A qualitative study exploring the epistemology of suffering within a Malaysian Indigenous tribe.

Despite the universal nature of suffering, few studies have examined how Indigenous ethnic minorities in non-western regions understand and respond to adversity. This study explored the epistemology of suffering among the Temiar ethnic group of Peninsular Malaysia using participant observation and semi-structured interviews. Interview transcripts of 43 participants were coded through inductive thematic analysis and a consensual qualitative approach. Three-tier themes were defined and named after subsequent analysis of core ideas and domains in the data. Major adversities reported included a lack of basic needs, lack of land-rights and unjust treatment from authorities, destruction of the forest environment and livelihood, and lack of accessibility and facilities, which were attributed to authorities' negligence of responsibilities, increasing human-animal conflict, environmental threats and imposed lifestyle changes. Faced with adversity, the Temiar endeavoured to survive by working crops and gathering forest resources. They utilized resources from family, fellow villagers, external agencies and spiritual-religious traditions. Theoretical mapping of attribution styles into the Ecological Rationality Framework revealed predominantly external-focused and concrete-perceptual rationalities privileged by strong-ties societies. These findings pointed to the resilience of a strong-ties community while adapting to the systemic suffering and risk factors stemming from a rationality mismatch with modernization and globalization trends. To conclude, we advocate for culture-sensitive mental health and psychiatric practices, as well as sustainable development for the well-being of Indigenous communities locally and globally.

Addressing Emotional Dysregulation and Potential Pharmacogenetic Implication of 5-HTTLPR Genotype in Attention Deficit Hyperactivity Disorder.

Background: This review unpacks the emotional presentation of externalizing behaviors in attention deficit hyperactivity disorder (ADHD), by diving into the psychophysiology, neurophysiology, and neurogenetics in relation to executive function. The correlations among these three variables are identified, showing that standard assessments for ADHD leave out the emotional dysregulation element. This may lead to suboptimal management outcomes during the developmental progression into adolescence and adulthood. Summary: The emotional impulsivity manifestation in adolescence and adulthood related to the under-managed emotional dysregulation in childhood is found to be associated with subtle confounding impact of 5-HTTLPR (serotonin-transporter-linked promoter region) genotype. The genotype of interest affects the neurochemistry, neurophysiology, and psychophysiology of the cognition for executive function. The established practice of using methylphenidate in treating ADHD surprisingly has a neurogenetic effect in targeting the genotype of interest. Methylphenidate provides neuroprotective effects throughout the neurodevelopment timeline from childhood to adulthood. Key Messages: The emotional dysregulation element in ADHD which is often overlooked should be addressed to improve the prognostic outcomes in adolescence and adulthood.

Genetic risk factors of systemic lupus erythematosus in the Malaysian population: a minireview.

SLE is an autoimmune disease that is not uncommon in Malaysia. In contrast to Malays and Indians, the Chinese seem to be most affected. SLE is characterized by deficiency of body's immune response that leads to production of autoantibodies and failure of immune complex clearance. This minireview attempts to summarize the association of several candidate genes with risk for SLE in the Malaysian population and discuss the genetic heterogeneity that exists locally in Asians and in comparison with SLE in Caucasians. Several groups of researchers have been actively investigating genes that are associated with SLE susceptibility in the Malaysian population by screening possible reported candidate genes across the SLE patients and healthy controls. These candidate genes include MHC genes and genes encoding complement components, TNF, FcγR, T-cell receptors, and interleukins. However, most of the polymorphisms investigated in these genes did not show significant associations with susceptibility to SLE in the Malaysian scenario, except for those occurring in MHC genes and genes coding for TNF-α, IL-1ß, IL-1RN, and IL-6.

The Oral, Gut Microbiota and Cardiometabolic Health of Indigenous Orang Asli Communities.

The Orang Asli (OA) of Malaysia have been relatively understudied where little is known about their oral and gut microbiomes. As human health is closely intertwined with the human microbiome, this study first assessed the cardiometabolic health in four OA communities ranging from urban, rural to semi-nomadic hunter-gatherers. The urban Temuan suffered from poorer cardiometabolic health while rural OA communities were undergoing epidemiological transition. The oral microbiota of the OA were characterised by sequencing the V4 region of the 16S rRNA gene. The OA oral microbiota were unexpectedly homogenous, with comparably low alpha diversity across all four communities. The rural Jehai and Temiar PP oral microbiota were enriched for uncharacterised bacteria, exhibiting potential for discoveries. This finding also highlights the importance of including under-represented populations in large cohort studies. The Temuan oral microbiota were also elevated in opportunistic pathogens such as Corynebacterium, Prevotella, and Mogibacterium, suggesting possible oral dysbiosis in these urban settlers. The semi-nomadic Jehai gut microbiota had the highest alpha diversity, while urban Temuan exhibited the lowest. Rural OA gut microbiota were distinct from urban-like microbiota and were elevated in bacteria genera such as Prevotella 2, Prevotella 9, Lachnospiraceae ND3007, and Solobacterium. Urban Temuan microbiota were enriched in Odoribacter, Blautia, Parabacetroides, Bacteroides and Ruminococcacecae UCG-013. This study brings to light the current health trend of these indigenous people who have minimal access to healthcare and lays the groundwork for future, in-depth studies in these populations.

A genome-wide characterization of copy number variations in native populations of Peninsular Malaysia.

Copy number variations (CNVs) are genomic structural variations that result from the deletion or duplication of large genomic segments. The characterization of CNVs is largely underrepresented, particularly those of indigenous populations, such as the Orang Asli in Peninsular Malaysia. In the present study, we first characterized the genome-wide CNVs of four major native populations from Peninsular Malaysia, including the Malays and three Orang Asli populations; namely, Proto-Malay, Senoi, and Negrito (collectively called PM). We subsequently assessed the distribution of CNVs across the four populations. The resulting global CNV map revealed 3102 CNVs, with an average of more than 100 CNVs per individual. We identified genes harboring CNVs that are highly differentiated between PM and global populations, indicating that these genes are predominantly enriched in immune responses and defense functions, including APOBEC3A_B, beta-defensin genes, and CCL3L1, followed by other biological functions, such as drug and toxin metabolism and responses to radiation, suggesting some attributions between CNV variations and adaptations of the PM groups to the local environmental conditions of tropical rainforests.

Seroprevalence of dengue among healthy adults in a rural community in Southern Malaysia: a pilot study.

BACKGROUND: The frequency and magnitude of dengue epidemics continue to increase exponentially in Malaysia, with a shift in the age range predominance toward adults and an expansion to rural areas. Despite this, information pertaining to the extent of transmission of dengue virus (DENV) in the rural community is lacking. This community-based pilot study was conducted to establish DENV seroprevalence amongst healthy adults in a rural district in Southern Malaysia, and to identify influencing factors. METHODS: In this study undertaken between April and May 2015, a total of 277 adult participants were recruited from households across three localities in the Sungai Segamat subdistrict in Segamat district. Sera were tested for immunoglobulin G (IgG) (Panbio® Dengue Indirect IgG ELISA/high-titer capture) and immunoglobulin M (IgM) (Panbio®) antibodies. The plaque reduction neutralization test (PRNT) was conducted on random samples of IgG-positive sera for further confirmation. Medical history and a recall of previous history of dengue were collected through interviews, whereas sociodemographic information was obtained from an existing database. RESULTS: The overall seroprevalence for DENV infection was 86.6% (240/277) (95% CI: 83-91%). Serological evidence of recent infection (IgM/high-titer capture IgG) was noted in 11.2% (31/277) of participants, whereas there was evidence of past infection in 75.5% (209/277) of participants (indirect IgG minus recent infections). The PRNT assay showed that the detected antibodies were indeed specific to DENV. The multivariate analysis showed that the older age group was significantly associated with past DENV infections. Seropositivity increased with age; 48.5% in the age group of <25 years to more than 85% in age group of >45 years (P < 0.001). No associations with occupation, study site, housing type, comorbidity, educational level, and marital status were observed, although the latter two were statistically significant in the univariate analysis. None of the studied factors were significantly associated with recent DENV infections in the multivariate analysis, although there was a pattern suggestive of recent outbreak in two study sites populated predominately by Chinese people. The majority of infections did not give rise to recognizable disease (either asymptomatic or nonspecific symptoms) as only 12.9% of participants (31/240) recalled having dengue in the past. CONCLUSIONS: The predominantly rural community under study had a very high previous exposure to dengue. The finding of a high proportion of unreported cases possibly due to subclinical infections underscores the need for enhanced surveillance and control methods. This finding also has implications for measuring disease burden, understanding transmission dynamics, and hypothesizing effects on DENV vaccine efficacy and uptake.

A community-based prospective cohort study of dengue viral infection in Malaysia: the study protocol.

BACKGROUND: Globally, dengue infections constitute a significant public health burden. In recent decades, Malaysia has become a dengue hyper-endemic country with the co-circulation of the four dengue virus serotypes. The cyclical dominance of sub-types contributes to a pattern of major outbreaks. The consequences can be observed in the rising incidence of reported dengue cases and dengue related deaths. Understanding the complex interaction of the dengue virus, its human hosts and the mosquito vectors at the community level may help develop strategies for addressing the problem. METHODS: A prospective cohort study will be conducted in Segamat district of Johor State in Peninsular Malaysia. Researchers received approval from the Malaysian Medical Research Ethics Committee and Monash University Human Research Ethics Committee. The study will be conducted at a Malaysian based health and demographic surveillance site over a 1 year period in three different settings (urban, semi-urban and rural). The study will recruit healthy adults (male and female) aged 18 years and over, from three ethnic groups (Malay, Chinese and Indian). The sample size calculated using the Fleiss method with continuity correction is 333. Sero-surveillance of participants will be undertaken to identify asymptomatic, otherwise healthy cases; cases with dengue fever who are managed as out-patients; and cases with dengue fever admitted to a hospital. A genetic analysis of the participants will be undertaken to determine whether there is a relationship between genetic predisposition and disease severity. A detailed medical history, past history of dengue infection, vaccination history against other flaviviruses such as Japanese encephalitis and Yellow fever, and the family history of dengue infection will also be collected. In addition, a mosquito surveillance will be carried out simultaneously in recruitment areas to determine the molecular taxonomy of circulating vectors. DISCUSSION: The research findings will estimate the burden of asymptomatic and symptomatic dengue at the community level. It will also examine the relationship between virus serotypes and host genotypes, and the association of the clinical manifestation of the early phase with the entire course of illness.

Insight into gene polymorphisms involved in toll-like receptor/interferon signalling pathways for systemic lupus erythematosus in South East Asia.

Polymorphisms in genes involved in toll-like receptor/interferon signalling pathways have been reported previously to be associated with SLE in many populations. This study aimed to investigate the role of seven single nucleotide polymorphisms within TNFAIP3, STAT4, and IRF5, which are involved in upstream and downstream pathways of type I interferon production, in SLE in the South East Asian populations. Genotyping of 360 Malaysian SLE patients and 430 normal healthy individuals revealed that minor alleles of STAT4 rs7574865 and rs10168266 were associated with elevated risk of SLE in the Chinese and Malay patients, respectively (P = 0.028, odds ratio (OR) = 1.42; P = 0.035, OR = 1.80, respectively). Polymorphisms in TNFAIP3 and IRF5 did not show significant associations with SLE in any of the ethnicities. Combined analysis of the Malays, Chinese, and Indians for each SNP indicated that STAT4 rs10168266 was significantly associated with the Malaysian SLE as a whole (P = 0.014; OR = 1.435). The meta-analysis of STAT4 rs10168266, which combined the data of other studies and this study, further confirmed its importance as the risk factor for SLE by having pooled OR of 1.559 and P value of <0.001.

HLA-A*11 and novel associations in Malays and Chinese with systemic lupus erythematosus.

We investigated the association of the HLA genes in Malaysian patients with systemic lupus erythematosus (SLE) and their associations with the clinical manifestations in 160 SLE patients (99 Chinese and 61 Malays) and 107 healthy control individuals (58 Chinese and 49 Malays) were studied. Sequence specific primer amplification (PCR-SSP) phototyping techniques were used to analyse 25 HLA-A allele groups, 31 HLA-DR allele groups and 9 HLA-DQ allele groups. Appreciable increases in allele frequencies of HLA-A*11, DRB1*0701, DRB1*1601-1606, DRB5*01-02 and DQB1*05, and decrease in HLA-DRB1*1101-1121, 1411, DRB1*1201-3, DRB1*1301-22, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 1304 in SLE patients compared with healthy control individuals. However, after Bonferroni correction (p(c)<0.05) only HLA-A*1101, 1102, DRB5*01-02, DQB1*05, DRB1*1201-3, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 0304 remained significant. Allele frequencies of DRB1*0701 and DRB4*0101101, 0102, 0103, DQB1*05, DRB1*1301-22, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 0304 were significantly increased in Malay SLE patients compared with healthy control individuals. In contrast, Chinese SLE patients had increased allele frequencies of DRB1*1601-1606, DQB1*05, DRB1*1201-3, DRB3*0101, 0201, 0202, 0203, 0301, DRB3*0101, 0201, 0202, 0203, 0301 and DQB1*0301, 0304 compared with healthy control individuals. HLA-A*6801-02 and DRB1*1601-1606 frequencies appeared elevated in a subset of patients with serositis and DRB1* 0401-1122 frequency was elevated in those displaying neurologic disorder. However, unequivocal evidence of these associations would require investigation of substantially larger cohorts. On the whole, our findings suggest that HLA allele associations with SLE are race specific in Malays and Chinese.

An update of the general health status in the indigenous populations of Malaysia.

OBJECTIVES: Health scenarios are constantly evolving, particularly in developing countries but little is known regarding the health status of indigenous groups in Malaysia. This study aims to elucidate the current health status in four indigenous populations in the country, who by and large been left out of mainstream healthcare developments. METHODS: Participants were recruited from the Temuan, Jehai, Kensiu and Bidayuh indigenous groups throughout Peninsula Malaysia and Sarawak. Health parameters including body mass index (BMI), blood pressure, casual blood glucose and, total cholesterol levels were measured using established methods. Malondialdehyde (MDA) and ferric-reducing antioxidant power (FRAP) levels were measured to assess oxidative stress status. Blood films were screened for evidence of microbial or parasitic infections and leukocyte differential counting was performed. RESULTS: The Temuan and Bidayuh who are more urbanized, had significantly higher mean body weight, BMI, total cholesterol (p<0.05) and higher prevalence of obesity and hypercholesterolemia. Low cholesterol levels, elevated eosinophil counts and increased total IgE, indicative of immune responses to infection or allergy, were recorded in the rural Kensiu and Jehai. The Kensiu had higher levels of FRAP and lower levels of MDA, whereas the reverse was found in the Temuan. This suggests reduced oxidative stress in the Kensiu compared to the Temuan. Expected correlations between FRAP and MDA levels with age, were evident in Jehai. CONCLUSIONS: Our findings reflect a shifting health burden and an epidemiological transition, particularly in the Temuan and Bidayuh. These changes could be attributed to dietary habits, lifestyles and socio-economic factors brought about by urbanization.