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PLOS ONE

Background Acute diarrhea is a common health problem in children, especially those under five yea... more Background Acute diarrhea is a common health problem in children, especially those under five years of age (U5). The mortality rate due to acute diarrhea among U5 children accounted for 11% in Lao PDR in 2016. No study has been done to investigate the etiologic pathogens of acute diarrhea and the risk factors associated with dehydration status among U5 children hospitalized with acute diarrhea in this region. Objectives The study aimed to evaluate the clinical characteristics, etiological agents and associated factors of dehydration status of acute diarrhea among hospitalized U5 children in Savannakhet Province, Lao PDR. Methods This retrospective study reviewed paper-based medical records with available stool examination results of 33 U5 children hospitalized with acute diarrhea in Savannakhet Provincial Hospital, Lao PDR between Jan. 2018 and Dec. 2019. Descriptive statistics were used to describe clinical characteristics and etiologic agents of acute diarrhea of the children. Non...

International Journal of Environmental Research and Public Health

Introduction: The Non-Invasive Prenatal Testing (NIPT) guideline was issued and applied in 2013 b... more Introduction: The Non-Invasive Prenatal Testing (NIPT) guideline was issued and applied in 2013 by the Japanese Medical Association. Since being issued, the NIPT practice in Japan still has some problems related to indication, access, cost coverage and uniformity. Therefore, our study aimed to identify the Japanese challenges of adopting NIPT into prenatal diagnosis by comparing the system and process with other countries. Method: The United Kingdom, Germany, Italy, Sweden, and Taiwan were purposefully selected for comparison. All the countries, including Japan, introduced NIPT. The literature and information searches were conducted using PubMed, SCOPUS, Google Scholar, CiNii and Google searching engine. Results: The process of NIPT in Japan was very different from the other countries. Japan is the only country that indicated NIPT for only pregnant women over 35 years old in certificated facilities and did not have a policy regarding providing information on prenatal screening and N...

PLOS ONE

Background Caesarean section and associated factors require detailed investigation globally. This... more Background Caesarean section and associated factors require detailed investigation globally. This study aims to determine the rate and associated factors of caesarean deliveries in urban areas of Vietnam. Methods A cross-sectional study using questionnaire answered by women who had infants aged under 30 months was conducted from March to May 2021. Data were collected in 18 commune health centres in two cities during the day of routine immunization. Multivariable logistic regression was performed to assess factors associated with caesarean section. Results The overall caesarean section rate was 49.6%. The caesarean section rate in private hospitals (57.8%) were significantly higher than in public hospitals (49.1%). Caesarean section rate in first-time mothers (47.1%) were as high as this rate among mothers who had given birth before (50.6%). Factors associated with higher rate of caesarean section include increasing in women’s age, pre-pregnancy body mass index, gestational weight ga...

BMC Medical Education

Background Students face hardships in determining what are the main points that need more studyin... more Background Students face hardships in determining what are the main points that need more studying in every subject. Checklists are one of the ways that can help students identify the most important pieces of information. Accordingly, in this study, we aimed at examining the impact of using educational checklists on the learning process of postgraduate students at Nagasaki University, Japan. Methods Thirty-one Master's students, who finished a “how to write a research protocol” course were recruited by sending them an invitation email that had an attached link to a previously developed and tested questionnaire on the SurveyMonkey® platform. After signing the electronic informed consent, twenty-two participants (response rate = 71%) finished the survey. The data was analyzed using Microsoft Excel and expressed in the form of frequencies and percentages. Results More than half of the students declared that they know the checklist will be used in the course that we investigated. On...

BMC Pediatrics

Background Early essential newborn care has been implemented in countries regardless high or low ... more Background Early essential newborn care has been implemented in countries regardless high or low neonatal mortality. This study aims to investigate the current practice of skin-to-skin contact (SSC) and its effect on exclusive breastfeeding during the hospital stay. Methods This is a cross-sectional study of 1812 Vietnamese mothers in multicenter. A questionnaire answered by the mothers was used to assess the duration of both SSC and breastfeeding practices. Multivariable logistic regression was used to identify a dose–response relationship between early SSC and prevalence of exclusive breastfeeding in hospital. Results There were 88.7% of mothers experiencing SSC with their infants right after birth and the highest prevalence of SSC was found in district hospitals. Among those experiencing SSC, 18.8% of the infants received more than 90 min of SSC and completed the first breastfeeding during SSC time. Prevalence of exclusive breastfeeding during maternity hospital stay was 46.7%. W...

The Lancet Regional Health - Southeast Asia

Background Tackling the spread of COVID-19 remains a crucial part of ending the pandemic. Its hig... more Background Tackling the spread of COVID-19 remains a crucial part of ending the pandemic. Its highly contagious nature and constant evolution coupled with a relative lack of immunity make the virus difficult to control. For this, various strategies have been proposed and adopted including limiting contact, social isolation, vaccination, contact tracing, etc. However, given the heterogeneity in the enforcement of these strategies and constant fluctuations in the strictness levels of these strategies, it becomes challenging to assess the true impact of these strategies in controlling the spread of COVID-19.

Background Although protocol registration of systematic reviews/meta-analysis (SR/MA) is still no... more Background Although protocol registration of systematic reviews/meta-analysis (SR/MA) is still not mandatory, authors are strongly suggested to publish their SR/MA protocols prior to submitting their manuscripts for publication as recommended by the Cochrane guidelines for conducting SR/MAs. We aimed to assess awareness, obstacles, and opinions of SR/MA authors about the protocol registration process.Methods A cross-sectional survey study included all authors who published SR/MAs during the period from 2010 to 2016 were contacted for participation in our survey study. They were identified through the literature search of SR/MAs in Scopus database. Upon receiving their approval to join our study, an online questionnaire was sent via e-mail to each participant.Results A total of 270 authors' responses were complete and were included in the final analysis. Our results showed that PROSPERO was the most commonly used database for protocol registration (71.3%). The registration-to-acc...

Frontiers in Public Health, 2021

Background: The outbreak of Coronavirus disease (COVID-19) caused by a novel coronavirus (named S... more Background: The outbreak of Coronavirus disease (COVID-19) caused by a novel coronavirus (named SARS-CoV-2) has gained attention globally and has been recognized as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) due to the rapidly increasing number of deaths and confirmed cases. Health care workers (HCWs) are vulnerable to this crisis as they are the first frontline to receive and manage COVID-19 patients. In this multicenter multinational survey, we aim to assess the level of awareness and preparedness of hospital staff regarding COVID-19 all over the world.Methods: From February to March 2020, the web-based or paper-based survey to gather information about the hospital staff's awareness and preparedness in the participants' countries will be carried out using a structured questionnaire based on the United States Centers for Disease Control and Prevention (CDC) checklist and delivered to participants by the local collaborat...

Patient Preference and Adherence, 2020

Background: While patients' satisfaction is a barometer for healthcare quality, Myanmar did not d... more Background: While patients' satisfaction is a barometer for healthcare quality, Myanmar did not do enough to assess the antenatal care (ANC) satisfaction. Objective: In this study, we aim to assess the satisfaction level of pregnant women with ANC services provided by a public hospital in Myanmar. Methods: A cross-sectional study was conducted with 125 women in the quantitative and 27 in the qualitative study at South Okkalapa Women and Children Hospital in Myanmar. Satisfaction was measured by using a five-point Likert scale with 25-item services. Statistical software SPSS version 16 was used for quantitative data analysis. Qualitative data were manually analyzed by thematic analysis. Results: The proportion of pregnant women who were satisfied with healthcare services ranged from 18% to 35%. Provider's service yielded satisfaction ranging between 25% and 35%; meanwhile, facilities in the waiting area had the lowest mean score (2.78) for satisfaction. Laboratory service and waiting time at the antenatal clinic were major sources of dissatisfaction. Overall, 48% of the pregnant women were in high satisfaction with ANC services. Out of 25 items, cleanliness of ANC clinic, the process of ANC procedure, drug supply by the hospital, ventilation, and lighting in the waiting area, waiting time to see doctors, and working hours (availability of services) showed significant association with overall satisfaction. Conclusion: Nearly half of the pregnant women in the study were very satisfied with the total healthcare services they received. Facilities in the waiting area, laboratory service, and waiting time to see doctors were dissatisfied services and need to be upgraded.

Background: Meta-analyses are on top of the evidence-based medicine pyramid, yet many of them are... more Background: Meta-analyses are on top of the evidence-based medicine pyramid, yet many of them are not completed after they are begun. Many factors impacting the publication of meta-analysis works have been discussed, and their association with publication likelihood has been investigated. These factors include the type of systematic review, journal metrics, h-index of the corresponding author, country of the corresponding author, funding sources, and duration of publication. In our current review, we aim to investigate these various factors and their impact on the likelihood of publication. A comprehensive review of 397 registered protocols retrieved from five databases was performed to investigate the different factors that might affect the likelihood of publication. These factors include the type of systematic review, journal metrics, h-index of the corresponding author, country of the corresponding author, funding sources, and duration of publication.Results: We found that corres...

Introduction: Transplant patients are a vulnerable group due to their immunocompromised status. U... more Introduction: Transplant patients are a vulnerable group due to their immunocompromised status. Understanding how COVID-19 can present in this group is clinically important. Therefore, we conduct a systematic review and meta-analysis on clinical features and management of transplant patients with COVID-19.Methods: Five databases were searched in May 2020 to include all relevant studies reporting clinical features or outcomes of COVID-19 infection in transplant patients. Data on clinical presentation, outcomes, lab values, imaging, and drug regimen were extracted. CMA software was used for meta-analysis. Protocol was registered in PROSPERO (CRD42020189458).Results: A total of 49 studies were finally included for analysis. Patients mainly complained from fever with event rate 74.40 % (95% CI= 69.4-78.8), cough 61.10% (95% CI= 55.8-66), and dyspnea 46.60% (95% CI= 69.4-78.8). Blood urea nitrogen 78.90% (95% CI= 54.7-92), ESR 78.10% (95% CI=52.3-92.1), and D-dimer 74.10% (95 % CI= 53-87...

PurposeApplying machine learning in medical statistics offers more accurate prediction models. In... more PurposeApplying machine learning in medical statistics offers more accurate prediction models. In this paper, we aimed to compare the performance of the Cox Proportional Hazard model (CPH), Classification and Regression Trees (CART), and Random Survival Forest (RSF) in short-, and long-term prediction in glioblastoma patients.MethodsWe extracted glioblastoma cancer data from the Surveillance, Epidemiology, and End Results database (SEER). We used the CPH, CART, and RSF for the prediction of 1- to 10-year survival probabilities. The Brier Score for each duration was calculated, and the model with the least score was considered the most accurate.ResultsThe cohort included 26473 glioblastoma patients divided into two groups: training (n = 18538) and validation set (n = 7935). The average survival duration was seven months. For the short- and long-term predictions, RSF was the best algorithm followed by CPH and CART.ConclusionFor big data, RSF was found to have the highest accuracy and ...

Acta Pharmaceutica, 2021

The epidemic of the novel coronavirus disease (COVID-19) that started in 2019 has evoked an urgen... more The epidemic of the novel coronavirus disease (COVID-19) that started in 2019 has evoked an urgent demand for finding new potential therapeutic agents. In this study, we performed a molecular docking of anti-HIV drugs to refine HIV protease inhibitors and nucleotide analogues to target COVID-19. The evaluation was based on docking scores calculated by AutoDock Vina and top binding poses were analyzed. Our results suggested that lopinavir, darunavir, atazanavir, remdesivir, and tipranavir have the best binding affinity for the 3-chymotrypsin-like protease of COVID-19. The comparison of the binding sites of three drugs, namely, darunavir, atazanavir and remdesivir, showed an overlap region of the protein pocket. Our study showed a strong affinity between lopinavir, darunavir, atazanavir, tipranavir and COVID-19 protease. However, their efficacy should be confirmed by in vitro studies since there are concerns related to interference with their active sites.

PLOS ONE, 2021

Background In response to the spread of the coronavirus disease 2019 (COVID-19), plenty of contro... more Background In response to the spread of the coronavirus disease 2019 (COVID-19), plenty of control measures were proposed. To assess the impact of current control measures on the number of new case indices 14 countries with the highest confirmed cases, highest mortality rate, and having a close relationship with the outbreak’s origin; were selected and analyzed. Methods In the study, we analyzed the impact of five control measures, including centralized isolation of all confirmed cases, closure of schools, closure of public areas, closure of cities, and closure of borders of the 14 targeted countries according to their timing; by comparing its absolute effect average, its absolute effect cumulative, and its relative effect average. Results Our analysis determined that early centralized isolation of all confirmed cases was represented as a core intervention in significantly disrupting the pandemic’s spread. This strategy helped in successfully controlling the early stage of the outbr...

School closure was the only main control measure that Japan took into action from late February t... more School closure was the only main control measure that Japan took into action from late February to late March in 2020. Accurate evaluation of how Japanese citizens responded to the impact of school closure remains a challenge. Data from the Google COVID-19 Community Mobility Report was used to analyze the mobility trend of Japanese citizens regarding six categories, including retail and recreation, grocery and pharmacy, parks, transit stations, workplace, and residential. The median percentage of mobility in all 47 prefectures of Japan was calculated during five periods of time, including one week before school closure, one week, two weeks, three weeks, and four weeks after school closure. There was a significant decline in the mobility trend of transit stations, grocery and pharmacy, parks, retail and recreation, and workplace at the moment after school closure compared to the prior period. Inversely, the mobility trend in staying at home remarkably increased following the implemen...

Parasitology International, 2021

Background: Malaria is caused by protozoan parasites of the genus Plasmodium infecting red blood ... more Background: Malaria is caused by protozoan parasites of the genus Plasmodium infecting red blood cells. Malaria infection during pregnancy is a signi cant public health problem that puts pregnant women at risk. Due to the asymptomatic nature of malaria patients, diagnosis has been di cult, de nitions have been inconsistent, and there has been a general lack of urgency to explore this illness outcome. Because asymptomatic malaria represents a challenge in interrupting transmission in a population and the asymptomatic host serves as a reservoir for the malaria parasite, it is now recognized as a major barrier to malaria elimination. This study aims to assess the prevalence of asymptomatic malaria and associated factors among pregnant women in the Boset District, East Shoa Zone, Oromia, Ethiopia Methods: A community-based cross-sectional study was conducted to assess the prevalence and associated factors of asymptomatic malaria in pregnant women from February to March 2022. Using multistage sample techniques, 328 asymptomatic pregnant women were enrolled. Data were collected using a structured questionnaire. A rapid test and Giemsa-stained blood smear microscopy were used to diagnose Plasmodium infections. Epi info version 7 was used to code, enter, and clean data before being uploaded to SPSS version 25.0 for analysis. Bivariable and multivariable binary logistic regression were utilized to nd the associated factors. Results: Of the total 328 pregnant women who participated in this study, 9(2.74%) and 10(3.05%) were con rmed to be infected with Plasmodium species by microscopy and rapid diagnostic tests, respectively. Malaria during pregnancy was found to be signi cantly associated with not using an insecticide-treated bed net [

PLOS ONE, 2021

Background Home delivery (HD) without skilled birth attendants (SBAs) are considered crucial risk... more Background Home delivery (HD) without skilled birth attendants (SBAs) are considered crucial risk factors increasing maternal and child mortality rates in Loa PDR. While a few studies in the literature discuss the choice of delivery in remote areas of minority ethnic groups; our work aims to identify factors that indicated their delivery place, at home or in the health facilities. Methods A community-based qualitative study was conducted between February and March 2020. Three types of interviews were implemented, In-depth interviews with 16 women of eight rural villages who delivered in the last 12 months in Xepon District, Savannakhet Province, Lao PDR. Also, three focus group discussions (FGDs) with nine HCPs and key-informant interviews of ten VHVs were managed. Factors affecting the choice of the delivery place were categorized according to the social-ecological model. Results Our sample included five Tri women and two Mangkong women in the HD group, while the FD group included ...

Frontiers in Public Health, 2021

COVID-19 is a rapidly growing pandemic with its first case identified during December 2019 in Wuh... more COVID-19 is a rapidly growing pandemic with its first case identified during December 2019 in Wuhan, Hubei Province, China. Due to the rampant rise in the number of cases in China and globally, WHO declared COVID-19 as a pandemic on 11th March 2020. The disease is transmitted via respiratory droplets of infected patients during coughing or sneezing and affects primarily the lung parenchyma. The spectrum of clinical manifestations can be seen in COVID-19 patients ranging from asymptomatic infections to severe disease resulting in mortality. Although respiratory involvement is most common in COVID-19 patients, the virus can affect other organ systems as well. The systemic inflammation induced by the disease along with multisystem expression of Angiotensin Converting Enzyme 2 (ACE2), a receptor which allows viral entry into cells, explains the manifestation of extra-pulmonary symptoms affecting the gastrointestinal, cardiovascular, hematological, renal, musculoskeletal, and endocrine s...

Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2018

Introduction: Malaria is critical global health issue, especially tropical and subtropical countr... more Introduction: Malaria is critical global health issue, especially tropical and subtropical countries. The emergence of resistance to the currently approved drug is a recurring problem thus the urgent development of new medicine with new mechanisms of action is needed. Herbal medicine is still an attractive source of the new antimalarial drug since the isolation of quinine and artemisinin. Kampo is known Japanese traditional medicine that has been used for long periods of

IIUM Medical Journal Malaysia, 2020

Introduction: Scholarship applicants often receive different advice on what should be included in... more Introduction: Scholarship applicants often receive different advice on what should be included in their Curriculum Vitae (CV). This study aims to investigate what the essential components of a CV being prepared for scholarships are, how to present them, and what their level of impact is. Materials and Methods: The authors sent an online structured questionnaire to 7512 corresponding authors of recent published papers in Scopus; 124 completed questionnaires were returned. Recommended elements for a CV were chosen according to the Delphi consensus technique with a threshold of 50%. Results: This survey revealed that headings, bullet points and careful error checking were essential parts of the layout. For the content of the CV, besides publications, education and training background, research experience and research interest were also necessary. Moreover, almost all respondents ranked publications as the most important qualification of an academic scholarship candidate. Publications a...

PLOS ONE

International Journal of Environmental Research and Public Health

PLOS ONE

BMC Medical Education

BMC Pediatrics

The Lancet Regional Health - Southeast Asia

Frontiers in Public Health, 2021

Patient Preference and Adherence, 2020

Acta Pharmaceutica, 2021

PLOS ONE, 2021

Parasitology International, 2021

PLOS ONE, 2021

Frontiers in Public Health, 2021

Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2018

IIUM Medical Journal Malaysia, 2020

Background: Dengue virus infection is a major public health problem. A hypothesis put forward for... more Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case control study in Vietnam, children with dengue fever, other febrile illness and healthy controls were recruited. Dengue virus infection was confirmed by several diagnostic tests. Multiplex immunoassay using Luminex technology was used to measure cytokines simultaneously. A positive association with dengue shock syndrome was found for VCAM-1, whereas a negative association was found for IFNγ. Furthermore, multivariate logistic analysis also showed that VCAM-1 and IFNγ were independently correlated with dengue shock syndrome. Conclusion: IFNγ and VCAM-1 were associated with dengue shock syndrome, although their role in the severe dengue pathogenesis remains unclear. Additional studies are required to shed further light on the function of these cytokines in severe dengue. © 2014 by The Japanese Society of Tropical Medicine.

Streptococcus suis, a bacterium that affects pigs, is a neglected pathogen that causes systemic d... more Streptococcus suis, a bacterium that affects pigs, is a neglected pathogen that causes systemic disease in humans. We conducted a systematic review and meta-analysis to summarize global estimates of the epidemiology, clinical characteristics, and outcomes of this zoonosis. We searched main literature databases for all studies through December 2012 using the search term "streptococcus suis." The prevalence of S. suis infection is highest in Asia; the primary risk factors are occupational exposure and eating of contaminated food. The pooled proportions of case-patients with pig-related occupations and history of eating high-risk food were 38.1% and 37.3%, respectively. The main clinical syndrome was meningitis (pooled rate 68.0%), followed by sepsis, arthritis, endocarditis, and endophthalmitis. The pooled case-fatality rate was 12.8%. Sequelae included hearing loss (39.1%) and vestibular dysfunction (22.7%). Our analysis identified gaps in the literature, particularly in assessing risk factors and sequelae of this infection.

BACKGROUND: Ethics is one of the main pillars in the development of science. We performed a JoinP... more BACKGROUND: Ethics is one of the main pillars in the development of science. We performed a JoinPoint regression analysis to analyze the trends of ethical issue research over the past half century. The question is whether ethical issues are neglected despite their importance in modern research. METHOD: PubMed electronic library was used to retrieve publications of all fields and ethical issues. JoinPoint regression analysis was used to identify the significant time trends of publications of all fields and ethical issues, as well as the proportion of publications on ethical issues to all fields over the past half century. Annual percent changes (APC) were computed with their 95% confidence intervals, and a p-value < 0.05 was considered statistically significant. RESULTS: We found that publications of ethical issues increased during the period of 1965-1996 but slightly fell in recent years (from 1996 to 2013). When comparing the absolute number of ethics related articles (APEI) to all publications of all fields (APAF) on PubMed, the results showed that the proportion of APEI to APAF statistically increased during the periods of 1965-1974, 1974-1986, and 1986-1993, with APCs of 11.0, 2.1, and 8.8, respectively. However, the trend has gradually dropped since 1993 and shown a marked decrease from 2002 to 2013 with an annual percent change of-7.4%. CONCLUSIONS: Scientific productivity in ethical issues research on over the past half century rapidly increased during the first 30-year period but has recently been in decline. Since ethics is an important aspect of scientific research, we suggest that greater attention is needed in order to emphasize the role of ethics in modern research. © 2014 by The Japanese Society of Tropical Medicine.

Background: Schistosomiasis is still a major public health burden in the tropics and subtropics. ... more Background: Schistosomiasis is still a major public health burden in the tropics and subtropics. Although there is an effective chemotherapy (Praziquantel) for this disease, reinfection occurs rapidly after mass drug administration (MDA). Because the entire population do not get reinfected at the same rate, it is possible that host factors may play a dominant role in determining resistance or susceptibility to reinfection with schistosomes. Here, we systematically reviewed and meta-analyzed studies that reported associations between reinfection with the principal human-infecting species (S. mansoni, S. japonicum and S. haematobium) and host socio-demographic, epidemiological, immunological and genetic factors. Methodology/Principal Findings: PubMed, Scopus, Google Scholar, Cochrane Review Library and African Journals Online public databases were searched in October 2013 to retrieve studies assessing association of host factors with reinfection with schistosomes. Meta-analysis was performed to generate pooled odds ratios and standardized mean differences as overall effect estimates for dichotomous and continuous variables, respectively. Quality assessment of included studies, heterogeneity between studies and publication bias were also assessed. Out of the initial 2739 records, 109 studies were included in the analyses, of which only 32 studies with 37 data sets were eligible for quantitative data synthesis. Among several host factors identified, strong positive association was found with age and pre-treatment intensity, and only slightly for gender. These factors are major determinants of exposure and disease transmission. Significant positive association was found with anti-SWA IgG4 level, and a negative overall effect for association with IgE levels. This reconfirmed the concept that IgE/IgG4 balance is a major determinant of protective immunity against schistosomiasis. Other identified determinants were reported by a small number of studies to enable interpretation. Conclusions: Our data contribute to the understanding of host-parasite interaction as it affects reinfection, and is a potential tool to guide planning and tailoring of community interventions to target high-risk groups. © 2014 Mbanefo et al.

Background: Immunity to malaria requires innate, adaptive immune responses and Plasmodium-specifi... more Background: Immunity to malaria requires innate, adaptive immune responses and Plasmodium-specific memory cells. Previously, mice semi-immune to malaria was developed. Three cycles of infection and cure ('three-cure') were required to protect mice against Plasmodium berghei (ANKA strain) infection. Methods: C57BL/6 J mice underwent three cycles of P. berghei infection and drug-cure to become semi-immune. The spleens of infected semi-immune mice were collected for flow cytometry analysis. CD11c(+) cells of semiimmune mice were isolated and transferred into naïve mice which were subsequently challenged and followed up by survival and parasitaemia. Results: The percentages of splenic CD4(+) and CD11c(+) cells were increased in semi-immune mice on day 7 post-infection. The proportion and number of B220(+)CD11c(+)low cells (plasmacytoid dendritic cells, DCs) was higher in semi-immune, three-cure mice than in their naïve littermates on day 7 post-infection (2.6 vs 1.1% and 491,031 vs 149,699, respectively). In adoptive transfer experiment, three months after the third cured P. berghei infection, splenic CD11c(+) DCs of non-infected, semi-immune, three-cure mice slowed Plasmodium proliferation and decreased the death rate due to neurological pathology in recipient mice. In addition, anti-P. berghei IgG1 level was higher in mice transferred with CD11c(+) cells of semi-immune, three-cure mice than mice transferred with CD11c(+) cells of naïve counterparts. Conclusion: CD11c(+) cells of semi-immune mice protect against experimental cerebral malaria three months after the third cured malaria, potentially through protective plasmacytoid DCs and enhanced production of malaria-specific antibody. © 2015 Bao et al.; licensee Biomed Central.

Dengue virus infection is a leading cause of morbidity among children in the Philippines in recen... more Dengue virus infection is a leading cause of morbidity among children in the Philippines in recent years. In order to investigate the association of HLA Class I and II alleles and dengue disease severity in a cohort of Filipino children, we performed a case control study in 2 hospitals in Metro Manila from June 2008 to December 2009. A total of 250 laboratory confirmed dengue patients and 300 healthy individuals aged 5 to 15 years old were typed for HLA-A, B and DRB1 alleles. The frequency of HLA-A 33:01 was significantly decreased in severe dengue (DHF/ DSS; Pc = 0.0016)) and DSS (Pc = 0.0032) compared to the background population. These findings support a previous study that this allele may confer protection against the severe form of dengue and provide the first evidence of HLA association with dengue in the Philippines. Future studies should be directed in investigating the possible mechanisms of protection. © 2015 Mercado et al.

Background Evidence-based medicine (EBM) has developed as the dominant paradigm of assessment of ... more Background Evidence-based medicine (EBM) has developed as the dominant paradigm of assessment of evidence that is used in clinical practice. Since its development, EBM has been applied to integrate the best available research into diagnosis and treatment with the purpose of improving patient care. In the EBM era, a hierarchy of evidence has been proposed, including various types of research methods, such as meta-analysis (MA), systematic review (SRV), randomized controlled trial (RCT), case report (CR), practice guideline (PGL), and so on. Although there are numerous studies examining the impact and importance of specific cases of EBM in clinical practice, there is a lack of research quantitatively measuring publication trends in the growth and development of EBM. Therefore, a bibliometric analysis was constructed to determine the scientific productivity of EBM research over decades. Methods NCBI PubMed database was used to search, retrieve and classify publications according to research method and year of publication. Joinpoint regression analysis was undertaken to analyze trends in research productivity and the prevalence of individual research methods. Findings Analysis indicates that MA and SRV, which are classified as the highest ranking of evidence in the EBM, accounted for a relatively small but auspicious number of publications. For most research methods, the annual percent change (APC) indicates a consistent increase in publication frequency. MA, SRV and RCT show the highest rate of publication growth in the past twenty years. Only controlled clinical trials (CCT) shows a non-significant reduction in publications over the past ten years. Conclusions Higher quality research methods, such as MA, SRV and RCT, are showing continuous publication growth, which suggests an acknowledgement of the value of these methods. This study provides the first quantitative assessment of research method publication trends in EBM. © 2015 Hung et al.

We previously reported, significantly higher levels of Chymase and Tryptase in early stage plasma... more We previously reported, significantly higher levels of Chymase and Tryptase in early stage plasma of DSS patients prior to the occurrence of shock suggesting a possible role of mast cells in dengue pathogenesis. To further investigate, we analyzed CMA1 promoter SNP (rs1800875) and TPSAB1 gene alleles. , which encode the Human Chymase and α- and β- tryptase 1 enzymes respectively, for susceptibility to Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in patients from hospitals in Vietnam (Ho Chi Minh City and Vinh Long) and the Philippines. While the CMA1 promoter SNP (rs1800875) was not associated with DHF/DSS, the homozygous form of α-tryptase allele was associated with DSS patients in Vinh Long and the Philippines (OR= 3.52, p<= 0.0001; OR= 3.37, p< 0.0001, respectively) and with DHF in Ho Chi Minh City (OR= 2.54, p= 0.0084). Also, a statistically significant association was observed when DHF and DSS were combined in Vinh Long (OR= 1.5, p= 0.034) and the Philippines (OR= 2.36, p= 0.0004); in Ho Chi Minh City when DHF and DSS were combine an association was observed, but it was not statistically significant (OR= 1.5, p= 0.0505). Therefore, the α-tryptase might have a possible effect on the susceptibility to severe form of Dengue infection. © 2015 American Society for Histocompatibility and Immunogenetics.

There is still urgent need for a vaccine against schistosomiasis, especially in Schistosoma japon... more There is still urgent need for a vaccine against schistosomiasis, especially in Schistosoma japonicum endemic areas where even a vaccine that will interrupt zoonotic transmission will be potentially effective as an intervention tool. We had developed a novel nanoparticle gene delivery system, which has proven efficacious in gene transfection to target immune cells with complementary adjuvant effect and high protective efficacy in several diseases. Here, we applied this nanoparticle system in combination with S. japonicum glutathione S-transferase (SjGST) DNA vaccine to show the immunogenicity and anti-fecundity effect of the nanoparticle coated vaccine formulation against murine schistosomiasis. The nanoparticle-coated DNA vaccine formulation induced desired immune responses. In comparison with the nanoparticle coated empty vector, it produced significantly increased antigen-specific humoral response, T-helper 1 polarized cytokine environment, higher proportion of IFN-γ producing CD4+ T-cells and the concomitant decrease in IL-4 producing CD4+ T-cells. Although there was no effect on worm burden, we recorded a marked reduction in tissue egg burden. There was up to 71.3% decrease in tissue egg burden and 55% reduction in the fecundity of female adult worms. Our data showed that SjGST DNA vaccine, delivered using the nanoparticle gene delivery system, produced anti-fecundity effect on female adult schistosomes as previously described by using conventional subunit vaccine with adjuvant, proving this DNA vaccine formulation as a promising candidate for anti-pathology and transmission blocking application. © 2015 Elsevier Ireland Ltd.

Tacrolimus and mycophenolate mofetil are immunosuppressants frequently used in human organ transp... more Tacrolimus and mycophenolate mofetil are immunosuppressants frequently used in human organ transplantation. Tacrolimus is also reported to inhibit Plasmodium falciparum growth in vitro. Here, we report that tacrolimus prevented the death from cerebral malaria of Plasmodium berghei ANKA-infected C57BL/6J mice, but not their death from malaria due to the high parasitaemia and severe anaemia. The mycophenolate mofetil-treated mice showed higher mortality from cerebral malaria and succumbed to malaria earlier than tacrolimus-treated littermates. Tacrolimus attenuated the infiltration of mononuclear cells including pathogenic CD8+ T cells into the brain. It appears to prevent murine cerebral malaria through the inhibition of cerebral infiltration of CD8+ T cells. © 2016 John Wiley & Sons Ltd.

Background: Severe dengue with severe plasma leakage (SD-SPL) is the most frequent of dengue seve... more Background: Severe dengue with severe plasma leakage (SD-SPL) is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death. Methodology: Among 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS). To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6–48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ) technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients. Principal findings: Nineteen plasma proteins exhibited significantly different relative concentrations (p<0.05), with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport-related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy. Conclusion: Proteins identified here may serve as candidate predictive markers to diagnose SD-SPL for timely clinical management. Since the number of subjects are small, so further studies are needed to confirm all these biomarkers. © 2016 Nhi et al.

Background: Dengue infection has various clinical manifestations, often with unpredictable clinic... more Background: Dengue infection has various clinical manifestations, often with unpredictable clinical evolutions and outcomes. Several factors including nutritional status have been studied to find the relationship with dengue severity. However, the nutritional status had conflicting effects on the complication of dengue in some previous studies. Therefore, we conducted a systematic review and performed a meta-analysis to analyze the association between nutritional status and the outcome of dengue infection. Methods: Eleven electronic databases and manual searching of reference lists were used to identify the relevant studies published before August 2013. At least two authors worked independently in every step to select eligible studies and extract data. Dengue severity in the included studies must be classified into three categories: dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Results: Thirteen articles that met the inclusion criteria came to final analysis. A meta-analysis using fixed- or random-effects models was conducted to calculate pooled odds ratios (OR) with corresponding 95% confidence intervals. It has shown that there was no statistically significant association between DHF group and DSS group in malnutritional and overweight/obesity patients with OR: 1.17 (95% CI: 0.99-1.39), 1.31 (0.91-1.88), respectively. A significantly inverse relation between DF and DHF groups of malnutritional patients was revealed (OR=0.71, 95% CI: 0.56-0.90). Our meta-analysis also indicated a statistically significant negative correlation between malnourished children with dengue virus infection and healthy children (OR=0.46, 95% CI: 0.3-0.70). When analyzing patients with normal nutrition status, we found out that there was a significantly negative relationship between DHF and DSS groups (0.87; 95% CI: 0.77-0.99). Other comparisons of DSS with DF/DHF groups, DSS/DHF with DF groups, and DHF with DF groups in normal nutritional patients showed no significant correlation. However, the findings should be interpreted cautiously because all significant associations were lost after removing of the largest study. Conclusions: Results from previous studies failed to show any solid consistency regarding the association between the nutritional status and dengue infection. Consequently, the effects of nutritional status on dengue disease outcome has been controversial. Further studies are recommended to clarify the impact of nutritional status on dengue infection. © 2016 Trang et al.

Perilipins are evolutionarily conserved from Drosophila to humans, the lipid storage droplet 1 (L... more Perilipins are evolutionarily conserved from Drosophila to humans, the lipid storage droplet 1 (Lsd1) is a Drosophila homolog of human perilipin 1. The function of Lsd1 as a regulator of lipolysis in Drosophila has been demonstrated, as the Lsd1 mutant causes an increase of lipid droplet size. However, the functions of this gene during development are still under investigation. In order to determine the function of Lsd1 during development, Lsd1 was knocked down in Drosophila using the GAL4-UAS system. Selective knockdown of Lsd1 in the dorsal wing disc caused an atrophied wing phenotype. The generation of reactive oxygen species in the wing pouch compartment of the Lsd1-knockdown flies was significantly higher than in the control. Immunostaining with caspase-3 antibody revealed a greater number of apoptotic cells in Lsd1-knockdown wing discs than in the control. Cell death by autophagy was also induced in the knockdown flies. Moreover, cells deprived of Lsd1 showed mitochondrial expansion and decreased ATP levels. These results strongly suggest that knockdown of Lsd1 induces mitochondrial stress and the production of reactive oxygen species that result in cell death, via apoptosis and the autophagy pathway. These results highlight the roles of Drosophila Lsd1 during wing development. © 2016 by the authors; licensee MDPI, Basel, Switzerland.

Introduction: Dengue is a viral disease that spreads rapidly in the tropic and subtropic regions ... more Introduction: Dengue is a viral disease that spreads rapidly in the tropic and subtropic regions of the world and causes 22,000 deaths annually. In 2009, the World Health Organization (WHO) released a new classification of dengue infections, which divided them into three categories: dengue without warning sign (D), dengue with warning sign (DWS), and severe dengue (SD). However, researchers have been using different criteria to define persistent vomiting; therefore, we aimed to evaluate the ability of the number of vomiting times in early prediction of SD development among D/DWS patients. Method: A hospital-based cohort study was conducted in Ben Tre-south of Vietnam. We enrolled confirmed dengue patients with D and DWS at admission. The final classification was determined on the discharged day for every patient based on the classification of WHO 2009 without using vomiting symptom, using the receiver operating characteristic (ROC) curve to evaluate the ability of the number of vomiting times in early prediction of SD development among D/DWS patients. Result: The prevalence of vomiting symptom was higher in SD group than D/DWS group (92 versus 46 %, p = 0.006), and the median of the number of vomiting times was higher in SD group than D/DWS group (2.5 versus 0, p = 0.001). To distinguish SD from D/DWS, the ROC curve of the number of vomiting episodes showed that the area under the curve was 0.77; with the cut point of two, the sensitivity and specificity were 92 and 52 %, respectively. Conclusion: The number of vomiting times could be a good clinical sign which can early predict SD from the group of D/DWS. We suggest the definition of persistent vomiting should be vomiting two times or more per day. © 2016 Vuong et al.

The objective was to assess the immunoequivalence and protective efficacy of the novel, relativel... more The objective was to assess the immunoequivalence and protective efficacy of the novel, relatively safe dendrigraft poly-l-lysine-based nanoparticle formulation in comparison to the non-degradable polyethylenimine-based system. Groups of 6-week-old female C57BL/6 mice were immunized three times biweekly. Each mouse received 100 μg of the Plasmodium yoelii GPI8p-transamidase PyTAM formulated with nanoball that consisted of PyTAM/PEI/γ-PGA or PyTAM/DGL/γ-PGA and their respective nanoparticle-coated blank vector controls. Two weeks after the last immunization, the humoral responses and cellular immune response were assessed. The survival and parasitemia were evaluated in each group challenged intraperitoneally with 106 of a lethal strain of P. yoelii 17XL-parasitized red blood cells. Mice immunized with PyTAM/PEI/γ-PGA or PyTAM/DGL/γ-PGA showed similar survival rates, humoral responses and T helper 1 pro-inflammatory cellular immune responses in vivo and ex vivo. In particular, the PyTAM/DGL/γ-PGA formulation showed a significant increase in conventional dendritic cells in the spleen, which were consistently associated with high interleukin-12 production, the driver of the T helper 1 response. We show that the substitution of non-degradable polyethylenimine with the biodegradable dendrigraft poly-l-lysine in the nanoparticle formulation is immunoequivalent and elicits protective immunity against the lethal strain of P. yoelii. Therefore, this new gene-delivery vehicle with a good safety profile presents an exciting prospect for application in vaccination strategies. © The Author(s) 2016.