indonesia and the United States, respectively. The case discussions range from ongoing and fundamental concerns over broad patient rights issues, such as access to health care and informed consent, to rights concerns of those suffering from HIV/AIDS, to a novel consideration over ethical and legal issues concerning ownership of infant organs. It is the hope of the authors that individually, and collectively, the cases will provide helpful insights into this core area of medical law.
Fulltext Vertical stratification of adult mosquitoes (Diptera: Culicidae) within a tropical rainforest in Sabah, Malaysia

Brant HL, Ewers RM, Vythilingam I, Drakeley C, Benedick S, Mumford JD

Malar J, 2016 07 19;15(1):370.
PMID: 27430261 DOI: 10.1186/s12936-016-1416-1

BACKGROUND: Malaria cases caused by Plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques, are increasing rapidly in Sabah, Malaysia. One hypothesis is that this increase is associated with changes in land use. A study was carried out to identify the anopheline vectors present in different forest types and to observe the human landing behaviour of mosquitoes.
METHODS: Mosquito collections were carried out using human landing catches at ground and canopy levels in the Tawau Division of Sabah. Collections were conducted along an anthropogenic disturbance gradient (primary forest, lightly logged virgin jungle reserve and salvage logged forest) between 18:00 and 22:00 h.
RESULTS: Anopheles balabacensis, a vector of P. knowlesi, was the predominant species in all collection areas, accounting for 70 % of the total catch, with a peak landing time of 18:30-20:00 h. Anopheles balabacensis had a preference for landing on humans at ground level compared to the canopy (p
Fulltext Loss of Sunda clouded leopards and forest integrity drive potential impacts of mesopredator release on vulnerable avifauna

Mayhew DS, Hearn AJ, Devineau O, Linnell JDC, Macdonald DW

Heliyon, 2024 Jun 30;10(12):e32801.
PMID: 38975237 DOI: 10.1016/j.heliyon.2024.e32801

Amongst the unintended consequences of anthropogenic landscape conversion is declining apex predator abundance linked to loss of forest integrity, which can potentially re-order trophic networks. One such re-ordering, known as mesopredator release, occurs when medium-sized predators, also called mesopredators, rapidly increase in abundance following the decline in apex predator abundance, consequently reducing the abundance of mesopredator prey, notably including terrestrial avifauna. We examine the cascading impacts of declining Sunda clouded leopard abundance, itself consequent upon a reduction in forest integrity, on the mesopredator community of Sabah, Malaysia, to determine whether the phenomenon of mesopredator release is manifest and specifically whether it impacts the terrestrial avifauna community of pheasants and pittas. To explore this trophic interaction, we used a piecewise structural equation model to compare changes in the relative abundance of organisms. Our results suggest that loss of forest integrity may have broad impacts on the community and trigger mesopredator release, the two acting additively in their impact on already vulnerable species of terrestrial avifauna: a result not previously documented in tropical systems and rarely detected even on a global scale. The limiting effect that the Sunda clouded leopard has on the Sunda leopard cat could illuminate the mechanism whereby mesopredator release impacts this system. Both Bulwer's pheasant and pittas appear to be significantly impacted by the increase in Sunda leopard cats, while the great argus pheasant shows similar compelling, although not statistically significant, declines as Sunda leopard cats increase. The inverse relationship between Sunda clouded leopards and Sunda leopard cats suggests that if a mesopredator release exists it could have downstream consequences for some terrestrial avifauna. These results suggest the under-studied interface between mammalian carnivores and avifauna, or more broadly species interactions in general, could offer important conservation tool for holistic ecosystem conservation efforts.
Cerebrospinal fluid inflammatory cytokine profiles of patients with neurotropic parasitic infections

John DV, Sreenivas N, Deora H, Purushottam M, Debnath M, Mahadevan A, et al.

Trop Biomed, 2023 Dec 01;40(4):406-415.
PMID: 38308827 DOI: 10.47665/tb.40.4.005

The pathogenesis of chronic parasitic central nervous system (CNS) infections, including granulomatous amoebic meningoencephalitis (GAE), cerebral toxoplasmosis (CT), and neurocysticercosis (NCC), is primarily due to an inflammatory host reaction to the parasite. Inflammatory cytokines produced by invading T cells, monocytes, and CNS resident cells lead to neuroinflammation which underlie the immunopathology of these infections. Immune molecules, especially cytokines, can therefore emerge as potential biomarker(s) of CNS parasitic infections. In this study, cerebral spinal fluid (CSF) samples from suspected patients with parasitic infections were screened for pathogenic free-living amoebae by culture (n=2506) and PCR (n=275). Six proinflammatory cytokines in smear and culture-negative CSF samples from patients with GAE (n = 2), NCC (n = 7), and CT (n = 23) as well as control (n = 7) patients were measured using the Multiplex Suspension assay. None of the CSF samples tested was positive for neurotropic free-living amoebae by culture and only two samples showed Acanthamoeba 18S rRNA by PCR. Of the six cytokines measured, only IL-6 and IL-8 were significantly increased in all three infection groups compared to the control group. In addition, TNFa levels were higher in the GAE and NCC groups and IL-17 in the GAE group compared to controls. The levels of IL-1b and IFNg were very low in all the infection groups and the control group. There was a correlation between CSF cellularity and increased levels of IL-6, IL-8, and TNFa in 11 patients. Thus, quantifying inflammatory cytokine levels in CSF might help with understanding the level of neuroinflammation in patients with neurotropic parasitic diseases. Further studies with clinico-microbiological correlation in the form of reduction of cytokine levels with treatment and the correlation with neurological deficits are needed.
A hospital-based surveillance for Japanese encephalitis in Bali, Indonesia

Kari K, Liu W, Gautama K, Mammen MP, Clemens JD, Nisalak A, et al.

BMC Med, 2006;4:8.
PMID: 16603053

Japanese encephalitis (JE) is presumed to be endemic throughout Asia, yet only a few cases have been reported in tropical Asian countries such as Indonesia, Malaysia and the Philippines. To estimate the true disease burden due to JE in this region, we conducted a prospective, hospital-based surveillance with a catchment population of 599,120 children less than 12 years of age in Bali, Indonesia, from July 2001 through December 2003.
Fulltext Antrodia cinnamomea induces anti-tumor activity by inhibiting the STAT3 signaling pathway in lung cancer cells

Huang TT, Lan YW, Chen CM, Ko YF, Ojcius DM, Martel J, et al.

Sci Rep, 2019 03 26;9(1):5145.
PMID: 30914735 DOI: 10.1038/s41598-019-41653-9

We examined the effects of an Antrodia cinnamomea ethanol extract (ACEE) on lung cancer cells in vitro and tumor growth in vivo. ACEE produced dose-dependent cytotoxic effects and induced apoptosis in Lewis lung carcinoma (LLC) cells. ACEE treatment increased expression of p53 and Bax, as well as cleavage of caspase-3 and PARP, while reducing expression of survivin and Bcl-2. ACEE also reduced the levels of JAK2 and phosphorylated STAT3 in LLC cells. In a murine allograft tumor model, oral administration of ACEE significantly inhibited LLC tumor growth and metastasis without affecting serum biological parameters or body weight. ACEE increased cleavage of caspase-3 in murine tumors, while decreasing STAT3 phosphorylation. In addition, ACEE reduced the growth of human tumor xenografts in nude mice. Our findings therefore indicate that ACEE inhibits lung tumor growth and metastasis by inducing apoptosis and by inhibiting the STAT3 signaling pathway in cancer cells.
Clinical Ethics in Pediatrics: An International Perspective

Lantos JD, Saleem S, Raza F, Syltern J, Khoo EJ, Iyengar A, et al.

J Clin Ethics, 2019 3 22;30(1):35-45.
PMID: 30896442

In this article, we first review the development of clinical ethics in pediatrics in the United States. We report that, over the last 40 years, most children's hospitals have ethics committees but that those committees are rarely consulted. We speculate that the reasons for the paucity of ethics consults might be because ethical dilemmas are aired in other venues. The role of the ethics consultant, then, might be to shape the institutional climate and create safe spaces for the discussion of difficult and sometimes contentious issues. Finally, we report how pediatric clinical ethics has evolved differently in a number of other countries around the world.
Comparative transcriptomics of the chilling stress response in two Asian mangrove species, Bruguiera gymnorhiza and Rhizophora apiculata

Short AW, Sebastian JSV, Huang J, Wang G, Dassanayake M, Finnegan PM, et al.

Tree Physiol, 2024 Feb 11;44(3).
PMID: 38366388 DOI: 10.1093/treephys/tpae019

Low temperatures largely determine the geographic limits of plant species by reducing survival and growth. Inter-specific differences in the geographic distribution of mangrove species have been associated with cold tolerance, with exclusively tropical species being highly cold-sensitive and subtropical species being relatively cold-tolerant. To identify species-specific adaptations to low temperatures, we compared the chilling stress response of two widespread Indo-West Pacific mangrove species from Rhizophoraceae with differing latitudinal range limits-Bruguiera gymnorhiza (L.) Lam. ex Savigny (subtropical range limit) and Rhizophora apiculata Blume (tropical range limit). For both species, we measured the maximum photochemical efficiency of photosystem II (Fv/Fm) as a proxy for the physiological condition of the plants and examined gene expression profiles during chilling at 15 and 5 °C. At 15 °C, B. gymnorhiza maintained a significantly higher Fv/Fm than R. apiculata. However, at 5 °C, both species displayed equivalent Fv/Fm values. Thus, species-specific differences in chilling tolerance were only found at 15 °C, and both species were sensitive to chilling at 5 °C. At 15 °C, B. gymnorhiza downregulated genes related to the light reactions of photosynthesis and upregulated a gene involved in cyclic electron flow regulation, whereas R. apiculata downregulated more RuBisCo-related genes. At 5 °C, both species repressed genes related to CO2 assimilation. The downregulation of genes related to light absorption and upregulation of genes related to cyclic electron flow regulation are photoprotective mechanisms that likely contributed to the greater photosystem II photochemical efficiency of B. gymnorhiza at 15 °C. The results of this study provide evidence that the distributional range limits and potentially the expansion rates of plant species are associated with differences in the regulation of photosynthesis and photoprotective mechanisms under low temperatures.
Fulltext Engaging actively with issues in the responsible conduct of science: lessons from international efforts are relevant for undergraduate education in the United States

Clements JD, Connell ND, Dirks C, El-Faham M, Hay A, Heitman E, et al.

CBE Life Sci Educ, 2013;12(4):596-603.
PMID: 24297287 DOI: 10.1187/cbe.13-09-0184

Numerous studies are demonstrating that engaging undergraduate students in original research can improve their achievement in the science, technology, engineering, and mathematics (STEM) fields and increase the likelihood that some of them will decide to pursue careers in these disciplines. Associated with this increased prominence of research in the undergraduate curriculum are greater expectations from funders, colleges, and universities that faculty mentors will help those students, along with their graduate students and postdoctoral fellows, develop an understanding and sense of personal and collective obligation for responsible conduct of science (RCS). This Feature describes an ongoing National Research Council (NRC) project and a recent report about educating faculty members in culturally diverse settings (Middle East/North Africa and Asia) to employ active-learning strategies to engage their students and colleagues deeply in issues related to RCS. The NRC report describes the first phase of this project, which took place in Aqaba and Amman, Jordan, in September 2012 and April 2013, respectively. Here we highlight the findings from that report and our subsequent experience with a similar interactive institute in Kuala Lumpur, Malaysia. Our work provides insights and perspectives for faculty members in the United States as they engage undergraduate and graduate students, as well as postdoctoral fellows, to help them better understand the intricacies of and connections among various components of RCS. Further, our experiences can provide insights for those who may wish to establish "train-the-trainer" programs at their home institutions.
Fulltext Mixed-methods approach to exploring patients' perspectives on the acceptability of a urinary biomarker test in replacing cystoscopy for bladder cancer surveillance

Tan WS, Teo CH, Chan D, Heinrich M, Feber A, Sarpong R, et al.

BJU Int, 2019 09;124(3):408-417.
PMID: 30694612 DOI: 10.1111/bju.14690

OBJECTIVES: To determine the minimal accepted sensitivity (MAS) of a urine biomarker that patients are willing to accept to replace cystoscopy and to assess qualitatively their views and reasons.
PATIENTS AND METHODS: Patients were part of a prospective multicentre observational study recruiting people with bladder cancer for a urine biomarker study (DETECT II; ClinicalTrials.gov: NCT02781428). A mixed-methods approach comprising (1) a questionnaire to assess patients' experience with cystoscopy and patients' preference for cystoscopy vs urinary biomarker, and (2) semi-structured interviews to understand patient views, choice and reasons for their preference.
RESULTS: A urine biomarker with an MAS of 90% would be accepted by 75.8% of patients. This was despite a high self-reported prevalence of haematuria (51.0%), dysuria/lower urinary tract symptoms (69.1%) and urinary tract infection requiring antibiotics (25.8%). There was no association between MAS with patient demographics, adverse events experienced, cancer characteristics or distance of patients' home to hospital. The qualitative analysis suggested that patients acknowledge that cystoscopy is invasive, embarrassing and associated with adverse events but are willing to tolerate the procedure because of its high sensitivity. Patients have confidence in cystoscopy and appreciate the visual diagnosis of cancer. Both low- and high-risk patients would consider a biomarker with a reported sensitivity similar to that of cystoscopy.
CONCLUSION: Patients value the high sensitivity of cystoscopy despite the reported discomfort and adverse events experienced after it. The sensitivity of a urinary biomarker must be close to cystoscopy to gain patients' acceptance.
Fulltext DTI Profiles for Rapid Description of Cohorts at the Clinical-Research Interface

Lock C, Kwok J, Kumar S, Ahmad-Annuar A, Narayanan V, Ng ASL, et al.

Front Med (Lausanne), 2018;5:357.
PMID: 30687707 DOI: 10.3389/fmed.2018.00357

Normal pressure hydrocephalus (NPH) is a syndrome comprising gait disturbance, cognitive decline and urinary incontinence that is an unique model of reversible brain injury, but it presents as a challenging spectrum of disease cohorts. Diffusion Tensor Imaging (DTI), with its ability to interrogate structural white matter patterns at a microarchitectural level, is a potentially useful tool for the confirmation and characterization of disease cohorts at the clinical-research interface. However, obstacles to its widespread use involve the need for consistent DTI analysis and interpretation tools across collaborator sites. We present the use of DTI profiles, a simplistic methodology to interpret white matter injury patterns based on the morphology of diffusivity parameters. We examined 13 patients with complex NPH, i.e., patients with NPH and overlay from multiple comorbidities, including vascular risk burden and neurodegenerative disease, undergoing extended CSF drainage, clinical assessments, and multi-modal MR imaging. Following appropriate exclusions, we compared the morphology of DTI profiles in such complex NPH patients (n = 12, comprising 4 responders and 8 non-responders) to exemplar DTI profiles from a cohort of classic NPH patients (n = 16) demonstrating responsiveness of white matter injury to ventriculo-peritoneal shunting. In the cohort of complex NPH patients, mean age was 71.3 ± 7.6 years (10 males, 2 females) with a mean MMSE score of 21.1. There were 5 age-matched healthy controls, mean age was 73.4 ± 7.2 years (1 male, 4 females) and mean MMSE score was 26.8. In the exemplar cohort of classic NPH patients, mean age was 74.7 ± 5.9 years (10 males, 6 females) and mean MMSE score was 24.1. There were 9 age-matched healthy controls, mean age was 69.4 ± 9.7 years (4 males, 5 females) and mean MMSE score was 28.6. We found that, despite the challenges of acquiring DTI metrics from differing scanners across collaborator sites and NPH patients presenting as differing cohorts along the spectrum of disease, DTI profiles for responsiveness to interventions were comparable. Distinct DTI characteristics were demonstrated for complex NPH responders vs. non-responders. The morphology of DTI profiles for complex NPH responders mimicked DTI patterns found in predominantly shunt-responsive patients undergoing intervention for classic NPH. However, DTI profiles for complex NPH non-responders was suggestive of atrophy. Our findings suggest that it is possible to use DTI profiles to provide a methodology for rapid description of differing cohorts of disease at the clinical-research interface. By describing DTI measures morphologically, it was possible to consistently compare white matter injury patterns across international collaborator datasets.
Fulltext Recommendations on Topical Fluoride Usage for Caries Management in East Asia

Zheng FM, Adiatman M, Chu CH, Crystal YO, Featherstone JD, Hoang TH, et al.

Int Dent J, 2024 Oct;74(5):910-916.
PMID: 38871599 DOI: 10.1016/j.identj.2024.04.016

Dental caries is a widespread oral health issue in Asia, affecting an estimated 30% to 90% of children and adults. Many caries cases remain untreated, resulting in pain and infection. In response, the Asian Academy of Preventive Dentistry (AAPD) emphasises comprehensive caries management and organised a fluoride workshop at the 15th International Conference of the AAPD in 2023. The AAPD invited a group of experts to form a fluoride working group to review existing literature and develop fluoride recommendations for stakeholders across Asian countries and regions. The working group assessed caries risk and identified commonly used topical fluoride products for home care, professional, and community settings in Asia. The working group concluded that fluoride is a safe and highly effective strategy to reduce caries prevalence and incidence. The working group provided key recommendations based on successful regional caries management practices: (1) use topical fluoride for prevention and control of dental caries; (2) encourage the use of fluoride toothpaste with a concentration of at least 1,000 ppm for effective caries reduction; (3) advise a 0.05% fluoride mouth rinse as soon as children can spit it out to prevent early childhood caries; (4) deliver professionally administered fluoride, such as 5% sodium fluoride varnish, 2% fluoride gel, or 1.23% acidulated phosphate fluoride preparations, to decrease dental caries in at-risk individuals; and (5) apply 38% silver diamine fluoride to arrest cavitated caries. These recommendations aim to help practitioners, health care providers, and parents/caregivers make informed decisions about fluoride use as part of comprehensive oral health care in the region.

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