Critical windows for exposure to chemical composition of ambient particulate matter and human semen quality decline.

BACKGROUND: Critical windows for exposure to chemical components of particulate matter (PM <2.5 µm in diameter [PM2.5]) associated with the human semen quality decline remain unclear. OBJECTIVES: To address this gap, we developed a new analytical framework by integrating a Linear Mixed Model (LMM) with subject- and center-specific intercepts and a Distributed Lag Model (DLM) to fully account for correlations between finely vulnerable exposure windows based on complete profile of the spermatogenesis cycle. METHODS: We constructed a multicenter cohort involving 33,234 sperm donors with 78,952 semen samples covering 6 representative regions across China from 2014 to 2020 to investigate the week-scale critical windows for the exposure. Daily exposure to PM2.5 chemical components of donors was derived from grid data based on 1-km spatial resolution surface measurements. RESULTS: Decreased sperm count was significantly associated with NO3- and SO42- at 9-10 weeks (e.g., ß: -0.05 %, 95%CI: [-0.10 %, -0.00 %] at the 9th week) and 0-2 weeks (e.g., ß: -0.66 %, 95%CI: [-1.24 %, -0.07 %] at the 1st week), respectively. Critical windows of progressive motility decline were 0-10 weeks for BC (e.g., ß: -0.07 %, 95%CI: [-0.11 %, -0.03 %] at the 5th week), Cl- at 1-4 weeks (e.g., ß: -2.21 %, 95%CI: [-3.77 %, -0.66 %] at the 2nd week), 0-6 weeks and 9-10 weeks for NO3- (e.g., ß: -0.05 %, 95%CI: [-0.09 %, -0.01 %] at the 4th week), 1-3 weeks and the 8th week for NH4+ (e.g., ß: -0.06 %, 95%CI: [-0.11 %, -0.01 %] at the 2nd week). Total motility is significantly negatively associated with BC at entire windows, Cl- at 0-3 weeks, the 5th week and 9-10 weeks. CONCLUSIONS: There are week-scale vulnerable windows of exposure to PM2.5 chemical components for human semen quality. This highlights the need for more targeted pollution control strategies addressing PM2.5 and its chemical components.

Epidemiological characteristics and transmission dynamics of dengue fever in China.

China has experienced successive waves of dengue epidemics over the past decade. Nationwide data on 95,339 dengue cases, 89 surveillance sites for mosquito density and population mobility between 337 cities during 2013-20 were extracted. Weekly dengue time series including time trends and harmonic terms were fitted using seasonal regression models, and the amplitude and peak timing of the annual and semiannual cycles were estimated. A data-driven model-inference approach was used to simulate the epidemic at city-scale and estimate time-evolving epidemiological parameters. We found that the geographical distribution of dengue cases was expanding, and the main imported areas as well as external sources of imported cases changed. Dengue cases were predominantly concentrated in southern China and it exhibited an annual peak of activity, typically peaking in September. The annual amplitude of dengue epidemic varied with latitude (F = 19.62, P = 0.0001), mainly characterizing by large in southern cities and small in northern cities. The effective reproduction number Reff across cities is commonly greater than 1 in several specific months from July to November, further confirming the seasonal fluctuations and spatial heterogeneity of dengue epidemics. The results of this national study help to better informing interventions for future dengue epidemics in China.

Association Between Particulate Matter Exposure and Preterm Birth in Women With Abnormal Preconception Thyrotropin Levels: Large Cohort Study.

Background: Prior research has linked exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) with preterm birth (PTB). However, the modulating effect of preconception thyroid stimulating hormone (TSH) levels on the relationship between PM2.5 exposure and PTB has not been investigated. Objective: This study aimed to assess whether preconception TSH levels modulate the impact of PM2.5 exposure on PTB. Methods: This cohort study was conducted in Guangdong, China, as a part of the National Free Pre-Pregnancy Checkups Project. PM2.5 exposure was estimated by using the inverse distance weighting method. To investigate the moderating effects of TSH levels on trimester-specific PM2.5 exposure and PTB, we used the Cox proportional hazards model. Additionally, to identify the susceptible exposure windows for weekly specific PM2.5 exposure and PTB, we built distributed lag models incorporating Cox proportional hazards models. Results: A total of 633,516 women who delivered between January 1, 2014, to December 31, 2019, were included. In total, 34,081 (5.4%) of them had abnormal preconception TSH levels. During the entire pregnancy, each 10-µg/m3 increase in PM2.5 was linked to elevated risks of PTB (hazard ratio [HR] 1.559, 95% CI 1.390-1.748), early PTB (HR 1.559, 95% CI 1.227-1.980), and late PTB (HR 1.571, 95% CI 1.379-1.791) among women with abnormal TSH levels. For women with normal preconception TSH levels, PM2.5 exposure during the entire pregnancy was positively associated with the risk of PTB (HR 1.345, 95% CI 1.307-1.385), early PTB (HR 1.203, 95% CI 1.126-1.285), and late PTB (HR 1.386, 95% CI 1.342-1432). The critical susceptible exposure windows were the 3rd-13th and 28th-35th gestational weeks for women with abnormal preconception TSH levels, compared to the 1st-13th and 21st-35th gestational weeks for those with normal preconception TSH levels. Conclusions: PM2.5 exposure was linked with a higher PTB risk, particularly in women with abnormal preconception TSH levels. PM2.5 exposure appears to have a greater effect on pregnant women who are in the early or late stages of pregnancy.

Potentially inappropriate prescribing among older adults with hypertension in China: prevalence and related comorbidities across different outpatient settings.

Purpose: Potentially inappropriate prescribing (PIP) is commonly encountered in older adults; yet, there is limited information on the occurrence of PIP among older adults with hypertension. This study aims to determine and compare the prevalence of PIP and its association with comorbidities in older adult outpatients with hypertension across hospitals and community health centers (CHCs). Methods: This 3-year (2015-2017) repeated cross-sectional study used electronic medical records from Shenzhen, China, involving 62 hospitals and 678 primary medical institutions. PIP was defined using the 2019 Beers Criteria. Older adults (≥65 years) with hypertension and at least one outpatient prescription were included. Modified Poisson regression analysis was used to assess the association between chronic comorbidities, healthcare settings, and PIP. Results: The prevalence of PIP in old adult outpatients with hypertension in 2015, 2016, and 2017 was 46.32%, 46.98%, and 46.58% in hospitals, with a sample size of 38,411, 46,235, and 50,495, respectively, and 29.14%, 26.66%, and 29.84% in CHCs, with a sample size of 26,876, 29,434, and 34,775 respectively. The top four most popular PIP in hospitals and CHCs was proton-pump inhibitors (PPIs), diuretics, benzodiazepines, and non-cyclooxygenase-selective non-steroidal anti-inflammatory drugs (NSAIDs), respectively. PIP was most associated with chronic gastrointestinal disease (adjusted prevalence ratio = 1.54, 95% confidence interval [CI] = 1.50-1.59) and mental and behavioral disorders (adjusted prevalence ratio = 1.49, 95% CI = 1.46-1.53) in hospitals and with mental and behavioral disorders (adjusted prevalence ratio = 1.99; 95% CI = 1.95-2.03) and musculoskeletal system and connective tissue disorders (adjusted prevalence ratio = 1.33; 95% CI = 1.31-1.36) in CHCs. The prevalence of PIP was significantly higher in hospital settings than in CHCs (adjusted prevalence ratio = 1.65; 95% CI = 1.63-1.66). Conclusion: Among older adult outpatients with hypertension in Shenzhen, PIP was more prevalent in hospitals than in CHCs. The comorbidities most strongly associated with PIP were chronic gastrointestinal disease and mental and behavioral disorders in hospitals and mental and behavioral disorders in CHCs. Clinical pharmacy integration needs to be considered to reduce inappropriate prescribing in this vulnerable population.

Prostacyclin Synthase Deficiency Leads to Exacerbation or Occurrence of Endothelium-Dependent Contraction and Causes Cardiovascular Disorders Mainly via the Non-TxA2 Prostanoids/TP Axis.

BACKGROUND: Prostaglandin I2 synthesized by endothelial COX (cyclooxygenase) evokes potent vasodilation in some blood vessels but is paradoxically responsible for endothelium-dependent constriction (EDC) in others. Prostaglandin I2 production and EDC may be enhanced in diseases such as hypertension. However, how PGIS (prostaglandin I2 synthase) deficiency affects EDC and how this is implicated in the consequent cardiovascular pathologies remain largely unknown. METHODS: Experiments were performed with wild-type, Pgis knockout (Pgis-/-) and Pgis/thromboxane-prostanoid receptor gene (Tp) double knockout (Pgis-/-Tp-/-) mice and Pgis-/- mice transplanted with unfractionated wild-type or Cox-1-/- bone marrow cells, as well as human umbilical arteries. COX-derived prostanoids were measured by high-performance liquid chromatography-mass spectrometry. Vasomotor responses of distinct types of arteries were assessed by isometric force measurement. Parameters of hypertension, vascular remodeling, and cardiac hypertrophy in mice at different ages were monitored. RESULTS: PGF2α, PGE2, and a trace amount of PGD2, but not thromboxane A2 (TxA2), were produced in response to acetylcholine in Pgis-/- or PGIS-inhibited arteries. PGIS deficiency resulted in exacerbation or occurrence of EDC ex vivo and in vivo. Endothelium-dependent hyperpolarization was unchanged, but phosphorylation levels of eNOS (endothelial nitric oxide synthase) at Ser1177 and Thr495 were altered and NO production and the NO-dependent relaxation evoked by acetylcholine were remarkably reduced in Pgis-/- aortas. Pgis-/- mice developed high blood pressure and vascular remodeling at 16 to 17 weeks and subsequently cardiac hypertrophy at 24 to 26 weeks. Meanwhile, blood pressure and cardiac parameters remained normal at 8 to 10 weeks. Additional ablation of TP (TxA2 receptor) not only restrained EDC and the downregulation of NO signaling in Pgis-/- mice but also ameliorated the cardiovascular abnormalities. Stimulation of Pgis-/- vessels with acetylcholine in the presence of platelets led to increased TxA2 generation. COX-1 disruption in bone marrow-derived cells failed to affect the development of high blood pressure and vascular remodeling in Pgis-/- mice though it largely suppressed the increase of plasma TxB2 (TxA2 metabolite) level. CONCLUSIONS: Our study demonstrates that the non-TxA2 prostanoids/TP axis plays an essential role in mediating the augmentation of EDC and cardiovascular disorders when PGIS is deficient, suggesting TP as a promising therapeutic target in diseases associated with PGIS insufficiency.

Impact of Ambient Temperature on Mortality Burden and Spatial Heterogeneity in 16 Prefecture-Level Cities of a Low-Latitude Plateau Area in Yunnan Province: Time-Series Study.

Background: The relation between climate change and human health has become one of the major worldwide public health issues. However, the evidence for low-latitude plateau regions is limited, where the climate is unique and diverse with a complex geography and topography. objectives: This study aimed to evaluate the effect of ambient temperature on the mortality burden of nonaccidental deaths in Yunnan Province and to further explore its spatial heterogeneity among different regions. Methods: We collected mortality and meteorological data from all 129 counties in Yunnan Province from 2014 to 2020, and 16 prefecture-level cities were analyzed as units. A distributed lagged nonlinear model was used to estimate the effect of temperature exposure on years of life lost (YLL) for nonaccidental deaths in each prefecture-level city. The attributable fraction of YLL due to ambient temperature was calculated. A multivariate meta-analysis was used to obtain an overall aggregated estimate of effects, and spatial heterogeneity among 16 prefecture-level cities was evaluated by adjusting the city-specific geographical characteristics, demographic characteristics, economic factors, and health resources factors. Results: The temperature-YLL association was nonlinear and followed slide-shaped curves in all regions. The cumulative cold and heat effect estimates along lag 0-21 days on YLL for nonaccidental deaths were 403.16 (95% empirical confidence interval [eCI] 148.14-615.18) and 247.83 (95% eCI 45.73-418.85), respectively. The attributable fraction for nonaccidental mortality due to daily mean temperature was 7.45% (95% eCI 3.73%-10.38%). Cold temperature was responsible for most of the mortality burden (4.61%, 95% eCI 1.70-7.04), whereas the burden due to heat was 2.84% (95% eCI 0.58-4.83). The vulnerable subpopulations include male individuals, people aged <75 years, people with education below junior college level, farmers, nonmarried individuals, and ethnic minorities. In the cause-specific subgroup analysis, the total attributable fraction (%) for mean temperature was 13.97% (95% eCI 6.70-14.02) for heart disease, 11.12% (95% eCI 2.52-16.82) for respiratory disease, 10.85% (95% eCI 6.70-14.02) for cardiovascular disease, and 10.13% (95% eCI 6.03-13.18) for stroke. The attributable risk of cold effect for cardiovascular disease was higher than that for respiratory disease cause of death (9.71% vs 4.54%). Furthermore, we found 48.2% heterogeneity in the effect of mean temperature on YLL after considering the inherent characteristics of the 16 prefecture-level cities, with urbanization rate accounting for the highest proportion of heterogeneity (15.7%) among urban characteristics. Conclusions: This study suggests that the cold effect dominated the total effect of temperature on mortality burden in Yunnan Province, and its effect was heterogeneous among different regions, which provides a basis for spatial planning and health policy formulation for disease prevention.

Beneficial effect of residential greenness on sperm quality and the role of air pollution: A multicenter population-based study.

BACKGROUND: Poor sperm quality is a major cause of male infertility. However, evidence remains scarce on how greenness affects male sperm quality. OBJECTIVES: To assess the associations of residential greenness with male sperm quality and the modification effect of air pollution exposure on the relationship. METHODS: A total of 78,742 samples from 33,184 sperm donors from 6 regions across China during 2014-2020 were included and analyzed. Individual residential greenness exposures of study subjects were estimated using the Normalized Difference Vegetation Index (NDVI) during the entire (0-90 lag days) and two key stages (0-37, and 34-77 lag days) of sperm development. Contemporaneous personal exposure levels to air pollutants were estimated using a spatio-temporal deep learning method. Linear mixed models were employed to assess the impact of greenspace in relation to sperm quality. The modification effect of air pollution on the greenspace-sperm quality relationship was also estimated. RESULTS: Per IQR increment in NDVI exposure throughout spermatogenesis were statistically associated with increasing sperm count by 0.0122 (95 % CI: 0.0007, 0.0237), progressive motility by 0.0162 (95 % CI: 0.0045, 0.0280), and total motility by 0.0147 (95 % CI: 0.0014, 0.0281), respectively. Similar results were observed when the model added air pollutants (PM1, PM2.5 or O3) for adjustment. Additionally, specific air pollutants, including PM1, PM2.5, and O3, were found to modify this association. Notably, the protective effects of greenness exposure were more pronounced at higher concentrations of PM1 and PM2.5 and lower concentrations of O3 (all Pinteraction < 0.05). Statistically significant positive effects of NDVI were observed on sperm motility in early spermatogenesis and sperm count in late spermatogenesis. CONCLUSIONS: Exposure to residential greenness may have beneficial effects on sperm quality and air pollution modifies their relationship. These findings highlight the importance of adopting adaptable urban greenspace planning and policies to safeguard male fertility against environmental factors.

Air Pollutants and Mortality Risk in Patients with Aortic Dissection: Evidence from a Clinical Cohort, Single-Cell Sequencing, and Proteomics.

We aimed to evaluate the association between air pollutants and mortality risk in patients with acute aortic dissection (AAD) in a longitudinal cohort and to explore the potential mechanisms of adverse prognosis induced by fine particulate matter (PM2.5). Air pollutants data, including PM2.5, PM10.0, nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3), were collected from official monitoring stations, and multivariable Cox regression models were applied. Single-cell sequencing and proteomics of aortic tissue were conducted to explore the potential mechanisms. In total, 1,267 patients with AAD were included. Exposure to higher concentrations of air pollutants was independently associated with an increased mortality risk. The high-PM2.5 group carried approximately 2 times increased mortality risk. There were linear associations of PM10, NO2, CO, and SO2 exposures with long-term mortality risk. Single-cell sequencing revealed an increase in mast cells in aortic tissue in the high-PM2.5 exposure group. Enrichment analysis of the differentially expressed genes identified the inflammatory response as one of the main pathways, with IL-17 and TNF signaling pathways being among the top pathways. Analysis of proteomics also identified these pathways. This study suggests that exposure to higher PM2.5, PM10, NO2, CO, and SO2 are associated with increased mortality risk in patients with AAD. PM2.5-related activation and degranulation of mast cells may be involved in this process.

Effects of temperature anomaly on sperm quality: A multi-center study of 33,234 men.

Backgrounds: Global fertility rates continue to decline and sperm quality is a prime factor affecting male fertility. Both extreme cold and heat have been demonstrated to be associated with decreased sperm quality, but no epidemiological studies have considered human adaptation to long-term temperature. Our aim was to conduct a multi-center retrospective cohort study to investigate exposure-response relationship between temperature anomaly (TA) that deviate from long-term climate patterns and sperm quality. Methods: A total of 78,952 semen samples measured in 33,234 donors from 6 provincial human sperm banks in China were collected. This study considered heat and cold acclimatization to prolonged exposure in humans and explored the exposure-response relationship between TAs and sperm quality parameters (sperm concentrations, sperm count, progressive motility, progressive sperm count, total motility and total motile sperm count) during the hot and cold seasons, respectively. Linear mixed models and generalized linear models were built separately for specific centers to pool in a meta-analysis to obtain the pooled effect of TA on sperm quality, considering repeated measurements data structure and spatial heterogeneity. Results: We identified an inverted U-shaped exposure-response relationship between TA and sperm quality during the hot season. Significant negative effect of anomalous cold on sperm quality during the hot season was found after additional adjustment for Body mass index, marital status and childbearing history. The heat-related TA in hot season was significantly negatively associated with sperm concentration, progressive sperm count and total motile sperm count (all P-values<0.05). After adjusting the relative humidity, the cold-related TA in cold season was negatively associated with the sperm total motility (P-values<0.05). Conclusions: Our results suggest both heat-related and cold-related TAs are associated with decreased sperm quality. The findings highlight the importance of reducing exposure to anomalous temperatures to protect male fertility.

Persistence of severe global inequalities in the burden of blindness and vision loss from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

AIMS: To assess the global burden and economic inequalities in the distribution of blindness and vision loss between 1990 and 2019. METHODS: A secondary analysis of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. Data for disability-adjusted life-years (DALYs) due to blindness and vision loss were extracted from the GBD 2019. Data for gross domestic product per capita were extracted from the World Bank database. Slope index of inequality (SII) and concentration index were computed to assess absolute and relative cross-national health inequality, respectively. RESULTS: Countries with high, high-middle, middle, low-middle and low Socio-demographic Index (SDI) had decline of age-standardised DALY rate of 4.3%, 5.2%, 16.0%, 21.4% and 11.30% from 1990 to 2019, respectively. The poorest 50% of world citizens bore 59.0% and 66.2% of the burden of blindness and vision loss in 1990 and 2019, respectively. The absolute cross-national inequality (SII) fell from -303.5 (95% CI -370.8 to -236.2) in 1990 to -256.0 (95% CI -288.1 to -223.8) in 2019. The relative inequality (concentration index) for global blindness and vision loss remained essentially constant between 1991 (-0.197, 95% CI -0.234 to -0.160) and 2019 (-0.193, 95% CI -0.216 to -0.169). CONCLUSION: Though countries with middle and low-middle SDI were the most successful in decreasing burden of blindness and vision loss, a high level of cross-national health inequality persisted over the past three decades. More attention must be paid to the elimination of avoidable blindness and vision loss in low-income and middle-income countries.

Associated adverse health outcomes of polypharmacy and potentially inappropriate medications in community-dwelling older adults with diabetes.

Aim: This study aimed to identify the association of chronic polypharmacy and potentially inappropriate medications (PIMs) with adverse health outcomes (AHOs) in community-dwelling older adults with diabetes in China. Methods: A 2-year retrospective cohort study was conducted using 11,829 community-followed older adults with diabetes and medical records from 83 hospitals and 702 primary care centers in Shenzhen, China. Chronic polypharmacy and PIMs were identified from prescription records using Beers' criteria, and their associated AHO was analyzed using multivariable logistic regression analysis. Results: The prevalence of chronic polypharmacy and at least one PIM exposure was 46.37% and 55.09%, respectively. The top five PIMs were diuretics, benzodiazepines, first-generation antihistamines, sulfonylureas, and insulin (sliding scale). Chronic polypharmacy was positively associated with all-cause hospital admission, admission for coronary heart disease, admission for stroke, admission for dementia, and emergency department visits. Exposure to PIMs was positively associated with all-cause hospital admission, admission for heart failure (PIMs ≥2), admission for stroke (PIMs ≥3), emergency department visits, bone fracture, constipation, and diarrhea. Conclusion: Chronic polypharmacy and PIMs were prevalent in older adults with diabetes in Chinese communities. Iatrogenic exposure to chronic polypharmacy and PIMs is associated with a higher incidence of different AHOs. This observational evidence highlights the necessity of patient-centered medication reviews for chronic polypharmacy and PIMs use in older patients with diabetes in primary care facilities in China and draws attention to the caution of polypharmacy, especially PIM use in older adults with diabetes in clinical practice.

Sperm quality decline associated with gaseous pollutant exposure: Evidence from a large cohort multicenter study.

BACKGROUND: Poor sperm quality is a prevalent cause of male infertility, and the association between gaseous ambient air pollutants exposure and semen quality remains unclear. OBJECTIVES: To examine the relationship between gaseous air pollution exposure with semen quality in a large-scale and multi-center study. METHODS: We analyzed 78,952 samples corresponding to 33,234 study subjects from 2014 to 2020. The high-resolution grid pollution dataset was used to estimate personal exposures to CO, SO2, NO2 and O3 across entire stage of semen formation and three crucial stages. The linear mixed models were performed to evaluate the relationships. RESULTS: The results showed that sperm count was inversely related to SO2 exposure (-0.0070, -0.0128 to -0.0011). Decreased sperm concentration was associated with SO2 (-0.0083, -0.0142 to -0.0024), NO2 (-0.0162, -0.0320 to -0.0005) and O3 (-0.0306, -0.0480 to -0.0133) during 0-90 lag days, respectively. Additionally, we observed significant decline of PR and total motility with SO2 exposure. Similar trends were observed for SO2 and CO exposure during 3 key periods. CONCLUSIONS: Our findings suggest that exposure to gaseous air pollutants may have negative impacts on sperm quality. These findings highlight the importance that critical periods of sperm development should be considered when implementing protective measures.

Exposure to Fine Particulate Matter Constituents and Human Semen Quality Decline: A Multicenter Study.

Exposure to fine particulate matter (PM < 2.5 µm in diameter [PM2.5]) may accelerate human sperm quality decline, although research on this association is limited. Our objective was to investigate the relationship between exposure to the chemical constituents of PM2.5 air pollution and decreased sperm quality and to further explore the exposure-response relationship. We conducted a multicenter population-based cohort study including 78,952 semen samples from 33,234 donors at 6 provincial human sperm banks (covering central, northern, southern, eastern, and southwestern parts of China) between 2014 and 2020. Daily exposure to PM2.5 chemical composition was estimated using a deep learning model integrating a density ground-based measure network at a 1 km resolution. Linear mixed models with subject- and center-specific intercepts were used to quantify the harmful impacts of PM2.5 constituents on semen quality and explore their exposure-response relationships. Per interquartile range (IQR) increase in PM2.5 exposure levels during spermatogenesis was significantly associated with decreased sperm concentration, progressive motility, and total motility. For PM2.5 constituents, per IQR increment in Cl- (ß: -0.02, 95% CI: [-0.03, -0.00]) and NO3- (ß: -0.05, 95% CI: [-0.08, -0.02]) exposure was negatively associated with sperm count, while NH4+ (ß: -0.03, 95% CI: [-0.06, -0.00]) was significantly linked to decreased progressive motility. These results suggest that exposure to PM2.5 chemical constituents may adversely affect human sperm quality, highlighting the urgent need to reduce PM2.5 exposure.

Dengue transmission dynamics prediction by combining metapopulation networks and Kalman filter algorithm.

Predicting the specific magnitude and the temporal peak of the epidemic of individual local outbreaks is critical for infectious disease control. Previous studies have indicated that significant differences in spatial transmission and epidemic magnitude of dengue were influenced by multiple factors, such as mosquito population density, climatic conditions, and population movement patterns. However, there is a lack of studies that combine the above factors to explain their complex nonlinear relationships in dengue transmission and generate accurate predictions. Therefore, to study the complex spatial diffusion of dengue, this research combined the above factors and developed a network model for spatiotemporal transmission prediction of dengue fever using metapopulation networks based on human mobility. For improving the prediction accuracy of the epidemic model, the ensemble adjusted Kalman filter (EAKF), a data assimilation algorithm, was used to iteratively assimilate the observed case data and adjust the model and parameters. Our study demonstrated that the metapopulation network-EAKF system provided accurate predictions for city-level dengue transmission trajectories in retrospective forecasts of 12 cities in Guangdong province, China. Specifically, the system accurately predicts local dengue outbreak magnitude and the temporal peak of the epidemic up to 10 wk in advance. In addition, the system predicted the peak time, peak intensity, and total number of dengue cases more accurately than isolated city-specific forecasts. The general metapopulation assimilation framework presented in our study provides a methodological foundation for establishing an accurate system with finer temporal and spatial resolution for retrospectively forecasting the magnitude and temporal peak of dengue fever outbreaks. These forecasts based on the proposed method can be interoperated to better support intervention decisions and inform the public of potential risks of disease transmission.

Elevated serum lead and cadmium levels associated with increased risk of dyslipidemia in children aged 6 to 9 years in Shenzhen, China.

Exposure to heavy metals can influence on metabolism, but studies have not fully evaluated young children. We investigated the association between levels of serum lead (Pb), cadmium (Cd), chromium (Cr), and arsenic (As) and risk of dyslipidemia in children. A total of 4513 children aged 6 to 9 years at 19 primary schools in Shenzhen were enrolled. Overall, 663 children with dyslipidemia were matched 1:1 with control by sex and age, and levels of serum Pb, Cd, Cr, and As were detected by inductively coupled plasma-mass spectrometry. Demographic characteristics and lifestyle were covariates in the logistic regression to determine the association of heavy metal levels with risk of dyslipidemia. Serum Pb and Cd levels were significantly higher in children with dyslipidemia than controls (133.08 vs. 84.19 µg/L; 0.45 vs. 0.29 µg/L; all P < 0.05), but this association was not found in Cr and As. We found significant upward trends for the odds ratios (ORs) of dyslipidemia associated with increasing quartiles of Pb and Cd levels (highest quartile of serum Pb OR 1.86, 95% confidence interval (CI) 1.46-2.38; Cd OR 2.51, 95% CI 1.94-3.24). Elevated serum Pb and Cd levels were associated with increased risk of dyslipidemia among children.

Machine-learning predictive model of pregnancy-induced hypertension in the first trimester.

In the first trimester of pregnancy, accurately predicting the occurrence of pregnancy-induced hypertension (PIH) is important for both identifying high-risk women and adopting early intervention. In this study, we used four machine-learning models (LASSO logistic regression, random forest, backpropagation neural network, and support vector machines) to predict the occurrence of PIH in a prospective cohort. Candidate features for predicting the occurrence of middle and late PIH were acquired using a LASSO algorithm. The performance of predictive models was assessed using receiver operating characteristic analysis. Finally, a nomogram was established with the model scores, age, and nulliparity. Calibration, clinical usefulness, and internal validation were used to assess the performance of the nomogram. In the training set (2258 pregnant women), eleven candidate factors in the first trimester were significantly associated with the occurrence of PIH (P < 0.001 in the training set). Four models showed AUCs from 0.780 to 0.816 in the training set. For the validation set (939 pregnant women), AUCs varied from 0.516 to 0.795. The nomogram showed good discrimination, with an AUC of 0.847 (95% CI: 0.805-0.889) in the training set and 0.753 (95% CI: 0.653-0.853) in the validation set. Decision curve analysis suggested that the model was clinically useful. The model developed using LASSO logistic regression achieved the best performance in predicting the occurrence of PIH. The derived nomogram, which incorporates the model score and maternal risk factors, can be used to predict PIH in clinical practice. We develop a model with good performance for clinical prediction of PIH in the first trimester.

Global, regional, and national burden of multiple sclerosis from 1990 to 2019: Findings of global burden of disease study 2019.

Background: The global rising prevalence and incidence of multiple sclerosis (MS) has been reported during the past decades. However, details regarding the evolution of MS burden have not been fully studied. This study aimed to investigate the global, regional, and national burden and temporal trends in MS incidence, deaths, and disability-adjusted life years (DALYs) from 1990 to 2019 using the age-period-cohort analysis. Methods: We performed a secondary comprehensive analysis of incidence, deaths, and DALYs of MS by calculating the estimated annual percentage change from 1990 to 2019 obtained from the Global Burden of Disease (GBD) 2019 study. The independent age, period, and birth cohort effects were evaluated by an age-period-cohort model. Results: In 2019, there were 59,345 incident MS cases and 22,439 MS deaths worldwide. The global number of incidences, deaths, and DALYs of MS followed an upward trend, whereas the age-standardized rates (ASR) slightly declined from 1990 to 2019. High socio-demographic index (SDI) regions had the highest ASR of incidences, deaths, and DALYs in 2019, while the rate of deaths and DALYs in medium SDI regions are the lowest. Six regions which include high-income North America, Western Europe, Australasia, Central Europe, and Eastern Europe had higher ASR of incidences, deaths, and DALYs than other regions in 2019. The age effect showed that the relative risks (RRs) of incidence and DALYs reached the peak at ages 30-39 and 50-59, respectively. The period effect showed that the RRs of deaths and DALYs increased with the period. The cohort effect showed that the later cohort has lower RRs of deaths and DALYs than the early cohort. Conclusion: The global cases of incidence, deaths, and DALYs of MS have all increased, whereas ASR has declined, with different trends in different regions. High SDI regions such as European countries have a substantial burden of MS. There are significant age effects for incidence, deaths, and DALYs of MS globally, and period effects and cohort effects for deaths and DALYs.

The size of the susceptible pool differentiates climate effects on seasonal epidemics of bacillary dysentery.

OBJECTIVES: At present, some studies have pointed out several possible climate drivers of bacillary dysentery. However, there is a complex nonlinear interaction between climate drivers and susceptible population in the spread of diseases, which makes it challenging to detect climate drivers at the size of susceptible population. METHODS: By using empirical dynamic modeling (EDM), the climate drivers of bacillary dysentery dynamic were explored in China's five temperature zones. RESULTS: We verified the availability of climate drivers and susceptible population size on bacillary dysentery, and used this information for bacillary dysentery dynamic prediction. Moreover, we found that their respective effects increased with the increase of temperature and relative humidity, and their states (temperature and relative humidity) were different when they reached their maximum effects, and the negative effect between the effect of temperature and disease incidence increased with the change of temperature zone (from temperate zone to warm temperate zone to subtropical zone) and the climate driving effect of the temperate zone (warm temperate zone) was greater than that of the colder (temperate zone) and warmer (subtropics) zones. When we viewed from single temperature zone, the climatic effect arose only when the size of the susceptible pool was large. CONCLUSIONS: These results provide empirical evidence that the climate factors on bacillary dysentery are nonlinear, complex but dependent on the size of susceptible populations and different climate scenarios.

Prevalence of potentially inappropriate medications and association with comorbidities in older adults with diabetes in an outpatient visitation setting.

Aims: Potentially inappropriate medications had been found associated with adverse drug events such as falls, emergency department admissions and hospital readmissions. There is lack of information about the prevalence of potentially inappropriate medications and associated chronic conditions in older patients with diabetes in China. This study aimed to assess the prevalence of potentially inappropriate medications in older adults with diabetes in an outpatient visitation setting and the association with polypharmacy due to comorbidities. Materials and methods: This was a 3-year repeated cross-sectional study which conducted in outpatient setting of 52 hospitals in Shenzhen, China, using 2019 Beers criteria. The prevalence of potentially inappropriate medications, polypharmacy and comorbidities in older adults with diabetes in an outpatient setting was expressed as percentages. Logistic models were used to investigate the association between potentially inappropriate medication exposure and age, sex, polypharmacy and comorbidities. Results: Among the 28,484 older adults with diabetes in 2015, 31,757 in 2016 and 24,675 in 2017, the prevalence of potentially inappropriate medications was 43.2%, 44.88% and 42.40%, respectively. The top five potentially inappropriate medications were diuretics (20.56%), benzodiazepines (13.85%), androgens (13.18%), non-steroidal anti-inflammatory drugs (12.94%) and sulfonylureas (6.23%). After adjustment for age and polypharmacy, the probability of potentially inappropriate medication exposure was associated with chronic gastrointestinal diseases, followed by osteoarthritis and rheumatoid arthritis, chronic pulmonary disease, chronic kidney disease, tumor, dementia, chronic liver disease, hypertension, cardiovascular disease, cerebrovascular disease and hyperlipemia. Conclusion: Potentially inappropriate medications were common in older patients with diabetes in an outpatient visitation setting. Higher probability of potentially inappropriate medication exposure was associated with the comorbidity chronic gastrointestinal diseases as well as osteoarthritis and rheumatoid arthritis. To ensure that iatrogenic risks remain minimal for older adults with diabetes, the clinical comorbidities should be considered.

Combination of Quantitative Susceptibility Mapping and Diffusion Kurtosis Imaging Provides Potential Biomarkers for Early-Stage Parkinson's Disease.

Purpose: This study aimed to detect changes in iron deposition and neural microstructure in the substantia nigra (SN), red nucleus (RN), and basal ganglia of Parkinson's disease (PD) patients at different stages using quantitative susceptibility mapping and diffusion kurtosis imaging to identify potential indicators of early-stage PD. Methods: We enrolled 20 early-stage and 15 late-stage PD patients, as well as 20 age- and sex-matched controls. All participants underwent quantitative susceptibility mapping and diffusion kurtosis imaging to determine magnetic susceptibility (MS), fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) in several brain regions. Results: Compared with the control group, MS and MK values in the SN were significantly increased in the early- and late-stage PD group, whereas MS values in the red nucleus (RN), globus pallidus (GP), and caudate nucleus (CN), FA value in the CN and GP, and MK value in the CN and putamen (PU) were significantly increased in the late-stage PD group. There were positive correlations between MS and MK values in the CN and MS and FA values in the GP. Furthermore, the combination of MS and MK values in the SN provided high accuracy for distinguishing early-stage PD patients from controls. Conclusions: This study identified MS and MK in the SN as potential indicators of early-stage PD.