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  1. Noor DAM, Jeyapalan JN, Alhazmi S, Carr M, Squibb B, Wallace C, et al.
    NPJ Genom Med, 2016;1:15009.
    PMID: 29263807 DOI: 10.1038/npjgenmed.2015.9
    Silencing of genes by DNA methylation is a common phenomenon in many types of cancer. However, the genome-wide effect of DNA methylation on gene expression has been analysed in relatively few cancers. Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. Previous analyses have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. The genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumours' biology have not yet been established. In this study, genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data from primary tumours to address this question. Genome methylation was analysed using the Illumina infinium HumanMethylome450 bead chip system and gene expression was analysed using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Regulation by methylation was confirmed by demethylation using 5-aza-2-deoxycytidine and reverse transcription-quantitative PCR. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested played a role in their silencing in yolk sac tumour cells and many of these genes were also differentially expressed in primary tumours. Genes silenced by methylation in the various GCT cell lines were identified. Several pluripotency-associated genes were identified as a major functional group of silenced genes.
  2. Grigg MJ, William T, Barber BE, Rajahram GS, Menon J, Schimann E, et al.
    Clin Infect Dis, 2018 Jan 06;66(2):229-236.
    PMID: 29020373 DOI: 10.1093/cid/cix779
    BACKGROUND: Plasmodium knowlesi is reported increasingly across Southeast Asia and is the most common cause of malaria in Malaysia. No randomized trials have assessed the comparative efficacy of artemether-lumefantrine (AL) for knowlesi malaria.

    METHODS: A randomized controlled trial was conducted in 3 district hospitals in Sabah, Malaysia to compare the efficacy of AL against chloroquine (CQ) for uncomplicated knowlesi malaria. Participants were included if they weighed >10 kg, had a parasitemia count <20000/μL, and had a negative rapid diagnostic test result for Plasmodium falciparum histidine-rich protein 2. Diagnosis was confirmed by means of polymerase chain reaction. Patients were block randomized to AL (total target dose, 12 mg/kg for artemether and 60 mg/kg for lumefantrine) or CQ (25 mg/kg). The primary outcome was parasite clearance at 24 hours in a modified intention-to-treat analysis.

    RESULTS: From November 2014 to January 2016, a total of 123 patients (including 18 children) were enrolled. At 24 hours after treatment 76% of patients administered AL (95% confidence interval [CI], 63%-86%; 44 of 58) were aparasitemic, compared with 60% administered CQ (47%-72%; 39 of 65; risk ratio, 1.3 [95% CI, 1.0-1.6]; P = .06). Overall parasite clearance was shorter after AL than after CQ (median, 18 vs 24 hours, respectively; P = .02), with all patients aparasitemic by 48 hours. By day 42 there were no treatment failures. The risk of anemia during follow-up was similar between arms. Patients treated with AL would require lower bed occupancy than those treated with CQ (2414 vs 2800 days per 1000 patients; incidence rate ratio, 0.86 [95% CI, .82-.91]; P < .001). There were no serious adverse events.

    CONCLUSIONS: AL is highly efficacious for treating uncomplicated knowlesi malaria; its excellent tolerability and rapid therapeutic response allow earlier hospital discharge, and support its use as a first-line artemisinin-combination treatment policy for all Plasmodium species in Malaysia.

    CLINICAL TRIALS REGISTRATION: NCT02001012.

  3. Wong MYZ, Yap JJL, Chih HJ, Yan BPY, Fong AYY, Beltrame JF, et al.
    Int J Cardiol, 2023 Jan 15;371:84-91.
    PMID: 36220505 DOI: 10.1016/j.ijcard.2022.10.001
    BACKGROUND: Diabetes is associated with poorer outcomes and increased complication rates in STEMI patients undergoing percutaneous coronary intervention (PCI). Data are notably lacking in the Asia-Pacific region. We report the overall association of Diabetes with clinical characteristics and outcomes in STEMI patients undergoing PCI across the Asia-Pacific, with a particular focus on regional differences.

    METHODOLOGY: The Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) collaboration consists of data from various PCI registries across Australia, Hong Kong, Singapore, Malaysia, Indonesia and Vietnam. Clinical characteristics, lesion characteristics, and outcomes were provided for STEMI patients. Key outcomes included 30-day overall mortality and major adverse cardiovascular events (MACE).

    RESULTS: A total of 12,144 STEMI patients (mean(SD) age 59.3(12.3)) were included, of which 3912 (32.2%) had diabetes. Patients with diabetes were likely to have a higher baseline risk profile, poorer clinical presentation, and more complex lesion patterns (all p 

  4. Li PK, Lu W, Mak SK, Boudville N, Yu X, Wu MJ, et al.
    Nephrology (Carlton), 2022 Oct;27(10):787-794.
    PMID: 35393750 DOI: 10.1111/nep.14042
    Peritoneal dialysis (PD) first policy has been established in Hong Kong since 1985. After 35 years of practice, the PD first policy in Hong Kong has influenced many countries around the world including governments, health ministries, nephrologists and renal nurses on the overall health policy structure and clinical practice in treating kidney failure patients using PD as an important dialysis modality. In 2021, the International Association of Chinese Nephrologists and the Hong Kong Society of Nephrology jointly held a symposium celebrating the 35 years of PD first policy in Hong Kong. In that symposium, experts and opinion leaders from around the world have shared their perspectives on how the PD first policy has grown and how it has affected PD and home dialysis practice globally. The advantages of PD during COVID-19 pandemic were highlighted and the use of telemedicine as an important adjunct was discussed in treating kidney failure patients to improve the overall quality of care. Barriers to PD and the need for sustainability of PD first policy were also emphasized. Overall, the knowledge awareness of PD as a home dialysis for patients, families, care providers and learners is a prerequisite for the success of PD first. A critical mass of PD regional hubs is needed for training and mentorship. Importantly, the alignment of policy and clinical goals are enablers of PD first program.
  5. Schliemann D, Ramanathan K, Ibrahim Tamin NSB, O'Neill C, Cardwell CR, Ismail R, et al.
    BMJ Open, 2022 Sep 01;12(9):e058420.
    PMID: 36581978 DOI: 10.1136/bmjopen-2021-058420
    INTRODUCTION: Colorectal cancer (CRC) is the second most common cancer in Malaysia and cases are often detected late. Improving screening uptake is key in down-staging cancer and improving patient outcomes. The aim of this study is to develop, implement and evaluate an intervention to improve CRC screening uptake in Malaysia in the context of the COVID-19 pandemic. The evaluation will include ascertaining the budgetary impact of implementing and delivering the intervention.

    METHODS AND ANALYSIS: The implementation research logic model guided the development of the study and implementation outcome measures were informed by the 'Reach, Effectiveness, Adoption, Implementation and Maintenance' (RE-AIM) framework. This CRC screening intervention for Malaysia uses home-testing and digital, small media, communication to improve CRC screening uptake. A sample of 780 people aged 50-75 years living in Segamat district, Malaysia, will be selected randomly from the South East Asia Community Observatory (SEACO) database. Participants will receive a screening pack as well as a WhatsApp video of a local doctor to undertake a stool test safely and to send a photo of the test result to a confidential mobile number. SEACO staff will inform participants of their result. Quantitative data about follow-up clinic attendance, subsequent hospital tests and outcomes will be collected. Logistic regression will be used to investigate variables that influence screening completion and we will conduct a budget impact-analysis of the intervention and its implementation. Qualitative data about intervention implementation from the perspective of participants and stakeholders will be analysed thematically.

    ETHICS AND DISSEMINATION: Ethics approval has been granted by Monash University Human Research Ethics Committee (MUHREC ID: 29107) and the Medical Review and Ethics Committee (Reference: 21-02045-O7G(2)). Results will be disseminated through publications, conferences and community engagement activities.

    TRIAL REGISTRATION NUMBER: National Medical Research Register Malaysia: 21-02045-O7G(2).

  6. Liam CCK, Boo YL, Lee YL, Law KB, Ho KW, Shahnaz SAKS, et al.
    Blood Cell Ther, 2021 Feb 25;4(1):1-8.
    PMID: 36712843 DOI: 10.31547/bct-2020-009
    BACKGROUND: Multiple Myeloma (MM) is characterized by the presence of clonal plasma cells. These often result in complications including bone destruction, hypercalcemia, renal insufficiency, and anaemia. Induction with a triplet or quadruplet regimen followed by autologous stem cell transplantation (ASCT) has been the standard of care for transplant eligible patients to achieve durable remission.

    PURPOSE: This is a retrospective analytical study to determine the outcome of Multiple Myeloma patients who underwent ASCT in Ampang Hospital.

    MATERIALS AND METHODS: We included a 5-year cohort of patients transplanted from 1st July 2014 to 30th June 2019. Data were obtained through electronic medical records. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed using simple and multiple Cox proportional hazard regression analysis. All analyses were done using software R version 3.6.2 with validated statistical packages.

    RESULTS: 139 patients were analyzed. The median age at transplant was 56 years old and 56.1% are males (n=78). The most common subtype is IgG Kappa (n=67, 48.2%). Only 93 patients in which the International Staging System (ISS) could be determined, and among them, 33.3% of patients (n=31) have advanced stage Ⅲ disease. The most common induction received before ASCT was a bortezomib based regimen and/or an immunomodulatory (IMiD) based regimen. 63.3% of patients achieved at least a very good partial response (VGPR) before ASCT. Most patients received myeloablative conditioning (MAC) (n=119, 85.6%). The mean cell dose is 3.68×106/kg. The median time to engraftment was 11 days for both platelet and absolute neutrophil count (ANC). With the median follow-up of 17.3 (range, 6.2-33.4) months, the median OS and PFS were not reached. The 1-year and 2-year PFS were 75% (95% CI 66-82%) and 52% (95% CI 42-62%), respectively. The 1-year and 2-year OS were 82% (95% CI 74-88%) and 70% (95% CI 60-78%), respectively. 6 patients (4.3%) had transplant-related mortality (TRM). IgA subtype was found to adversely affect PFS. Maintenance therapy and the absence of renal impairment was associated with better PFS and OS.

    DISCUSSION AND CONCLUSIONS: Our study found that ASCT following induction treatment is safe and beneficial to achieve a deeper remission status. In our study, the addition of maintenance therapy is associated with an improved outcome in PFS and OS.

  7. Htay MNN, Schliemann D, Dahlui M, Cardwell CR, Loh SY, Tamin NSBI, et al.
    Int J Environ Res Public Health, 2021 Sep 03;18(17).
    PMID: 34501903 DOI: 10.3390/ijerph18179311
    Breast cancer (BC) is the most common cancer among women globally, including in Malaysia. There is a need to assess women's beliefs about BC and screening in different cultural settings. This study aimed to translate and validate an adapted version of the United States (US) Champion Health Belief Model Scale (CHBMS) for an investigation of predictors of BC screening in Malaysia. The CHBMS was adapted, and forward and backward translated into the Malay language. The validity and reliability of the CHBMS-BC-M (M for Malay language) was investigated in a community sample of 251 multi-ethnic Malay-speaking women. Principal component analysis with varimax rotation indicated that the structure of the adapted CHBMS-BC-M comprised three subscales with 21 items, and an Item-Content Validity Index (I-CVI) of 0.83 and above for all items. The explanatory factor analysis (EFA) showed acceptable to high factor loadings on items. Cronbach's alpha for the subscales ranged from 0.59 to 0.87. The reproducibility of the scale was fair to high, with an Intraclass Correlation Coefficient (ICC) of 0.53 to 0.80 for the subscales. Overall, the analysis indicated that the translated CHBMS-BC-M is a valid and reliable scale to measure beliefs about BC and screening in the Malay-speaking ethnic population of Malaysia.
  8. Kang H, Auzenbergs M, Clapham H, Maure C, Kim JH, Salje H, et al.
    Lancet Infect Dis, 2024 May;24(5):488-503.
    PMID: 38342105 DOI: 10.1016/S1473-3099(23)00810-1
    BACKGROUND: Chikungunya is an arboviral disease transmitted by Aedes aegypti and Aedes albopictus mosquitoes with a growing global burden linked to climate change and globalisation. We aimed to estimate chikungunya seroprevalence, force of infection (FOI), and prevalence of related chronic disability and hospital admissions in endemic and epidemic settings.

    METHODS: In this systematic review, meta-analysis, and modelling study, we searched PubMed, Ovid, and Web of Science for articles published from database inception until Sept 26, 2022, for prospective and retrospective cross-sectional studies that addressed serological chikungunya virus infection in any geographical region, age group, and population subgroup and for longitudinal prospective and retrospective cohort studies with data on chronic chikungunya or hospital admissions in people with chikungunya. We did a systematic review of studies on chikungunya seroprevalence and fitted catalytic models to each survey to estimate location-specific FOI (ie, the rate at which susceptible individuals acquire chikungunya infection). We performed a meta-analysis to estimate the proportion of symptomatic patients with laboratory-confirmed chikungunya who had chronic chikungunya or were admitted to hospital following infection. We used a random-effects model to assess the relationship between chronic sequelae and follow-up length using linear regression. The systematic review protocol is registered online on PROSPERO, CRD42022363102.

    FINDINGS: We identified 60 studies with data on seroprevalence and chronic chikungunya symptoms done across 76 locations in 38 countries, and classified 17 (22%) of 76 locations as endemic settings and 59 (78%) as epidemic settings. The global long-term median annual FOI was 0·007 (95% uncertainty interval [UI] 0·003-0·010) and varied from 0·0001 (0·00004-0·0002) to 0·113 (0·07-0·20). The highest estimated median seroprevalence at age 10 years was in south Asia (8·0% [95% UI 6·5-9·6]), followed by Latin America and the Caribbean (7·8% [4·9-14·6]), whereas median seroprevalence was lowest in the Middle East (1·0% [0·5-1·9]). We estimated that 51% (95% CI 45-58) of people with laboratory-confirmed symptomatic chikungunya had chronic disability after infection and 4% (3-5) were admitted to hospital following infection.

    INTERPRETATION: We inferred subnational heterogeneity in long-term average annual FOI and transmission dynamics and identified both endemic and epidemic settings across different countries. Brazil, Ethiopia, Malaysia, and India included both endemic and epidemic settings. Long-term average annual FOI was higher in epidemic settings than endemic settings. However, long-term cumulative incidence of chikungunya can be similar between large outbreaks in epidemic settings with a high FOI and endemic settings with a relatively low FOI.

    FUNDING: International Vaccine Institute.

  9. Konukman F, Filiz B, Moghimehfar F, Maghanoy MA, Graber K, Richards KA, et al.
    Behav Sci (Basel), 2024 Apr 09;14(4).
    PMID: 38667101 DOI: 10.3390/bs14040305
    Guided by the theory of planned behavior, this study aimed to determine the influence of Physical Education (PE) teachers' attitudes, their perceived behavioral control, and the influence of subjective norms on their intention and constraints (intrapersonal, interpersonal, and structural) to offer a high-quality class based on best practices to deliver PE lessons online during the COVID-19 pandemic. This cross-sectional, multi-country survey study recruited PE teachers from five countries (China, Malaysia, the Philippines, Turkey, and the United States). A total of 928 online questionnaires were used in the analysis. In terms of the overall intention to teach online, our findings showed that American and Filipino teachers had higher levels of intention to continue teaching online. In contrast, Turkish, Malaysian, and Chinese teachers showed a lower interest. Moreover, Malaysian teachers had more intrapersonal constraints while the teachers in the other four countries were not as restrained intrapersonally. The results highlight the significant influence of perceived behavioral control and attitudes on PE teachers' intention to deliver online courses. Constraints to online teaching had a considerably large negative impact on attitudes, subjective norms, and perceived behavioral control. Based on the results, the proposed extension to the theory of planned behavior was an appropriate framework for understanding the behavioral intent of PE teachers.
  10. Mohd Mokhtar MA, Azhar ZI, Jamaluddin SF, Cone DC, Shin SD, Shaun GE, et al.
    Prehosp Emerg Care, 2023;27(7):875-885.
    PMID: 37459651 DOI: 10.1080/10903127.2023.2237107
    OBJECTIVE: Asia is experiencing a demographic shift toward an aging population at an unrivaled rate. This can influence the characteristics and outcomes of trauma. We aim to examine different characteristics of older adult trauma patients compared to younger adult trauma patients and describe factors that affect the outcomes in Asian countries.

    METHODS: This is a retrospective, international, multicenter study of trauma across participating centers in the Pan Asian Trauma Outcome Study (PATOS) registry, which included trauma cases aged ≥18 years, brought to the emergency department (ED) by emergency medical services (EMS) from October 2015 to November 2018. Data of older adults (≥65 years) and younger adults (<65 years) were analyzed and compared. The primary outcome measure was in-hospital mortality, and secondary outcomes were disability at discharge and hospital and intensive care unit (ICU) length of stays.

    RESULTS: Of 39,804 trauma patients, 10,770 (27.1%) were older adults. Trauma occurred more among older adult women (54.7% vs 33.2%, p 

  11. Bossart KN, Rockx B, Feldmann F, Brining D, Scott D, LaCasse R, et al.
    Sci Transl Med, 2012 Aug 08;4(146):146ra107.
    PMID: 22875827 DOI: 10.1126/scitranslmed.3004241
    In the 1990s, Hendra virus and Nipah virus (NiV), two closely related and previously unrecognized paramyxoviruses that cause severe disease and death in humans and a variety of animals, were discovered in Australia and Malaysia, respectively. Outbreaks of disease have occurred nearly every year since NiV was first discovered, with case fatality ranging from 10 to 100%. In the African green monkey (AGM), NiV causes a severe lethal respiratory and/or neurological disease that essentially mirrors fatal human disease. Thus, the AGM represents a reliable disease model for vaccine and therapeutic efficacy testing. We show that vaccination of AGMs with a recombinant subunit vaccine based on the henipavirus attachment G glycoprotein affords complete protection against subsequent NiV infection with no evidence of clinical disease, virus replication, or pathology observed in any challenged subjects. Success of the recombinant subunit vaccine in nonhuman primates provides crucial data in supporting its further preclinical development for potential human use.
  12. Xu WQ, Ren CQ, Zhang XY, Comes HP, Liu XH, Li YG, et al.
    Plant J, 2024 Feb 11.
    PMID: 38343032 DOI: 10.1111/tpj.16675
    Understanding the genetic basis of population divergence and adaptation is an important goal in population genetics and evolutionary biology. However, the relative roles of demographic history, gene flow, and/or selective regime in driving genomic divergence, climatic adaptation, and speciation in non-model tree species are not yet fully understood. To address this issue, we generated whole-genome resequencing data of Liquidambar formosana and L. acalycina, which are broadly sympatric but altitudinally segregated in the Tertiary relict forests of subtropical China. We integrated genomic and environmental data to investigate the demographic history, genomic divergence, and climatic adaptation of these two sister species. We inferred a scenario of allopatric species divergence during the late Miocene, followed by secondary contact during the Holocene. We identified multiple genomic islands of elevated divergence that mainly evolved through divergence hitchhiking and recombination rate variation, likely fostered by long-term refugial isolation and recent differential introgression in low-recombination genomic regions. We also found some candidate genes with divergent selection signatures potentially involved in climatic adaptation and reproductive isolation. Our results contribute to a better understanding of how late Tertiary/Quaternary climatic change influenced speciation, genomic divergence, climatic adaptation, and introgressive hybridization in East Asia's Tertiary relict flora. In addition, they should facilitate future evolutionary, conservation genomics, and molecular breeding studies in Liquidambar, a genus of important medicinal and ornamental values.
  13. Diez Benavente E, Florez de Sessions P, Moon RW, Holder AA, Blackman MJ, Roper C, et al.
    PLoS Genet, 2017 Sep;13(9):e1007008.
    PMID: 28922357 DOI: 10.1371/journal.pgen.1007008
    The macaque parasite Plasmodium knowlesi is a significant concern in Malaysia where cases of human infection are increasing. Parasites infecting humans originate from genetically distinct subpopulations associated with the long-tailed (Macaca fascicularis (Mf)) or pig-tailed macaques (Macaca nemestrina (Mn)). We used a new high-quality reference genome to re-evaluate previously described subpopulations among human and macaque isolates from Malaysian-Borneo and Peninsular-Malaysia. Nuclear genomes were dimorphic, as expected, but new evidence of chromosomal-segment exchanges between subpopulations was found. A large segment on chromosome 8 originating from the Mn subpopulation and containing genes encoding proteins expressed in mosquito-borne parasite stages, was found in Mf genotypes. By contrast, non-recombining organelle genomes partitioned into 3 deeply branched lineages, unlinked with nuclear genomic dimorphism. Subpopulations which diverged in isolation have re-connected, possibly due to deforestation and disruption of wild macaque habitats. The resulting genomic mosaics reveal traits selected by host-vector-parasite interactions in a setting of ecological transition.
  14. Palmer L, Maviglia F, Wickersham JA, Khati A, Kennedy O, Copenhaver NM, et al.
    J Psychoactive Drugs, 2023 Aug 23.
    PMID: 37610135 DOI: 10.1080/02791072.2023.2250342
    Chemsex is a form of sexualized drug use commonly practiced among MSM with psychoactive substances, such as methamphetamine. While this phenomenon has gained global attention in the past two decades, there is a dearth of empirical data to inform culturally competent interventions. The current work investigates the socio-contextual factors related to chemsex and harm reduction practices among Malaysian MSM. Between February and August 2022, we conducted six online focus group sessions with Malaysian MSM who had engaged in chemsex during the previous 6 months (N = 22). We queried participants about perceived benefits and harms, harm reduction practices, and informational needs. Most participants' first chemsex experience occurred in a casual sexual encounter, often facilitated by mobile technology. Participants reported engaging in harm reduction practices before (e.g. medication reminders), during (e.g. peer support), and after (e.g. rest) chemsex. These findings have implications for future efforts to develop and implement tailored interventions to address the specific and acute needs of Malaysian MSM engaging in chemsex.
  15. Chase JG, Preiser JC, Dickson JL, Pironet A, Chiew YS, Pretty CG, et al.
    Biomed Eng Online, 2018 Feb 20;17(1):24.
    PMID: 29463246 DOI: 10.1186/s12938-018-0455-y
    Critical care, like many healthcare areas, is under a dual assault from significantly increasing demographic and economic pressures. Intensive care unit (ICU) patients are highly variable in response to treatment, and increasingly aging populations mean ICUs are under increasing demand and their cohorts are increasingly ill. Equally, patient expectations are growing, while the economic ability to deliver care to all is declining. Better, more productive care is thus the big challenge. One means to that end is personalised care designed to manage the significant inter- and intra-patient variability that makes the ICU patient difficult. Thus, moving from current "one size fits all" protocolised care to adaptive, model-based "one method fits all" personalised care could deliver the required step change in the quality, and simultaneously the productivity and cost, of care. Computer models of human physiology are a unique tool to personalise care, as they can couple clinical data with mathematical methods to create subject-specific models and virtual patients to design new, personalised and more optimal protocols, as well as to guide care in real-time. They rely on identifying time varying patient-specific parameters in the model that capture inter- and intra-patient variability, the difference between patients and the evolution of patient condition. Properly validated, virtual patients represent the real patients, and can be used in silico to test different protocols or interventions, or in real-time to guide care. Hence, the underlying models and methods create the foundation for next generation care, as well as a tool for safely and rapidly developing personalised treatment protocols over large virtual cohorts using virtual trials. This review examines the models and methods used to create virtual patients. Specifically, it presents the models types and structures used and the data required. It then covers how to validate the resulting virtual patients and trials, and how these virtual trials can help design and optimise clinical trial. Links between these models and higher order, more complex physiome models are also discussed. In each section, it explores the progress reported up to date, especially on core ICU therapies in glycemic, circulatory and mechanical ventilation management, where high cost and frequency of occurrence provide a significant opportunity for model-based methods to have measurable clinical and economic impact. The outcomes are readily generalised to other areas of medical care.
  16. Lubis AR, Sumon MAA, Dinh-Hung N, Dhar AK, Delamare-Deboutteville J, Kim DH, et al.
    J Fish Dis, 2024 Mar 24.
    PMID: 38523339 DOI: 10.1111/jfd.13941
    The emergence of antibiotic-resistant bacteria (ARBs) and genes (ARGs) in aquaculture underscores the urgent need for alternative veterinary strategies to combat antimicrobial resistance (AMR). These measures are vital to reduce the likelihood of entering a post-antibiotic era. Identifying environmentally friendly biotechnological solutions to prevent and treat bacterial diseases is crucial for the sustainability of aquaculture and for minimizing the use of antimicrobials, especially antibiotics. The development of probiotics with quorum-quenching (QQ) capabilities presents a promising non-antibiotic strategy for sustainable aquaculture. Recent research has demonstrated the effectiveness of QQ probiotics (QQPs) against a range of significant fish pathogens in aquaculture. QQ disrupts microbial communication (quorum sensing, QS) by inhibiting the production, replication, and detection of signalling molecules, thereby reducing bacterial virulence factors. With their targeted anti-virulence approach, QQPs have substantial promise as a potential alternative to antibiotics. The application of QQPs in aquaculture, however, is still in its early stages and requires additional research. Key challenges include determining the optimal dosage and treatment regimens, understanding the long-term effects, and integrating QQPs with other disease control methods in diverse aquaculture systems. This review scrutinizes the current literature on antibiotic usage, AMR prevalence in aquaculture, QQ mechanisms and the application of QQPs as a sustainable alternative to antibiotics.
  17. Grigg MJ, William T, Menon J, Barber BE, Wilkes CS, Rajahram GS, et al.
    Clin Infect Dis, 2016 Jun 01;62(11):1403-1411.
    PMID: 27107287 DOI: 10.1093/cid/ciw121
    BACKGROUND: Chloroquine (CQ)-resistant Plasmodium vivax is increasingly reported throughout southeast Asia. The efficacy of CQ and alternative artemisinin combination therapies (ACTs) for vivax malaria in Malaysia is unknown.

    METHODS: A randomized, controlled trial of CQ vs artesunate-mefloquine (AS-MQ) for uncomplicated vivax malaria was conducted in 3 district hospitals in Sabah, Malaysia. Primaquine was administered on day 28. The primary outcome was the cumulative risk of treatment failure by day 28 by Kaplan-Meier analysis.

    RESULTS: From 2012 to 2014, 103 adults and children were enrolled. Treatment failure by day 28 was 61.1% (95% confidence interval [CI], 46.8-75.6) after CQ and 0% (95% CI, 0-.08) following AS-MQ (P < .001), of which 8.2% (95% CI, 2.5-9.6) were early treatment failures. All patients with treatment failure had therapeutic plasma CQ concentrations at day 7. Compared with CQ, AS-MQ was associated with faster parasite clearance (normalized clearance slope, 0.311 vs 0.127; P < .001) and fever clearance (mean, 19.0 vs 37.7 hours; P =001) and with lower risk of anemia at day 28 (odds ratio = 3.7; 95% CI, 1.5-9.3; P =005). Gametocytes were present at day 28 in 23.8% (10/42) of patients following CQ vs none with AS-MQ (P < .001). AS-MQ resulted in lower bed occupancy: 4037 vs 6510 days/1000 patients (incidence rate ratio 0.62; 95% CI, .60-.65; P < .001). One patient developed severe anemia not regarded as related to their AS-MQ treatment.

    CONCLUSIONS: High-grade CQ-resistant P. vivax is prevalent in eastern Malaysia. AS-MQ is an efficacious ACT for all malaria species. Wider CQ-efficacy surveillance is needed in vivax-endemic regions with earlier replacement with ACT when treatment failure is detected.Clinical Trials Registration NCT01708876.

  18. Etti IC, Abdullah R, Kadir A, Hashim NM, Yeap SK, Imam MU, et al.
    PLoS One, 2017;12(8):e0182357.
    PMID: 28771532 DOI: 10.1371/journal.pone.0182357
    Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer.
  19. Ferro EG, Culbert GJ, Wickersham JA, Marcus R, Steffen AD, Pauls HA, et al.
    Open Forum Infect Dis, 2017;4(1):ofw219.
    PMID: 28480230 DOI: 10.1093/ofid/ofw219
    BACKGROUND: Antiretroviral therapy (ART) is recommended for all people living with human immunodeficiency virus (HIV), yet physician attitudes and prescribing behaviors toward members of key risk populations may limit ART access and undermine treatment as prevention strategies.

    METHODS: Physicians in Malaysia (N = 214) who prescribe antiretroviral therapy (ART) responded in an Internet-based survey to hypothetical clinical scenarios of HIV patients, varying by key risk population and CD4+ T-cell count, on whether they would initiate or defer ART compared with a control patient with sexually acquired HIV.

    RESULTS: The proportion of physicians who would defer ART in patients with advanced HIV (CD4 = 17 cells/μL) was significantly higher (P < .0001) for 4 key populations, including people who inject drugs ([PWID] 45.3%) or consume alcohol (42.1%), released prisoners (35.0%), and those lacking social support (26.6%), compared with a control patient (4.2%). People who inject drugs with advanced HIV (CD4 = 17 cells/μL) were 19-fold (adjusted odds ratio [AOR] = 18.9; 95% confidence interval [CI], 9.8-36.5) more likely to have ART deferred compared with the control. This effect was partially mitigated for PWID receiving methadone (AOR = 2.9; 95% CI, 1.5-5.7). At the highest CD4+ T-cell count (CD4 = 470 cells/μL), sex workers (AOR = 0.55; 95% CI, .44-.70) and patients with an HIV-uninfected sexual partner (AOR = 0.43; 95% CI, .34-.57) were significantly less likely to have ART deferred.

    CONCLUSIONS: Physicians who prescribe antiretroviral therapy in Malaysia may defer ART in some key populations including PWID and released prisoners, regardless of CD4+ T-cell count, which may help to explain very low rates of ART coverage among PWID in Malaysia. Reducing HIV incidence and mortality in Malaysia, where HIV is concentrated in PWID and other key populations, requires clinician-level interventions and monitoring physician adherence to international evidence-based treatment guidelines.

  20. Zhou K, He S, Zhou Y, Popeska B, Kuan G, Chen L, et al.
    PMID: 33401384 DOI: 10.3390/ijerph18010272
    This study aimed to examine the effects of three-months of classroom-based Brain Breaks Physical Activity Solution (Brain Breaks®) on attitudes toward physical activity levels of primary school children in Henan Province, China. The participants were 704 children enrolled in grades 3-5 who were randomly assigned to either an experimental or a control group. The experimental group participated in Brain Breaks® video intervention for 3-5 min daily, at low-to-moderate intensity for three consecutive months. The control group resumed their normal routine. The children's attitudes in both groups towards physical activity (PA) were evaluated using the self-reported Attitudes toward Physical Activity Scale (APAS), before and after the intervention. The effects of the intervention on APAS scores were analyzed using mixed model analysis of variance with Time as within-subject, and Group as between-subject factors. The analysis revealed evidence in support of the positive effect of classroom video interventions such as Brain Break on children's attitudes toward importance, fun, and trying to do their personal best in physical activity. Also revealed was the important role the teacher plays in this process.
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