The non-pharmaceutical interventions may affect the advantage in transmission of mutated variants during epidemics: A conceptual model for COVID-19.

As the COVID-19 pandemic continues, genetic mutations in SARS-CoV-2 emerge, and some of them are found more contagious than the previously identified strains, acting as the major mechanism for many large-scale epidemics. The transmission advantage of mutated variants is widely believed as an innate biological feature that is difficult to be altered by artificial factors. In this study, we explore how non-pharmaceutical interventions (NPI) may affect transmission advantage. A two-strain compartmental epidemic model is proposed and simulated to investigate the biological mechanism of the relationships among different NPIs, the changes in transmissibility of each strain and transmission advantage. Although the NPIs are effective in flattening the epidemic curve, we demonstrate that NPIs probably lead to a decline in transmission advantage, which is likely to occur if the NPIs become intensive. Our findings uncover the mechanistic relationship between NPIs and transmission advantage dynamically, and highlight the important role of NPIs not only in controlling the intensity of epidemics but also in slowing or even containing the growth of the proportion of variants.

Excess deaths from Alzheimer's disease and Parkinson's disease during the COVID-19 pandemic in the USA.

BACKGROUND: COVID-19 pandemic has indirect impacts on patients with chronic medical conditions, which may increase mortality risks for various non-COVID-19 causes. This study updates excess death statistics for Alzheimer's disease (AD) and Parkinson's disease (PD) up to 2022 and evaluates their demographic and spatial disparities in the USA. METHODS: This is an ecological time-series analysis of AD and PD mortality in the USA from January 2018 to March 2022. Poisson log-linear regressions were utilised to fit the weekly death data. Excess deaths were calculated with the difference between the observed and expected deaths under a counterfactual scenario of pandemic absence. RESULTS: From March 2020 to March 2022, we observed 41,115 and 10,328 excess deaths for AD and PD, respectively. The largest percentage increases in excess AD and PD deaths were found in the initial pandemic wave. For people aged ≥85 years, excess mortalities of AD and PD (per million persons) were 3946.0 (95% confidence interval [CI]: 2954.3, 4892.3) and 624.3 (95% CI: 369.4, 862.5), which were about 23 and 9 times higher than those aged 55-84 years, respectively. Females had a three-time higher excess mortality of AD than males (182.6 vs. 67.7 per million persons). The non-Hispanic Black people experienced larger increases in AD or PD deaths (excess percentage: 31.8% for AD and 34.6% for PD) than the non-Hispanic White population (17.1% for AD and 14.7% for PD). CONCLUSION: Under the continuing threats of COVID-19, efforts should be made to optimise health care capacity for patients with AD and PD.

Indoor Environmental Factors and Acute Respiratory Illness in a Prospective Cohort of Community-Dwelling Older Adults.

BACKGROUND: Ambient environmental factors have been associated with respiratory infections in ecological studies, but few studies have explored the impact of indoor environmental factors in detail. The current study aimed to investigate the impact of indoor environment on the risk of acute respiratory illness (ARI) in a subtropical city. METHOD: A prospective cohort study was conducted in 285 community-dwelling older adults from December 2016 through May 2019. Individual household indoor environment data and ARI incidence were continuously collected. A time-stratified case-crossover analysis was conducted to estimate the excess risk of ARI associated with per-unit increase of daily mean indoor temperature, relative humidity, and absolute humidity (AH). RESULT: In total, 168 episodes of ARI were reported with an average risk of 36.8% per year. We observed a negative association of ARI with indoor AH up to 5 lag days in cool seasons, with a 6-day cumulative excess risk estimate of -9.0% (95% confidence interval, -15.9% to -1.5%). Negative associations between household temperature or relative humidity and ARI were less consistent across warm and cool seasons. CONCLUSIONS: Lower indoor AH in household was associated with a higher risk of ARI in the community-dwelling older adults in Hong Kong during cold seasons.

Maternal and Neonatal Outcomes of Pregnant Women With Coronavirus Disease 2019 (COVID-19) Pneumonia: A Case-Control Study.

BACKGROUND: The ongoing pandemic of coronavirus disease 2019 (COVID-19) has caused serious concerns about its potential adverse effects on pregnancy. There are limited data on maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia. METHODS: We conducted a case-control study to compare clinical characteristics and maternal and neonatal outcomes of pregnant women with and without COVID-19 pneumonia. RESULTS: During the period 24 January-29 February 2020, there were 16 pregnant women with confirmed COVID-19 pneumonia and 18 suspected cases who were admitted to labor in the third trimester. Two had vaginal delivery and the rest were cesarean delivery. Few patients presented respiratory symptoms (fever and cough) on admission, but most had typical chest computed tomographic images of COVID-19 pneumonia. Compared to the controls, patients with COVID-19 pneumonia had lower counts of white blood cells (WBCs), neutrophils, C-reactive protein (CRP), and alanine aminotransferase on admission. Increased levels of WBCs, neutrophils, eosinophils, and CRP were found in postpartum blood tests of pneumonia patients. Three (18.8%) of the mothers with confirmed COVID-19 pneumonia and 3 (16.7%) with suspected COVID-19 pneumonia had preterm delivery due to maternal complications, which were significantly higher than in the control group. None experienced respiratory failure during their hospital stay. COVID-19 infection was not found in the newborns, and none developed severe neonatal complications. CONCLUSIONS: Severe maternal and neonatal complications were not observed in pregnant women with COVID-19 pneumonia who had vaginal or cesarean delivery. Mild respiratory symptoms of pregnant women with COVID-19 pneumonia highlight the need of effective screening on admission.

Long-Term Exposure to Ambient Fine Particulate Matter and Mortality From Renal Failure: A Retrospective Cohort Study in Hong Kong, China.

Numerous studies have indicated that ambient particulate matter is closely associated with increased risk of cardiovascular disease, yet the evidence for its association with renal disease remains underrecognized. We aimed to estimate the association between long-term exposure to fine particulate matter, defined as particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5), and mortality from renal failure (RF) among participants in the Elderly Health Service Cohort in Hong Kong, China, from 1998 to 2010. PM2.5 concentration at the residential address of each participant was estimated based on a satellite-based spatiotemporal model. We used Cox proportional hazards regression to estimate risks of overall RF and cause-specific mortality associated with PM2.5. After excluding 5,373 subjects without information on residential address or relevant covariates, we included 61,447 participants in data analyses. We identified 443 RF deaths during the 10 years of follow-up. For an interquartile-range increase in PM2.5 concentration (3.22 µg/m3), hazard ratios for RF mortality were 1.23 (95% confidence interval: 1.06, 1.43) among all cohort participants and 1.42 (95% confidence interval: 1.16, 1.74) among patients with chronic kidney disease. Long-term exposure to atmospheric PM2.5 might be an important risk factor for RF mortality in the elderly, especially among persons with existing renal diseases.

Smoking and Influenza-associated Morbidity and Mortality: A Systematic Review and Meta-analysis.

BACKGROUND: Although smoking has been recognized as a risk factor for many respiratory diseases, its effects of influenza-associated morbidity and mortality remain controversial. We conducted a systematic review and meta-analysis to assess the impact of smoking on influenza-associated hospital admissions, intensive care unit (ICU) admissions, and deaths. METHODS: We searched the databases of PubMed, CINAHL, EMBASE, and the China National Knowledge Infrastructure for all observational studies published between 1 January 2000 and 30 November 2017 on ever-active/secondhand smoking and influenza-associated hospital admissions, ICU admissions, and deaths. We pooled data using random effect models. RESULTS: The initial search retrieved 7495 articles, of which 20 studies were included for systematic review, and 12 studies (eight case-control studies, two cohort studies, and two cross-sectional studies) with 18612 subjects were included in meta-analysis. The overall quality of selected studies was moderate. Ever-active smokers had higher odds of hospital admissions (odds ratio [OR] = 1.5; 95% confidence interval [CI] = 1.3, 1.7) and ICU admissions (OR 2.2; 95% CI = 1.4, 3.4) after influenza infections, as compared with never smokers. No association was observed between ever-active smoking and influenza-associated deaths. We found a positive association between secondhand smoking and influenza-associated hospital admissions, but only in children below 15 years of age. CONCLUSIONS: The literature evidence showed that smoking was consistently associated with higher risk of hospital admissions after influenza infection, but the results for ICU admissions and deaths were less conclusive because of the limited number of studies.

Chronic Low-Grade Inflammation and Brain Structure in the Middle-Aged and Elderly Adults.

Low-grade inflammation (LGI) mainly acted as the mediator of the association of obesity and inflammatory diet with numerous chronic diseases, including neuropsychiatric diseases. However, the evidence about the effect of LGI on brain structure is limited but important, especially in the context of accelerating aging. This study was then designed to close the gap, and we leveraged a total of 37,699 participants from the UK Biobank and utilized inflammation score (INFLA-score) to measure LGI. We built the longitudinal relationships of INFLA-score with brain imaging phenotypes using multiple linear regression models. We further analyzed the interactive effects of specific covariates. The results showed high level inflammation reduced the volumes of the subcortex and cortex, especially the globus pallidus (ß [95% confidence interval] = -0.062 [-0.083, -0.041]), thalamus (-0.053 [-0.073, -0.033]), insula (-0.052 [-0.072, -0.032]), superior temporal gyrus (-0.049 [-0.069, -0.028]), lateral orbitofrontal cortex (-0.047 [-0.068, -0.027]), and others. Most significant effects were observed among urban residents. Furthermore, males and individuals with physical frailty were susceptive to the associations. The study provided potential insights into pathological changes during disease progression and might aid in the development of preventive and control targets in an age-friendly city to promote great health and well-being for sustainable development goals.

Associations of long-term exposure to low-level PM2.5 and brain disorders in 260,922 middle-aged and older adults.

Long-term exposure to high-level ambient PM2.5 was associated with increased risks of brain disorders, while the associations remain uncertain when the exposure is lower than current air quality standards in numerous countries. This study aimed to assess the effects of PM2.5 exposure on the brain system in the population with annual mean concentrations ≤15 µg/m3. We analyzed data from 260,922 participants without preexisting brain diseases at baseline in the UK Biobank. The geographical distribution of PM2.5 in 2010 was estimated by a land use regression model and linked with individual residential address. We investigated associations of ambient PM2.5 with incident neurological (dementia, Parkinson's diseases [PD], epilepsy, and migraine) and psychiatric (major depressive disorder [MDD] and anxiety disorder) diseases through Cox proportional hazard models. We further estimated the links with brain imaging phenotypes by neuroimaging analysis. Results showed that in the population with PM2.5 concentrations ≤15 µg/m3, each interquartile range (IQR, 1.28 µg/m3) increment in PM2.5 was related to incidence risks of dementia, epilepsy, migraine, MDD, and anxiety disorder with hazard ratios of 1.08 (95% confidence interval [CI]: 1.03, 1.13), 1.12 (1.05, 1.20), 1.07 (1.00, 1.13), 1.06 (1.03, 1.09), and 1.05 (1.02, 1.08), respectively. We did not observe a significant association with PD. The association with dementia was stronger among the population with poor cardiovascular health (measured by Life's Essential 8) than the counterpart (P for interaction = 0.037). Likewise, per IQR increase was associated with specific brain imaging phenotypes, including volumes of total brain (ß = -0.036; 95% CI: -0.050, -0.022), white matter (-0.030; -0.046, -0.014), grey matter (-0.030; -0.042, -0.017), respectively. The findings suggest long-term exposure to ambient PM2.5 at low-level still has an adverse impact on the neuro-psychiatric systems. The brain-relevant epidemiological assessment suggests that each country should update the standard for ambient PM2.5 following the World Health Organization Air Quality Guidelines 2021.

Hypoxia and Singlet Oxygen Dual-Responsive Micelles for Photodynamic and Chemotherapy Therapy Featured with Enhanced Cellular Uptake and Triggered Cargo Delivery.

Introduction: Combination therapy provides better outcomes than a single therapy and becomes an efficient strategy for cancer treatment. In this study, we designed a hypoxia- and singlet oxygen-responsive polymeric micelles which contain azo and nitroimidazole groups for enhanced cellular uptake, repaid cargo release, and codelivery of photosensitizer Ce6 and hypoxia-activated prodrug tirapazamine TPZ (DHM-Ce6@TPZ), which could be used for combining Ce6-mediated photodynamic therapy (PDT) and PDT-activated chemotherapy to enhance the therapy effect of cancer. Methods: The hypoxia- and singlet oxygen-responsive polymeric micelles DHM-Ce6@TPZ were prepared by film hydration method. The morphology, physicochemical properties, stimuli responsiveness, in vitro singlet oxygen production, cellular uptake, and cell viability were evaluated. In addition, the in vivo therapeutic effects of the micelles were verified using a tumor xenograft mice model. Results: The resulting dual-responsive micelles not only increased the concentration of intracellular photosensitizer and TPZ, but also facilitated photosensitizer and TPZ release for enhanced integration of photodynamic and chemotherapy therapy. As a photosensitizer, Ce6 induced PDT by generating toxic singlet reactive oxygen species (ROS), resulting in a hypoxic tumor environment to activate the prodrug TPZ to achieve efficient chemotherapy, thereby evoking a synergistic photodynamic and chemotherapy therapeutic effect. The cascade synergistic therapeutic effect of DHM-Ce6@TPZ was effectively evaluated both in vitro and in vivo to inhibit tumor growth in a breast cancer mice model. Conclusion: The designed multifunctional micellar nano platform could be a convenient and powerful vehicle for the efficient co-delivery of photosensitizers and chemical drugs for enhanced synergistic photodynamic and chemotherapy therapeutic effect of cancer.

Global burden of enteric infections related foodborne diseases, 1990-2021: findings from the Global Burden of Disease Study 2021.

Background: Understanding the global burden of enteric infections is crucial for prioritizing control strategies for foodborne and waterborne diseases. This study aimed to assess the global burden of enteric infections in 2021 and identify risk factors from One Health aspects. Methods: Leveraging the Global Burden of Disease (GBD) 2021 database, the incidence, disability-adjusted life years (DALYs), and deaths of enteric infections and the subtypes were estimated, including diarrheal diseases, typhoid and paratyphoid fever, invasive non-typhoidal Salmonella (iNTS) infections, and other intestinal infectious diseases. The estimates were quantified by absolute number, age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) and age-standardized DALY rate with 95% uncertainty intervals (UIs). Thirteen pathogens and three risk factors associated with diarrheal diseases were analyzed. Results: In 2021, the global age-standardized DALY rate of enteric infections was 1020.15 per 100,000 popultion (95% UI: 822.70-1259.39 per 100,000 population) with an estimated annual percentage change (EAPC) of -4.11% (95% confidence interval: -4.31% to -3.90%) in 1990-2021. A larger burden was observed in regions with lower Socio-demographic index (SDI) levels. Diarrheal disease was the most serious subtype with Western Sub-Saharan Africa exhibiting the highest age-standardized DALY rate (2769.81 per 100,000 population, 95% UI: 1976.80-3674.41 per 100,000 population). Children under 5 and adults over 65 years suffered more from diarrheal diseases with the former experiencing the highest global age-standardized DALY rate (9382.46 per 100,000 population, 95% UI: 6771.76-13,075.12 per 100,000 population). Rotavirus remained the leading cause of diarrheal diseases despite a cross-year decline in the observed age-standardized DALY rate. Unsafe water, sanitation, and handwashing contributed most to the disease burden. Conclusion: The reduced burden of enteric infections suggested the effectiveness of previous control strategies; however, more efforts should be made in vulnerable regions and populations through a One Health approach.

Global burden of viral infectious diseases of poverty based on Global Burden of Diseases Study 2021.

BACKGROUND: Viral infectious diseases of poverty (vIDPs) remain a significant global health challenge. Despite their profound impact, the burden of these diseases is not comprehensively quantified. This study aims to analyze the global burden of six major vIDPs, including coronavirus disease 2019 (COVID-19), HIV/AIDS, acute hepatitis, dengue, rabies, and Ebola virus disease (EVD), using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021). METHODS: Following the GBD 2021 framework, we analyzed the incidence, mortality, and disability-adjusted life years (DALYs) of the six vIDPs across 204 countries and territories from 1990 to 2021. We examined the association between the Socio-Demographic Index (SDI) and the burden of vIDPs. All estimates were reported as numbers and rates per 100,000 population, calculated using the Bayesian statistical model employed by GBD 2021, with 95% uncertainty intervals (UI). RESULTS: In 2021, vIDPs caused approximately 8.7 million deaths and 259.2 million DALYs, accounting for 12.8% and 9.0% of the global all-cause totals, respectively. Globally, the burden of vIDPs varied significantly: COVID-19 caused around 7.9 million (95% UI: 7.5, 8.4) deaths and 212.0 million (95% UI 197.9, 234.7) DALYs in 2021. Acute hepatitis had the second-highest age-standardized incidence rate, with 3411.5 (95% UI: 3201.8, 3631.3) per 100,000 population, while HIV/AIDS had a high age-standardized prevalence rate, with 483.1 (95% UI: 459.0, 511.4) per 100,000 population. Dengue incidence cases rose from 26.5 million (95% UI: 3.9, 51.9) in 1990 to 59.0 million (95% UI: 15.5, 106.9) in 2021. Rabies, although reduced in prevalence, continued to pose a significant mortality risk. EVD had the lowest overall burden but significant outbreak impacts. Age-standardized DALY rates for vIDPs were significantly negatively correlated with SDI: acute hepatitis (r = -0.8, P < 0.0001), rabies (r = -0.7, P < 0.0001), HIV/AIDS (r = -0.6, P < 0.0001), COVID-19 (r = -0.5, P < 0.0001), dengue (r = -0.4, P < 0.0001), and EVD (r = -0.2, P < 0.005). CONCLUSIONS: VIDPs pose major public health challenges worldwide, with significant regional, age, and gender disparities. The results underscore the need for targeted interventions and international cooperation to mitigate the burden of these diseases. Policymakers can use these findings to implement cost-effective interventions and improve health outcomes, particularly in regions with high or increasing burdens.

Projection of dengue fever transmissibility under climate change in South and Southeast Asian countries.

Vector-borne infectious disease such as dengue fever (DF) has spread rapidly due to more suitable living environments. Considering the limited studies investigating the disease spread under climate change in South and Southeast Asia, this study aimed to project the DF transmission potential in 30 locations across four South and Southeast Asian countries. In this study, weekly DF incidence data, daily mean temperature, and rainfall data in 30 locations in Singapore, Sri Lanka, Malaysia, and Thailand from 2012 to 2020 were collected. The effects of temperature and rainfall on the time-varying reproduction number (Rt) of DF transmission were examined using generalized additive models. Projections of location-specific Rt from 2030s to 2090s were determined using projected temperature and rainfall under three Shared Socioeconomic Pathways (SSP126, SSP245, and SSP585), and the peak DF transmissibility and epidemic duration in the future were estimated. According to the results, the projected changes in the peak Rt and epidemic duration varied across locations, and the most significant change was observed under middle-to-high greenhouse gas emission scenarios. Under SSP585, the country-specific peak Rt was projected to decrease from 1.63 (95% confidence interval: 1.39-1.91), 2.60 (1.89-3.57), and 1.41 (1.22-1.64) in 2030s to 1.22 (0.98-1.51), 2.09 (1.26-3.47), and 1.37 (0.83-2.27) in 2090s in Singapore, Thailand, and Malaysia, respectively. Yet, the peak Rt in Sri Lanka changed slightly from 2030s to 2090s under SSP585. The epidemic duration in Singapore and Malaysia was projected to decline under SSP585. In conclusion, the change of peak DF transmission potential and disease outbreak duration would vary across locations, particularly under middle-to-high greenhouse gas emission scenarios. Interventions should be considered to slow down global warming as well as the potential increase in DF transmissibility in some locations of South and Southeast Asia.

Towards an actionable One Health approach.

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

How far has the globe gone in achieving One Health? Current evidence and policy implications based on global One Health index.

Background: In the 21st century, as globalization accelerates and global public health crises occur, the One Health approach, guided by the holistic thinking of human-animal-environment and emphasizing interdisciplinary collaboration to address global health issues, has been strongly advocated by the international community. An immediate requirement exists for the creation of an assessment tool to foster One Health initiatives on both global and national scales. Methods: Built upon extensive expert consultations and dialogues, this follow-up study enhances the 2022 global One Health index (GOHI) indicator system. The GOHI framework is enriched by covering three indices, e.g. external drivers index (EDI), intrinsic drivers index (IDI), and core drivers index (CDI). The comprehensive indicator system incorporates 13 key indicators, 50 indicators, and 170 sub I-indicators, utilizing a fuzzy analytic hierarchy process to ascertain the weight for each indicator. Weighted and summed, the EDI, IDI, and CDI scores contribute to the computation of the overall GOHI 2022 score. By comparing the ranking and the overall scores among the seven regions and across 160 countries/territories, we have not only derived an overall profile of the GOHI 2022 scores, but also assessed the GOHI framework. We also compared rankings of indicators and sub I-indicators to provide greater clarity on the strengths and weaknesses of each region within the One Health domains. Results: The GOHI 2022 performance reveals significant disparities between countries/territories ranged from 39.03 to 70.61. The global average score of the GOHI 2022 is 54.82. The average score for EDI, IDI, and CDI are 46.57, 58.01, and 57.25, respectively. In terms of global rankings, countries from North America, Europe and Central Asia, East Asia and Pacific present higher scores. In terms of One Health domains of CDI, the lowest scores are observed in antimicrobial resistance (median: 43.09), followed by food security (median: 53.78), governance (median: 54.77), climate change (median: 64.12) and zoonotic diseases (median: 69.23). Globally, the scores of GOHI vary spatially, with the highest score in North America while lowest in sub-Saharan Africa. In addition, evidence shows associations between the socio-demographic profile of countries/territories and their GOHI performance in certain One Health scenarios. Conclusion: The objective of GOHI is to guide impactful strategies for enhancing capacity building in One Health. With advanced technology and an annually updated database, intensifying efforts to refine GOHI's data-mining methodologies become imperative. The goal is to offer profound insights into disparities and progressions in practical One Health implementation, particularly in anticipation of future pandemics.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Metal-Organic Framework for Hypoxia/ROS/pH Triple-Responsive Cargo Release.

Nanoparticulate antitumor photodynamic therapy (PDT) is suffering from a very short lifetime, limited diffusion distance of reactive oxygen species (ROS). Herein, a hypoxia/ROS/pH triple-responsive metal-organic framework (MOF) is designed to facilitate the on-demand release of photosensitizers and hence enhanced PDT efficacy. Tailored azo-containing imidazole ligand is coordinated with zinc to form MOF where photosensitizer (Chlorin e6/Ce6) is encapsulated. Azo can be reduced by overexpressed azoreductase in hypoxic tumor cells, resulting in depletion of glutathione (GSH) and thioredoxin (Trx) which are major antioxidants against ROS oxidative damage in PDT, resulting in rapid cargo release and additional efficacy amplification. The imidazole ionization causes a proton sponge effect to ensure the disintegration of the nanocarriers in acidic organelles, allowing the rapid release of Ce6 through lysosome escape. Under light irradiation, ROS produced by Ce6 may oxidize imidazole to urea, resulting in rapid cargo release. All of the triggers are expected to show interactive synergism. The pH- and hypoxia-responsiveness can improve the release rate of Ce6 for enhanced PDT therapy, whereas the consumption of oxygen by PDT may induce elevated hypoxia and hence in turn enhanced cargo release. This work highlights the role of triple-responsive nanocarriers for triggered photosensitizer release and improved antitumor PDT efficacy.

Temporal variation of excess deaths from diabetes during the COVID-19 pandemic in the United States.

BACKGROUND: Although the COVID-19 pandemic has persisted for more than two years with the evident excess mortality from diabetes, few studies have investigated its temporal patterns. This study aims to estimate the excess deaths from diabetes in the United States (US) during the COVID-19 pandemic and evaluate the excess deaths by spatiotemporal pattern, age groups, sex, and race/ethnicity. METHODS: Diabetes as one of multiple causes of death or an underlying cause of death were both considered into analyses. The Poisson log-linear regression model was used to estimate weekly expected counts of deaths during the pandemic with adjustments for long-term trend and seasonality. Excess deaths were measured by the difference between observed and expected death counts, including weekly average excess deaths, excess death rate, and excess risk. We calculated the excess estimates by pandemic wave, US state, and demographic characteristic. RESULTS: From March 2020 to March 2022, deaths that diabetes as one of multiple causes of death and an underlying cause of death were about 47.6 % and 18.4 % higher than the expected. The excess deaths of diabetes had evident temporal patterns with two large percentage increases observed during March 2020, to June 2020, and June 2021 to November 2021. The regional heterogeneity and underlying age and racial/ethnic disparities of the excess deaths were also clearly observed. CONCLUSIONS: This study highlighted the increased risks of diabetes mortality, heterogeneous spatiotemporal patterns, and associated demographic disparities during the pandemic. Practical actions are warranted to monitor disease progression, and lessen health disparities in patients with diabetes during the COVID-19 pandemic.