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- PublicationMethamphetamine abuse disturbs the dopaminergic system to impair hippocampal-based learning and memory: An overview of animal and human investigations(2021-12-01) Mayuri Shukla; Bruno Vincent; Institute of Molecular Biosciences, Mahidol University; CNRS Centre National de la Recherche ScientifiqueDiverse intellectual functions including memory are some important aspects of cognition. Dopamine is a neurotransmitter of the catecholamine family, which contributes to the experience of pleasure and/or emotional states but also plays crucial roles in learning and memory. Methamphetamine is an illegal drug, the abuse of which leads to long lasting pathological manifestations in the brain. Chronic methamphetamine-induced neurotoxicity results in an alteration of various parts of the memory systems by affecting learning processes, an effect attributed to the structural similarities of this drug with dopamine. An evolving field of research established how cognitive deficits in abusers arise and how they could possibly trigger neurodegenerative disorders. Thus, the drugs-induced tenacious neurophysiological changes of the dopamine system trigger cognitive deficits, thereby affirming the influence of this addictive drug on learning, memory and executive function in human abusers. Here we present an overview of the effects of methamphetamine abuse on cognitive functions, dopaminergic transmission and hippocampal integrity as they have been validated in animals and in humans during the past 20 years.
- PublicationThe impact of pulmonary tuberculosis morbidity on household production, consumption, investment and community participation in Prey Veng province, Cambodia(2021-05-01) Ny Net; Sukhontha Kongsin; Sukhum Jiamton; Siriraj Hospital; Mahidol UniversityTuberculosis (TB) is a major public health problem in Cambodia where its impact on household production is little known. This study aimed to assess the impact of pulmonary TB morbidity on the production, financial resources and rice seeds used for investment, satisfaction with food and non-food consumption, and participation in a community of households and to inform policy makers of better strategies to mitigate this impact. During October-November 2014, 186/186 TB /chronic disease cases were randomly recruited into the study. A TB case was defined as a household that had one patient diagnosed with pulmonary TB from one of the 24 health centers in Prey Veng Province, Cambodia. A chronic disease case was defined as a household that had a patient diagnosed with other chronic illnesses and lived in the same area of TB cases. Head of household completed the study questionnaire on socio-demographic and economic characteristics, satisfaction with food and non-food consumption, financial resources and rice seeds used for investment, and participation in the community. Mean (SD) ages of patients with TB and chronic disease were 47.8(12.9) and 51.7(9.6) years, respectively. Annual household expenditure of TB cases vs. chronic disease cases was US$2,339.50 vs. US$2,869.30, p=0.008. Reduction in household consumption, investment in assets, child education and community participation was reported for TB and chronic disease cases. Reduction of non-agricultural household production of TB cases was significantly more than that of chronic disease cases (US$49.00 vs. US$ 7.30), p=0.006. Annual household expenditure and income of TB cases were lower than that of chronic disease cases. This suggests that free health care for TB might help to reduce the household expenditure of TB cases; however, pulmonary TB morbidity still caused greater loss of household production, in particular, income earned from non-agricultural production than other chronic diseases did. Further studies are needed to determine the best way to assist TB patients’ house production in rural areas during the treatment in a sustainable manner.
- PublicationA Deliverable Delay Management of Software Development in Railway Project using an OKR-Based Scrum Process(2021-01-16) Chutiwan Sowkasem; Phumin Kirawanich; Mahidol UniversityDelay, one of the challenging topics several corporates have to face in running the complex project, such as those implementing a railway system. This article mainly focuses on the development of the Scrum framework with the Objective and Key Results (OKRs) scheme that can assess the performance information at both team and individual levels. The technique manipulates the goals from the team to individual levels to be measurable while aligning them in the same global direction. Here, the case study of implementing the OKRs-based Scrum framework in the process occupied by the Computer-Based Interlocking adaptation (CBI) team is reported. The process was evaluated continuously during the project life cycle of the railway software development. From the total of 22 tasks, only 27.20% of which were delay from the target deliverable date while 72.80% of which were completed prior to or on the target dates. Therefore, the correct implementation of measurable OKRs has shown in providing a collaboration visibility through tracking progress activities with clear priorities of tasks, thus providing the improved time deliverable performance.
- PublicationArterolane–piperaquine–mefloquine versus arterolane–piperaquine and artemether–lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial(2021-10-01) Mainga Hamaluba; Rob W. van der Pluijm; Joseph Weya; Patricia Njuguna; Mwanajuma Ngama; Peter Kalume; Gabriel Mwambingu; Caroline Ngetsa; Juliana Wambua; Mwanamvua Boga; Neema Mturi; Altaf A. Lal; Arshad Khuroo; Walter R.J. Taylor; Sónia Gonçalves; Olivo Miotto; Mehul Dhorda; Brian Mutinda; Mavuto Mukaka; Naomi Waithira; Richard M. Hoglund; Mallika Imwong; Joel Tarning; Nicholas P.J. Day; Nicholas J. White; Philip Bejon; Arjen M. Dondorp; Faculty of Tropical Medicine, Mahidol University; Wellcome Trust Research Laboratories Nairobi; Nuffield Department of Medicine; Wellcome Sanger Institute; Sun Pharmaceutical Industries Ltd.; Worldwide Antimalarial Resistance NetworkBackground: Triple antimalarial combination therapies combine potent and rapidly cleared artemisinins or related synthetic ozonides, such as arterolane, with two, more slowly eliminated partner drugs to reduce the risk of resistance. We aimed to assess the safety, tolerability, and efficacy of arterolane–piperaquine–mefloquine versus arterolane–piperaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Kenyan children. Methods: In this single-centre, open-label, randomised, non-inferiority trial done in Kilifi County Hospital, Kilifi, coastal Kenya, children with uncomplicated Plasmodium falciparum malaria were recruited. Eligible patients were aged 2–12 years and had an asexual parasitaemia of 5000–250 000 parasites per μL. The exclusion criteria included the presence of an acute illness other than malaria, the inability to tolerate oral medications, treatment with an artemisinin derivative in the previous 7 days, a known hypersensitivity or contraindication to any of the study drugs, and a QT interval corrected for heart rate (QTc interval) longer than 450 ms. Patients were randomly assigned (1:1:1), by use of blocks of six, nine, and 12, and opaque, sealed, and sequentially numbered envelopes, to receive either arterolane–piperaquine, arterolane–piperaquine–mefloquine, or artemether–lumefantrine. Laboratory staff, but not the patients, the patients' parents or caregivers, clinical or medical officers, nurses, or trial statistician, were masked to the intervention groups. For 3 days, oral artemether–lumefantrine was administered twice daily (target dose 5–24 mg/kg of bodyweight of artemether and 29–144 mg/kg of bodyweight of lumefantrine), and oral arterolane–piperaquine (arterolane dose 4 mg/kg of bodyweight; piperaquine dose 20 mg/kg of bodyweight) and oral arterolane–piperaquine–mefloquine (mefloquine dose 8 mg/kg of bodyweight) were administered once daily. All patients received 0·25 mg/kg of bodyweight of oral primaquine at hour 24. All patients were admitted to Kilifi County Hospital for at least 3 consecutive days and followed up at day 7 and, thereafter, weekly for up to 42 days. The primary endpoint was 42-day PCR-corrected efficacy, defined as the absence of treatment failure in the first 42 days post-treatment, of arterolane–piperaquine–mefloquine versus artemether–lumefantrine, and, along with safety, was analysed in the intention-to-treat population, which comprised all patients who received at least one dose of a study drug. The 42-day PCR-corrected efficacy of arterolane–piperaquine–mefloquine versus arterolane–piperaquine was an important secondary endpoint and was also analysed in the intention-to-treat population. The non-inferiority margin for the risk difference between treatments was −7%. The study is registered in ClinicalTrials.gov, NCT03452475, and is completed. Findings: Between March 7, 2018, and May 2, 2019, 533 children with P falciparum were screened, of whom 217 were randomly assigned to receive either arterolane–piperaquine (n=73), arterolane–piperaquine–mefloquine (n=72), or artemether–lumefantrine (n=72) and comprised the intention-to-treat population. The 42-day PCR-corrected efficacy after treatment with arterolane–piperaquine–mefloquine (100%, 95% CI 95–100; 72/72) was non-inferior to that after treatment with artemether–lumefantrine (96%, 95% CI 88–99; 69/72; risk difference 4%, 95% CI 0–9; p=0·25). The 42-day PCR-corrected efficacy of arterolane–piperaquine–mefloquine was non-inferior to that of arterolane–piperaquine (100%, 95% CI 95–100; 73/73; risk difference 0%). Vomiting rates in the first hour post-drug administration were significantly higher in patients treated with arterolane–piperaquine (5%, 95% CI 2–9; ten of 203 drug administrations; p=0·0013) or arterolane–piperaquine–mefloquine (5%, 3–9; 11 of 209 drug administrations; p=0·0006) than in patients treated with artemether–lumefantrine (1%, 0–2; three of 415 drug administrations). Upper respiratory tract complaints (n=26 for artemether–lumefantrine; n=19 for arterolane–piperaquine–mefloquine; n=23 for arterolane–piperaquine), headache (n=13; n=4; n=5), and abdominal pain (n=7; n=5; n=5) were the most frequently reported adverse events. There were no deaths. Interpretation: This study shows that arterolane–piperaquine–mefloquine is an efficacious and safe treatment for uncomplicated falciparum malaria in children and could potentially be used to prevent or delay the emergence of antimalarial resistance. Funding: UK Department for International Development, The Wellcome Trust, The Bill & Melinda Gates Foundation, Sun Pharmaceutical Industries
- PublicationInteraction of Cigarette Smoking and Polygenic Risk Score on Reduced Lung Function(2021-12-16) Woori Kim; Matthew Moll; Dandi Qiao; Brian D. Hobbs; Nick Shrine; Phuwanat Sakornsakolpat; Martin D. Tobin; Frank Dudbridge; Louise V. Wain; Christine Ladd-Acosta; Nilanjan Chatterjee; Edwin K. Silverman; Michael H. Cho; Terri H. Beaty; Siriraj Hospital; University of Leicester; Massachusetts Institute of Technology; Brigham and Women's Hospital; National Cancer Institute (NCI); Glenfield Hospital; Johns Hopkins Bloomberg School of Public Health; Harvard Medical School; Johns Hopkins School of MedicineImportance: The risk of airflow limitation and chronic obstructive pulmonary disease (COPD) is influenced by combinations of cigarette smoking and genetic susceptibility, yet it remains unclear whether gene-by-smoking interactions are associated with quantitative measures of lung function. Objective: To assess the interaction of cigarette smoking and polygenic risk score in association with reduced lung function. Design, Setting, and Participants: This UK Biobank cohort study included UK citizens of European ancestry aged 40 to 69 years with genetic and spirometry data passing quality control metrics. Data was analyzed from July 2020 to March 2021. Exposures: PRS of combined forced expiratory volume in 1 second (FEV1) and percent of forced vital capacity exhaled in the first second (FEV1/FVC), self-reported pack-years of smoking, ever- vs never-smoking status, and current- vs former- or never-smoking status. Main Outcomes and Measures: FEV1/FVC was the primary outcome. Models were used to test for interactions with models, including the main effects of PRS, different smoking variables, and their cross-product terms. The association between pack-years of smoking and FEV1/FVC were compared for those in the highest vs lowest decile of estimated genetic risk for low lung function. Results: We included 319730 individuals, of whom 24915 (8%) had moderate-to-severe COPD cases, and 44.4% were men. Participants had a mean (SD) age 56.5 of (8.02) years. The PRS and pack-years were significantly associated with lower FEV1/FVC (PRS: β, -0.03; 95% CI, -0.031 to -0.03; pack-years: β, -0.0064; 95% CI, -0.0064 to -0.0063) and the interaction term (β, -0.0028; 95% CI, -0.0029 to -0.0026). A stepwise increment in estimated effect sizes for these interaction terms was observed per 10 pack-years of smoking exposure. The interaction of PRS with 11 to 20, 31 to 40, and more than 50 pack-years categories were β (interaction) -0.0038 (95% CI, -0.0046 to -0.0031); -0.013 (95% CI, -0.014 to -0.012); and -0.017 (95% CI, -0.019 to -0.016), respectively. There was evidence of significant interaction between PRS with ever- or never- smoking status (β, interaction; -0.0064; 95% CI, -0.0068 to -0.0060) and current or not-current smoking (β, interaction; -0.0091; 95% CI, -0.0097 to -0.0084). For any given level of pack-years of smoking exposure, FEV1/FVC was significantly lower for individuals in the tenth decile (ie, highest risk) than the first decile (ie, lowest risk) of genetic risk. For every 20 pack-years of smoking, those in the tenth decile compared with the first decile of genetic risk showed nearly a 2-fold reduction in FEV1/FVC. Conclusions and Relevance: COPD is characterized by diminished lung function, and our analyses suggest there is substantial interaction between genome-wide PRS and smoking exposures. While smoking was associated with decreased lung function across all genetic risk categories, the associations were strongest in individuals with higher estimated genetic risk..
- PublicationA comparison of success rate in off-pump coronary artery bypass grafting surgery among patients with varying preoperative left ventricular ejection fractions: Retrospective observational study(2021-01-01) Amorn Vijitpavan; Srisuda Laithongkom; Naruemol Prachanpanich; Ramathibodi HospitalBackground: Off-pump coronary artery bypass grafting (OPCAB) is an alternative to coronary artery revascularization and avoids the complications of cardiopulmonary bypass (CPB). The procedure's success, however, depends on intraoperative hemodynamic stability. Preoperative cardiac function can predict the tolerance to compromised hemodynamics during cardiac surgery. Inability to manage hypotension and low cardiac output while manipulating the heart is the most frequent cause of intraoperative conversion to CPB. Objective: The authors investigated the effects of the preoperative left ventricular ejection fraction (LVEF) on the success of OPCAB surgery and the relation of intraoperative factors to the success of OPCAB surgery. Material and Methods: Medical records of 284 patients who underwent OPCAB surgery in Ramathibodi Hospital between January 2015 and December 2017 were retrospectively reviewed. Preoperatively, the patients were classified into groups 1 to 4 based on LVEFs of 50% to 70%, 40% to 49%, 30% to 39%, and <30%, respectively. Preoperative characteristics were collected. Intraoperative success of OPCAB surgery, application of inotropes, vasopressor, fluid, and intra-aortic balloon pump (IABP), and post-operative outcomes were analyzed and compared among the four LVEF groups. Results: No significant differences in success of OPCAB surgery emerged among the four groups (p=0.430). Intraoperative requirements of IABP were significantly higher for LVEF <30% patients (p=0.001). In addition, the time to extubation was significantly delayed (p=0.001) and the LVEF <30% patients stayed longer in intensive care unit (ICU) (p=0.002) when compared with the good LVEF patients. There were no significant differences in the operative time, amount of intravenous fluid, blood transfusion requirement, or blood loss among the groups. There were no significant differences in major postoperative morbidities. Conclusion: OPCAB surgery can be performed successfully in patients with severe cardiac dysfunction (LVEF <30%) without significant differences from LVEF ≥30% patients, although the need for an intraoperative IABP device and inotropic drugs for hemodynamic support were greater and the extubation times and ICU stays were longer.
- PublicationAutoantibody profiles and clinical association in Thai patients with autoimmune retinopathy(2021-12-01) Aulia Rahmi Pawestri; Niracha Arjkongharn; Ragkit Suvannaboon; Aekkachai Tuekprakhon; Vichien Srimuninnimit; Suthipol Udompunthurak; La ongsri Atchaneeyasakul; Ajchara Koolvisoot; Adisak Trinavarat; Siriraj Hospital; Brawijaya University; Nuffield Department of MedicineAutoimmune retinopathy (AIR) is a rare immune-mediated inflammation of the retina. The autoantibodies against retinal proteins and glycolytic enzymes were reported to be involved in the pathogenesis. This retrospective cohort study assessed the antiretinal autoantibody profiles and their association with clinical outcomes of AIR patients in Thailand. We included 44 patients, 75% were females, with the overall median age of onset of 48 (17–74, IQR 40–55.5) years. Common clinical presentations were nyctalopia (65.9%), blurred vision (52.3%), constricted visual field (43.2%), and nonrecordable electroretinography (65.9%). Underlying malignancy and autoimmune diseases were found in 2 and 12 female patients, respectively. We found 41 autoantibodies, with anti-α-enolase (65.9%) showing the highest prevalence, followed by anti-CAII (43.2%), anti-aldolase (40.9%), and anti-GAPDH (36.4%). Anti-aldolase was associated with male gender (P = 0.012, OR 7.11, 95% CI 1.54–32.91). Anti-CAII showed significant association with age of onset (P = 0.025, 95% CI − 17.28 to − 1.24), while anti-α-enolase (P = 0.002, OR 4.37, 95% CI 1.83–10.37) and anti-GAPDH (P = 0.001, OR 1.87, 95% CI 1.32–2.64) were significantly associated with nonrecordable electroretinography. Association between the antibody profiles and clinical outcomes may be used to direct and adjust the treatment plans and provide insights in the pathogenesis of AIR.
- PublicationA Novel Methodology Using Dexamethasone to Induce Neuronal Differentiation in the CNS-Derived Catecholaminergic CAD Cells(2021-01-01) Ekkaphot Khongkla; Kwanchanok Uppakara; Nittaya Boonmuen; Kanit Bhukhai; Witchuda Seangsawang; Mahidol UniversityThe Cath.a-differentiated (CAD) cell line is a central nervous system-derived catecholaminergic cell line originating from tyrosine hydroxylase (TH)-producing neurons located around the locus coeruleus area of the mouse brain. CAD cells have been used as an in vitro model for cellular and molecular studies due to their ability to differentiate under serum-free media conditions. However, the lack of serum-derived survival factors, limits the longevity for differentiated CAD cells to be maintained in healthy conditions; thereby, limiting their use in long-term culture studies. Here, we present a novel differentiation method that utilizes dexamethasone (Dex), a synthetic glucocorticoid receptor agonist. Specifically, we discovered that the addition of 100 µM of Dex into the 1% fetal bovine serum (FBS)-supplemented media effectively induced neuronal differentiation of CAD cells, as characterized by neurite formation and elongation. Dex-differentiated CAD cells exited the cell cycle, stopped proliferating, extended the neurites, and expressed neuronal markers. These effects were dependent on the glucocorticoid receptors (GR) as they were abolished by GR knockdown. Importantly, Dex-differentiated CAD cells showed longer survival duration than serum-free differentiated CAD cells. In addition, RNA-sequencing and qPCR data demonstrate that several genes involved in proliferation, neuronal differentiation, and survival pathways were differentially expressed in the Dex-differentiated cells. This is the first study to reveal Dex as a novel differentiation methodology used to generate postmitotic neuronal CAD cells, which may be utilized as an in vitro neuronal model for cellular and molecular neurobiology research.
- PublicationEffects of natural sugar on acidogenic potential, biofilm biomass, and antiseptic resistance of oral streptococci(2021-01-01) Pimpikar Kanchanadumkerng; Karn Wongsariya; King Mongkut's Institute of Technology Ladkrabang; Mahidol UniversityNatural sugar is deliberated as ordinary, non-chemical, and healthy alternatives. However, a diet rich in sugar is well documented as a causative agent for dental caries. The purpose of this study was to investigate the effects of natural sugars, including raw cane, palmyra palm and coconut sugar on the acidogenic profiles, biofilm formation and antiseptic treatment efficacy compared with refined sugar. The study was based on single-species and dual-species of Streptococcus mutans ATCC 25175 and Streptococcus sobrinus ATCC 33402. Our results showed that sucrose was a major component of all samples, with percentages of relative content higher than 89.0. Palmyra sugar gave the least pH change at 180 min of 4.84-4.93, which indicated it was the least acidogenic. Coconut sugar formed the lowest level of biofilm biomass compared to refined sugar (p < 0.05) and other samples. Antiseptic treatment was performed to study the level of percent eradication of bacterial plaque using MTT assay to determine cell viability under biofilm in each sugar medium. Biofilm derived from coconut sugar had a susceptibility to antiseptic treatment with 56.2-61.99% eradication which was higher than the biofilm from palmyra and raw cane sugar. As a result, this study points out the effects of various natural sugars (especially different sources of plant material) on cariogenic potential. However, further experiment should be done to confirm the results in vivo and further study the cariogenic effects of diet supplementation of these fermentable sugars.
- PublicationImpact of sex on use of low tidal volume ventilation in invasively ventilated ICU patients-A mediation analysis using two observational cohorts(2021-07-01) Pien Swart; Rodrigo Octavio Deliberato; Alistair E.W. Johnson; Tom J. Pollard; Lucas Bulgarelli; Paolo Pelosi; Marcelo Gama de Abreu; Marcus J. Schultz; Ary Serpa Neto; Universitätsklinikum Carl Gustav Carus Dresden; IRCCS San Martino Polyclinic Hospital; Università degli Studi di Genova; Massachusetts Institute of Technology; Monash University; Hospital Israelita Albert Einstein; Mahidol University; Nuffield Department of Medicine; Universidade de São Paulo; Amsterdam UMC; Outcomes Research ConsortiumBackground Studies in patients receiving invasive ventilation show important differences in use of low tidal volume (VT) ventilation (LTVV) between females and males. The aims of this study were to describe temporal changes in VT and to determine what factors drive the sex difference in use of LTVV. Methods and findings This is a posthoc analysis of 2 large longitudinal projects in 59 ICUs in the United States, the 'Medical information Mart for Intensive Care III' (MIMIC III) and the 'eICU Collaborative Research DataBase'. The proportion of patients under LTVV (median VT < 8 ml/kg PBW), was the primary outcome. Mediation analysis, a method to dissect total effect into direct and indirect effects, was used to understand which factors drive the sex difference. We included 3614 (44%) females and 4593 (56%) males. Median VT declined over the years, but with a persistent difference between females (from median 10.2 (9.1 to 11.4) to 8.2 (7.5 to 9.1) ml/kg PBW) vs. males (from median 9.2 [IQR 8.2 to 10.1] to 7.3 [IQR 6.6 to 8.0] ml/kg PBW) (P < .001). In females versus males, use of LTVV increased from 5 to 50% versus from 12 to 78% (difference, -27% [-29% to -25%]; P < .001). The sex difference was mainly driven by patients' body height and actual body weight (adjusted average causal mediation effect, -30% [-33% to -27%]; P < .001, and 4 [3% to 4%]; P < .001). Conclusions While LTVV is increasingly used in females and males, females continue to receive LTVV less often than males. The sex difference is mainly driven by patients' body height and actual body weight, and not necessarily by sex. Use of LTVV in females could improve by paying more attention to a correct calculation of VT, i.e., using the correct body height.