Analyzing temperature, humidity, and precipitation trends in six regions of Thailand using innovative trend analysis.

The change of temperature and weather parameters is a major concern affecting sustainable development and impacting various sectors, such as agriculture, tourism, and industry. Changing weather patterns and their impact on water resources are important climatic factors that society is facing. In Thailand, climatological features such as ambient temperature, relative humidity, and precipitation play a substantial role in affecting extreme weather events, which cause damage to the economy, agriculture, tourism, and livelihood of people. To investigate recent serious changes in annual trends of temperature, relative humidity, and precipitation in Thailand, this study used the Mann-Kendall (MK) test and innovative trend analysis (ITA) methods. The MK test showed that all six regions had an upward trend in temperature and humidity index (humidex, how hot the weather feels to the average person), while relative humidity and precipitation showed both upward and downward trends across different regions. The ITA method further confirmed the upward trend in temperature and humidex and showed that most data points fell above the 1:1 line. However, the upward trend in most variables was not significant at the 5% level. The southern and eastern regions showed a significant upward trend in relative humidity and humidex at a 5% level of significance according to the MK test. The output of this study can help in the understanding of weather variations and predict future situations and can be used for adaptation strategies.

Impact of Climate on the Incidence of Acute Coronary Syndrome　- Differences Between Japan and Thailand.

Background: Although there are many reports of temperature being associated with the onset of acute coronary syndrome (ACS), few studies have examined differences in ACS due to climatic differences between Japan and Thailand. The aim of this joint Japan-Thailand study was to compare patients with myocardial infarction in Japanese and Thai hospitals in different climates. Methods and Results: We estimated the climate data in 2021 for the Wakayama Prefecture and Chonburi Province, two medium-sized cities in Japan and Thailand, respectively, and ACS patients who were treated at the Wakayama Medical University (WMU) and Burapha University Hospital (BUH), the two main hospitals in these provinces (ACS patient numbers: WMU, n=177; BUH, n=93), respectively. In the Chonburi Province, although the average temperature was above 25℃, the number of ACS cases in BUH varied up to threefold between months (minimum: July, 4 cases; maximum: October, 14 cases). In Japan and Thailand, there was a mild to moderate negative correlation between temperature-atmospheric pressure at the onset of ACS, but different patterns for temperature-humidity (temperature-atmospheric pressure, temperature-humidity, and atmospheric pressure-humidity: correlation index; r=-0.561, 0.196, and -0.296 in WMU vs. r=-0.356, -0.606, and -0.502 in BUH). Conclusions: The present study suggests that other climatic conditions and factors, not just temperature, might be involved in the mechanism of ACS.

Association of cause-specific hospital admissions with high and low temperatures in Thailand: a nationwide time series study.

Background: Non-optimum temperatures are associated with a considerable mortality burden. However, evidence of temperature with all-cause and cause-specific hospital admissions in tropical countries like Thailand is still limited. Methods: Daily all-cause and cause-specific hospital admissions for outpatient and inpatient visits were collected from 77 provinces in Thailand from January 2013 to August 2019. A two-stage time-series approach was applied to assess the association between non-optimum temperatures and hospital admission. We first fitted the province-specific temperature-morbidity association and then obtained the national association in the second stage using a random-effects meta-analysis regression. The attributable fraction (AF) of hospital admissions with 95% empirical confidence interval (eCI) was calculated. Findings: A total of 878,513,460 all-cause outpatient admissions and 32,616,600 all-cause inpatient admissions were included in this study. We observed a J-shaped relationship with the risk of hospital admissions increasing for both cold and hot temperatures. The overall AFs of all-cause hospital admissions due to non-optimum temperatures were 7.57% (95% eCI: 6.47%, 8.39%) for outpatient visits and 6.17% (95% eCI: 4.88%, 7.20%) for inpatient visits. Hot temperatures were responsible for most of the AFs of hospital admissions, with 6.71% (95% eCI: 5.80%, 7.41%) for outpatient visits and 4.50% (95% eCI: 3.62%, 5.19%) for inpatient visits. The burden of hospital admissions was greater in females and in children and adolescents (0-19 years). The fractions of hospital admissions attributable to non-optimum temperatures exhibited variation among disease categories and geographical areas. Interpretation: The results indicate that low and high temperature has a significant impact on hospital admissions, especially among the females, and children and adolescents (0-19 years). The current investigation could provide evidence for policymakers to develop adaptation strategies and mitigate the adverse effects of climate change on public health in Thailand and other tropical countries. Funding: National Research Council of Thailand (NRCT): E-Asia Joint Research Program: Climate change impact on natural and human systems (N33A650979).

Effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques.

Measles is a systemic disease initiated in the respiratory tract with widespread measles virus (MeV) infection of lymphoid tissue. Mortality can be substantial, but no licensed antiviral therapy is available. We evaluated both post-exposure prophylaxis and treatment with remdesivir, a broad-spectrum antiviral, using a well-characterized rhesus macaque model of measles. Animals were treated with intravenous remdesivir for 12 days beginning either 3 days after intratracheal infection (post-exposure prophylaxis, PEP) or 11 days after infection at the onset of disease (late treatment, LT). As PEP, remdesivir lowered levels of viral RNA in peripheral blood mononuclear cells, but RNA rebounded at the end of the treatment period and infectious virus was continuously recoverable. MeV RNA was cleared more rapidly from lymphoid tissue, was variably detected in the respiratory tract, and not detected in urine. PEP did not improve clinical disease nor lymphopenia and reduced the antibody response to infection. In contrast, LT had little effect on levels of viral RNA or the antibody response but also did not decrease clinical disease. Therefore, remdesivir transiently suppressed expression of viral RNA and limited dissemination when provided as PEP, but virus was not cleared and resumed replication without improvement in the clinical disease parameters evaluated.

Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production.

In humans and non-human primates, wild type (WT) measles virus (MeV) replicates extensively in lymphoid tissue and induces an innate response characteristic of NF-κB and inflammasome activation without type I interferon. In contrast, the live attenuated MeV vaccine (LAMV) replicates poorly in lymphoid tissue with little detectable in vivo cytokine production. To characterize the innate responses of macrophages to WT MeV and LAMV infection, we analyzed primary human monocyte-derived macrophages and phorbol myristic acid-matured monocytic THP-1 cells (M0) polarized to inflammatory (M1) and anti-inflammatory (M2) phenotypes 24 h after MeV infection. LAMV infected macrophages more efficiently than WT MeV but produced less virus than WT MeV-infected macrophages. Both strains induced production of NF-κB-responsive cytokines IL-6 and TNFα and inflammasome products IL-1ß and IL-18 without evidence of pyroptosis. Analysis of THP-1 cells deficient in inflammasome sensors NOD-like receptor pyrin (NLRP)3, IFN-γ-inducible protein 16 (IFI16) or absent in melanoma (AIM)2; adaptor apoptosis-associated speck-like protein containing a CARD (ASC) or effector caspase 1 showed that IL-18 production was dependent on NLRP3, ASC, and caspase 1. However, M1 cells produced IL-1ß in the absence of ASC or caspase 1 indicating alternate pathways for MeV-induced pro-IL-1ß processing. Therefore, the innate response to in vitro infection of macrophages with both LAMV and WT MeV includes production of IL-6 and TNFα and activation of the NLRP3 inflammasome to release IL-1ß and IL-18. LAMV attenuation impairs production of infectious virus but does not reduce ability to infect macrophages or innate responses to infection.

The association of meteorological parameters and AirQ+ health risk assessment of PM2.5 in Ratchaburi province, Thailand.

Air quality is heavily influenced by rising pollution distribution levels which are a consequence of many artificial activities from numerous sources. This study aims to determine the relationship between meteorological data and air pollutants. The health effects of long-term PM2.5 were estimated on expected life remaining (ELR) and years of life lost (YLL) indices in Ratchaburi province during the years 2015-2019 using AirQ+ software. Values obtained from the PM2.5 averaging, and YLL data were processed for the whole population in the age range of 0-29, 30-60 and over 60. These values were entered into AirQ+ software. The mean annual concentration of PM2.5 was highly variable, with the highest concentration being 136.42 µg/m3 and the lowest being 2.33 µg/m3. The results estimated that the highest and lowest YLL in the next 10 years for all age groups would be 24,970.60 and 11,484.50 in 2017 and 2019, respectively. The number of deaths due to COPD, IHD, and stroke related to long-term exposure to ambient PM2.5 were 125, 27 and 26, respectively. The results showed that older people (> 64) had a higher YLL index than the groups aged under 64 years. The highest and lowest values for all ages were 307.15 (2015) and 159 (2017). Thus, this study demonstrated that the PM2.5 effect to all age groups, especially the the elderly people, which the policy level should be awared and fomulated the stratergies to protecting the sensitive group.

B-Cell Responses in Hospitalized Severe Acute Respiratory Syndrome Coronavirus 2-Infected Children With and Without Multisystem Inflammatory Syndrome.

Multisystem inflammatory syndrome in children (MIS-C) can complicate infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but differences in the immune responses during MIS-C compared to coronavirus disease 2019 (COVID-19) are poorly understood. We longitudinally compared the amounts and avidity of plasma anti-nucleocapsid (N) and spike (S) antibodies, phenotypes of B cells, and numbers of virus-specific antibody-secreting cells in circulation of children hospitalized with COVID-19 (n = 10) and with MIS-C (n = 12). N-specific immunoglobulin G (IgG) was higher early after presentation for MIS-C than COVID-19 patients and avidity of N- and S-specific IgG at presentation did not mature further during follow-up as it did for COVID-19. Both groups had waning proportions of B cells in circulation and decreasing but sustained production of virus-specific antibody-secreting cells for months. Overall, B-cell responses were similar, but those with MIS-C demonstrated a more mature antibody response at presentation compared to COVID-19, suggesting a postinfectious entity.

Continued Virus-Specific Antibody-Secreting Cell Production, Avidity Maturation and B Cell Evolution in Patients Hospitalized with COVID-19.

Understanding the development and sustainability of the virus-specific protective immune response to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains incomplete with respect to the appearance and disappearance of virus-specific antibody-secreting cells (ASCs) in circulation. Therefore, we performed cross-sectional and longitudinal analyses of peripheral blood mononuclear cells and plasma collected from 55 hospitalized patients up to 4 months after onset of COVID-19 symptoms. Spike (S)- and nucleocapsid (N)-specific IgM and IgG ASCs appeared within 2 weeks accompanied by flow cytometry increases in double negative plasmablasts consistent with a rapid extrafollicular B cell response. Total and virus-specific IgM and IgG ASCs peaked at 3-4 weeks and were still being produced at 3-4 months accompanied by increasing antibody avidity consistent with a slower germinal center B cell response. N-specific ASCs were produced for longer than S-specific ASCs and avidity maturation was greater for antibody to N than S. Patients with more severe disease produced more S-specific IgM and IgG ASCs than those with mild disease and had higher levels of N- and S-specific antibody. Women had more B cells in circulation than men and produced more S-specific IgA and IgG and N-specific IgG ASCs. Flow cytometry analysis of B cell phenotypes showed an increase in circulating B cells at 4-6 weeks with decreased percentages of switched and unswitched memory B cells. These data indicate ongoing antigen-specific stimulation, maturation, and production of ASCs for several months after onset of symptoms in patients hospitalized with COVID-19.

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection.

Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here, we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: healthy controls (HCs) weeks (early) or months (late) following vaccination in comparison with symptomatic patients with SARS-CoV-2 after partial or full mRNA vaccination. During the period of the study, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant. Neutralizing antibody levels in the HCs were sustained over time against the vaccine parent virus but decreased against the Alpha variant, whereas IgG titers and T cell responses against the parent virus and Alpha variant declined over time. Both partially and fully vaccinated patients with symptomatic infections had lower virus neutralizing antibody levels against the parent virus than the HCs, similar IgG antibody titers, and similar virus-specific T cell responses measured by IFN-γ. Compared with HCs, neutralization activity against the Alpha variant was lower in the partially vaccinated infected patients and tended to be lower in the fully vaccinated infected patients. In this cohort of breakthrough infections, parent virus neutralization was the superior predictor of breakthrough infections with the Alpha variant of SARS-CoV-2.

Suppression of the pathogenicity of Candida albicans by the quorum-sensing molecules farnesol and tryptophol.

This study examines the ability of the quorum-sensing molecules (QSMs) farnesol and tryptophol to induce programmed cell death of the pathogenic fungus Candida albicans, to alter the expression of apoptosis-related genes, and to reduce the pathogenicity and virulence of C. albicans in Galleria mellonella. Our results showed that both farnesol and tryptophol inhibited C. albicans germ tube formation. In the QSM-treated group, the expression levels of the apoptosis genes increased, whereas the expression level of the anti-apoptosis gene decreased. Further, pretreatment of C. albicans with tryptophol or farnesol prior to G. mellonella larval infection significantly enhanced host survival compared with larvae infected with untreated C. albicans. Thus, farnesol and tryptophol may trigger apoptosis of C. albicans in vitro and reduce the virulence of C. albicans in vivo. Although further study is needed to identify the precise mechanisms underlying the antifungal properties of farnesol and tryptophol, these results suggest that QSMs may be effective agents for controlling fungal infection.

Inhibition of N-myristoyltransferase1 affects dengue virus replication.

Dengue virus (DENV) causes dengue fever, a self-limiting disease that could be fatal due to serious complications. No specific treatment is currently available and the preventative vaccine is only partially protective. To develop a potential drug target for dengue fever, we need to understand its biology and pathogenesis thoroughly. N-myristoyltransferase (NMT) is an N-terminal protein lipidation enzyme that catalyzes the covalent cotranslational attachment of fatty acids to the amino-terminal glycine residue of a number of proteins, leading to the modulation of various signaling molecules. In this study, we investigated the interaction of dengue viral proteins with host NMT and its subsequent effect on DENV. Our bioinformatics, molecular docking, and far-western blotting analyses demonstrated the interaction of viral envelope protein (E) with NMT. The gene expression of NMT was strongly elevated in a dependent manner during the viral replication phase in dendritic cells. Moreover, NMT gene silencing significantly inhibited DENV replication in dendritic cells. Further studies investigating the target cell types of other host factors are suggested.

A powerful in vivo alternative model in scientific research: Galleria mellonella.

Murine models are suggested as the gold standard for scientific research, but they have many limitations of ethical and logistical concern. Then, the alternative host models have been developed to use in many aspects especially in invertebrate animals. These models are selected for many areas of research including genetics, physiology, biochemistry, evolution, disease, neurobiology, and behavior. During the past decade, Galleria mellonella has been used for several medical and scientific researches focusing on human pathogens. This model commonly used their larvae stage due to their easy to use, non-essential special tools or special technique, inexpensive, short life span, and no specific ethical requirement. Moreover, their innate immune response close similarly to mammals, which correlate with murine immunity. In this review, not only the current knowledge of characteristics and immune response of G. mellonella, and the practical use of these larvae in medical mycology research have been presented, but also the better understanding of their limitations has been provided.

Distribution of Scedosporium species in soil from areas with high human population density and tourist popularity in six geographic regions in Thailand.

Scedosporium is a genus comprising at least 10 species of airborne fungi (saprobes) that survive and grow on decaying organic matter. These fungi are found in high density in human-affected areas such as sewage-contaminated water, and five species, namely Scedosporium apiospermum, S. boydii, S. aurantiacum, S. dehoogii, and S. minutisporum, cause human infections. Thailand is a popular travel destination in the world, with many attractions present in densely populated areas; thus, large numbers of people may be exposed to pathogens present in these areas. We conducted a comprehensive survey of Scedosporium species in 350 soil samples obtained from 35 sites of high human population density and tourist popularity distributed over 23 provinces and six geographic regions of Thailand. Soil suspensions of each sample were inoculated on three plates of Scedo-Select III medium to isolate Scedosporium species. In total, 191 Scedosporium colonies were isolated from four provinces. The species were then identified using PCR and sequencing of the beta-tubulin (BT2) gene. Of the 191 isolates, 188 were S. apiospermum, one was S. dehoogii, and species of two could not be exactly identified. Genetic diversity analysis revealed high haplotype diversity of S. apiospermum. Soil is a major ecological niche for Scedosporium and may contain S. apiospermum populations with high genetic diversity. This study of Scedosporium distribution might encourage health care providers to consider Scedosporium infection in their patients.

Monitoring arbovirus in Thailand: Surveillance of dengue, chikungunya and zika virus, with a focus on coinfections.

Infections caused by arboviruses such as dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) frequently occur in tropical and subtropical regions. These three viruses are transmitted by Aedes (Ae.) aegypti and Ae. albopictus. In Thailand, the highest incidence of arbovirus infection and the high circulation of Aedes mosquito mainly occurs in the Southern provinces of the country. Few studies have focused on the incidence of co-infection of arboviruses in this region. In the present study, a cross-sectional study was conducted on a cohort of 182 febrile patients from three hospitals located in Southern Thailand. Surveillance of DENV, CHIKV and ZIKV was conducted from May to October 2016 during the rainy season. The serological analysis and molecular detection of arboviruses were performed by ELISA and multiplex RT-PCR respectively. The results demonstrated that 163 cases out of 182 patients (89.56%) were infected with DENV, with a predominance of DENV-2. Among these DENV positive cases, a co-infection with CHIKV for 6 patients (3.68%) and with ZIKV for 1 patient (0.61%) were found. 19 patients out of 182 were negative for arboviruses. This study provides evidence of co-infection of arboviruses in Southern Thailand and highlight the importance of testing DENV and other medically important arboviruses, such as CHIKV and ZIKV simultaneously.

Effects of UVC Irradiation on Growth and Apoptosis of Scedosporium apiospermum and Lomentospora prolificans.

Scedosporium apiospermum and Lomentospora prolificans are important fungal species isolated from immunocompromised patients. Previous studies have demonstrated that these filamentous fungi exist as saprophytes in the soil and showed the highest minimum inhibitory concentration to several drugs. We aimed to examine how UVC affects the S. apiospermum and L. prolificans by investigating the role of UVC on growth, induction of apoptosis by ethidium bromide (EB)/acridine orange (AO) staining, and transcriptomic study of caspase recruitment domain family, member 9 (CARD-9) gene. Our studies showed that 15 minutes of exposure to UVC light effectively increased reduction in both organisms and caused changes in colony morphology, color, and hyphal growth pattern. After 15 min of UVC irradiation, apoptotic cells were quantitated by EB/AO staining, and the percentage of apoptosis was 96.06% in S. apiospermum and 28.30% in L. prolificans. CARD-9 gene expression results confirmed that apoptosis was induced in S. apiospermum and L. prolificans after UVC treatment and that S. apiospermum showed a higher expression of apoptosis signaling than L. prolificans. Our study explored the effects of UVC in the inactivation of S. apiospermum and L. prolificans. We hope that our data is useful to other researchers in future studies.

The impact of Zika virus infection on human neuroblastoma (SH-SY5Y) cell line.

BACKGROUND & OBJECTIVES: An increase in Zika virus (ZIKV) epidemic during the last decade has become a major global concern as the virus affects both newborns and adult humans. Earlier studies have shown the impact of ZIKV infection in developing human foetus. However, effective in vitro model of target cells for studying the ZIKV infection in adult human neurons is not available. This study aimed to establish the use of human neuroblastoma cell line (SH-SY5Y) for studying an infection of ZIKV in vitro. METHODS: ZIKV growth kinetics, viral toxicity, and SH-SY5Y cell vialibity were determined after ZIKV infection in SH-SY5Y cells in vitro. ZIKV-infected SH-SY5Y cells were morphologically analysed and compared with nonhuman primate Vero cells. Furthermore, the susceptibility of SH-SY5Y cells to ZIKV infection was also determined. RESULTS: The results showed that ZIKV efficiently infects SH-SY5Y cell lines in vitro. Gradual changes of several cellular homeostasis parameters including cell viability, cytotoxicity, and cell morphology were observed in ZIKVinfected SH-SY5Y cells when compared to mock-treated or non-human primate cells. Interestingly, ZIKV particles were detected in the nucleoplasmic compartment of the infected SH-SY5Y cells. INTERPRETATION & CONCLUSION: The results suggest that ZIKV particle can be detected in the nucleoplasmic compartment of the infected SH-SY5Y cells beside the known viral replicating cytoplasmic area. Hence, SH-SY5Y cells can be used as an in vitro adult human neuronal cell-based model, for further elucidating the ZIKV biology, and highlight other possible significance of Zika virus distribution through nuclear localization, which may correlate to the neuropathological defects in ZIKV-infected adult humans.

In vitro study of Zika virus infection in boar semen.

Zika virus (ZIKV) is an important arbovirus that is capable of directly infecting neuronal cells. Infection can cause microcephaly in fetuses and Guillain-Barré syndrome in adults. Recent epidemiological studies have shown that ZIKV is sexually transmitted, especially from infected males to uninfected females. This study aimed to investigate the transmission pattern of ZIKV in semen using boar semen. Experiments were performed ex vivo using semen from healthy boar. The samples were infected with ZIKV, and viral RNA was detected and cell morphology was examined at different time points postinfection. ZIKV infection was confirmed by transmission electron microscopy. Viral RNA levels were found to markedly decrease as the time postinfection increased, without any evidence of virus replication. The sperm showed no significant changes in morphology. Transmission electron microscopy revealed the presence of virus-free sperm, suggesting that ZIKV cannot replicate in boar semen. We suggest three possible reasons underlying this phenomenon. First, the spermatozoa of boar might not be the target of ZIKV associated with sexual transmission. Second, the effect of the external environment on spermatozoa may affect ZIKV replication. Third, ZIKV may not be tropic for spermatozoa. This ex vivo study might be used as a platform to study the association of sexual transmission with ZIKV in other longer-lasting cells, such as Leydig or Sertoli cells.

Dengue and Zika viruses: lessons learned from the similarities between these Aedes mosquito-vectored arboviruses.

The currently spreading arbovirus epidemic is having a severe impact on human health worldwide. The two most common flaviviruses, dengue virus (DENV) and Zika virus (ZIKV), are transmitted through the same viral vector, Aedes spp. mosquitoes. Since the discovery of DENV in 1943, this virus has been reported to cause around 390 million human infections per year, approximately 500,000 of which require hospitalization and over 20,000 of which are lethal. The present DENV epidemic is primarily concentrated in Southeast Asia. ZIKV, which was discovered in 1952, is another important arthropod-borne flavivirus. The neurotropic role of ZIKV has been reported in infected newborns with microcephaly and in adults with Guillain-Barre syndrome. Despite DENV and ZIKV sharing the same viral vector, their complex pathogenic natures are poorly understood, and the infections they cause do not have specific treatments or effective vaccines. Therefore, this review will describe what is currently known about the clinical characteristics, pathogenesis mechanisms, and transmission of these two viruses. Better understanding of the interrelationships between DENV and ZIKV will provide a useful perspective for developing an effective strategy for controlling both viruses in the future.

Immunopathogenesis of Dengue Virus-Induced Redundant Cell Death: Apoptosis and Pyroptosis.

Dengue virus infection is a self-limited condition, which is of particular importance in tropical and subtropical regions and for which no specific treatment or effective vaccine is available. There are several hypotheses explaining dengue pathogenesis. These usually refer to host immune responses, including antibody-dependent enhancement, cytokine expression, and dengue virus particles including NS1 protein, which lead to cell death by both apoptosis and pyroptosis. A clear understanding of the pathogenesis should facilitate the development of vaccines and therapies. This review focuses on the immunopathogenesis in relation to clinical manifestations and patterns of cell death, focusing on the pathogenesis of severe dengue.