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  1. Younas M, Zou H, Laraib T, Abbas W, Akhtar MW, Aslam MN, et al.
    PLoS One, 2021;16(8):e0256450.
    PMID: 34432836 DOI: 10.1371/journal.pone.0256450
    Food production and waste recycling are the two major issues faced globally with rapidly increasing population. Recycling organic wastes to crop amendments could be a possible solution to these issues. Earthworms transfer organic waste to compost, which is used to grow crops and increase crop productivity. This study assessed the impact of vermicompost produced from the residues of six desert plant species, i.e., (Ziziphus mauritiana, Aerva javanica, Calligonum comosum, Sacchrum benghalens, Calligonum polygonoides and Prosopis cineraria) combined with farmyard manure (5 t ha-1) on growth, yield and photosynthetic activity of maize crop. Earthworm species Eisenia fetida (Savigny, 1826) was used to prepare vermicomposting of all tested plant species. The desert species were collected from natural habitats, chopped, dried, mixed with FYM and then earthworms were released to prepare the vermicompost. The earthworms were excluded twenty days after release and resultant was considered as compost and used in the experiment. Results revealed that application of P. cineraria vermicompost resulted in the highest plant height (75.33 cm), stem diameter (22.66 mm), cob length (17.66 cm), number of grains/cob (374.67), 1000-grain weight (260.41 g) and grains yield (3.20 t/ha). Application of P. cineraria vermicompost resulted in the highest uptake of macronutrients, i.e., N (91.01%), P (22.07%), K (80.41%), micronutrients, i.e., Fe (19.07 ppm), Zn (40.05 ppm), and phenolic contents (150). Application of P. cineraria vermicompost also resulted in the highest quantum photosynthetic yield (0.42 mole C/mole of photon), chlorophyll florescence (355.18 moles of photon m-2s-1) and electron transport rate (310.18 micro mole m-2s-1). It is concluded that vermicomposting has the potential to improve growth and yield of maize crop. Particularly, application of vermicompost obtained from P. cineraria can be used to improve the growth and yield of maize crop. Nonetheless, field trials are necessary for a wide scale recommendation.
  2. Morris DE, McNeil H, Hocknell RE, Anderson R, Tuck AC, Tricarico S, et al.
    Pneumonia (Nathan), 2021 Apr 25;13(1):6.
    PMID: 33894778 DOI: 10.1186/s41479-021-00084-9
    INTRODUCTION: Pneumonia is a leading cause of death in Malaysia. Whilst many studies have reported the aetiology of pneumonia in Western countries, the epidemiology of pneumonia in Malaysia remains poorly understood. As carriage is a prerequisite for disease, we sought to improve our understanding of the carriage and antimicrobial resistance (AMR) of respiratory tract pathogens in Malaysia. The rural communities of Sarawak are an understudied part of the Malaysian population and were the focus of this study, allowing us to gain a better understanding of bacterial epidemiology in this population.

    METHODS: A population-based survey of bacterial carriage was undertaken in participants of all ages from rural communities in Sarawak, Malaysia. Nasopharyngeal, nasal, mouth and oropharyngeal swabs were taken. Bacteria were isolated from each swab and identified by culture-based methods and antimicrobial susceptibility testing conducted by disk diffusion or E test.

    RESULTS: 140 participants were recruited from five rural communities. Klebsiella pneumoniae was most commonly isolated from participants (30.0%), followed by Staphylococcus aureus (20.7%), Streptococcus pneumoniae (10.7%), Haemophilus influenzae (9.3%), Moraxella catarrhalis (6.4%), Pseudomonas aeruginosa (6.4%) and Neisseria meningitidis (5.0%). Of the 21 S. pneumoniae isolated, 33.3 and 14.3% were serotypes included in the 13 valent PCV (PCV13) and 10 valent PCV (PCV10) respectively. 33.8% of all species were resistant to at least one antibiotic, however all bacterial species except S. pneumoniae were susceptible to at least one type of antibiotic.

    CONCLUSION: To our knowledge, this is the first bacterial carriage study undertaken in East Malaysia. We provide valuable and timely data regarding the epidemiology and AMR of respiratory pathogens commonly associated with pneumonia. Further surveillance in Malaysia is necessary to monitor changes in the carriage prevalence of upper respiratory tract pathogens and the emergence of AMR, particularly as PCV is added to the National Immunisation Programme (NIP).

  3. Marzo RR, Sami W, Alam MZ, Acharya S, Jermsittiparsert K, Songwathana K, et al.
    Trop Med Health, 2022 Jan 05;50(1):4.
    PMID: 34983692 DOI: 10.1186/s41182-021-00393-1
    BACKGROUND: Vaccines are effective and reliable public health interventions against viral outbreaks and pandemics. However, hesitancy regarding the Coronavirus disease (COVID-19) vaccine is evident worldwide. Therefore, understanding vaccination-related behavior is critical in expanding the vaccine coverage to flatten the infection curve. This study explores the public perception regarding COVID-19 vaccination and identifies factors associated with vaccine hesitancy among the general adult populations in six Southeast Asian countries.

    METHODS: Using a snowball sampling approach, we conducted a descriptive cross-sectional study among 5260 participants in Indonesia, Malaysia, Myanmar, Philippines, Thailand, and Vietnam between February and May 2021. Binary logistic regression analysis with a backward conditional approach was applied to identify factors associated with COVID-19 vaccine hesitancy.

    RESULTS: Of the total, 50.6% were female, and the median age was 30 years (range: 15-83 years). The majority of the participants believed that vaccination effectively prevents and controls COVID-19 (81.2%), and 84.0% would accept COVID-19 vaccines when they become available. They agreed that health providers' advice (83.0%), vaccination convenience (75.6%), and vaccine costs (62.8%) are essential for people to decide whether to accept COVID-19 vaccines. About half (49.3%) expressed their hesitancy to receive the COVID-19 vaccines. After adjustment for other covariates, COVID-19 vaccine hesitancy was significantly associated with age, residential area, education levels, employment status, and family economic status. Participants from Indonesia, Myanmar, Thailand, and Vietnam were significantly more likely to express hesitancy in receiving COVID-19 vaccines than those from Philippines.

    CONCLUSIONS: In general, participants in this multi-country study showed their optimistic perception of COVID-19 vaccines' effectiveness and willingness to receive them. However, about half of them still expressed their hesitancy in getting vaccinated. The hesitation was associated with several socioeconomic factors and varied by country. Therefore, COVID-19 vaccination programs should consider these factors essential for increasing vaccine uptake in the populations.

  4. Eng-Chong T, Yean-Kee L, Chin-Fei C, Choon-Han H, Sher-Ming W, Li-Ping CT, et al.
    PMID: 23243448 DOI: 10.1155/2012/473637
    Boesenbergia rotunda is a herb from the Boesenbergia genera under the Zingiberaceae family. B. rotunda is widely found in Asian countries where it is commonly used as a food ingredient and in ethnomedicinal preparations. The popularity of its ethnomedicinal usage has drawn the attention of scientists worldwide to further investigate its medicinal properties. Advancement in drug design and discovery research has led to the development of synthetic drugs from B. rotunda metabolites via bioinformatics and medicinal chemistry studies. Furthermore, with the advent of genomics, transcriptomics, proteomics, and metabolomics, new insights on the biosynthetic pathways of B. rotunda metabolites can be elucidated, enabling researchers to predict the potential bioactive compounds responsible for the medicinal properties of the plant. The vast biological activities exhibited by the compounds obtained from B. rotunda warrant further investigation through studies such as drug discovery, polypharmacology, and drug delivery using nanotechnology.
  5. Meng CE, Sharifah Robiah Mohamad CW, Mohd Nasir NF, Fhan KS, Liang OH, Jian TX, et al.
    Heliyon, 2024 Jan 15;10(1):e23847.
    PMID: 38332888 DOI: 10.1016/j.heliyon.2023.e23847
    The mineral composition, crystallinity, and dielectric properties of salts can provide valuable insights into the quality and suitability of different types of salt for various applications. In this study, comprehensive analysis of the X-Ray Diffraction (XRD), X-ray fluorescence (XRF) and dielectric analysis of the Ba'kelalan salt, Himalaya salt and Bamboo salt have been investigated. The mineral composition of these salts, encompassing vital elements such as iodine and other trace minerals, significantly influences the salt's nutritional profile and overall excellence. Nonetheless, gauging the dispersion and density of these minerals poses difficulties due to conventional techniques that can be arduous, damaging, and expensive. Sample preparation is carried out before conducting X-ray diffraction (XRD), X-ray fluorescence (XRF), and dielectric analysis. XRD measurements are performed using the Bruker D2 Phaser to identify crystalline material phases. XRD operates on the principle of constructive X-ray interference within crystalline samples. For elemental analysis across a broad spectrum of materials, XRF is employed. Elemental peaks are scanned, starting from the lowest to the highest angle of incidence. The X-ray intensity at characteristic peaks is compared to the standard series. Dielectric spectroscopy analysis examines the dielectric behaviour of Ba'kelalan salt, Himalaya salt, and Bamboo salt. The setup involves a vector network analyser (VNA) paired with an open-ended coaxial probe, utilizing the microwave method. This approach ensures rapid, efficient, and non-destructive measurements of dielectric constants (ε') and loss factors (ε"). The dielectric permittivity spectra are acquired within the frequency range of 4 GHz-20 GHz. ε' of these salts increase with frequency. Meanwhile, ε" seem varies insignificantly over frequency. Mineral contents and crystallinity are the crucial factors lead to these responses. Based on the study, the quality and suitability of the selected salts for specific applications can be determined by considering their mineral composition, crystallinity, and dielectric properties in the context of the intended use. This gives an insight for some applications that may benefit from certain minerals or crystalline structures, others may require specific dielectric properties for effective use. Therefore, understanding these properties allows for decision-making in choosing the right type of salt for a given purpose, whether it's for foods, medical, industrial, healthcare, and technological applications.
  6. Khaliq A, Li WF, Ali S, Shah ST, Ma ZH, Mao J, et al.
    PLoS One, 2022;17(3):e0265111.
    PMID: 35353819 DOI: 10.1371/journal.pone.0265111
    Poor postharvest handling, microbial infestation, and high respiration rate are some the factors are responsible for poor storage life of perishable commodities. Therefore, effective preservation of these commodities is needed to lower the damages and extend shelf life. Preservation is regarded as the action taken to maintain desired properties of a perishable commodity as long as possible. Persimmon (Diospyros kaki) is perishable fruit with high nutritive value; however, has very short shelf-life. Therefore, effective preservation and drying is needed to extend its storage life. Drying temperature and preservatives significantly influence the quality of perishable vegetables and fruits during drying. The current study investigated the effect of different temperatures and preservatives on drying kinetics and organoleptic quality attributes of persimmon. Persimmon fruits were treated with preservatives (25% honey, 25% aloe vera, 2% sodium benzoate, 1% potassium metabisulfite, and 2% citric acid solutions) under different drying temperatures (40, 45, and 50°C). All observed parameters were significantly affected by individual effects of temperatures and preservatives, except ash contents. Similarly, interactive effects were significant for all parameters except total soluble sugars, ash contents, and vitamin C. Generally, fruits treated with citric acid and dried under 50°C had 8.2% moisture loss hour-1, 14.9 drying hours, 0.030 g H2O g-1 hr-1, 1.23° Brix of total soluble solids, 6.71 pH, 1.35% acidity, and 6.3 mg vitamin C. These values were better than the rest of the preservatives and drying temperatures used in the study. Therefore, treating fruits with citric acid and drying at 50°C was found a promising technique to extend storage life of persimmon fruits. It is recommended that persimmon fruits dried at 50°C and preserved in citric acid can be used for longer storage period.
  7. Ng WL, Ng CJ, Teo CH, Ang TF, Lee YK, Abdul Hadi H, et al.
    Digit Health, 2024;10:20552076241277710.
    PMID: 39247097 DOI: 10.1177/20552076241277710
    OBJECTIVE: Most dengue cases are managed in an outpatient setting, where patients are advised to return to the clinic daily for monitoring. Some patients can develop severe dengue at home and fail to recognise the deterioration. An application called DengueAid was designed as a self-monitoring tool for patients to reduce delay in seeking timely treatment. This study aimed to assess the feasibility of conducting a randomised controlled trial to determine the effectiveness of the DengueAid application.

    METHODS: Dengue patients were recruited from a public health clinic in Malaysia and randomised to either use the DengueAid application plus standard care for dengue or receive only the standard care. The outcomes evaluated were the (1) feasibility of recruitment, data collection and follow-up procedures; (2) preliminary clinical outcome measures; and (3) acceptability of DengueAid. Qualitative interviews were conducted for participants in the intervention arm to assess the acceptability of DengueAid.

    RESULTS: Thirty-seven patients were recruited with 97% (n = 36) retention rates. The recruitment rate was low (63% refusal rate, n = 62/99) with difficulty in data collection and follow-up due to the variable interval of care for dengue in an outpatient setting. DengueAid application was acceptable to the participants, but preliminary clinical outcomes and qualitative data suggested limited utility of the application. Unwell conditions of patients and limited access to healthcare are important factors impacting the application's utility.

    CONCLUSION: The feasibility trial uncovered issues with recruitment, data collection and follow-up processes. Further research and modification to the application are needed to improve its utility and usability.

  8. Han M, Liang J, Wang K, Si Q, Zhu C, Zhao Y, et al.
    Sci Total Environ, 2024 Sep 03;953:176017.
    PMID: 39236815 DOI: 10.1016/j.scitotenv.2024.176017
    The extensive use of plastic products has exacerbated micro/nanoplastic (MPs/NPs) pollution in the atmosphere, increasing the incidence of respiratory diseases and lung cancer. This study investigates the uptake and cytotoxicity mechanisms of polystyrene (PS) NPs in human lung epithelial cells. Transcriptional analysis revealed significant changes in cell adhesion pathways following PS-NPs exposure. Integrin α5β1-mediated endocytosis was identified as a key promoter of PS-NPs entry into lung epithelial cells. Overexpression of integrin α5β1 enhanced PS-NPs internalization, exacerbating mitochondrial Ca2+ dysfunction and depolarization, which induced reactive oxygen species (ROS) production. Mitochondrial dysfunction triggered by PS-NPs led to oxidative damage, inflammation, DNA damage, and necrosis, contributing to lung diseases. This study elucidates the molecular mechanism by which integrin α5β1 facilitates PS-NPs internalization and enhances its cytotoxicity, offering new insights into potential therapeutic targets for microplastic-induced lung diseases.
  9. Thuya WL, Peyper JM, Myen TT, Anuar ND, Anwar A, Gudimella R, et al.
    Mil Med Res, 2024 Nov 18;11(1):72.
    PMID: 39558443 DOI: 10.1186/s40779-024-00575-y
  10. Grill G, Lehner B, Thieme M, Geenen B, Tickner D, Antonelli F, et al.
    Nature, 2019 05;569(7755):215-221.
    PMID: 31068722 DOI: 10.1038/s41586-019-1111-9
    Free-flowing rivers (FFRs) support diverse, complex and dynamic ecosystems globally, providing important societal and economic services. Infrastructure development threatens the ecosystem processes, biodiversity and services that these rivers support. Here we assess the connectivity status of 12 million kilometres of rivers globally and identify those that remain free-flowing in their entire length. Only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length and 23 per cent flow uninterrupted to the ocean. Very long FFRs are largely restricted to remote regions of the Arctic and of the Amazon and Congo basins. In densely populated areas only few very long rivers remain free-flowing, such as the Irrawaddy and Salween. Dams and reservoirs and their up- and downstream propagation of fragmentation and flow regulation are the leading contributors to the loss of river connectivity. By applying a new method to quantify riverine connectivity and map FFRs, we provide a foundation for concerted global and national strategies to maintain or restore them.
  11. Lee JL, Yushchenko PV, Suwannapoom C, Pawangkhanant P, Grismer LL, Nguyen TV, et al.
    Mol Phylogenet Evol, 2024 Dec;201:108215.
    PMID: 39396561 DOI: 10.1016/j.ympev.2024.108215
    With 90 recognized species, kukri snakes in the genus Oligodon Fitzinger constitute the second largest snake radiation in the world. Oligodon species are collectively distributed across the Asian continent and possess several ecological and morphological attributes that are unique amongst other snakes. Despite their high levels of species richness, evolutionary relationships within Oligodon are poorly understood due to a limited number of samples and genetic markers available in earlier phylogenies. In this study, we assembled the largest molecular dataset of Oligodon to date, which we use to assess the systematics and biogeography of the entire genus. Based on a combination of maximum likelihood and Bayesian phylogenies using fragments of three mitochondrial genes (12 s, 16 s, CytB) and three nuclear genes (Rag1, C-mos, BDNF), we identify eight deeply divergent clades within Oligodon, of which only two correspond with species groupings that were recognized by previous morphological classifications. Four species delimitation methods employed on the mitochondrial portion of the dataset resulted in dramatically divergent estimations of molecular operational taxonomic units (mOTUs). When combined, all four methods support the existence of unrecognized species-level lineages, but also indicate that several other Oligodon species are poorly differentiated genetically and require additional integrative taxonomic research to properly resolve. Based on divergence dating, we demonstrate that Oligodon began to diversify during the early Neogene and hypothesize that the most recent common ancestor of the genus originated in mainland Southeast Asia. We conclude by recognizing eight phylogenetically defined species groups and identify sampling gaps that require further investigation once new data becomes available. This study contributes to a greater understanding of snake evolution on the Asian continent and acts as a baseline for future studies of this speciose genus.
  12. Aththar AF, Raushani F, Sekaringtyas FC, Muttaqien SE, Setyawati DR, Pratiwi RD, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2025 Dec;398(12):17415-17433.
    PMID: 40498095 DOI: 10.1007/s00210-025-04296-4
    Tocotrienols (T3) have been known to have potential cytotoxic activity against cancer cells. However, their ability to effectively target cancerous tissue is hampered by their lipophilic characteristics and poor bioavailability. In this study, encapsulating T3 into nanoemulsions (NE) prepared from palm oil (5-20%) and Tween-80 (3-7%) assisted with ultrasonication (5-20 min) resulted in improved stability of NE-T3 (kinetic, thermodynamic, long-term storage) and biological activity. Response Surface Methodology with Box-Behnken Design predicted the significant effect of palm oil concentrations on nanosized particle formation, while Tween-80 concentration and ultrasonication time had minimal effect on particle size. The optimum formulation achieved nanoscale characteristics of NE-T3, including a mean particle size of 64.8 ± 8 nm, polydispersity index of 0.288, and ζ-potential of - 19.16 mV, with only 5.2 ± 0.8% size variation after 60-day storage at 40 °C. It also demonstrated condition-specific thermodynamic stability, long-term storage capability, controlled drug release properties (77.97 ± 4.41% cumulative release over 54 h), and significantly enhanced antioxidant activity. The antioxidant activity (ABTS and DPPH) of NE-T3 showed IC50 values of 26.63 ± 1.8 µg/mL (ABTS) and 9.38 ± 1.24 µg/mL (DPPH), representing 1.5-2.0-fold improvement over free form of T3. The NE-T3 significantly enhanced cytotoxicity (IC50 45.07 ± 4.84 µg/mL) compared to free-T3 (IC50 78.75 ± 4.68 µg/mL) in B16F0 melanoma cells, while both showed minimal toxicity on normal NIH-3T3 cells (IC50 > 230 µg/mL). Additional anticancer assays revealed that NE-T3 induced 12.83 ± 2.1% late apoptosis and caused G1 phase cell cycle arrest. This study highlights the potential of NE-T3 as a promising platform for r combinatory cancer therapies.
  13. Sulaiman W, Othman M, Mokhtar AM, Rosman A, Ong SG, Soo IS, et al.
    APLAR Journal of Rheumatology, 2006;9 Suppl 1:A54-A55.
    DOI: 10.1111/j.1479-8077.2006.00199_24.x
    Objective: To determine the number of RA cases and to evaluate the demographic patterns in all 4 Rheumatology Referral Centers under the Ministry of Health Malaysia. Materials and methods: One thousand and eighty-four rheumatoid arthritis patients from all 4 centers i.e. Hospital Selayang, Putra Jaya, Seremban and Taiping which are situated in the west coast of West Malaysia, using rheumatoid arthritis database comprising of basic clinical and patient questionnaire, until the end of year 2004 were analysed. Results: At the time of documentation, 88.6% were female at all range of ages especially between age of 25 and 54 years (77.6%) with female to male ratio 8 :1. 52.1% were housewives. Mean age of onset of RA was 49.6 ± 11.8 SD with female 49.3 ± 11.7 SD and male 52.0 ± 12.0 SD (p < 0.05). Indian was the predominant ethnic group (54.5%), followed by Malay (31.4%), Chinese (11.6%) and others (27%). Majority had their education up to secondary level (50.8%), followed by primary (32.6%), and tertiary (6.3%) levels while 10.3% of cases had not received any formal education in their lives. 74.4% were seropositive and 87.3% fulfilled at least 4 out of 7 American College of Rheumatology (ACR) revised criteria for rheumatoid arthritis. 74% were diagnosed RA within 2 years after the onset of arthritis. Seropositivity was not significantly related to gender. Positive rheumatoid factor was dominated by Indian followed by Malay and Chinese. 83.3% were married. 23.3% female and 33.9% male between age group 25-54 were employed. 7.4% had achieved their retirement at time of entry whilst 8.9% were unemployed. Employment status was statistically significant across gender (p < 0.001). The cases differed between rheumatology centers as well as individual practices. Conclusion: There are increasing numbers of RA cases in Malaysia. Results from this study did not reflect the true prevalence of RA in Malaysia. Hence, a larger and more comprehensive database on RA with collaboration of all Government and Private Hospitals in the whole nation will provide better information about the patient case mix in different healthcare settings, treatment practice as well as disease complications. The implementation of rheumatology centers with better regional cooperation, will lead to better treatment and outcome in terms of identification of early as well as established RA cases. Early referral to the centers will be made possible for proper treatment institution and rehabilitation. Hence, improve quality of life including socio-economic status especially among those within the productive age.
  14. Dalakoti M, Lin NHY, Yap J, Cader A, Dipanker P, Lee D, et al.
    JACC Adv, 2025 Mar 21;4(4):101676.
    PMID: 40120215 DOI: 10.1016/j.jacadv.2025.101676
    IMPORTANCE: Asia faces a rapidly rising burden of cardiovascular disease (CVD). Preventive cardiology efforts may help address the CVD epidemic.

    OBSERVATIONS: Solutions to address the CVD burden include a cardiovascular risk assessment framework, improving health screening efforts, better cardiovascular risk factor management, novel innovation strategies encompassing targeted lifestyle measures, and strengthening governmental efforts. With the region's wide socioeconomic and other disparities, contextualizing and practical adaptation of various strategies into local practices, especially in low-middle-income countries, will determine the success of CVD prevention efforts.

    CONCLUSIONS: A differential approach addressing cardiovascular risk factor screening, prevention, and management that considers the context-specific socioeconomic, governmental, and cultural aspects in diverse Asian populations may help reduce the rapidly rising CVD trajectory in Asia.

  15. Tricarico S, McNeil HC, Cleary DW, Head MG, Lim V, Yap IKS, et al.
    PMID: 28702308 DOI: 10.1186/s41479-017-0030-5
    BACKGROUND: Since 2000, the widespread adoption of pneumococcal conjugate vaccines (PCVs) has had a major impact in the prevention of pneumonia. Limited access to international financial support means some middle-income countries (MICs) are trailing in the widespread use of PCVs. We review the status of PCV implementation, and discuss any needs and gaps related to low levels of PCV implementation in MICs, with analysis of possible solutions to strengthen the PCV implementation process in MICs.

    MAIN BODY: We searched PubMed, PubMed Central, Ovid MEDLINE, and SCOPUS databases using search terms related to pneumococcal immunization, governmental health policy or programmes, and MICs. Two authors independently reviewed the full text of the references, which were assessed for eligibility using pre-defined inclusion and exclusion criteria. The search terms identified 1,165 articles and the full texts of 21 were assessed for suitability, with eight articles included in the systematic review. MICs are implementing PCVs at a slower rate than donor-funded low-income countries and wealthier developed countries. A significant difference in the uptake of PCV in lower middle-income countries (LMICs) (71%) and upper middle-income countries (UMICs) (48%) is largely due to an unsuccessful process of "graduation" of MICs from GAVI assistance, an issue that arises as countries cross the income eligibility threshold and are no longer eligible to receive the same levels of financial assistance. A lack of country-specific data on disease burden, a lack of local expertise in economic evaluation, and the cost of PCV were identified as the leading causes of the slow uptake of PCVs in MICs. Potential solutions mentioned in the reviewed papers include the use of vaccine cost-effectiveness analysis and the provision of economic evidence to strengthen decision-making, the evaluation of the burden of disease, and post-introduction surveillance to monitor vaccine impact.

    CONCLUSION: The global community needs to recognise the impediments to vaccine introduction into MICs. Improving PCV access could help decrease the incidence of pneumonia and reduce the selection pressure for pneumococcal antimicrobial resistance.

  16. Choudhury A, Jindal A, Maiwall R, Sharma MK, Sharma BC, Pamecha V, et al.
    Hepatol Int, 2017 Sep;11(5):461-471.
    PMID: 28856540 DOI: 10.1007/s12072-017-9816-z
    BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models.

    METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922).

    RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001).

    CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

  17. Mohan A, Podin Y, Tai N, Chieng CH, Rigas V, Machunter B, et al.
    PLoS Negl Trop Dis, 2017 Jun;11(6):e0005650.
    PMID: 28599008 DOI: 10.1371/journal.pntd.0005650
    BACKGROUND: Melioidosis is a serious, and potentially fatal community-acquired infection endemic to northern Australia and Southeast Asia, including Sarawak, Malaysia. The disease, caused by the usually intrinsically aminoglycoside-resistant Burkholderia pseudomallei, most commonly affects adults with predisposing risk factors. There are limited data on pediatric melioidosis in Sarawak.

    METHODS: A part prospective, part retrospective study of children aged <15 years with culture-confirmed melioidosis was conducted in the 3 major public hospitals in Central Sarawak between 2009 and 2014. We examined epidemiological, clinical and microbiological characteristics.

    FINDINGS: Forty-two patients were recruited during the 6-year study period. The overall annual incidence was estimated to be 4.1 per 100,000 children <15 years, with marked variation between districts. No children had pre-existing medical conditions. Twenty-three (55%) had disseminated disease, 10 (43%) of whom died. The commonest site of infection was the lungs, which occurred in 21 (50%) children. Other important sites of infection included lymph nodes, spleen, joints and lacrimal glands. Seven (17%) children had bacteremia with no overt focus of infection. Delays in diagnosis and in melioidosis-appropriate antibiotic treatment were observed in nearly 90% of children. Of the clinical isolates tested, 35/36 (97%) were susceptible to gentamicin. Of these, all 11 isolates that were genotyped were of a single multi-locus sequence type, ST881, and possessed the putative B. pseudomallei virulence determinants bimABp, fhaB3, and the YLF gene cluster.

    CONCLUSIONS: Central Sarawak has a very high incidence of pediatric melioidosis, caused predominantly by gentamicin-susceptible B. pseudomallei strains. Children frequently presented with disseminated disease and had an alarmingly high death rate, despite the absence of any apparent predisposing risk factor.

  18. Reijnders MRF, Ansor NM, Kousi M, Yue WW, Tan PL, Clarkson K, et al.
    Am J Hum Genet, 2017 Sep 07;101(3):466-477.
    PMID: 28886345 DOI: 10.1016/j.ajhg.2017.08.007
    RAC1 is a widely studied Rho GTPase, a class of molecules that modulate numerous cellular functions essential for normal development. RAC1 is highly conserved across species and is under strict mutational constraint. We report seven individuals with distinct de novo missense RAC1 mutations and varying degrees of developmental delay, brain malformations, and additional phenotypes. Four individuals, each harboring one of c.53G>A (p.Cys18Tyr), c.116A>G (p.Asn39Ser), c.218C>T (p.Pro73Leu), and c.470G>A (p.Cys157Tyr) variants, were microcephalic, with head circumferences between -2.5 to -5 SD. In contrast, two individuals with c.151G>A (p.Val51Met) and c.151G>C (p.Val51Leu) alleles were macrocephalic with head circumferences of +4.16 and +4.5 SD. One individual harboring a c.190T>G (p.Tyr64Asp) allele had head circumference in the normal range. Collectively, we observed an extraordinary spread of ∼10 SD of head circumferences orchestrated by distinct mutations in the same gene. In silico modeling, mouse fibroblasts spreading assays, and in vivo overexpression assays using zebrafish as a surrogate model demonstrated that the p.Cys18Tyr and p.Asn39Ser RAC1 variants function as dominant-negative alleles and result in microcephaly, reduced neuronal proliferation, and cerebellar abnormalities in vivo. Conversely, the p.Tyr64Asp substitution is constitutively active. The remaining mutations are probably weakly dominant negative or their effects are context dependent. These findings highlight the importance of RAC1 in neuronal development. Along with TRIO and HACE1, a sub-category of rare developmental disorders is emerging with RAC1 as the central player. We show that ultra-rare disorders caused by private, non-recurrent missense mutations that result in varying phenotypes are challenging to dissect, but can be delineated through focused international collaboration.
  19. Zhong XM, Wang F, Zhang Q, Ungvari GS, Ng CH, Chiu HFK, et al.
    Int Psychogeriatr, 2019 May;31(5):685-691.
    PMID: 29212560 DOI: 10.1017/S1041610217002563
    ABSTRACTBackground:Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates.

    METHODS: The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed.

    RESULTS: The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants.

    CONCLUSIONS: Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.

  20. Manosroi W, Tan JW, Rariy CM, Sun B, Goodarzi MO, Saxena AR, et al.
    J Clin Endocrinol Metab, 2017 11 01;102(11):4124-4135.
    PMID: 28938457 DOI: 10.1210/jc.2017-00957
    Context: Hypertension in young women is uncommon compared with young men and older women. Estrogen appears to protect most women against hypertension, with incidence increasing after menopause. Because some premenopausal women develop hypertension, estrogen may play a different role in these women. Genetic variations in the estrogen receptor (ER) are associated with cardiovascular disease. ER-β, encoded by ESR2, is the ER predominantly expressed in vascular smooth muscle.

    Objective: To determine an association of single nucleotide polymorphisms in ESR2 with salt sensitivity of blood pressure (SSBP) and estrogen status in women.

    Methods: Candidate gene association study with ESR2 and SSBP conducted in normotensive and hypertensive women and men in two cohorts: International Hypertensive Pathotype (HyperPATH) (n = 584) (discovery) and Mexican American Hypertension-Insulin Resistance Study (n = 662) (validation). Single nucleotide polymorphisms in ESR1 (ER-α) were also analyzed. Analysis conducted in younger (<51 years, premenopausal, "estrogen-replete") and older women (≥51 years, postmenopausal, "estrogen-deplete"). Men were analyzed to control for aging.

    Results: Multivariate analyses of HyperPATH data between variants of ESR2 and SSBP documented that ESR2 rs10144225 minor (risk) allele carriers had a significantly positive association with SSBP driven by estrogen-replete women (β = +4.4 mm Hg per risk allele, P = 0.004). Findings were confirmed in Hypertension Insulin-Resistance Study premenopausal women. HyperPATH cohort analyses revealed risk allele carriers vs noncarriers had increased aldosterone/renin ratios. No associations were detected with ESR1.

    Conclusions: The variation at rs10144225 in ESR2 was associated with SSBP in premenopausal women (estrogen-replete) and not in men or postmenopausal women (estrogen-deplete). Inappropriate aldosterone levels on a liberal salt diet may mediate the SSBP.

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