All-cause, cardiovascular, and respiratory mortality and wildfire-related ozone: a multicountry two-stage time series analysis.

BACKGROUND: Wildfire activity is an important source of tropospheric ozone (O3) pollution. However, no study to date has systematically examined the associations of wildfire-related O3 exposure with mortality globally. METHODS: We did a multicountry two-stage time series analysis. From the Multi-City Multi-Country (MCC) Collaborative Research Network, data on daily all-cause, cardiovascular, and respiratory deaths were obtained from 749 locations in 43 countries or areas, representing overlapping periods from Jan 1, 2000, to Dec 31, 2016. We estimated the daily concentration of wildfire-related O3 in study locations using a chemical transport model, and then calibrated and downscaled O3 estimates to a resolution of 0·25°â€ˆ× 0·25° (approximately 28 km2 at the equator). Using a random-effects meta-analysis, we examined the associations of short-term wildfire-related O3 exposure (lag period of 0-2 days) with daily mortality, first at the location level and then pooled at the country, regional, and global levels. Annual excess mortality fraction in each location attributable to wildfire-related O3 was calculated with pooled effect estimates and used to obtain excess mortality fractions at country, regional, and global levels. FINDINGS: Between 2000 and 2016, the highest maximum daily wildfire-related O3 concentrations (≥30 µg/m3) were observed in locations in South America, central America, and southeastern Asia, and the country of South Africa. Across all locations, an increase of 1 µg/m3 in the mean daily concentration of wildfire-related O3 during lag 0-2 days was associated with increases of 0·55% (95% CI 0·29 to 0·80) in daily all-cause mortality, 0·44% (-0·10 to 0·99) in daily cardiovascular mortality, and 0·82% (0·18 to 1·47) in daily respiratory mortality. The associations of daily mortality rates with wildfire-related O3 exposure showed substantial geographical heterogeneity at the country and regional levels. Across all locations, estimated annual excess mortality fractions of 0·58% (95% CI 0·31 to 0·85; 31 606 deaths [95% CI 17 038 to 46 027]) for all-cause mortality, 0·41% (-0·10 to 0·91; 5249 [-1244 to 11 620]) for cardiovascular mortality, and 0·86% (0·18 to 1·51; 4657 [999 to 8206]) for respiratory mortality were attributable to short-term exposure to wildfire-related O3. INTERPRETATION: In this study, we observed an increase in all-cause and respiratory mortality associated with short-term wildfire-related O3 exposure. Effective risk and smoke management strategies should be implemented to protect the public from the impacts of wildfires. FUNDING: Australian Research Council and the Australian National Health and Medical Research Council.

SIRT7 knockdown promotes gemcitabine sensitivity of pancreatic cancer cell via upregulation of GLUT3 expression.

Gemcitabine serves as a first-line chemotherapeutic treatment for pancreatic cancer (PC), but it is prone to rapid drug resistance. Increasing the sensitivity of PC to gemcitabine has long been a focus of research. Fasting interventions may augment the effects of chemotherapy and present new options. SIRT7 is known to link metabolism with various cellular processes through post-translational modifications. We found upregulation of SIRT7 in PC cells is associated with poor prognosis and gemcitabine resistance. Cross-analysis of RNA-seq and ATAC-seq data suggested that GLUT3 might be a downstream target gene of SIRT7. Subsequent investigations demonstrated that SIRT7 directly interacts with the enhancer region of GLUT3 to desuccinylate H3K122. Our group's another study revealed that GLUT3 can transport gemcitabine in breast cancer cells. Here, we found GLUT3 KD reduces the sensitivity of PC cells to gemcitabine, and SIRT7 KD-associated gemcitabine-sensitizing could be reversed by GLUT3 KD. While fasting mimicking induced upregulation of SIRT7 expression in PC cells, knocking down SIRT7 enhanced sensitivity to gemcitabine through upregulating GLUT3 expression. We further confirmed the effect of SIRT7 deficiency on the sensitivity of gemcitabine under fasting conditions using a mouse xenograft model. In summary, our study demonstrates that SIRT7 can regulate GLUT3 expression by binding to its enhancer and altering H3K122 succinylation levels, thus affecting gemcitabine sensitivity in PC cells. Additionally, combining SIRT7 knockdown with fasting may improve the efficacy of gemcitabine. This unveils a novel mechanism by which SIRT7 influences gemcitabine sensitivity in PC and offer innovative strategies for clinical combination therapy with gemcitabine.

A Highly Stable, Multifunctional Janus Dressing for Treating Infected Wounds.

The limited and unstable absorption of excess exudate is a major challenge during the healing of infected wounds. In this study, a highly stable, multifunctional Janus dressing with unidirectional exudate transfer capacity is fabricated based on a single poly(lactide caprolactone) (PLCL). The success of this method relies on an acid hydrolysis reaction that transforms PLCL fibers from hydrophobic to hydrophilic in situ. The resulting interfacial affinity between the hydrophilic/phobic PLCL fibers endows the Janus structure with excellent unidirectional liquid transfer and high structural stability against repeated stretching, bending, and twisting. Various other functions, including wound status detection, antibacterial, antioxidant, and anti-inflammatory properties, are also integrated into the dressing by incorporating phenol red and epigallocatechin gallate. An in vivo methicillin-resistant Staphylococcus aureus-infected wound model confirms that the Janus dressing, with the capability to remove exudate from the infected site, not only facilitates epithelialization and collagen deposition, but also ensures low inflammation and high angiogenesis, thus reaching an ideal closure rate up to 98.4% on day 14. The simple structure, multiple functions, and easy fabrication of the dressing may offer a promising strategy for treating chronic wounds, rooted in the challenges of bacterial infection, excessive exudate, and persistent inflammation.

Short-Term Exposure to Wildfire-Specific PM2.5 and Hospitalization for Diabetes Morbidity: A Study in Multiple Countries and Territories.

OBJECTIVE: To evaluate associations of wildfire fine particulate matter (PM2.5) with diabetes across multiple countries and territories. RESEARCH DESIGN AND METHODS: We collected data on 3,612,135 diabetes hospitalizations from 1,008 locations in Australia, Brazil, Canada, Chile, New Zealand, Thailand, and Taiwan during 2000-2019. Daily wildfire-specific PM2.5 levels were estimated through chemical transport models and machine-learning calibration. Quasi-Poisson regression with distributed lag nonlinear models and random-effects meta-analysis were applied to estimate associations between wildfire-specific PM2.5 and diabetes hospitalization. Subgroup analyses were by age, sex, location income level, and country or territory. Diabetes hospitalizations attributable to wildfire-specific PM2.5 and nonwildfire PM2.5 were compared. RESULTS: Each 10 µg/m3 increase in wildfire-specific PM2.5 levels over the current day and previous 3 days was associated with relative risks (95% CI) of 1.017 (1.011-1.022), 1.023 (1.011-1.035), 1.023 (1.015-1.032), 0.962 (0.823-1.032), 1.033 (1.001-1.066), and 1.013 (1.004-1.022) for all-cause, type 1, type 2, malnutrition-related, other specified, and unspecified diabetes hospitalization, respectively. Stronger associations were observed for all-cause, type 1, and type 2 diabetes in Thailand, Australia, and Brazil; unspecified diabetes in New Zealand; and type 2 diabetes in high-income locations. Relative risks (95% CI) of 0.67% (0.16-1.18%) and 1.02% (0.20-1.81%) for all cause and type 2 diabetes hospitalizations were attributable to wildfire-specific PM2.5. Compared with nonwildfire PM2.5, wildfire-specific PM2.5 posed greater risks of all-cause, type 1, and type 2 diabetes and were responsible for 38.7% of PM2.5-related diabetes hospitalizations. CONCLUSIONS: We show the relatively underappreciated links between diabetes and wildfire air pollution, which can lead to a nonnegligible proportion of PM2.5-related diabetes hospitalizations. Precision prevention and mitigation should be developed for those in advantaged communities and in Thailand, Australia, and Brazil.

Macrophage polarisation and inflammatory mechanisms in atherosclerosis: Implications for prevention and treatment.

Atherosclerosis is a chronic inflammatory disease characterised by plaque accumulation in the arteries. Macrophages are immune cells that are crucial in the development of atherosclerosis. Macrophages can adopt different phenotypes, with the M1 phenotype promoting inflammation while the M2 phenotype counteracting it. This review focuses on the factors that drive the polarisation of M1 macrophages towards a pro-inflammatory phenotype during AS. Additionally, we explored metabolic reprogramming mechanisms and cytokines secretion by M1 macrophages. Hyperlipidaemia is widely recognised as a major risk factor for atherosclerosis. Modified lipoproteins released in the presence of hyperlipidaemia can trigger the release of cytokines and recruit circulating monocytes, which adhere to the damaged endothelium and differentiate into macrophages. Macrophages engulf lipids, leading to the formation of foam cells. As atherosclerosis progresses, foam cells become the necrotic core within the atherosclerotic plaques, destabilising them and triggering ischaemic disease. Furthermore, we discuss recent research focusing on targeting macrophages or inflammatory pathways for preventive or therapeutic purposes. These include statins, PCSK9 inhibitors, and promising nanotargeted drugs. These new developments hold the potential for the prevention and treatment of atherosclerosis and its related complications.

Efficacy of a smartphone application assisting home-based rehabilitation and symptom management for patients with lung cancer undergoing video-assisted thoracoscopic lobectomy: a prospective, single-blinded, randomised control trial (POPPER study).

BACKGROUND: Video-assisted thoracoscopic (VATS) lobectomy can affect patients' pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and post-discharge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation. METHODS: The app was developed based on three modules: a symptom reporting system with alerts, aerobic and respiratory training exercises, and educational material. Four core symptoms were selected based on a questionnaire survey of 201 patients and three rounds of Delphi voting by 30 experts. We screened 265 patients and randomly assigned 136 equally to the app group and usual care group. The primary outcome was pulmonary function recovery at 30 days postoperatively. Secondary outcomes included symptom burden and interference with daily living (both rated using the MD Anderson Symptom Inventory for Lung Cancer), aerobic exercise intensity, emergency department visits, app-related safety, and satisfaction with the app. FINDINGS: Of the 136 participants, 56.6% were women and their mean age was 61 years. The pulmonary function recovery ratio 1 month after surgery in the app group was significantly higher than that in the usual care group (79.32% vs. 75.73%; P=0.040). The app group also recorded significantly lower symptom burden and interference with daily living scores and higher aerobic exercise intensity after surgery than the usual care group. Thirty-two alerts were triggered in the app group. The highest pulmonary function recovery ratio and aerobic exercise intensity were recorded in those patients who triggered alerts in both groups. INTERPRETATION: Using a smartphone app is an effective approach to accelerate home-based rehabilitation after VATS lobectomy. The symptom alert mechanism of this app could optimise recovery outcomes, possibly driven by patients' increased self-awareness.

Uni-directional release of ibuprofen from an asymmetric fibrous membrane enables effective peritendinous anti-adhesion.

Drug-loaded porous membranes have been deemed to be effective physicochemical barriers to separate postoperative adhesion-prone tissues in tendon healing. However, cell viability and subsequent tissue regeneration might be severely interfered with the unrestricted release and the locally excessive concentration of anti-inflammatory drugs. Herein, we report a double-layered membrane with sustained and uni-directional drug delivery features to prevent peritendinous adhesion without hampering the healing outcome. A vortex-assisted electrospinning system in combination with ibuprofen (IBU)-in-water emulsion was utilized to fabricate IBU-loaded poly-ʟ-lactic-acid (PLLA) fiber bundle membrane (PFB-IBU) as the anti-adhesion layer. The resultant highly porous structure, oleophilic and hydrophobic nature of PLLA fibers enabled in situ loading of IBU with a concentration gradient across the membrane thickness. Aligned collagen nanofibers were further deposited at the low IBU concentration side of the membrane for regulating cell growth and achieving uni-directional release of IBU. Drug release kinetics showed that the release amount of IBU from the high concentration side reached 79.32% at 14 d, while it was only 0.35% at the collagen side. Therefore, fibroblast proliferation at the high concentration side was successfully inhibited without affecting the oriented growth of tendon-derived stem cells at the other side. In vivo evaluation of the rat Achilles adhesion model confirmed the successful peritendinous anti-adhesion of our double-layered membrane, in that the macrophage recruitment, the inflammatory factor secretion and the deposition of pathological adhesion markers such as α-SMA and COL-III were all inhibited, which greatly improved the peritendinous fibrosis and restored the motor function of tendon.

Ambient fine particulate matter and daily mortality: a comparative analysis of observed and estimated exposure in 347 cities.

BACKGROUND: Model-estimated air pollution exposure products have been widely used in epidemiological studies to assess the health risks of particulate matter with diameters of ≤2.5 µm (PM2.5). However, few studies have assessed the disparities in health effects between model-estimated and station-observed PM2.5 exposures. METHODS: We collected daily all-cause, respiratory and cardiovascular mortality data in 347 cities across 15 countries and regions worldwide based on the Multi-City Multi-Country collaborative research network. The station-observed PM2.5 data were obtained from official monitoring stations. The model-estimated global PM2.5 product was developed using a machine-learning approach. The associations between daily exposure to PM2.5 and mortality were evaluated using a two-stage analytical approach. RESULTS: We included 15.8 million all-cause, 1.5 million respiratory and 4.5 million cardiovascular deaths from 2000 to 2018. Short-term exposure to PM2.5 was associated with a relative risk increase (RRI) of mortality from both station-observed and model-estimated exposures. Every 10-µg/m3 increase in the 2-day moving average PM2.5 was associated with overall RRIs of 0.67% (95% CI: 0.49 to 0.85), 0.68% (95% CI: -0.03 to 1.39) and 0.45% (95% CI: 0.08 to 0.82) for all-cause, respiratory, and cardiovascular mortality based on station-observed PM2.5 and RRIs of 0.87% (95% CI: 0.68 to 1.06), 0.81% (95% CI: 0.08 to 1.55) and 0.71% (95% CI: 0.32 to 1.09) based on model-estimated exposure, respectively. CONCLUSIONS: Mortality risks associated with daily PM2.5 exposure were consistent for both station-observed and model-estimated exposures, suggesting the reliability and potential applicability of the global PM2.5 product in epidemiological studies.

Fine-grained image classification on bats using VGG16-CBAM: a practical example with 7 horseshoe bats taxa (CHIROPTERA: Rhinolophidae: Rhinolophus) from Southern China.

BACKGROUND: Rapid identification and classification of bats are critical for practical applications. However, species identification of bats is a typically detrimental and time-consuming manual task that depends on taxonomists and well-trained experts. Deep Convolutional Neural Networks (DCNNs) provide a practical approach for the extraction of the visual features and classification of objects, with potential application for bat classification. RESULTS: In this study, we investigated the capability of deep learning models to classify 7 horseshoe bat taxa (CHIROPTERA: Rhinolophus) from Southern China. We constructed an image dataset of 879 front, oblique, and lateral targeted facial images of live individuals collected during surveys between 2012 and 2021. All images were taken using a standard photograph protocol and setting aimed at enhancing the effectiveness of the DCNNs classification. The results demonstrated that our customized VGG16-CBAM model achieved up to 92.15% classification accuracy with better performance than other mainstream models. Furthermore, the Grad-CAM visualization reveals that the model pays more attention to the taxonomic key regions in the decision-making process, and these regions are often preferred by bat taxonomists for the classification of horseshoe bats, corroborating the validity of our methods. CONCLUSION: Our finding will inspire further research on image-based automatic classification of chiropteran species for early detection and potential application in taxonomy.

Pain Intensity and Satisfaction of Pain Relief in Discharged Cancer Patients: A Large Sample Study in China.

BACKGROUND: Many studies have focused on the quality of pain management in hospitalized patients with cancer pain, while what happens after discharge remains unclear. AIM: The purpose of this study was to investigate the pain intensity and satisfaction of pain relief among a large sample of Chinese patients with cancer pain after discharge. DESIGN: Cross-sectional, descriptive, correlational research. SETTINGS AND SAMPLE: ABOUT: 1,013 patients were recruited in a tertiary cancer hospital, and their residence addresses were distributed in 6 geographical regions, including 26 provinces, municipalities, and autonomous regions. METHODS: The 1,013 patients with cancer pain were discharged from the wards of a national cancer hospital in China from July 2020 to October 2021. A nurse in the pain clinic followed the patients based on a whole-process information system and collected the data after the cancer pain patients were discharged. The study methods followed the STROBE guidelines. RESULTS: The average age of 1,013 discharged patients was 61.30 (±12.56) years. Moderate and severe background pain (BGP) was reported in 749 patients (73.94%), and more than 3 instances of breakthrough pain (BTP) in the past 24 hours were reported in 541 patients (53.41%). More severe BGP was associated with more frequent BTP (p < .01). In addition, there were 572 patients (56.47%) whose satisfaction with pain relief was lower than 70%. More severe BGP was associated with a lower satisfaction degree (r = -0.796, p < .01). CONCLUSIONS: Pain among discharged Chinese patients with cancer is poorly managed, and there is a low degree of satisfaction with pain relief. Nurses can do more work to assist cancer patients in managing pain more effectively by ensuring they have a plan to report and manage pain after discharge.

Effect of different strains on quality characteristics of soy yogurt: Physicochemical, nutritional, safety features, sensory, and formation mechanism.

The purpose of the study was to explore effect of four different strains on quality characteristics of soy yogurt. The results showed that four strains were all related to the genus Lactobacillus and N1 was Lacticaseibacillus rhamnosus, N2 was Lacticaseibacillus paracasei, N3 was Lacticaseibacillus plantarum, and N4 was Lacticaseibacillus acidophilus. The result analysis of biochemical, sensory, nutritional, functional and safety properties of fermentation process and end products showed that the soy yogurt fermented with L. rhamnosus N1 had the highest isoflavone content and the lowest phytic acid content; the soy yogurt fermented with L. paracasei N2 had the highest content of free amino acids and oligosaccharides, the lowest content of trypsin inhibitors; the soy yogurt fermented with L. plantarum N3 had the lowest oil content; the soy yogurt fermented with L. acidophilus N4 had optimal functional properties. In summary, N4 was suitable as a fermentation strain for soymilk.

Advancements in hospice and palliative care in China: A five-year review.

In response to the challenges posed by an aging population, an increasing cancer incidence, and the growing demand for hospice care services, China has actively promoted the development of hospice and palliative care, achieving significant progress in the past five years. This article provides a retrospective analysis of the efforts and accomplishments in the field of hospice and palliative care in China, focusing on government policy support, quality standards and regulations, drug management, health provider training, and public education. Additionally, the study explores the current issues and challenges in the field.

Is model-estimated PM2.5 exposure equivalent to station-observed in mortality risk assessment? A literature review and meta-analysis.

Model-estimated air pollution exposure assessments have been extensively employed in the evaluation of health risks associated with air pollution. However, few studies synthetically evaluate the reliability of model-estimated PM2.5 products in health risk assessment by comparing them with ground-based monitoring station air quality data. In response to this gap, we undertook a meticulously structured systematic review and meta-analysis. Our objective was to aggregate existing comparative studies to ascertain the disparity in mortality effect estimates derived from model-estimated ambient PM2.5 exposure versus those based on monitoring station-observed PM2.5 exposure. We conducted searches across multiple databases, namely PubMed, Scopus, and Web of Science, using predefined keywords. Ultimately, ten studies were included in the review. Of these, seven investigated long-term annual exposure, while the remaining three studies focused on short-term daily PM2.5 exposure. Despite variances in the estimated Exposure-Response (E-R) associations, most studies revealed positive associations between ambient PM2.5 exposure and all-cause and cardiovascular mortality, irrespective of the exposure being estimated through models or observed at monitoring stations. Our meta-analysis revealed that all-cause mortality risk associated with model-estimated PM2.5 exposure was in line with that derived from station-observed sources. The pooled Relative Risk (RR) was 1.083 (95% CI: 1.047, 1.119) for model-estimated exposure, and 1.089 (95% CI: 1.054, 1.125) for station-observed sources (p = 0.795). In conclusion, most model-estimated air pollution products have demonstrated consistency in estimating mortality risk compared to data from monitoring stations. However, only a limited number of studies have undertaken such comparative analyses, underscoring the necessity for more comprehensive investigations to validate the reliability of these model-estimated exposure in mortality risk assessment.

Estimates of global mortality burden associated with short-term exposure to fine particulate matter (PM2·5).

BACKGROUND: The acute health effects of short-term (hours to days) exposure to fine particulate matter (PM2·5) have been well documented; however, the global mortality burden attributable to this exposure has not been estimated. We aimed to estimate the global, regional, and urban mortality burden associated with short-term exposure to PM2·5 and the spatiotemporal variations in this burden from 2000 to 2019. METHODS: We combined estimated global daily PM2·5 concentrations, annual population counts, country-level mortality rates, and epidemiologically derived exposure-response functions to estimate the mortality attributable to short-term PM2·5 exposure from 2000 to 2019, in the continental regions and in 13 189 urban centres worldwide at a spatial resolution of 0·1°â€ˆ× 0·1°. We tested the robustness of our mortality estimates with different theoretical minimum risk exposure levels, lag effects, and exposure-response functions. FINDINGS: Approximately 1 million (95% CI 690 000-1·3 million) premature deaths per year from 2000 to 2019 were attributable to short-term PM2·5 exposure, representing 2·08% (1·41-2·75) of total global deaths or 17 (11-22) premature deaths per 100 000 population. Annually, 0·23 million (0·15 million-0·30 million) deaths attributable to short-term PM2·5 exposure were in urban areas, constituting 22·74% of the total global deaths attributable to this cause and accounting for 2·30% (1·56-3·05) of total global deaths in urban areas. The sensitivity analyses showed that our worldwide estimates of mortality attributed to short-term PM2·5 exposure were robust. INTERPRETATION: Short-term exposure to PM2·5 contributes a substantial global mortality burden, particularly in Asia and Africa, as well as in global urban areas. Our results highlight the importance of mitigation strategies to reduce short-term exposure to air pollution and its adverse effects on human health. FUNDING: Australian Research Council and the Australian National Health and Medical Research Council.

The Concentration of Lactoferrin in Breast Milk Correlates with Maternal Body Mass Index and Parity.

Background: Lactoferrin (LF) is a multifunctional glycoprotein found in human milk and body fluids, which has been shown to play a vital role in regulating the immunity and supporting the intestinal health of infants. Aim: This study evaluated the association between maternal/parturient factors and LF concentration in the breast milk of Chinese mothers. Methods: 207 breast milk samples were collected from healthy mothers with in the first year of lactation. Maternal and parturient information was collected for these participants through questionnaires. The content of lactoferrin in breast milk was detected by liquid chromatography, and macronutrient concentration in breast milk was measured by human milk analyzer in only 109 samples. Results: Our findings demonstrated that the LF content was much higher within the first month of lactation than it was after that period (p < 0.05). When compared with normal and lean mothers, the LF content of obese mothers was considerably higher (p < 0.05). The parity and LF content showed a favorable correlation. The proportion of LF to total protein tended to decrease as lactation progressed. Protein, fat, dry matter, and energy content were significantly positively correlated with LF content (p < 0.001). Conclusion: Early breast milk tends to have a higher level of LF, and the change of LF concentration in breast milk is associated with the parity and body mass index of the mother.

Huperzine A ameliorates neurological deficits after spontaneous subarachnoid hemorrhage through endothelial cell pyroptosis inhibition.

Spontaneous subarachnoid hemorrhage (SAH) is a kind of hemorrhagic stroke which causes neurological deficits in survivors. Huperzine A has a neuroprotective effect, but its role in SAH is unclear. Therefore, we explore the effect of Huperzine A on neurological deficits induced by SAH and the related mechanism. In this study, Evans blue assay, TUNEL staining, immunofluorescence, western blot analysis, and ELISA are conducted. We find that Huperzine A can improve neurological deficits and inhibit the apoptosis of nerve cells in SAH rats. Huperzine A treatment can improve the upregulation of brain water content, damage of blood-brain barrier, fibrinogen and matrix metalloprotein 9 expressions and the downregulation of ZO-1 and occludin expressions induced by SAH. Huperzine A inhibit the expressions of proteins involved in pyroptosis in endothelial cells in SAH rats. The increase in MDA content and decrease in SOD activity in SAH rats can be partly reversed by Huperzine A. The ROS inducer H 2O 2 can induce pyroptosis and inhibit the expressions of ZO-1 and occludin in endothelial cells, which can be blocked by Huperzine A. In addition, the increase in the entry of p65 into the nucleus in endothelial cells can be partly reversed by Huperzine A. Huperzine A may delay the damage of blood-brain barrier in SAH rats by inhibiting oxidative stress-mediated pyroptosis and tight junction protein expression downregulation through the NF-κB pathway. Overall, Huperzine A may have clinical value for treating SAH.

Tropical cyclone-specific mortality risks and the periods of concern: A multicountry time-series study.

BACKGROUND: More intense tropical cyclones (TCs) are expected in the future under a warming climate scenario, but little is known about their mortality effect pattern across countries and over decades. We aim to evaluate the TC-specific mortality risks, periods of concern (POC) and characterize the spatiotemporal pattern and exposure-response (ER) relationships on a multicountry scale. METHODS AND FINDINGS: Daily all-cause, cardiovascular, and respiratory mortality among the general population were collected from 494 locations in 18 countries or territories during 1980 to 2019. Daily TC exposures were defined when the maximum sustained windspeed associated with a TC was ≥34 knots using a parametric wind field model at a 0.5° × 0.5° resolution. We first estimated the TC-specific mortality risks and POC using an advanced flexible statistical framework of mixed Poisson model, accounting for the population changes, natural variation, seasonal and day of the week effects. Then, a mixed meta-regression model was used to pool the TC-specific mortality risks to estimate the overall and country-specific ER relationships of TC characteristics (windspeed, rainfall, and year) with mortality. Overall, 47.7 million all-cause, 15.5 million cardiovascular, and 4.9 million respiratory deaths and 382 TCs were included in our analyses. An overall average POC of around 20 days was observed for TC-related all-cause and cardiopulmonary mortality, with relatively longer POC for the United States of America, Brazil, and Taiwan (>30 days). The TC-specific relative risks (RR) varied substantially, ranging from 1.04 to 1.42, 1.07 to 1.77, and 1.12 to 1.92 among the top 100 TCs with highest RRs for all-cause, cardiovascular, and respiratory mortality, respectively. At country level, relatively higher TC-related mortality risks were observed in Guatemala, Brazil, and New Zealand for all-cause, cardiovascular, and respiratory mortality, respectively. We found an overall monotonically increasing and approximately linear ER curve of TC-related maximum sustained windspeed and cumulative rainfall with mortality, with heterogeneous patterns across countries and regions. The TC-related mortality risks were generally decreasing from 1980 to 2019, especially for the Philippines, Taiwan, and the USA, whereas potentially increasing trends in TC-related all-cause and cardiovascular mortality risks were observed for Japan. CONCLUSIONS: The TC mortality risks and POC varied greatly across TC events, locations, and countries. To minimize the TC-related health burdens, targeted strategies are particularly needed for different countries and regions, integrating epidemiological evidence on region-specific POC and ER curves that consider across-TC variability.