SARS-CoV-2 Mpro responds to oxidation by forming disulfide and NOS/SONOS bonds.

The main protease (Mpro) of SARS-CoV-2 is critical for viral function and a key drug target. Mpro is only active when reduced; turnover ceases upon oxidation but is restored by re-reduction. This suggests the system has evolved to survive periods in an oxidative environment, but the mechanism of this protection has not been confirmed. Here, we report a crystal structure of oxidized Mpro showing a disulfide bond between the active site cysteine, C145, and a distal cysteine, C117. Previous work proposed this disulfide provides the mechanism of protection from irreversible oxidation. Mpro forms an obligate homodimer, and the C117-C145 structure shows disruption of interactions bridging the dimer interface, implying a correlation between oxidation and dimerization. We confirm dimer stability is weakened in solution upon oxidation. Finally, we observe the protein's crystallization behavior is linked to its redox state. Oxidized Mpro spontaneously forms a distinct, more loosely packed lattice. Seeding with crystals of this lattice yields a structure with an oxidation pattern incorporating one cysteine-lysine-cysteine (SONOS) and two lysine-cysteine (NOS) bridges. These structures further our understanding of the oxidative regulation of Mpro and the crystallization conditions necessary to study this structurally.

Association between heat and hospital admissions in people with disabilities in South Korea: a nationwide, case-crossover study.

BACKGROUND: Despite extensive findings on the hazardous impacts of environmental heat exposure, little is known about the effect on people with disabilities. This study aimed to estimate the association between environmental heat exposure and emergency department admissions for people with disabilities compared with people without disabilities. METHODS: In this nationwide, case-crossover study, we linked data on emergency department admissions (cases) for any cause in the warm season in South Korea from the Korean National Health Insurance Service (NHIS)-National Sample Cohort database (a nationally representative database of 1 million systematically sampled beneficiaries covering all ages) from Jan 1, 2002, to Dec 31, 2019, and short-term daily mean temperature exposure (measured via Google Earth Engine at a 9 km spatial grid, aggregated to district). We defined beneficiaries with disabilities as those who were registered as disabled in the NHIS; disabilities included in our study were physical disability, brain lesion disorders, blindness or vision loss, and deafness or hearing loss. Other types of disability were not included for confidentiality reasons. A time-stratified case-crossover design, in which participants served as their own control, was used with conditional logistic regression to estimate the association between heat and emergency department admissions in people with and without disabilities. FINDINGS: 23 792 emergency department admissions were recorded for 59 527 people with disabilities. Of these 23 792 admissions, 10 234 (43·0%) individuals were female and 13 558 (57·0%) were male. The odds ratio (OR) of emergency department admissions associated with heat (99th temperature percentile vs 75th percentile) was 1·15 (95% CI 1·07-1·24) in people with disabilities and 1·06 (1·04-1·09) in people without disabilities. The annual excess number of emergency department admissions attributable to heat per 100 000 persons-years was 27·81 admissions (95% CI 9·20-45·69) and excess medical costs were US$638 739·47 (95% CI 201 900·12-1 059 641·87) in people with disabilities; these values were more than four times that of the non-disabled population. People with brain lesion disorders, people with severe physical disabilities, female individuals, and those aged 65 years or older showed higher heat risks. The risks of emergency department admissions due to mental disorder (1·89, 95% CI 1·18-3·00) and respiratory diseases (1·34, 1·06-1·70) also showed higher heat risks than for the other two analysed causes of admission (cardiovascular and genitourinary diseases). INTERPRETATION: Heat was associated with increased risk of emergency department admissions for people with and without disabilities, but the risk appeared to be higher for those with disabilities. These results can inform policy makers when establishing action plans for people with disabilities. FUNDING: National Research Foundation of Korea, the South Korean Ministry of Environment, and the South Korean Ministry of Education.

Apnea during moderate to deep sedation using continuous infusion of remimazolam compared to propofol and dexmedetomidine: A retrospective observational study.

Remimazolam's rapid onset and offset make it an innovative sedative for use during regional anesthesia. However, its respiratory safety profile is not well understood. We compared the continuous infusion of remimazolam with commonly used sedatives, propofol and dexmedetomidine, after regional anesthesia. In this retrospective study, the incidence of apnea (>10 seconds) was assessed in patients who underwent orthopedic surgery under regional anesthesia and received moderate to deep sedation using continuous infusion of remimazolam (group R: 0.1 mg/kg in 2 minutes followed by 0.5 mg/kg/hr). The incidence was compared with that of propofol (group P: 2-3 µg/mL target-controlled infusion) and dexmedetomidine (group D: 1 µg/kg in 10 minutes followed by 0.4-1 µg/kg/hr). Propensity score weighted multivariable logistic regression model was utilized to determine the effects of the sedative agents on the incidence of apnea. A total of 634 (191, 278, and 165 in group R, P, and D) cases were included in the final analysis. The incidence of apnea was 63.9%, 67.3%, and 48.5% in group R, P, and D, respectively. The adjusted odds ratios for apnea were 2.33 (95% CI, 1.50 to 3.61) and 2.50 (95% CI, 1.63 to 3.85) in group R and P, compared to group D. The incidence of apnea in patients receiving moderate to deep sedation using continuous infusion of remimazolam with dosage suggested in the current study was over 60%. Therefore, careful titration and respiratory monitoring is warranted.

Heat-related mortality and ambulance transport after a power outage in the Tokyo metropolitan area.

Background: Air conditioners can prevent heat-related illness and mortality, but the increased use of air conditioners may enhance susceptibility to heat-related illnesses during large-scale power failures. Here, we examined the risks of heat-related illness ambulance transport (HIAT) and mortality associated with typhoon-related electricity reduction (ER) in the summer months in the Tokyo metropolitan area. Methods: We conducted event study analyses to compare temperature-HIAT and mortality associations before and after the power outage (July to September 2019). To better understand the role of temperature during the power outage, we then examined whether the temperature-HIAT and mortality associations were modified by different power outage levels (0%, 10%, and 20% ER). We computed the ratios of relative risks to compare the risks associated with various ER values to the risks associated without ER. Results: We analyzed the data of 14,912 HIAT cases and 74,064 deaths. Overall, 93,200 power outage cases were observed when the typhoon hit. Event study results showed that the incidence rate ratio was 2.01 (95% confidence interval [CI] = 1.42, 2.84) with effects enduring up to 6 days, and 1.11 (95% CI = 1.02, 1.22) for mortality on the first 3 days after the typhoon hit. Comparing 20% to 0% ER, the ratios of relative risks of heat exposure were 2.32 (95% CI = 1.41, 3.82) for HIAT and 0.95 (95% CI = 0.75, 1.22) for mortality. Conclusions: A 20% ER was associated with a two-fold greater risk of HIAT because of summer heat during the power outage, but there was little evidence for the association with all-cause mortality.

Selective Flocculation and H2O2-Free Oxidative Etching-Based Synthesis of Highly Monodisperse Ag Nanospheres for Uniform Quantum Dot Photoluminescence-Enhancing Plasmonic Cavity Applications.

Ag nanoparticles have garnered significant attention for their excellent plasmonic properties and potential use as plasmonic cavities, primarily because of their intrinsically low ohmic losses and optical properties in the visible range. These are particularly crucial in systems involving quantum dots that absorb light at low wavelengths, where the need for a high threshold energy of interband transitions necessitates the incorporation of Ag nanostructures. However, the synthesis of Ag nanoparticles still encounters challenges in achieving structural uniformity and monodispersity, along with chemical stability, consequentially inducing inconsistent and poorly reliable optical responses. Here, we present a two-step approach for synthesizing highly uniform spherical Ag nanoparticles involving depletion-induced flocculation and Cu(II)-mediated oxidative etching. We found that the selective flocculation of multitwinned Ag nanocrystals significantly enhances the uniformity of the resulting Ag nanostructures, leaving behind only single-crystalline and single-twinned nanostructures. Subsequent oxidative etching, in which cupric ions are directly involved in the reaction, was designed based on Pourbaix diagrams to proceed following thermodynamically favorable states and circumvent the generation of reactive chemical species such as H2O2. This leads to perfectly spherical shapes of final Ag nanoparticles with a synthetic yield of 99.5% and additionally reduces the overall reaction time. Furthermore, we explore the potential applications of these monodisperse Ag nanospheres as uniform plasmonic cavities. The fabricated Ag nanosphere films uniformly enhanced the photoluminescence of InP/ZnSe/ZnS quantum dots, showcasing their capabilities in exhibiting consistent plasmonic responses across a large area.

Recent Studies on Metal-Embedded Silica Nanoparticles for Biological Applications.

Recently, silica nanoparticles (NPs) have attracted considerable attention as biocompatible and stable templates for embedding noble metals. Noble-metal-embedded silica NPs utilize the exceptional optical properties of novel metals while overcoming the limitations of individual novel metal NPs. In addition, the structure of metal-embedded silica NPs decorated with small metal NPs around the silica core results in strong signal enhancement in localized surface plasmon resonance and surface-enhanced Raman scattering. This review summarizes recent studies on metal-embedded silica NPs, focusing on their unique designs and applications. The characteristics of the metal-embedded silica NPs depend on the type and structure of the embedded metals. Based on this progress, metal-embedded silica NPs are currently utilized in various spectroscopic applications, serving as nanozymes, detection and imaging probes, drug carriers, photothermal inducers, and bioactivation molecule screening identifiers. Owing to their versatile roles, metal-embedded silica NPs are expected to be applied in various fields, such as biology and medicine, in the future.

Time-stratified case-crossover studies for aggregated data in environmental epidemiology: a tutorial.

The case-crossover design is widely used in environmental epidemiology as an effective alternative to the conventional time-series regression design to estimate short-term associations of environmental exposures with a range of acute events. This tutorial illustrates the implementation of the time-stratified case-crossover design to study aggregated health outcomes and environmental exposures, such as particulate matter air pollution, focusing on adjusting covariates and investigating effect modification using conditional Poisson regression. Time-varying confounders can be adjusted directly in the conditional regression model accounting for the adequate lagged exposure-response function. Time-invariant covariates at the subpopulation level require reshaping the typical time-series data set into a long format and conditioning out the covariate in the expanded stratum set. When environmental exposure data are available at geographical units, the stratum set should combine time and spatial dimensions. Moreover, it is possible to examine effect modification using interaction models. The time-stratified case-crossover design offers a flexible framework to properly account for a wide range of covariates in environmental epidemiology studies.

Associations between short-term exposure to ambient temperature and renal disease mortality in Japan during 1979-2019: A time-stratified case-crossover analysis.

Background: Previous studies have indicated that renal disease mortality is sensitive to ambient temperatures. However, most have been limited to the summer season with inconclusive evidence for changes in population vulnerability over time. Objective: This study aims to examine the association between short-term exposure to ambient temperatures and mortality due to renal diseases in Japan, and how this association varied over time. Methods: We conducted a two-stage, time-stratified case-crossover study from 1979 to 2019 across 47 prefectures of Japan. We obtained the data of daily mortality counts for all renal diseases, acute renal failure, and chronic renal disease. We fitted a conditional quasi-Poisson regression model with a distributed lag nonlinear model. A random-effects meta-analysis was applied to calculate national averages. We performed additional analyses by four subperiods, sex, and age groups. Results: We analyzed 997,590 renal mortality cases and observed a reversed J-shaped association. Lower temperatures were associated with increased mortality in all renal disease categories. The cumulative relative risks at 2.5th percentile compared to the minimum mortality temperature percentile were 1.34 (95% confidence interval [CI] = 1.29, 1.40), 1.51 (95% CI = 1.33, 1.71), and 1.33 (95% CI = 1.24, 1.43) for all renal, acute renal failure, and chronic renal disease mortality, respectively. The associations were observed in individuals of both sexes and aged 65 years and above. The associations of kidney mortality with low temperature remained consistent, while the associations with high temperature were pronounced in the past, but not in recent periods. Conclusions: Protection for individuals with impaired renal function from exposure to low temperatures during cold seasons is warranted.

High-Throughput Synthesis of Nanogap-Rich Gold Nanoshells Using Dual-Channel Infusion System.

Gold nanoshells have been actively applied in industries beyond the research stage because of their unique optical properties. Although numerous methods have been reported for gold nanoshell synthesis, the labor-intensive and time-consuming production process is an issue that must be overcome to meet industrial demands. To resolve this, we report a high-throughput synthesis method for nanogap-rich gold nanoshells based on a core silica support (denoted as SiO2@Au NS), affording a 50-fold increase in scale by combining it with a dual-channel infusion pump system. By continuously dropping the reactant solution through the pump, nanoshells with closely packed Au nanoparticles were prepared without interparticle aggregation. The thickness of the gold nanoshells was precisely controlled at 2.3-17.2 nm by regulating the volume of the reactant solution added dropwise. Depending on the shell thickness, the plasmonic characteristics of SiO2@Au NS prepared by the proposed method could be tuned. Moreover, SiO2@Au NS exhibited surface-enhanced Raman scattering activity comparable to that of gold nanoshells prepared by a previously reported low-throughput method at the same reactant ratio. The results indicate that the proposed high-throughput synthesis method involving the use of a dual-channel infusion system will contribute to improving the productivity of SiO2@Au NS with tunable plasmonic characteristics.

Serum thymidine kinase 1 protein concentrations and presence of its autoantibody as biomarkers for screening dogs with malignant tumors.

BACKGROUND: An accurate and easily accessible method for diagnosing malignancies in local veterinary clinics has not yet been established. OBJECTIVES: To investigate the usefulness of serum thymidine kinase 1 (TK1) protein and its autoantibody as tumor biomarkers in dogs. ANIMALS: Serum samples from 1702 dogs were collected from local animal hospitals and referral animal medical centers in South Korea. METHODS: TK1 protein OD value and TK1 autoantibody ratio (TK1 autoantibody OD/total IgG OD) in serum samples of dogs classified into healthy controls, group with nontumor disease, group with benign and group with malignant tumors were measured using lateral flow immunochromatographic assay methods. RESULTS: TK1 autoantibody levels were significantly higher in malignant tumor group (median 0.71) than in healthy controls (median 0.34), group with nontumor disease (median 0.34), and group with benign tumor (median 0.32, Welch t test, P < .0001). They were also significantly different among dogs with carcinomas (median 0.77), hematopoietic tumors (median 0.71), and sarcomas (median 0.56) than in healthy controls (median 0.34, post hoc Games-Howell test, P < .0001). In the receiver operating characteristic curve of TK1 protein, AUC was 0.633 (95% CI: 0.592-0.675, P < .0001). The AUC of TK1 autoantibody ratio was 0.758 (95% CI: 0.723-0.793, P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: TK1 autoantibody is a potentially useful biomarker for differentiating between healthy and tumor-bearing dogs, better than TK1 protein measurement. However, both were inadequate when used as single biomarkers for screening dogs to discover occult malignant tumors.

Fluctuating risk of acute kidney injury-related mortality for four weeks after exposure to air pollution: A multi-country time-series study in 6 countries.

BACKGROUND: Recent studies have reported that air pollution is related to kidney diseases. However, the global evidence on the risk of death from acute kidney injury (AKI) owing to air pollution is limited. Therefore, we investigated the association between short-term exposure to air pollution-particulate matter ≤ 2.5 µm (PM2.5), ozone (O3), and nitrogen dioxide (NO2)-and AKI-related mortality using a multi-country dataset. METHODS: This study included 41,379 AKI-related deaths in 136 locations in six countries during 1987-2018. A novel case time-series design was applied to each air pollutant during 0-28 lag days to estimate the association between air pollution and AKI-related deaths. Moreover, we calculated AKI deaths attributable to non-compliance with the World Health Organization (WHO) air quality guidelines. RESULTS: The relative risks (95% confidence interval) of AKI-related deaths are 1.052 (1.003, 1.103), 1.022 (0.994, 1.050), and 1.022 (0.982, 1.063) for 5, 10, and 10 µg/m3 increase in lag 0-28 days of PM2.5, warm-season O3, and NO2, respectively. The lag-distributed association showed that the risk appeared immediately on the day of exposure to air pollution, gradually decreased, and then increased again reaching the peak approximately 20 days after exposure to PM2.5 and O3. We also found that 1.9%, 6.3%, and 5.2% of AKI deaths were attributed to PM2.5, warm-season O3, and NO2 concentrations above the WHO guidelines. CONCLUSIONS: This study provides evidence that public health policies to reduce air pollution may alleviate the burden of death from AKI and suggests the need to investigate the several pathways between air pollution and AKI death.

A single-component, light-assisted uncaging switch for endoproteolytic release.

Proteases function as pivotal molecular switches, initiating numerous biological events. Notably, potyviral protease, derived from plant viruses, has emerged as a trusted proteolytic switch in synthetic biological circuits. To harness their capabilities, we have developed a single-component photocleavable switch, termed LAUNCHER (Light-Assisted UNcaging switCH for Endoproteolytic Release), by employing a circularly permutated tobacco etch virus protease and a blue-light-gated substrate, which are connected by fine-tuned intermodular linkers. As a single-component system, LAUNCHER exhibits a superior signal-to-noise ratio compared with multi-component systems, enabling precise and user-controllable release of payloads. This characteristic renders LAUNCHER highly suitable for diverse cellular applications, including transgene expression, tailored subcellular translocation and optochemogenetics. Additionally, the plug-and-play integration of LAUNCHER into existing synthetic circuits facilitates the enhancement of circuit performance. The demonstrated efficacy of LAUNCHER in improving existing circuitry underscores its significant potential for expanding its utilization in various applications.

Continuous cardiac output estimation using a new modified Fick method during off-pump coronary artery bypass graft surgery: a retrospective observational study.

PURPOSE: Several technical aspects of the Fick method limit its use intraoperatively. A data-driven modification of the Fick method may enable its use in intraoperative settings. METHODS: This two-center retrospective observational study included 57 (28 and 29 in each center) patients who underwent off-pump coronary artery bypass graft (OPCAB) surgery. Intraoperative recordings of physiological data were obtained and divided into training and test datasets. The Fick equation was used to calculate cardiac output (CO-Fick) using ventilator-determined variables, intraoperative hemoglobin level, and SvO2, with continuous thermodilution cardiac output (CCO) used as a reference. A modification CO-Fick was derived and validated: CO-Fick-AD, which adjusts the denominator of the original equation. RESULTS: Increased deviation between CO-Fick and CCO was observed when oxygen extraction was low. The root mean square error of CO-Fick was decreased from 6.07 L/min to 0.70 L/min after the modification. CO-Fick-AD showed a mean bias of 0.17 (95% CI 0.00-0.34) L/min, with a 36.4% (95% CI 30.6-44.4%) error. The concordance rates of CO-Fick-AD ranged from 73.3 to 87.1% depending on the time interval and exclusion zone. CONCLUSIONS: The original Fick method is not reliable when oxygen extraction is low, but a modification using data-driven approach could enable continuous estimation of cardiac output during the dynamic intraoperative period with minimal bias. However, further improvements in precision and trending ability are needed.

Effect of local anesthetic volume (20 vs. 40 ml) on the analgesic efficacy of costoclavicular block in arthroscopic shoulder surgery: a randomized controlled trial.

BACKGROUND: Among the various diaphragm-sparing alternatives to interscalene block, costoclavicular block (CCB) demonstrated a low hemidiaphragmatic paresis (HDP) occurrence but an inconsistent analgesic effect in arthroscopic shoulder surgery. We hypothesized that a larger volume of local anesthetic for CCB could provide sufficient analgesia by achieving sufficient supraclavicular spreading. METHODS: Sixty patients scheduled for arthroscopic rotator cuff repair were randomly assigned to receive CCB using one of two volumes of local anesthetic (CCB20, 0.75% ropivacaine 20 ml; CCB40, 0.375% ropivacaine 40 ml). The primary outcome was the rate of complete analgesia (0 on the numeric rating scale of pain) at 1 h postoperatively. The secondary outcomes included a sonographic assessment of local anesthetic spread, diaphragmatic function, pulmonary function, postoperative opioid use, and other pain-related experiences within 24 h postoperatively. RESULTS: The rates of complete analgesia were not significantly different (23.3% [7/30] and 33.3% [10/30] in the CCB20 and CCB40 groups, respectively; risk difference 10%, 95% CI [-13, 32], P = 0.567). There were no significant differences in other pain-related outcomes. Among the clinical factors considered, the only factor significantly associated with postoperative pain was the sonographic observation of supraclavicular spreading. There were no significant differences in the incidence of HDP and the change in pulmonary function between the two groups. CONCLUSIONS: Using 40 ml of local anesthetic does not guarantee supraclavicular spread during CCB. Moreover, it does not result in a higher rate of complete analgesia compared to using 20 ml of local anesthetic in arthroscopic shoulder surgery.

Associations of meteorological factors and dynamics of scrub typhus incidence in South Korea: A nationwide time-series study.

Scrub typhus, also known as Tsutsugamushi disease, is a climate-sensitive vector-borne disease that poses a growing public health threat. However, studies on the association between scrub typhus epidemics and meteorological factors in South Korea need to be complemented. Therefore, we aimed to analyze the association among ambient temperature, precipitation, and the incidence of scrub typhus in South Korea. First, we obtained data on the weekly number of scrub typhus cases and concurrent meteorological variables at the city-county level (Si-Gun) in South Korea between 2001 and 2019. Subsequently, a two-stage meta-regression analysis was conducted. In the first stage, we conducted time-series regression analyses using a distributed lag nonlinear model (DLNM) to investigate the association between temperature, precipitation, and scrub typhus incidence at each location. In the second stage, we employed a multivariate meta-regression model to combine the association estimates from all municipalities, considering regional indicators, such as mite species distribution, Normalized Difference Vegetation Index (NDVI), and urban-rural classification. Weekly mean temperature and weekly total precipitation exhibited a reversed U-shaped nonlinear association with the incidence of scrub typhus. The overall cumulative association with scrub typhus incidence peaked at 18.7 C° (with RRs of 9.73, 95% CI: 5.54-17.10) of ambient temperature (reference 9.7 C°) and 162.0 mm (with RRs of 1.87, 95% CI: 1.02-3.83) of precipitation (reference 2.8 mm), respectively. These findings suggest that meteorological factors contribute to scrub typhus epidemics by interacting with vectors, reservoir hosts, and human behaviors. This information serves as a reference for future public health policies and epidemiological research aimed at controlling scrub typhus infections.

Noninvasive tracking of mixed venous oxygen saturation via near-infrared spectroscopy cerebral oximetry: a retrospective observational study.

Although previous studies have shown correlation between regional cerebral oxygen saturation (rScO2) and mixed venous oxygen saturation (SvO2), there is a lack of pragmatic information on the clinical applicability of these findings, such as tracking ability. We retrospectively analyzed continuous intraoperative recordings of rScO2 and SvO2 obtained from a pulmonary artery catheter and either of two near-infrared spectroscopy (NIRS) devices (INVOS 5100C, Medtronic; O3, Masimo) during off-pump cardiopulmonary bypass (OPCAB) surgery in adult patients. The ability of rScO2 to track SvO2 was quantitatively evaluated with 5 min interval changes transformed into relative values. The analysis included 176 h of data acquired from 48 subjects (26 and 22 subjects for INVOS and O3 dataset, respectively). The area under ROC of the left-rScO2 for detecting change of SvO2 ≥ 10% in INVOS and O3 datasets were 0.919 (95% CI 0.903-0.936) and 0.852 (95% CI 0.818-0.885). The concordance rates between the interval changes of left-rScO2 and SvO2 in INVOS and O3 datasets were 90.6% and 91.9% with 10% exclusion zone. rScO2 can serve as a noninvasive tool for detecting changes in SvO2 levels, a critical hemodynamic measurement.

Utilizing a novel high-resolution malaria dataset for climate-informed predictions with a deep learning transformer model.

Climatic factors influence malaria transmission via the effect on the Anopheles vector and Plasmodium parasite. Modelling and understanding the complex effects that climate has on malaria incidence can enable important early warning capabilities. Deep learning applications across fields are proving valuable, however the field of epidemiological forecasting is still in its infancy with a lack of applied deep learning studies for malaria in southern Africa which leverage quality datasets. Using a novel high resolution malaria incidence dataset containing 23 years of daily data from 1998 to 2021, a statistical model and XGBOOST machine learning model were compared to a deep learning Transformer model by assessing the accuracy of their numerical predictions. A novel loss function, used to account for the variable nature of the data yielded performance around + 20% compared to the standard MSE loss. When numerical predictions were converted to alert thresholds to mimic use in a real-world setting, the Transformer's performance of 80% according to AUROC was 20-40% higher than the statistical and XGBOOST models and it had the highest overall accuracy of 98%. The Transformer performed consistently with increased accuracy as more climate variables were used, indicating further potential for this prediction framework to predict malaria incidence at a daily level using climate data for southern Africa.

Enhancing health resilience in Japan in a changing climate.

Climate change poses significant threats to human health, propelling Japan to take decisive action through the Climate Change Adaptation Act of 2018. This Act has led to the implementation of climate change adaptation policies across various sectors, including healthcare. In this review, we synthesized existing scientific evidence on the impacts of climate change on health in Japan and outlined the adaptation strategies and measures implemented by the central and local governments. The country has prioritized tackling heat-related illness and mortality and undertaken various adaptation measures to mitigate these risks. However, it faces unique challenges due to its super-aged society. Ensuring effective and coordinated strategies to address the growing uncertainties in vulnerability to climate change and the complex intersectoral impacts of disasters remains a critical issue. To combat the additional health risks by climate change, a comprehensive approach embracing adaptation and mitigation policies in the health sector is crucial. Encouraging intersectoral communication and collaboration will be vital for developing coherent and effective strategies to safeguard public health in the face of climate change.

Association between environmental factors and dengue incidence in Lao People's Democratic Republic: a nationwide time-series study.

BACKGROUND: Dengue fever is a vector-borne disease of global public health concern, with an increasing number of cases and a widening area of endemicity in recent years. Meteorological factors influence dengue transmission. This study aimed to estimate the association between meteorological factors (i.e., temperature and rainfall) and dengue incidence and the effect of altitude on this association in the Lao People's Democratic Republic (Lao PDR). METHODS: We used weekly dengue incidence and meteorological data, including temperature and rainfall, from 18 jurisdictions in Lao PDR from 2015 to 2019. A two-stage distributed lag nonlinear model with a quasi-Poisson distribution was used to account for the nonlinear and delayed associations between dengue incidence and meteorological variables, adjusting for long-term time trends and autocorrelation. RESULTS: A total of 55,561 cases were reported in Lao PDR from 2015 to 2019. The cumulative relative risk for the 90th percentile of weekly mean temperature (29 °C) over 22 weeks was estimated at 4.21 (95% confidence interval: 2.00-8.84), relative to the 25th percentile (24 °C). The cumulative relative risk for the weekly total rainfall over 12 weeks peaked at 82 mm (relative risk = 1.76, 95% confidence interval: 0.91-3.40) relative to no rain. However, the risk decreased significantly when heavy rain exceeded 200 mm. We found no evidence that altitude modified these associations. CONCLUSIONS: We found a lagged nonlinear relationship between meteorological factors and dengue incidence in Lao PDR. These findings can be used to develop climate-based early warning systems and provide insights for improving vector control in the country.

Net impact of air conditioning on heat-related mortality in Japanese cities.

BACKGROUND: Air conditioning (AC) presents a viable means of tackling the ill-effects of heat on human health. However, AC releases additional anthropogenic heat outdoors, and this could be detrimental to human health, especially in urban communities. This study determined the excess heat-related mortality attributable to anthropogenic heat from AC use under various projected global warming scenarios in seven Japanese cities. The overall protection from AC use was also measured. METHODS: Daily average 2-meter temperatures in the hottest month of August from 2000 to 2010 were modeled using the Weather Research and Forecasting (WRF) model with BEP+BEM (building effect parameterization and building energy model). Risk functions for heat-mortality associations were generated with and without AC use from a two-stage time series analysis. We coupled simulated August temperatures and heat-mortality risk functions to estimate averted deaths and unavoidable deaths from AC use. RESULTS: Anthropogenic heat from AC use slightly augmented the daily urban temperatures by 0.046 °C in Augusts of 2000-2010 and up to 0.181 °C in a future with 3 °C urban warming. This temperature rise was attributable to 3.1-3.5 % of heat-related deaths in Augusts of 2000-2010 under various urban warming scenarios. About 36-47 % of heat-related deaths could be averted by air conditioning use under various urban warming scenarios. DISCUSSION: AC has a valuable protective effect from heat despite some unavoidable mortality from anthropogenic heat release. Overall, the use of AC as a major adaptive strategy requires careful consideration.