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.

Floods and cause-specific mortality in the UK: a nested case-control study.

BACKGROUND: Floods are the most frequent weather-related disaster, causing significant health impacts worldwide. Limited studies have examined the long-term consequences of flooding exposure. METHODS: Flood data were retrieved from the Dartmouth Flood Observatory and linked with health data from 499,487 UK Biobank participants. To calculate the annual cumulative flooding exposure, we multiplied the duration and severity of each flood event and then summed these values for each year. We conducted a nested case-control analysis to evaluate the long-term effect of flooding exposure on all-cause and cause-specific mortality. Each case was matched with eight controls. Flooding exposure was modelled using a distributed lag non-linear model to capture its nonlinear and lagged effects. RESULTS: The risk of all-cause mortality increased by 6.7% (odds ratio (OR): 1.067, 95% confidence interval (CI): 1.063-1.071) for every unit increase in flood index after confounders had been controlled for. The mortality risk from neurological and mental diseases was negligible in the current year, but strongest in the lag years 3 and 4. By contrast, the risk of mortality from suicide was the strongest in the current year (OR: 1.018, 95% CI: 1.008-1.028), and attenuated to lag year 5. Participants with higher levels of education and household income had a higher estimated risk of death from most causes whereas the risk of suicide-related mortality was higher among participants who were obese, had lower household income, engaged in less physical activity, were non-moderate alcohol consumers, and those living in more deprived areas. CONCLUSIONS: Long-term exposure to floods is associated with an increased risk of mortality. The health consequences of flooding exposure would vary across different periods after the event, with different profiles of vulnerable populations identified for different causes of death. These findings contribute to a better understanding of the long-term impacts of flooding exposure.

Effect of surface viscoelasticity on top jet drops produced by bursting bubbles.

Jet drops resulting from bubble bursting at a liquid surface play a key role in various mass transfer processes across the interface, including sea spray aerosol generation and pathogen transmission. However, the impact of structurally compound interfaces, characterized by complex surface rheology introduced by surface-active contaminants, on the jet drop ejection still remains unclear. Here, we experimentally investigate the influence of surface viscoelasticity on the size and velocity of the top jet drops from surface bubble bursting, examining both pure protein and mixed protein-surfactant solutions. We document that for bubble bursting at a pure-protein-laden surface where surface elasticity dominates, the increase in Ec, i.e. the interfacial elastocapillary number as the ratio between the effects of interfacial elasticity and capillarity, efficiently increases the radius and decreases the velocity of the top jet drop, ultimately inhibiting the jet drop ejection. On the other hand, considering the mixed protein-surfactant solution, we show that the top jet drop radius and velocity exhibit a different variation trend with Ec, which is attributed to the additional dissipation on the capillary waves as well as the retardation and resistance on the converging flow for jet formation from surface viscoelasticity. Our work may advance the understanding of bubble bursting dynamics at contaminated liquid surfaces and shed light on the potential influence of surface viscoelasticity on the generation of bubble bursting aerosols.

Discovery of Hepatitis B Virus Surface Antigen Suppressor GS-8873.

Chronic hepatitis B (CHB) virus infection afflicts hundreds of millions of people and causes nearly one million deaths annually. The high levels of circulating viral surface antigen (HBsAg) that characterize CHB may lead to T-cell exhaustion, resulting in an impaired antiviral immune response in the host. Agents that suppress HBsAg could help invigorate immunity toward infected hepatocytes and facilitate a functional cure. A series of dihydropyridoisoquinolizinone (DHQ) inhibitors of human poly(A) polymerases PAPD5/7 were reported to suppress HBsAg in vitro. An example from this class, RG7834, briefly entered the clinic. We set out to identify a potent, orally bioavailable, and safe PAPD5/7 inhibitor as a potential component of a functional cure regimen. Our efforts led to the identification of a dihydropyridophthalazinone (DPP) core with improved pharmacokinetic properties. A conformational restriction strategy and optimization of core substitution led to GS-8873, which was projected to provide deep HBsAg suppression with once-daily dosing.

Spatiotemporal characteristics and influencing factors for joint events of air pollution wave and cold wave in China.

Climate change triggered more environmental extremes. The joint events of air pollution wave and cold wave showed higher health risks than independent events, but little evidence is available for the spatiotemporal features of their co-occurrence. To better understand and forecast the joint events, a method framework was developed in this study. The temporal trend and spatial distribution of count and duration for joint events were measured at each grid cell (0.5°×0.5°) by integrating the PM2.5 air pollution wave and cold wave. The generalized linear mixed model was used to screen influencing variables that took into account socioeconomic characteristics, meteorological variables, and annual PM2.5 levels. During 2000 and 2018, the average annual count of joint events was 4.1 ± 6.8 days and the average duration ranged from 1.0 to 9.7 days. High spatial heterogeneity was observed throughout China, with a significant increase in joint events observed in Xinjiang area (the largest province in China). The most average count of joint events was observed in Henan province (one of the most populous provinces), while the longest duration was in Chongqing (a municipality, one of the megacities). Areas with higher PM2.5 levels, prolonged air pollution wave, and cold wave durations would experience more joint events. These findings can assist China in locating vulnerable areas and establishing effective local early warning systems. The method framework offers broader perspectives on mitigating health risks associated with extreme events in other countries and regions.

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.

Glycosides of Buyang Huanwu decoction inhibits inflammation associated with cerebral ischemia-reperfusion via the PINK1/Parkin mitophagy pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: A classic stroke formula is Buyang Huanwu Decoction (BYHWD), Glycosides are the pharmacological components found in BYHWD, which are utilized for the prevention and management of cerebral ischemia-reperfusion (CIR), as demonstrated in a previous study. Its neuroprotective properties are closely related to its ability to modulate inflammation, but its mechanism is as yet unclear. AIM OF THE STUDY: A research was undertaken to investigate the impact of glycosides on the inflammation of CIR through the PTEN-induced putative kinase-1 (PINK1)/Parkin mitophagy pathway. MATERIALS AND METHODS: Analyzing glycosides containing serum components was performed with ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). Glycosides were applied to rat of Middle cerebral artery occlusion/reperfusion (MCAO/R) model and primary neural cell of Oxygen glucose deprivation/reperfusion (OGD/R) model. The neuroprotective effect and the regulation of mitophagy of glycosides were evaluated through neural damage and PINK1/Parkin mitophagy activation. Moreover, the assessment of the relationship between glycosides regulation of mitophagy and its anti-inflammatory effects subsequent to mitophagy blockade was conducted by examining neural damage, PINK1/Parkin mitophagy activation, and levels of pyroptosis. RESULTS: (1) It was observed that the administration of glycosides resulted in a decrease in neurological function scores, a reduction in cerebral infarction volume, an increase in mitochondrial autophagosome, and the maintenance of a high expression status of light chain 3 (LC3) II/LC3Ⅰ protein. Additionally, there was a significant inhibition of p62 protein expression and an enhancement of PINK1 and Parkin protein expression. Furthermore, it was found that the effect of glycosides at a dosage of 0.128 g · kg-1 was significantly superior to that of glycosides at a dosage of 0.064 g · kg-1. Notably, the neuroprotective effect and inhibition of pyroptosis protein of glycosides at a dosage of 0.128 g · kg-1 were attenuated when mitochondrial autophagy was blocked. (2) Glycosides repaired cellular morphological damage, enhanced cell survival, and reduced Lactate dehydrogenase (LDH) leakage, with glycosides (2.36 µg·mL-1 and 4.72 µg·mL-1) neuronal protection being the strongest. Glycosides (4.72 µg·mL-1) maintained LC3II/LC3Ⅰ protein high expression state, inhibited p62 protein expression, and promoted PINK1 and Parkin protein expression, which was stronger than glycosides (2.36 µg·mL-1). The blockade of mitophagy resulted in a reduction of neuroprotection and inhibition of pyroptosis protein exerted by glycosides. CONCLUSION: Glycosides demonstrate the ability to hinder inflammation through the activation of the PINK1/Parkin mitophagy pathway, thereby leading to subsequent neuroprotective effects on CIR.

The phosphokinase activity of IRE1ɑ prevents the oxidative stress injury through miR-25/Nox4 pathway after ICH.

BACKGROUND: Endoplasmic reticulum (ER) stress and oxidative stress are the major pathologies encountered after intracerebral hemorrhage (ICH). Inositol-requiring enzyme-1 alpha (IRE1α) is the most evolutionarily conserved ER stress sensor, which plays a role in monitoring and responding to the accumulation of unfolded/misfolded proteins in the ER lumen. Recent studies have shown that ER stress is profoundly related to oxidative stress in physiological or pathological conditions. The purpose of this study was to investigate the role of IRE1α in oxidative stress and the potential mechanism. METHODS: A mouse model of ICH was established by autologous blood injection. The IRE1α phosphokinase inhibitor KIRA6 was administrated intranasally at 1 h after ICH, antagomiR-25 and agomiR-25 were injected intraventricularly at 24 h before ICH. Western blot analysis, RT-qPCR, immunofluorescence staining, hematoma volume, neurobehavioral tests, dihydroethidium (DHE) staining, H2O2 content, brain water content, body weight, Hematoxylin and Eosin (HE) staining, Nissl staining, Morris Water Maze (MWM) and Elevated Plus Maze (EPM) were performed. RESULTS: Endogenous phosphorylated IRE1α (p-IRE1α), miR-25-3p, and Nox4 were increased in the ICH model. Administration of KIRA6 downregulated miR-25-3p expression, upregulated Nox4 expression, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, reduced body weight, aggravated spatial learning and memory deficits, and increased anxiety levels. Then antagomiR-25 further upregulated the expression of Nox4, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, whereas agomiR-25 reversed the effects promoted by KIRA6. CONCLUSION: The IRE1α phosphokinase activity is involved in the oxidative stress response through miR-25/Nox4 pathway in the mouse ICH brain.

Climate change, environmental extremes, and human health in Australia: challenges, adaptation strategies, and policy gaps.

Climate change presents a major public health concern in Australia, marked by unprecedented wildfires, heatwaves, floods, droughts, and the spread of climate-sensitive infectious diseases. Despite these challenges, Australia's response to the climate crisis has been inadequate and subject to change by politics, public sentiment, and global developments. This study illustrates the spatiotemporal patterns of selected climate-related environmental extremes (heatwaves, wildfires, floods, and droughts) across Australia during the past two decades, and summarizes climate adaptation measures and actions that have been taken by the national, state/territory, and local governments. Our findings reveal significant impacts of climate-related environmental extremes on the health and well-being of Australians. While governments have implemented various adaptation strategies, these plans must be further developed to yield concrete actions. Moreover, Indigenous Australians should not be left out in these adaptation efforts. A collaborative, comprehensive approach involving all levels of government is urgently needed to prevent, mitigate, and adapt to the health impacts of climate change.

Trends and hotspots in research on medical images with deep learning: a bibliometric analysis from 2013 to 2023.

Background: With the rapid development of the internet, the improvement of computer capabilities, and the continuous advancement of algorithms, deep learning has developed rapidly in recent years and has been widely applied in many fields. Previous studies have shown that deep learning has an excellent performance in image processing, and deep learning-based medical image processing may help solve the difficulties faced by traditional medical image processing. This technology has attracted the attention of many scholars in the fields of computer science and medicine. This study mainly summarizes the knowledge structure of deep learning-based medical image processing research through bibliometric analysis and explores the research hotspots and possible development trends in this field. Methods: Retrieve the Web of Science Core Collection database using the search terms "deep learning," "medical image processing," and their synonyms. Use CiteSpace for visual analysis of authors, institutions, countries, keywords, co-cited references, co-cited authors, and co-cited journals. Results: The analysis was conducted on 562 highly cited papers retrieved from the database. The trend chart of the annual publication volume shows an upward trend. Pheng-Ann Heng, Hao Chen, and Klaus Hermann Maier-Hein are among the active authors in this field. Chinese Academy of Sciences has the highest number of publications, while the institution with the highest centrality is Stanford University. The United States has the highest number of publications, followed by China. The most frequent keyword is "Deep Learning," and the highest centrality keyword is "Algorithm." The most cited author is Kaiming He, and the author with the highest centrality is Yoshua Bengio. Conclusion: The application of deep learning in medical image processing is becoming increasingly common, and there are many active authors, institutions, and countries in this field. Current research in medical image processing mainly focuses on deep learning, convolutional neural networks, classification, diagnosis, segmentation, image, algorithm, and artificial intelligence. The research focus and trends are gradually shifting toward more complex and systematic directions, and deep learning technology will continue to play an important role.

Vessel wall MRI characteristics associated with intraprocedural stent thrombosis during angioplasty for intracranial atherosclerotic stenosis.

BACKGROUND: Few studies have so far explored plaque characteristics on high-resolution magnetic resonance vessel wall imaging (HR-VWI) associated with intraprocedural stent thrombosis (IPST) during angioplasty for intracranial atherosclerotic stenosis (ICAS). We aimed to investigate the plaque features on HR-VWI associated with IPST during stenting for ICAS. METHODS: This study recruited 77 patients with ICAS who underwent intracranial stenting using the Gateway-Wingspan system, and were performed with enhanced pre- and post-contrast T1-weighted HR-VWI on a 3.0T MRI scanner before angioplasty. During stenting for ICAS, eight patients (male: 100%, age mean ± standard deviation (SD): 58.7±2.47) developed IPST within 30 minutes after stenting. To ensure comparability, 16 patients who had undergone intracranial stenting but did not develop IPST were matched as controls for this study. Univariable and binary logistic models were used to explore the plaque characteristics on HR-VWI associated with IPST. RESULTS: Patients who developed IPST had less plaque diffusion (37.50% vs 81.25%, p=0.036), a more severe degree of area stenosis (median 96.30% vs 81.65%, p<0.01), and a higher plaque enhancement index (median 37.99 vs 13.12, p<0.01) compared with those who did not. After multivariate adjustment, IPST was independently associated with a more severe degree of area stenosis (adjusted odds ratio (OR) 1.20, 95% confidence interval (CI) 1.01-1.43, p=0.044) and a higher plaque enhancement index (adjusted OR 1.17, 95% CI 1.01 to 1.36, p=0.036). CONCLUSION: Intraprocedural stent thrombosis during intracranial angioplasty for patients with ICAS may be independently associated with a higher plaque enhancement index and a more severe degree of area stenosis on HR-VWI.

Bidirectional Droplet Manipulation on Magnetically Actuated Superhydrophobic Ratchet Surfaces.

Droplet manipulation has garnered significant attention in various fields due to its wide range of applications. Among many different methods, magnetic actuation has emerged as a promising approach for remote and instantaneous droplet manipulation. In this study, we present the bidirectional droplet manipulation on a magnetically actuated superhydrophobic ratchet surface. The surface consists of silicon strips anchored on elastomer ridges with superhydrophobic black silicon structures on the top side and magnetic layers on the bottom side. The soft magnetic properties of the strips enable their bidirectional tilting to form a ratchet surface and thus bidirectional droplet manipulation upon varying external magnetic field location and strength. Computational multiphysics models were developed to predict the tilting of the strips, demonstrating the concept of bidirectional tilting along with a tilting angle hysteresis theory. Experimental results confirmed the soft magnetic hysteresis and consequential bidirectional tilting of the strips. The superhydrophobic ratchet surface formed by the tilting strips induced the bidirectional self-propulsion of dispensed droplets through the Laplace pressure gradient, and the horizontal acceleration of the droplets was found to be positively correlated with the tilting angle of the strips. Additionally, a finite element analysis was conducted to identify the critical conditions for dispensed droplet penetration through the gaps between the strips, which hinder the droplet's self-propulsion. The models and findings here provide substantial insights into the design and optimization of magnetically actuated superhydrophobic ratchet surfaces to manipulate droplets in the context of digital microfluidic applications.

Mortality risks associated with floods in 761 communities worldwide: time series study.

OBJECTIVE: To evaluate lag-response associations and effect modifications of exposure to floods with risks of all cause, cardiovascular, and respiratory mortality on a global scale. DESIGN: Time series study. SETTING: 761 communities in 35 countries or territories with at least one flood event during the study period. PARTICIPANTS: Multi-Country Multi-City Collaborative Research Network database, Australian Cause of Death Unit Record File, New Zealand Integrated Data Infrastructure, and the International Network for the Demographic Evaluation of Populations and their Health Network database. MAIN OUTCOME MEASURES: The main outcome was daily counts of deaths. An estimation for the lag-response association between flood and daily mortality risk was modelled, and the relative risks over the lag period were cumulated to calculate overall effects. Attributable fractions of mortality due to floods were further calculated. A quasi-Poisson model with a distributed lag non-linear function was used to examine how daily death risk was associated with flooded days in each community, and then the community specific associations were pooled using random effects multivariate meta-analyses. Flooded days were defined as days from the start date to the end date of flood events. RESULTS: A total of 47.6 million all cause deaths, 11.1 million cardiovascular deaths, and 4.9 million respiratory deaths were analysed. Over the 761 communities, mortality risks increased and persisted for up to 60 days (50 days for cardiovascular mortality) after a flooded day. The cumulative relative risks for all cause, cardiovascular, and respiratory mortality were 1.021 (95% confidence interval 1.006 to 1.036), 1.026 (1.005 to 1.047), and 1.049 (1.008 to 1.092), respectively. The associations varied across countries or territories and regions. The flood-mortality associations appeared to be modified by climate type and were stronger in low income countries and in populations with a low human development index or high proportion of older people. In communities impacted by flood, up to 0.10% of all cause deaths, 0.18% of cardiovascular deaths, and 0.41% of respiratory deaths were attributed to floods. CONCLUSIONS: This study found that the risks of all cause, cardiovascular, and respiratory mortality increased for up to 60 days after exposure to flood and the associations could vary by local climate type, socioeconomic status, and older age.

Secondary Bubble Entrainment via Primary Bubble Bursting at a Viscoelastic Surface.

Bubble bursting at liquid surfaces is ubiquitous and plays a key role for the mass transfer across interfaces, impacting global climate and human health. Here, we document an unexpected phenomenon that when a bubble bursts at a viscoelastic surface of a bovine serum albumin solution, a secondary (daughter) bubble is entrapped with no subsequent jet drop ejection, contrary to the counterpart experimentally observed at a Newtonian surface. We show that the strong surface dilatational elastic stress from the viscoelastic surface retards the cavity collapse and efficiently damps out the precursor waves, thus facilitating the dominant wave focusing above the cavity nadir. The onset of daughter bubble entrainment is well predicted by an interfacial elastocapillary number comparing the effects of surface dilatational elasticity and surface tension. Our Letter highlights the important role of surface rheology on free surface flows and may find important implications in bubble dynamics with a contaminated interface exhibiting complex surface rheology.

Global population exposure to landscape fire air pollution from 2000 to 2019.

Wildfires are thought to be increasing in severity and frequency as a result of climate change1-5. Air pollution from landscape fires can negatively affect human health4-6, but human exposure to landscape fire-sourced (LFS) air pollution has not been well characterized at the global scale7-23. Here, we estimate global daily LFS outdoor fine particulate matter (PM2.5) and surface ozone concentrations at 0.25° × 0.25° resolution during the period 2000-2019 with the help of machine learning and chemical transport models. We found that overall population-weighted average LFS PM2.5 and ozone concentrations were 2.5 µg m-3 (6.1% of all-source PM2.5) and 3.2 µg m-3 (3.6% of all-source ozone), respectively, in 2010-2019, with a slight increase for PM2.5, but not for ozone, compared with 2000-2009. Central Africa, Southeast Asia, South America and Siberia experienced the highest LFS PM2.5 and ozone concentrations. The concentrations of LFS PM2.5 and ozone were about four times higher in low-income countries than in high-income countries. During the period 2010-2019, 2.18 billion people were exposed to at least 1 day of substantial LFS air pollution per year, with each person in the world having, on average, 9.9 days of exposure per year. These two metrics increased by 6.8% and 2.1%, respectively, compared with 2000-2009. Overall, we find that the global population is increasingly exposed to LFS air pollution, with socioeconomic disparities.

Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series study.

BACKGROUND: The global spatiotemporal pattern of mortality risk and burden attributable to tropical cyclones is unclear. We aimed to evaluate the global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019. METHODS: The wind speed associated with cyclones from 1980 to 2019 was estimated globally through a parametric wind field model at a grid resolution of 0·5°â€ˆ× 0·5°. A total of 341 locations with daily mortality and temperature data from 14 countries that experienced at least one tropical cyclone day (a day with maximum sustained wind speed associated with cyclones ≥17·5 m/s) during the study period were included. A conditional quasi-Poisson regression with distributed lag non-linear model was applied to assess the tropical cyclone-mortality association. A meta-regression model was fitted to evaluate potential contributing factors and estimate grid cell-specific tropical cyclone effects. FINDINGS: Tropical cyclone exposure was associated with an overall 6% (95% CI 4-8) increase in mortality in the first 2 weeks following exposure. Globally, an estimate of 97 430 excess deaths (95% empirical CI [eCI] 71 651-126 438) per decade were observed over the 2 weeks following exposure to tropical cyclones, accounting for 20·7 (95% eCI 15·2-26·9) excess deaths per 100 000 residents (excess death rate) and 3·3 (95% eCI 2·4-4·3) excess deaths per 1000 deaths (excess death ratio) over 1980-2019. The mortality burden exhibited substantial temporal and spatial variation. East Asia and south Asia had the highest number of excess deaths during 1980-2019: 28 744 (95% eCI 16 863-42 188) and 27 267 (21 157-34 058) excess deaths per decade, respectively. In contrast, the regions with the highest excess death ratios and rates were southeast Asia and Latin America and the Caribbean. From 1980-99 to 2000-19, marked increases in tropical cyclone-related excess death numbers were observed globally, especially for Latin America and the Caribbean and south Asia. Grid cell-level and country-level results revealed further heterogeneous spatiotemporal patterns such as the high and increasing tropical cyclone-related mortality burden in Caribbean countries or regions. INTERPRETATION: Globally, short-term exposure to tropical cyclones was associated with a significant mortality burden, with highly heterogeneous spatiotemporal patterns. In-depth exploration of tropical cyclone epidemiology for those countries and regions estimated to have the highest and increasing tropical cyclone-related mortality burdens is urgently needed to help inform the development of targeted actions against the increasing adverse health impacts of tropical cyclones under a changing climate. FUNDING: Australian Research Council and Australian National Health and Medical Research Council.

Health Effects of Cyclones: A Systematic Review and Meta-Analysis of Epidemiological Studies.

BACKGROUND: More intense cyclones are expected in the future as a result of climate change. A comprehensive review is urgently needed to summarize and update the evidence on the health effects of cyclones. OBJECTIVES: We aimed to provide a systematic review with meta-analysis of current evidence on the risks of all reported health outcomes related to cyclones and to identify research gaps and make recommendations for further research. METHODS: We systematically searched five electronic databases (MEDLINE, Embase, PubMed, Scopus, and Web of Science) for relevant studies in English published before 21 December 2022. Following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, we developed inclusion criteria, screened the literature, and included epidemiological studies with a quantitative risk assessment of any mortality or morbidity-related outcomes associated with cyclone exposures. We extracted key data and assessed study quality for these studies and applied meta-analyses to quantify the overall effect estimate and the heterogeneity of comparable studies. RESULTS: In total, 71 studies from eight countries (the United States, China, India, Japan, the Philippines, South Korea, Australia, Brazil), mostly the United States, were included in the review. These studies investigated the all-cause and cause-specific mortality, as well as morbidity related to injury, cardiovascular diseases (CVDs), respiratory diseases, infectious diseases, mental disorders, adverse birth outcomes, cancer, diabetes, and other outcomes (e.g., suicide rates, gender-based violence). Studies mostly included only one high-amplitude cyclone (cyclones with a Saffir-Simpson category of 4 or 5, i.e., Hurricanes Katrina or Sandy) and focused on mental disorders morbidity and all-cause mortality and hospitalizations. Consistently elevated risks of overall mental health morbidity, post-traumatic stress disorder (PTSD), as well as all-cause mortality or hospitalizations, were found to be associated with cyclones. However, the results for other outcomes were generally mixed or limited. A statistically significant overall relative risk of 1.09 [95% confidence interval (CI): 1.04, 1.13], 1.18 (95% CI: 1.12, 1.25), 1.15 (95% CI: 1.13, 1.18), 1.26 (95% CI: 1.05, 1.50) was observed for all-cause mortality, all-cause hospitalizations, respiratory disease, and chronic obstructive pulmonary disease hospitalizations, respectively, after cyclone exposures, whereas no statistically significant risks were identified for diabetes mortality, heart disease mortality, and preterm birth. High between-study heterogeneity was observed. CONCLUSIONS: There is generally consistent evidence supporting the notion that high-amplitude cyclones could significantly increase risks of mental disorders, especially for PTSD, as well as mortality and hospitalizations, but the evidence for other health outcomes, such as chronic diseases (e.g., CVDs, cancer, diabetes), and adverse birth outcomes remains limited or inconsistent. More studies with rigorous exposure assessment, of larger spatial and temporal scales, and using advanced modeling strategy are warranted in the future, especially for those small cyclone-prone countries or regions with low and middle incomes. https://doi.org/10.1289/EHP12158.

Associations between neighborhood greenspace and multiple birth outcomes across two metropolitan areas in Australia.

BACKGROUND: Beneficial effects of greenspace on birth outcomes have been reported. However, insights on key windows of exposure and underlying mechanisms are needed. METHOD: Births in Sydney (2016-2019) were retrieved from NSW Midwives Data Collection. Births in Brisbane (2000-2014) were retrieved from Queensland Health Perinatal Data Collection. Satellite image-derived normalized difference vegetation index (NDVI) and night time light (NTL) index were used. For each city, linear regression models were used to assess associations between greenspace and birth weight, and logistic models to estimate the risks of preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA) per 0.1 increase in NDVI. We examined the trimester-specific associations, and heterogeneities by night time light. RESULTS: The study included 193,264 singleton births in Sydney and 155,606 singleton births in Brisbane. An 0.1 increase in greenspace during whole pregnancy was associated with 17.4 g (95%CI: 14.5 to 20.2) increase in birth weight in Sydney, and 15.1 g (95%CI: 12.0 to 18.5) in Brisbane. The odds ratios were 0.98 (95%CI: 0.97 to 0.99) for LBW, 0.99 (95%CI: 0.98 to 1.00) for PTB, and 0.98 (95%CI: 0.96 to 0.99) for SGA per 0.1 increase in NDVI during whole pregnancy for participants in Sydney. Similarly, reduced odds of adverse birth outcomes were observed in Brisbane. Trimester specific models demonstrated a consistent pattern of associations in the same direction across all outcomes. We found that effects of greenspace exposure on birth outcomes attenuated after adjusting for NTL, but stronger effects among babies of mothers from areas with more NTL. CONCLUSIONS AND RELEVANCE: These findings suggest a beneficial association between neighborhood greenspace and healthier pregnancies in urban areas. We provide novel evidence of interactions between greenspace and NTL.

Effects of Tirzepatide Versus Insulin Glargine on Cystatin C-Based Kidney Function: A SURPASS-4 Post Hoc Analysis.

OBJECTIVE: Tirzepatide reduces HbA1c and body weight, and creatinine-based estimated glomerular filtration rate (eGFR) decline. Unlike creatine-derived eGFR (eGFR-creatinine), cystatin C-derived eGFR (eGFR-cystatin C) is unaffected by muscle mass changes. We assessed effects of tirzepatide on eGFR-creatinine and eGFR-cystatin C. RESEARCH DESIGN AND METHODS: Our primary outcome was eGFR change from baseline at 52 weeks with pooled tirzepatide (5, 10, and 15 mg) and titrated insulin glargine in adults with type 2 diabetes and high cardiovascular risk (SURPASS-4). RESULTS: Least squares mean (SE) eGFR-creatinine (mL/min/1.73 m2) changes from baseline with tirzepatide and insulin glargine were -2.5 (0.38) and -3.9 (0.38) (between-group difference, 1.4 [95% CI 0.3-2.4]) and -3.5 (0.37) and -5.3 (0.37) (between-group difference, 1.8 [95% CI 0.8-2.8]) for eGFR-cystatin C. Baseline, 1-year, and 1-year change from baseline values significantly correlated between eGFR-cystatin C and eGFR-creatinine. Measures of eGFR changes did not correlate with body weight changes. CONCLUSIONS: Tirzepatide slows the eGFR decline rate, supporting a kidney-protective effect.

N-linoleyltyrosine resisted the growth of non-small cell lung cancer cells via the regulation of CB1 and CB2 involvement of PI3K and ERK pathways.

Background: N-linoleyltyrosine (NITyr), one of the anandamide analogs, exerts activity via the endocannabinoid receptors (CB1 and CB2), which showed anti-tumor effects in various tumors. Therefore, we speculated that NITyr might show anti-non-small cell lung cancer (NSCLC) effects via the CB1 or CB2 receptor. The purpose of the investigation was to reveal the anti-tumor ability of NITyr on A549 cells and its mechanisms. Methods: The viability of A549 cells was measured by MTT assay, and the cell cycle and apoptosis were both examined by flow cytometry; in addition, cell migration was tested by wound healing assay. Apoptosis-related markers were measured by immunofluorescence. The downstream signaling pathways (PI3K, ERK, and JNK) of CB1 or CB2 were examined through Western blotting. The expressions of CB1 and CB2 were detected by immunofluorescence. Finally, the AutoDock software was used to validate the binding affinity between the targets, such as CB1 and CB2, with NITyr. Results: We found that NITyr inhibited cell viability, hindered the cell cycle, resulted in apoptosis, and inhibited migration. The CB1 inhibitor, AM251, and the CB2 inhibitor, AM630, weakened the aforementioned phenomenon. The immunofluorescence assay suggested that NITyr upregulated the expression of CB1 and CB2. Western blot analysis indicated that NITyr upregulated the expression of p-ERK, downregulated the expression of p-PI3K, and did not affect p-JNK expression. In conclusion, NITyr showed a role in inhibiting NSCLC through the activation of CB1 and CB2 receptors involved in PI3K and ERK pathways.