Browse publications by year: 2021

  1. Sheng TM, Kumar PV
    Curr Drug Deliv, 2021 Oct 05.
    PMID: 34620064 DOI: 10.2174/1567201818666211006103452
    Natural cyclodextrins (CDs) are macrocyclic starch molecules discovered a decade ago, in which α-, β-, and γ-CD were commonly used. They originally acted as pharmaceutical excipients to enhance the aqueous solubility and alter the physicochemical properties of drugs that fall under class II and IV categories according to the Biopharmaceutics Classification System (BPS). The industrial significance of CDs became apparent during the 1970s as scientists started to discover more of CD's potential in chemical modifications and the formation of inclusion complexes. CDs can help in masking and prolonging the half-life of drugs used in cancer. Multiple optimization techniques were discovered to prepare the derivatives of CDs and increase their complexation and drug delivery efficiency. In recent years, due to the advancement of nanotechnology in pharmaceutical sectors, there has been growing interest in CDs. This review mainly focuses on the formulation of cyclodextrin conjugated nanocarriers using graphenes, carbon nanotubes, nanosponges, hydrogels, dendrimers, and polymers to achieve drug-release characteristics specific to cells. These approaches benefit the discovery of novel anti-cancer treatments, solubilization of new drug compounds, and cell specific drug delivery properties. Due to these unique properties of CDs, they are essential in achieving and enhancing tumor-specific cancer treatment.
  2. Loo SC, Said LN, Nakaswaram L, Hui LY, Ming YE, Talin BAA
    Curr Drug Saf, 2021 Oct 06.
    PMID: 34620068 DOI: 10.2174/1574886316666211006113948
    BACKGROUND: Compliance towards the requirements of labelling of dispensed medicine (LDM) among private primary health care facilities ensures appropriate use of medicines.

    AIM: This study aimed to examine the rate of compliance towards the requirements of LDM among retail pharmacies (RPs) and private medical clinics (PMCs).

    METHODS: A cross-sectional study was conducted from April 2019 to January 2020 across all inspected premises in Sarawak. Publics who attended RPs and PMCs and having medicines dispensed, have their medicine labels examined for compliance towards the requirements of LDM upon exiting the premises. Their verbal consents were obtained and the compliance score were recorded into self-developed data collection forms. Compliance rate was the percentage of requirements on the examined medicine labels that fulfil the requirements under Regulation 12 of Poisons Regulations 1952.

    RESULTS: A total of 414 LDM were examined, with 135 from RPs and 279 from PMCs. The full compliance towards the requirements of LDM among RPs and PMCs were 23.7% and 41.6%, respectively. The median compliance score of PMCs (0.83) was significantly higher (P<0.001) than RPs (0.67). The requirements of LDM with the lowest compliance was name of medicine (53.1%), followed by name of patient (31.9%) and date of dispensing (25.6%).

    CONCLUSION: The full compliance rate on the requirements of LDM among RPs and PMCs were low. More stringent enforcement and public education on their rights for fully compliant medicine labels could improve the compliance.

  3. Izham MNM, Hussin Y, Rahim NFC, Aziz MNM, Yeap SK, Rahman HS, et al.
    BMC Complement Med Ther, 2021 Oct 07;21(1):254.
    PMID: 34620132 DOI: 10.1186/s12906-021-03422-y
    BACKGROUND: Eucalyptol is an active compound of eucalyptus essential oil and was reported to have many medical attributes including cytotoxic effect on breast cancer cells. However, it has low solubility in aqueous solutions which limits its bioavailability and cytotoxic efficiency. In this study, nanostructured lipid carrier loaded with eucalyptol (NLC-Eu) was formulated and characterized and the cytotoxic effect of NLC-Eu towards breast cancer cell lines was determined. In addition, its toxicity in animal model, BALB/c mice was also incorporated into this study to validate the safety of NLC-Eu.

    METHODS: Eucalyptol, a monoterpene oxide active, was used to formulate the NLC-Eu by using high pressure homogenization technique. The physicochemical characterization of NLC-Eu was performed to assess its morphology, particle size, polydispersity index, and zeta potential. The in vitro cytotoxic effects of this encapsulated eucalyptol on human (MDA MB-231) and murine (4 T1) breast cancer cell lines were determined using the MTT assay. Additionally, acridine orange/propidium iodide assay was conducted on the NLC-Eu treated MDA MB-231 cells. The in vivo sub-chronic toxicity of the prepared NLC-Eu was investigated using an in vivo BALB/c mice model.

    RESULTS: As a result, the light, translucent, milky-colored NLC-Eu showed particle size of 71.800 ± 2.144 nm, poly-dispersity index of 0.258 ± 0.003, and zeta potential of - 2.927 ± 0.163 mV. Furthermore, the TEM results of NLC-Eu displayed irregular round to spherical morphology with narrow size distribution and relatively uniformed particles. The drug loading capacity and entrapment efficiency of NLC-Eu were 4.99 and 90.93%, respectively. Furthermore, NLC-Eu exhibited cytotoxic effects on both, human and mice, breast cancer cells with IC50 values of 10.00 ± 4.81 μg/mL and 17.70 ± 0.57 μg/mL, respectively at 72 h. NLC-Eu also induced apoptosis on the MDA MB-231 cells. In the sub-chronic toxicity study, all of the studied mice did not show any signs of toxicity, abnormality or mortality. Besides that, no significant changes were observed in the body weight, internal organ index, hepatic and renal histopathology, serum biochemistry, nitric oxide and malondialdehyde contents.

    CONCLUSIONS: This study suggests that the well-characterized NLC-Eu offers a safe and promising carrier system which has cytotoxic effect on breast cancer cell lines.

    MeSH terms: Animals; Antineoplastic Agents/pharmacology*; Breast Neoplasms/drug therapy*; Disease Models, Animal; Female; Humans; Lipids; Mice, Inbred BALB C; Cell Line, Tumor; Nanostructures/therapeutic use*; Mice
  4. Ibrahim MF, Kuan G, Hashim HA, Hamzah NA, Kueh YC
    BMC Public Health, 2021 10 07;21(1):1798.
    PMID: 34620133 DOI: 10.1186/s12889-021-11869-4
    BACKGROUND: This study aimed to verify a translated Malay version of the Achievement Emotions Questionnaire for Physical Education (AEQ-PE) by assessing the level of achievement emotions in six constructs among the Malaysian primary school pupils using the Confirmatory Factor Analysis (CFA).

    METHODS: A total of 607 Malay pupils, comprising 240 (39.5%) boys and 367 (60.5%) girls aged between 10 and 11, were recruited from 10 schools to answer the questionnaire, which measured their views on 24 items through a five-point Likert scale. The AEQ-PE was translated into Malay language (AEQ-PE-M) using forwarding to backward translation techniques. Certain phrases were adopted in accordance with the local culture and vocabulary appropriate for primary school pupils. CFA was performed using the Mplus 8.0 software, and the final model demonstrated high reliability in terms of the composite reliability and Cronbach's alpha.

    RESULTS: Analysis of the CFA showed an acceptable fit indices in CFI (0.936), TLI (0.926), RMSEA = 0.039 (90% CI, 0.034, 0.045) and SRMR (0.049) of the AEQ-PE measurement model. All of the items in the original AEQ-PE version were retained and deemed suitable for Malay primary school pupils.

    CONCLUSION: The AEQ-PE-M with 24 items was a suitable tool for measuring the level of school children's involvement in determining achievement emotions and their motivation towards physical education.

    MeSH terms: Child; Emotions; Female; Humans; Language*; Malaysia; Male; Physical Education and Training*; Psychometrics; Surveys and Questionnaires; Reproducibility of Results
  5. Houghton LC, Gibbons MP, Shekelle J, Oakley-Girvan I, Watterson JL, Magsamen-Conrad K, et al.
    BMC Public Health, 2021 10 07;21(1):1805.
    PMID: 34620141 DOI: 10.1186/s12889-021-11775-9
    BACKGROUND: Physical activity is central to chronic disease prevention. Low resource mothers face structural barriers preventing them from increasing their physical activity to reduce their chronic disease risk. We co-designed an intervention, with the ultimate goal of building social cohesion through social media to increase physical activity for low resourced mothers in urban settings.

    METHODS: In 2019, we interviewed 10 mothers of children (

    MeSH terms: Child; Female; Humans; Mothers*; Motivation; Neoplasms*; Exercise; Social Networking
  6. Gouda W, Alsaqabi F, Moshrif A, Abbas AS, Abdel-Aziz TM, Islam MA
    J Med Case Rep, 2021 Oct 07;15(1):497.
    PMID: 34620236 DOI: 10.1186/s13256-021-03072-1
    BACKGROUND: Macrophage activation syndrome is classified as a secondary form of hemophagocytic lymphohistiocytosis. It is a hyperinflammatory complication observed to be comorbid with a variety of autoimmune diseases, including adult-onset Still's disease and systemic juvenile idiopathic arthritis. Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus, which, if untreated, can be fatal, though determining the optimum treatment strategy is still a challenge.

    CASE PRESENTATION: Herein, we report a case of macrophage activation syndrome in a 33-year-old Egyptian female as an unusual complication of a systemic lupus erythematosus flare in adult patients. Our patient was initially treated with a combination of intravenous methylprednisolone pulse therapy and intravenous immunoglobulin therapy, which was followed by a course of oral prednisolone and oral cyclosporine with little response. Switching from oral prednisone to intravenous dexamethasone sodium phosphate showed a more favorable clinical and biochemical response.

    CONCLUSION: Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus. Our case demonstrates that dexamethasone sodium phosphate can be a successful alternative treatment for patients with systemic lupus erythematosus complicated by macrophage activation syndrome in whom the response to pulse methylprednisolone was inadequate to manage their illness, proving to be remarkably effective in a relatively short time frame.

    MeSH terms: Adult; Dexamethasone/analogs & derivatives; Female; Humans; Methylprednisolone/therapeutic use; Cyclosporine/therapeutic use; Immunoglobulins, Intravenous
  7. Wong LP, Alias H, Danaee M, Ahmed J, Lachyan A, Cai CZ, et al.
    Infect Dis Poverty, 2021 Oct 07;10(1):122.
    PMID: 34620243 DOI: 10.1186/s40249-021-00900-w
    BACKGROUND: The availability of various types of COVID-19 vaccines and diverse characteristics of the vaccines present a dilemma in vaccination choices, which may result in individuals refusing a particular COVID-19 vaccine offered, hence presenting a threat to immunisation coverage and reaching herd immunity. The study aimed to assess global COVID-19 vaccination intention, vaccine characteristics influencing vaccination acceptance and desirable vaccine characteristics influencing the choice of vaccines.

    METHODS: An anonymous cross-sectional survey was conducted between 4 January and 5 March 2021 in 17 countries worldwide. Proportions and the corresponding 95% confidence intervals (CI) of COVID-19 vaccine acceptance and vaccine characteristics influencing vaccination acceptance were generated and compared across countries and regions. Multivariable logistic regression analysis was used to determine the factors associated with COVID-19 vaccine hesitancy.

    RESULTS: Of the 19,714 responses received, 90.4% (95% CI 81.8-95.3) reported likely or extremely likely to receive COVID-19 vaccine. A high proportion of likely or extremely likely to receive the COVID-19 vaccine was reported in Australia (96.4%), China (95.3%) and Norway (95.3%), while a high proportion reported being unlikely or extremely unlikely to receive the vaccine in Japan (34.6%), the U.S. (29.4%) and Iran (27.9%). Males, those with a lower educational level and those of older age expressed a higher level of COVID-19 vaccine hesitancy. Less than two-thirds (59.7%; 95% CI 58.4-61.0) reported only being willing to accept a vaccine with an effectiveness of more than 90%, and 74.5% (95% CI 73.4-75.5) said they would accept a COVID-19 vaccine with minor adverse reactions. A total of 21.0% (95% CI 20.0-22.0) reported not accepting an mRNA vaccine and 51.8% (95% CI 50.3-53.1) reported that they would only accept a COVID-19 vaccine from a specific country-of-origin. Countries from the Southeast Asia region reported the highest proportion of not accepting mRNA technology. The highest proportion from Europe and the Americas would only accept a vaccine produced by certain countries. The foremost important vaccine characteristic influencing vaccine choice is adverse reactions (40.6%; 95% CI 39.3-41.9) of a vaccine and effectiveness threshold (35.1%; 95% CI 33.9-36.4).

    CONCLUSIONS: The inter-regional and individual country disparities in COVID-19 vaccine hesitancy highlight the importance of designing an efficient plan for the delivery of interventions dynamically tailored to the local population.

    MeSH terms: Adolescent; Adult; Aged; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Surveys and Questionnaires; Socioeconomic Factors; Global Health; Intention*; Young Adult
  8. Phua J, Lim CM, Faruq MO, Nafees KMK, Du B, Gomersall CD, et al.
    J Intensive Care, 2021 Oct 07;9(1):60.
    PMID: 34620252 DOI: 10.1186/s40560-021-00574-4
    BACKGROUND: Asia has more critically ill people than any other part of our planet. The aim of this article is to review the development of critical care as a specialty, critical care societies and education and research, the epidemiology of critical illness as well as epidemics and pandemics, accessibility and cost and quality of critical care, culture and end-of-life care, and future directions for critical care in Asia.

    MAIN BODY: Although the first Asian intensive care units (ICUs) surfaced in the 1960s and the 1970s and specialisation started in the 1990s, multiple challenges still exist, including the lack of intensivists, critical care nurses, and respiratory therapists in many countries. This is aggravated by the brain drain of skilled ICU staff to high-income countries. Critical care societies have been integral to the development of the discipline and have increasingly contributed to critical care education, although critical care research is only just starting to take off through collaboration across groups. Sepsis, increasingly aggravated by multidrug resistance, contributes to a significant burden of critical illness, while epidemics and pandemics continue to haunt the continent intermittently. In particular, the coronavirus disease 2019 (COVID-19) has highlighted the central role of critical care in pandemic response. Accessibility to critical care is affected by lack of ICU beds and high costs, and quality of critical care is affected by limited capability for investigations and treatment in low- and middle-income countries. Meanwhile, there are clear cultural differences across countries, with considerable variations in end-of-life care. Demand for critical care will rise across the continent due to ageing populations and rising comorbidity burdens. Even as countries respond by increasing critical care capacity, the critical care community must continue to focus on training for ICU healthcare workers, processes anchored on evidence-based medicine, technology guided by feasibility and impact, research applicable to Asian and local settings, and rallying of governments for support for the specialty.

    CONCLUSIONS: Critical care in Asia has progressed through the years, but multiple challenges remain. These challenges should be addressed through a collaborative approach across disciplines, ICUs, hospitals, societies, governments, and countries.

  9. Hashim SA, Mohd Yusof BN, Abu Saad H, Ismail S, Hamdy O, Mansour AA
    Clin Nutr ESPEN, 2021 Oct;45:141-149.
    PMID: 34620310 DOI: 10.1016/j.clnesp.2021.07.024
    BACKGROUND & AIMS: The study aimed to evaluate the effectiveness of the Simplified Diabetes Nutrition Education (SDNE) on glycemic control and other diabetes-related outcomes in patients with type 2 diabetes mellitus (T2DM).

    METHODS: This a randomized controlled trial (RCT) randomized 208 patients with T2DM [mean age = 48.8 ± 11.8 years, Glycated Hemoglobin (HbA1c) = 9.5 ± 2.4%, and Body Mass Index = 28.0 ± 5.6 kg/m2] to intervention group (n = 104) or control group (n = 104). Participants in the intervention group received a weekly diabetes nutrition module based on the health belief model for 12 weeks in addition to the usual care whereas the control participants were given the usual care. We evaluated HbA1c and diabetes-related outcomes (metabolic parameters, dietary intake, and physical activity level) at baseline, 12 weeks, and 22 weeks. Health beliefs, diabetes knowledge, and health literacy were also evaluated.

    RESULTS: After 22 weeks, HbA1c improved significantly in the intervention group (-1.7%) from the baseline value, compared to the control group (+0.01%) (p 

  10. Ali AS, Hasan SS, Kow CS, Merchant HA
    Clin Nutr ESPEN, 2021 10;45:26-32.
    PMID: 34620326 DOI: 10.1016/j.clnesp.2021.08.019
    BACKGROUND: Lactoferrin (Lf) is one of the key immunomodulatory substances found naturally in various body fluids, such as saliva, tears, and breast milk, and forms a vital part of the innate defense against invading pathogens. Various studies have demonstrated antibacterial, antifungal, and antiviral properties of Lf and its protective role against respiratory tract infections (RTIs). The present meta-analysis aims to elucidate the association of Lf administration in reducing the risk of RTIs by systematically reviewing the data from randomized controlled trials (RCTs).

    METHODS: We systematically searched PubMed, Cochrane Library, Medline & CINAHL, Turning Research into Practice (TRIP), ProQuest Theses & Dissertations Databases, and China National Knowledge Infrastructure (CNKI) from inception till March 15, 2021. The primary outcome measure was a reduction in respiratory illness; decrease in frequency, symptoms, and duration. Random-effects model was used to estimate the odds ratio (OR) and 95% confidence interval (CI). We used Cochrane's RoB-2 to appraise the risk of bias of included RCTs.

    RESULTS: A total of nine RCTs were eligible for this review, of which six were included in the meta-analysis. Overall, two studies demonstrated a high risk of bias. The meta-analysis revealed a significantly reduced odds of developing respiratory infections with the use of Lf relative to the control (pooled odds ratio = 0.57; 95% confidence interval 0.44 to 0.74, n = 1,194), with sufficient evidence against the hypothesis of 'no significant difference' at the current sample size.

    CONCLUSIONS: The administration of Lf shows promising efficacy in reducing the risk of RTIs. Current evidence also favours Lf fortification of infant formula. Lf may also have a beneficial role in managing symptoms and recovery of patients suffering from RTIs and may have potential for use as an adjunct in COVID-19, however this warrants further evidence from a large well-designed RCT.

    MeSH terms: Female; Humans; Lactoferrin; Randomized Controlled Trials as Topic
  11. Anstey NM, Grigg MJ, Rajahram GS, Cooper DJ, William T, Kho S, et al.
    Adv Parasitol, 2021;113:1-43.
    PMID: 34620381 DOI: 10.1016/bs.apar.2021.08.001
    Plasmodium knowlesi is endemic across Southeast Asia, and is the commonest cause of zoonotic malaria. The spectrum of clinical disease from P. knowlesi infection ranges from asymptomatic infection, through to severe malaria and death. Over 90% of clinical disease occurs in adults, mostly living in forest edge areas undergoing intensive land use change. With a 24-h asexual life cycle in humans, high parasite counts are possible, but most clinical cases of knowlesi malaria are uncomplicated with low parasitaemia. In co-endemic areas, median parasitaemia in knowlesi malaria is lower than that seen in vivax and falciparum malaria, suggesting a lower fever threshold. Severe malaria occurs in 6-9% of symptomatic adults. Manifestations of severe malaria from P. knowlesi are similar to those seen with falciparum malaria, with the notable absence of coma. Age, parasitaemia, cardiovascular comorbidities and delayed diagnosis are risk factors for severe disease and death, which are only seen in adults. Thrombocytopenia is near-universal in adults, likely related to platelet-red cell binding and clearance. Mechanisms underlying the microvascular sludging seen in fatal disease in non-natural primate hosts and the microvascular accumulation of parasites in fatal human disease are not clear. Marked reductions in deformability of both infected and uninfected red blood cells are associated with disease severity in both humans and other non-natural primate hosts, likely contributing to impaired microvascular perfusion and organ dysfunction. Endothelial activation, endothelial dysfunction, glycocalyx degradation and haemolysis are also associated with, and likely contribute to, severe disease and organ dysfunction, particularly acute kidney injury.
  12. Vythilingam I, Chua TH, Liew JWK, Manin BO, Ferguson HM
    Adv Parasitol, 2021;113:131-189.
    PMID: 34620382 DOI: 10.1016/bs.apar.2021.08.005
    Plasmodium knowlesi, a simian malaria parasite of great public health concern has been reported from most countries in Southeast Asia and exported to various countries around the world. Currently P. knowlesi is the predominant species infecting humans in Malaysia. Besides this species, other simian malaria parasites such as P. cynomolgi and P. inui are also infecting humans in the region. The vectors of P. knowlesi and other Asian simian malarias belong to the Leucosphyrus Group of Anopheles mosquitoes which are generally forest dwelling species. Continual deforestation has resulted in these species moving into forest fringes, farms, plantations and human settlements along with their macaque hosts. Limited studies have shown that mosquito vectors are attracted to both humans and macaque hosts, preferring to bite outdoors and in the early part of the night. We here review the current status of simian malaria vectors and their parasites, knowledge of vector competence from experimental infections and discuss possible vector control measures. The challenges encountered in simian malaria elimination are also discussed. We highlight key knowledge gaps on vector distribution and ecology that may impede effective control strategies.
  13. Divis PCS, Singh B, Conway DJ
    Adv Parasitol, 2021;113:191-223.
    PMID: 34620383 DOI: 10.1016/bs.apar.2021.08.003
    Molecular epidemiology has been central to uncovering P. knowlesi as an important cause of human malaria in Southeast Asia, and to understanding the complex nature of this zoonosis. Species-specific parasite detection and characterization of sequences were vital to show that P. knowlesi was distinct from the human parasite species that had been presumed to cause all malaria. With established sensitive and specific molecular detection tools, surveys subsequently indicated the distribution of P. knowlesi infections in humans, wild primate reservoir host species, and mosquito vector species. The importance of studying P. knowlesi genetic polymorphism was indicated initially by analysing a few nuclear gene loci as well as the mitochondrial genome, and subsequently by multi-locus microsatellite analyses and whole-genome sequencing. Different human infections generally have unrelated P. knowlesi genotypes, acquired from the diverse local parasite reservoirs in macaques. However, individual human infections are usually less genetically complex than those of wild macaques which experience more frequent superinfection with different P. knowlesi genotypes. Multi-locus analyses have revealed deep population subdivisions within P. knowlesi, which are structured both geographically and in relation to different macaque reservoir host species. Simplified genotypic discrimination assays now enable efficient large-scale surveillance of the sympatric P. knowlesi subpopulations within Malaysian Borneo. The whole-genome sequence analyses have also identified loci under recent positive natural selection in the P. knowlesi genome, with evidence that different loci are affected in different populations. These provide a foundation to understand recent adaptation of the zoonotic parasite populations, and to track and interpret future changes as they emerge.
  14. Cuenca PR, Key S, Jumail A, Surendra H, Ferguson HM, Drakeley CJ, et al.
    Adv Parasitol, 2021;113:225-286.
    PMID: 34620384 DOI: 10.1016/bs.apar.2021.08.006
    Within the past two decades, incidence of human cases of the zoonotic malaria Plasmodium knowlesi has increased markedly. P. knowlesi is now the most common cause of human malaria in Malaysia and threatens to undermine malaria control programmes across Southeast Asia. The emergence of zoonotic malaria corresponds to a period of rapid deforestation within this region. These environmental changes impact the distribution and behaviour of the simian hosts, mosquito vector species and human populations, creating new opportunities for P. knowlesi transmission. Here, we review how landscape changes can drive zoonotic disease emergence, examine the extent and causes of these changes across Southeast and identify how these mechanisms may be impacting P. knowlesi dynamics. We review the current spatial epidemiology of reported P. knowlesi infections in people and assess how these demographic and environmental changes may lead to changes in transmission patterns. Finally, we identify opportunities to improve P. knowlesi surveillance and develop targeted ecological interventions within these landscapes.
  15. Barber BE, Grigg MJ, Cooper DJ, van Schalkwyk DA, William T, Rajahram GS, et al.
    Adv Parasitol, 2021;113:45-76.
    PMID: 34620385 DOI: 10.1016/bs.apar.2021.08.004
    The zoonotic parasite Plasmodium knowlesi has emerged as an important cause of human malaria in parts of Southeast Asia. The parasite is indistinguishable by microscopy from the more benign P. malariae, but can result in high parasitaemias with multiorgan failure, and deaths have been reported. Recognition of severe knowlesi malaria, and prompt initiation of effective therapy is therefore essential to prevent adverse outcomes. Here we review all studies reporting treatment of uncomplicated and severe knowlesi malaria. We report that although chloroquine is effective for the treatment of uncomplicated knowlesi malaria, artemisinin combination treatment is associated with faster parasite clearance times and lower rates of anaemia during follow-up, and should be considered the treatment of choice, particularly given the risk of administering chloroquine to drug-resistant P. vivax or P. falciparum misdiagnosed as P. knowlesi malaria in co-endemic areas. For severe knowlesi malaria, intravenous artesunate has been shown to be highly effective and associated with reduced case-fatality rates, and should be commenced without delay. Regular paracetamol may also be considered for patients with severe knowlesi malaria or for those with acute kidney injury, to attenuate the renal damage resulting from haemolysis-induced lipid peroxidation.
  16. Grigg MJ, Lubis IN, Tetteh KKA, Barber BE, William T, Rajahram GS, et al.
    Adv Parasitol, 2021;113:77-130.
    PMID: 34620386 DOI: 10.1016/bs.apar.2021.08.002
    Within the overlapping geographical ranges of P. knowlesi monkey hosts and vectors in Southeast Asia, an estimated 1.5 billion people are considered at risk of infection. P. knowlesi can cause severe disease and death, the latter associated with delayed treatment occurring from misdiagnosis. Although microscopy is a sufficiently sensitive first-line tool for P. knowlesi detection for most low-level symptomatic infections, misdiagnosis as other Plasmodium species is common, and the majority of asymptomatic infections remain undetected. Current point-of-care rapid diagnostic tests demonstrate insufficient sensitivity and poor specificity for differentiating P. knowlesi from other Plasmodium species. Molecular tools including nested, real-time, and single-step PCR, and loop-mediated isothermal amplification (LAMP), are sensitive for P. knowlesi detection. However, higher cost and inability to provide the timely point-of-care diagnosis needed to guide appropriate clinical management has limited their routine use in most endemic clinical settings. P. knowlesi is likely underdiagnosed across the region, and improved diagnostic and surveillance tools are required. Reference laboratory molecular testing of malaria cases for both zoonotic and non-zoonotic Plasmodium species needs to be more widely implemented by National Malaria Control Programs across Southeast Asia to accurately identify the burden of zoonotic malaria and more precisely monitor the success of human-only malaria elimination programs. The implementation of specific serological tools for P. knowlesi would assist in determining the prevalence and distribution of asymptomatic and submicroscopic infections, the absence of transmission in certain areas, and associations with underlying land use change for future spatially targeted interventions.
  17. Al-Awadi A, Grove J, Taylor M, Valdes A, Vijay A, Bawden S, et al.
    BMJ Open, 2021 10 07;11(10):e045802.
    PMID: 34620653 DOI: 10.1136/bmjopen-2020-045802
    INTRODUCTION: A Low Glycaemic Index (LGI) diet is a proposed lifestyle intervention in non-alcoholic fatty liver diseases (NAFLD) which is designed to reduce circulating blood glucose levels, hepatic glucose influx, insulin resistance and de novo lipogenesis. A significant reduction in liver fat content through following a 1-week LGI diet has been reported in healthy volunteers. Changes in dietary fat and carbohydrates have also been shown to alter gut microbiota composition and lead to hepatic steatosis through the gut-liver axis. There are no available trials examining the effects of an LGI diet on liver fat accumulation in patients with NAFLD; nor has the impact of consuming an LGI diet on gut microbiota composition been studied in this population. The aim of this trial is to investigate the effects of LGI diet consumption on liver fat content and its effects on gut microbiota composition in participants with NAFLD compared with a High Glycaemic Index (HGI) control diet.

    METHODS AND ANALYSIS: A 2×2 cross-over randomised mechanistic dietary trial will allocate 16 participants with NAFLD to a 2-week either HGI or LGI diet followed by a 4-week wash-out period and then the LGI or HGI diet, alternative to that followed in the first 2 weeks. Baseline and postintervention (four visits) outcome measures will be collected to assess liver fat content (using MRI/S and controlled attenuation parameter-FibroScan), gut microbiota composition (using 16S RNA analysis) and blood biomarkers including glycaemic, insulinaemic, liver, lipid and haematological profiles, gut hormones levels and short-chain fatty acids.

    ETHICS AND DISSEMINATION: Study protocol has been approved by the ethics committees of The University of Nottingham and East Midlands Nottingham-2 Research Ethics Committee (REC reference 19/EM/0291). Data from this trial will be used as part of a Philosophy Doctorate thesis. Publications will be in peer-reviewed journals.

    TRIAL REGISTRATION NUMBER: NCT04415632.

    MeSH terms: Gastrointestinal Microbiome*; Diet; Humans; Liver; Randomized Controlled Trials as Topic; Glycemic Index; Non-alcoholic Fatty Liver Disease*
  18. Leong Bin Abdullah MFI, Mansor NS, Mohamad MA, Teoh SH
    BMJ Open, 2021 Oct 07;11(10):e048446.
    PMID: 34620656 DOI: 10.1136/bmjopen-2020-048446
    OBJECTIVE: This study aimed to evaluate the quality of life (QoL) and determine its association with various factors and social support among university students during the COVID-19 pandemic after the end of movement lockdown.

    DESIGN, SETTING AND PARTICIPANTS: This online cross-sectional study recruited 316 participants. The inclusion criteria were students 18 years and above who were registered with the faculties of medicine at Malaysian public universities located in Klang Valley and in the states of Penang and Kelantan in Peninsular Malaysia. The exclusion criteria were those who presented with psychotic disorders, bipolar mood disorder or a history of illicit drugs.

    OUTCOME MEASURES: Participants were administered a self-reported questionnaire to gather data on demographic, personal, clinical and psychological characteristics. The questionnaire comprised of the 21-item Depression, Anxiety and Stress Scale, the Multidimensional Scale of Perceived Social Support, and the WHO Quality of Life- Brief Version (WHOQoL-BREF).

    RESULTS: The psychological and social QoL scores were lower than the non-pandemic norms of the general population, while the physical health and environmental QoL scores were comparable. After adjusting for relevant demographic, personal and clinical variables, religious coping, greater number of hours of online classes attended, and greater social support from family, friends and significant others were significantly associated with higher QoL among the participants. Frustration due to study disruption, living in areas with a high prevalence of COVID-19 cases, and a higher severity of depressive and stress symptoms were significantly associated with lower QoL.

    CONCLUSION: COVID-19 impaired the QoL of university students even after the movement lockdown was lifted.

  19. Leddin D, Omary MB, Veitch A, Metz G, Amrani N, Aabakken L, et al.
    Gut, 2021 11;70(11):2025-2029.
    PMID: 34620696 DOI: 10.1136/gutjnl-2021-325789
    MeSH terms: Conservation of Natural Resources*; Gastroenterology/organization & administration*; Humans; Medical Waste*; Global Health; Climate Change*
  20. Ng KKS, Kobayashi MJ, Fawcett JA, Hatakeyama M, Paape T, Ng CH, et al.
    Commun Biol, 2021 Oct 07;4(1):1166.
    PMID: 34620991 DOI: 10.1038/s42003-021-02682-1
    Hyperdiverse tropical rainforests, such as the aseasonal forests in Southeast Asia, are supported by high annual rainfall. Its canopy is dominated by the species-rich tree family of Dipterocarpaceae (Asian dipterocarps), which has both ecological (e.g., supports flora and fauna) and economical (e.g., timber production) importance. Recent ecological studies suggested that rare irregular drought events may be an environmental stress and signal for the tropical trees. We assembled the genome of a widespread but near threatened dipterocarp, Shorea leprosula, and analyzed the transcriptome sequences of ten dipterocarp species representing seven genera. Comparative genomic and molecular dating analyses suggested a whole-genome duplication close to the Cretaceous-Paleogene extinction event followed by the diversification of major dipterocarp lineages (i.e. Dipterocarpoideae). Interestingly, the retained duplicated genes were enriched for genes upregulated by no-irrigation treatment. These findings provide molecular support for the relevance of drought for tropical trees despite the lack of an annual dry season.
    MeSH terms: Malaysia; Seasons; Genome, Plant*; Gene Duplication*; Dipterocarpaceae/genetics*; Droughts*; Rainforest*
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