Supplementation of red palm olein-enriched biscuits improves levels of provitamin A carotenes, iron, and erythropoiesis in vitamin A-deficient primary schoolchildren: a double-blinded randomised controlled trial.

PURPOSE: Vitamin A deficiency (VAD) remains a significant contributor to childhood morbidity and mortality in developing countries; therefore, the implementation of sustainable and cost-effective approaches to control VAD is of utmost pertinence. This study aims to investigate the efficacy of red palm olein (RPO)-enriched biscuit supplementation in improving vitamin A, haematological, iron, and inflammatory status among vitamin A-deficient schoolchildren. METHODS: We conducted a double-blinded, randomised controlled trial involving 651 rural primary schoolchildren (8-12 years) with VAD in Malaysia. The schoolchildren were randomised to receive either RPO-enriched biscuits (experimental group, n = 334) or palm olein-enriched biscuits (control group, n = 317) for 6-month duration. RESULTS: Significant improvements in retinol and retinol-binding protein 4 levels were observed in both groups after supplementation (P < 0.001). The improvement in retinol levels were similar across groups among subjects with confirmed VAD (P = 0.40). Among those with marginal VAD, greater improvement in retinol levels was recorded in the control group (P < 0.001) but lacked clinical significance. The levels of α- and ß-carotenes, haematological parameters (haemoglobin, packed cell volume, mean corpuscular volume and mean corpuscular haemoglobin) and iron enhanced more significantly in the experimental group (P < 0.05). The significant reduction in the prevalence of microcytic anaemia (- 21.8%) and high inflammation (- 8.1%) was only observed in the experimental group. CONCLUSION: The supplementation of RPO-enriched biscuits enhanced levels of provitamin A carotenes, iron, and erythropoiesis, and exhibited anti-inflammatory effects. Therefore, the incorporation of RPO into National Nutritional Intervention Programs may be a potential measure to improve the health status of vitamin A-deficient children, among various other interventions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03256123).

High prevalence of malnutrition and vitamin A deficiency among schoolchildren of rural areas in Malaysia using a multi-school assessment approach.

Childhood malnutrition is known as a public health concern globally. The present study aims to assess the anthropometry and blood biochemical status of rural primary schoolchildren in Malaysia. A total of 776 children (7-11 years old) from ten rural primary schools from five states were included in this study. Nutritional outcomes were assessed based on sex, age group and school categories among the children (median age: 9 years (P25:8, P75:10)). The overall prevalence of malnutrition was 53·4 %. Vitamin A deficiency (VAD) was recorded at 20·6 and 39·8 % based on retinol and retinol-binding protein (RBP) levels, respectively. Anaemia, iron deficiency (ID), iron-deficiency anaemia (IDA) and elevated inflammation were found at 14·9, 17·9, 9·1 and 11·5 %, respectively. Malnutrition, VAD, anaemia, ID, IDA and elevated inflammation were more prevalent among Orang Asli (OA) schoolchildren compared with Non-Orang Asli schoolchildren. Higher occurrences of VAD and anaemia were also found among children aged <10 years. Retinol, RBP, α-carotene, ferritin and haemoglobin levels were lower among undernourished children. Besides, overweight/obese children exhibited a higher level of high-sensitivity C-reactive protein. Multivariate analysis demonstrated that OA school children (adjusted OR (AOR): 6·1; 95 % CI 4·1, 9·0) and IDA (AOR: 3·6; 95 % CI 1·9, 6·6) were associated with stunting among this population. The present study revealed that malnutrition, micronutrient deficiencies and anaemia are prevalent among rural primary schoolchildren in Malaysia, especially those from OA schools and younger age children (<10 years). Hence, more appropriate and targeted measures are needed to improve the nutritional status of these children.

Prospective longitudinal analysis of clinical and immunological risk factors associated with oral and gastrointestinal mucositis following autologous stem cell transplant in adults.

PURPOSE: The study aimed to characterize the incidence of both oral and gastrointestinal (GI) mucositis, its' associated temporal changes in local and systemic pro-inflammatory cytokines, and to explore predictive clinical and immunological factors associated with their occurrences in hematopoietic stem cell transplant (HSCT). METHODS: Autologous HSCT patients aged 18 years old and above were recruited from Hospital Ampang, Malaysia, between April 2019 to December 2020. Mucositis assessments were conducted daily, whilst blood and saliva were collected prior to conditioning regimen, on Day 0, Day+7 and 6-month. Baseline and inflammatory predictors in a repeated time measurement of moderate-severe mucositis were assessed by multiple logistic regression and generalized estimating equations, respectively. RESULTS: Of the 142 patients analyzed, oral mucositis and diarrhea (representing GI mucositis) were reported as 68.3% and 95.8%, respectively. Predictive factors for moderate-severe oral mucositis were BEAM or busulphan-based regimens (odds ratio (OR)=9.2, 95% confidence interval (CI)=1.16-72.9, p-value (p) = 0.005) and vomiting (OR=4.6, 95% CI 1.68-12.3, p = 0.004). Predictive factors for moderate-severe GI mucositis were BEAM or busulphan-based regimens (OR=3.9, 95% CI 1.05-14.5, p = 0.023), female sex (OR = 3.3, 95% CI 1.43-7.44, p = 0.004) and body mass index (OR=1.08, 95% CI 1.02-1.15, p = 0.010). Cytokines analyses were performed in 96 patients. Saliva and plasma interleukin-6 (OR=1.003, 95% CI 1.001-1.004, p < 0.001 and OR=1.01, 95% CI 1.001-1.015, p = 0.029), and plasma tumor necrosis factor-alpha (OR=0.91, 95% CI 0.85-0.99, p = 0.019) were predictive of moderate-severe oral mucositis in a time-dependent model. CONCLUSION: This study provides real-world evidence and insights into patient- and treatment-related factors affecting oral and GI mucositis in HSCT.

Urbanisation and its associated factors affecting human gut microbiota: where are we heading to?

CONTEXT: The continuous rise in urbanisation and its associated factors has been reflected in the structure of the human gut ecosystem. OBJECTIVE: The main focus of this review is to discuss and summarise the major risk factors associated with urbanisation that affect human gut microbiota thus affecting human health. METHODS: Multiple medical literature databases, namely PubMed, Google, Google Scholar, and Web of Science were used to find relevant materials for urbanisation and its major factors affecting human gut microbiota/microbiome. Both layman and Medical Subject Headings (MeSH) terms were used in the search. Due to the scarcity of the data, no limitation was set on the publication date. Relevant materials in the English language which include case reports, chapters of books, journal articles, online news reports and medical records were included in this review. RESULTS: Based on the data discussed in the review, it is quite clear that urbanisation and its associated factors have long-standing effects on the human gut microbiota that result in alterations of gut microbial diversity and composition. This is a matter of serious concern as chronic inflammatory diseases are on the rise in urbanised societies. CONCLUSION: A better understanding of the factors associated with urbanisation will help us to identify and implement new biological and social approaches to prevent and treat diseases and improve health globally by deepening our understanding of these relationships and increasing studies across urbanisation gradients.HIGHLIGHTSHuman gut microbiota have been linked to almost every important function, including metabolism, intestinal homeostasis, immune system, biosynthesis of vitamins, brain processes, and behaviour.However, dysbiosis i.e., alteration in the composition and diversity of gut microbiota is associated with the pathogenesis of many chronic conditions.In the 21st century, urbanisation represents a major demographic shift in developed and developing countries.During this period of urbanisation, humans have been exposed to many environmental exposures, all of which have led to the dysbiosis of human gut microbiota.The main focus of the review is to discuss and summarise the major risk factors associated with urbanisation and how it affects the diversity and composition of gut microbiota which ultimately affects human health.

Dinuclear and mononuclear metal(II) polypyridyl complexes against drug-sensitive and drug-resistant Plasmodium falciparum and their mode of action.

BACKGROUND: Malaria remains one of the most virulent and deadliest parasitic disease in the world, particularly in Africa and Southeast Asia. Widespread occurrence of artemisinin-resistant Plasmodium falciparum strains from the Greater Mekong Subregion is alarming. This hinders the national economies, as well as being a major drawback in the effective control and elimination of malaria worldwide. Clearly, an effective anti-malarial drug is urgently needed. METHODS: The dinuclear and mononuclear copper(II) and zinc(II) complexes were synthesized in ethanolic solution and characterized by various physical measurements (FTIR, CHN elemental analysis, solubility, ESI-MS, UV-Visible, conductivity and magnetic moment, and NMR). X-ray crystal structure of the dicopper(II) complex was determined. The in vitro haemolytic activities of these metal complexes were evaluated spectroscopically on B+ blood while the anti-malarial potency was performed in vitro on blood stage drug-sensitive Plasmodium falciparum 3D7 (Pf3D7) and artemisinin-resistant Plasmodium falciparum IPC5202 (Pf5202) with fluorescence dye. Mode of action of metal complexes were conducted to determine the formation of reactive oxygen species using PNDA and DCFH-DA dyes, JC-1 depolarization of mitochondrial membrane potential, malarial 20S proteasome inhibition with parasite lysate, and morphological studies using Giemsa and Hoechst stains. RESULTS: Copper(II) complexes showed anti-malarial potency against both Pf3D7 and Pf5202 in sub-micromolar to micromolar range. The zinc(II) complexes were effective against Pf3D7 with excellent therapeutic index but encountered total resistance against Pf5202. Among the four, the dinuclear copper(II) complex was the most potent against both strains. The zinc(II) complexes caused no haemolysis of RBC while copper(II) complexes induced increased haemolysis with increasing concentration. Further mechanistic studies of both copper(II) complexes on both Pf3D7 and Pf5202 strains showed induction of ROS, 20S malarial proteasome inhibition, loss of mitochondrial membrane potential and morphological features indicative of apoptosis. CONCLUSION: The dinuclear [Cu(phen)-4,4'-bipy-Cu(phen)](NO3)4 is highly potent and can overcome the total drug-resistance of Pf5202 towards chloroquine and artemisinin. The other three copper(II) and zinc(II) complexes were only effective towards the drug-sensitive Pf3D7, with the latter causing no haemolysis of RBC. Their mode of action involves multiple targets.

Natural Human Infections with Plasmodium cynomolgi, P. inui, and 4 other Simian Malaria Parasites, Malaysia.

We detected the simian malaria parasites Plasmodium knowlesi, P. cynomolgi, P. inui, P. coatneyi, P. inui-like, and P. simiovale among forest fringe-living indigenous communities from various locations in Malaysia. Our findings underscore the importance of using molecular tools to identify newly emergent malaria parasites in humans.

Seroprevalence of Nipah Virus Infection in Peninsular Malaysia.

Nipah virus (NiV) outbreak occurred in Malaysia in 1998. The natural host reservoir for NiV is Pteropus bats, which are commonly found throughout Malaysia. Humans become infected when NiV spills over from the reservoir species. In this study, NiV serosurveillance in Peninsular Malaysia, particularly among the indigenous population, was performed. The collected samples were tested for presence of NiV antibodies using a comparative indirect enzyme-linked immunosorbent assay based on the recombinant NiV nucleocapsid (rNiV-N) protein. We found that 10.73% of the participants recruited in this study had antibodies against rNiV-N, suggesting possible exposure to NiV.

Serological evidence of DENV, JEV, and ZIKV among the indigenous people (Orang Asli) of Peninsular Malaysia.

Dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV) are mosquito-borne flavivirus of medical importance in tropical countries such as Malaysia. However, much remains unknown regarding their prevalence among the underserved indigenous people (Orang Asli) living in communities in the forest fringe areas of Peninsular Malaysia. Information on the prevalence of diseases is necessary to elevate the effectiveness of disease control and preventive measures. This study aimed to determine the seroprevalence of the three major flaviviruses among the Orang Asli and investigate the association between demographic factors and seropositivities. Sampling activities were conducted in the Orang Asli villages to obtain serum samples and demographic data from consenting volunteers. The presence of DENV, JEV, and ZIKV immunoglobulin G (IgG) antibodies in the sera were examined using commercial enzyme-linked immunosorbent assay kits. A focus reduction neutralization assay was performed to measure virus-specific neutralizing antibodies. A total of 872 serum samples were obtained from the Orang Asli volunteers. Serological assay results revealed that DENV IgG, JEV IgG, and ZIKV IgG seropositivities among the Orang Asli were at 4.9%, 48.4%, and 13.2%, respectively. Neutralizing antibodies (FRNT50 ≥ 1:40) against JEV and ZIKV were found in 86.7% and 100.0%, respectively, out of the samples tested. Positive serology to all three viruses corresponded significantly to the age of the volunteers with increasing seropositivity in older volunteers. Findings from the study suggest that Orang Asli are at significant risk of contracting JEV and ZIKV infections despite the lack of active transmission of the viruses in the country.

Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy.

BACKGROUND: Alteration in gut microbiota has been recently linked with childhood leukemia and the use of chemotherapy. Whether the perturbed microbiota community is restored after disease remission and cessation of cancer treatment has not been evaluated. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy. METHODOLOGY: We conducted a longitudinal observational study in gut microbiota profile in a group of paediatric patients diagnosed with ALL using 16 s ribosomal RNA sequencing and compared these patients' microbiota pattern with age and ethnicity-matched healthy children. Temporal changes of gut microbiota in these patients with ALL were also examined at different time-points in relation to chemotherapy. RESULTS: Prior to commencement of chemotherapy, gut microbiota in children with ALL had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging to Bacteroidetes phylum and Bacteroides genus. The relative abundance of Bacteroides decreased upon commencement of chemotherapy. Restitution of gut microbiota composition to resemble that of healthy controls occurred after cessation of chemotherapy. However, the microbiota composition (beta diversity) remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health. CONCLUSION: Our findings in this pilot study is the first to suggest that gut microbiota profile in children with ALL remains marginally different from healthy controls even after cessation of chemotherapy. These persistent microbiota changes may have a role in the long-term wellbeing in childhood cancer survivors but the impact of these changes in subsequent health perturbations in these survivors remain unexplored.

Updates on malaria incidence and profile in Malaysia from 2013 to 2017.

BACKGROUND: To date, most of the recent publications on malaria in Malaysia were conducted in Sabah, East Malaysia focusing on the emergence of Plasmodium knowlesi. This analysis aims to describe the incidence, mortality and case fatality rate of malaria caused by all Plasmodium species between Peninsular Malaysia and East Malaysia (Sabah and Sarawak) over a 5-year period (2013-2017). METHODS: This is a secondary data review of all diagnosed and reported malaria confirmed cases notified to the Ministry of Health, Malaysia between January 2013 and December 2017. RESULTS: From 2013 to 2017, a total of 16,500 malaria cases were notified in Malaysia. The cases were mainly contributed from Sabah (7150; 43.3%) and Sarawak (5684; 34.4%). Majority of the patients were male (13,552; 82.1%). The most common age group in Peninsular Malaysia was 20 to 29 years (1286; 35.1%), while Sabah and Sarawak reported highest number of malaria cases in age group of 30 to 39 years (2776; 21.6%). The top two races with malaria in Sabah and Sarawak were Bumiputera Sabah (5613; 43.7%) and Bumiputera Sarawak (4512; 35.1%), whereas other ethnic group (1232; 33.6%) and Malays (1025; 28.0%) were the two most common races in Peninsular Malaysia. Plasmodium knowlesi was the commonest species in Sabah and Sarawak (9902; 77.1%), while there were more Plasmodium vivax cases (1548; 42.2%) in Peninsular Malaysia. The overall average incidence rate, mortality rate and case fatality rates for malaria from 2013 to 2017 in Malaysia were 0.106/1000, 0.030/100,000 and 0.27%, respectively. Sarawak reported the highest average incidence rate of 0.420/1000 population followed by Sabah (0.383/1000). Other states in Peninsular Malaysia reported below the national average incidence rate with less than 0.100/1000. CONCLUSIONS: There were different trends and characteristics of notified malaria cases in Peninsular Malaysia and Sabah and Sarawak. They provide useful information to modify current prevention and control measures so that they are customised to the peculiarities of disease patterns in the two regions in order to successfully achieve the pre-elimination of human-only species in the near future.