Reevaluating the splice-altering variant in TECTA as a cause of nonsyndromic hearing loss DFNA8/12 by functional analysis of RNA.

PURPOSE: The aim of this study was to determine the genetic cause of early onset autosomal dominant hearing loss segregating in five-generation kindred of Chinese descent and provide preimplantation genetic testing (PGT)for them. METHODS: Clinical examination, pedigree analysis and exome sequencing were carried out on the family. Minigene-based splicing analysis, in vivo RNA analysis and protein structure prediction by molecular modeling were conducted on the candidate variant. PGT for the causative variation and chromosome aneuploidis based on SNP analysis has been used for avoidance of hearing loss in this family. RESULTS: All the affected individuals presented with moderate down-sloping hearing loss and whole-exome sequencing identified a novel splice-site variant c.5383+6T>A in the tested subjects within the TECTA locus. Genotyping of all the 32 family members confirmed segregation of this variant and the hearing loss phenotype in the extended family. Functional analysis of RNA and molecular modeling indicates that c.5383+6T>A is a pathogenic splice-site variant and should be considered as genetic cause of the hearing loss. Furthermore, a successful singleton pregnancy with no variation in TECTA c.5383+6 was established and a healthy male child was born by PGT. CONCLUSION: We have identified a novel variant c.5383+6T>A in TECTA ZA-ZP inter-domain, which could be attributable to the early-onset autosomal dominant hearing loss. The implications of our study are valuable in elucidating the disrupted RNA splicing and uncovering the genetic cause of hearing loss with TECTA pathogenic variants, as well as providing reproductive approaches to healthy offspring.

Pregnancy Complications and Long-Term Mortality in a Diverse Cohort.

BACKGROUND: Pregnancy complications are associated with increased risk of development of cardiometabolic diseases and earlier mortality. However, much of the previous research has been limited to White pregnant participants. We aimed to investigate pregnancy complications in association with total and cause-specific mortality in a racially diverse cohort and evaluate whether associations differ between Black and White pregnant participants. METHODS: The Collaborative Perinatal Project was a prospective cohort study of 48 197 pregnant participants at 12 US clinical centers (1959-1966). The Collaborative Perinatal Project Mortality Linkage Study ascertained participants' vital status through 2016 with linkage to the National Death Index and Social Security Death Master File. Adjusted hazard ratios (aHRs) for underlying all-cause and cause-specific mortality were estimated for preterm delivery (PTD), hypertensive disorders of pregnancy, and gestational diabetes/impaired glucose tolerance (GDM/IGT) using Cox models adjusted for age, prepregnancy body mass index, smoking, race and ethnicity, previous pregnancies, marital status, income, education, previous medical conditions, site, and year. RESULTS: Among 46 551 participants, 45% (21 107 of 46 551) were Black, and 46% (21 502 of 46 551) were White. The median time between the index pregnancy and death/censoring was 52 years (interquartile range, 45-54). Mortality was higher among Black (8714 of 21 107 [41%]) compared with White (8019 of 21 502 [37%]) participants. Overall, 15% (6753 of 43 969) of participants had PTD, 5% (2155 of 45 897) had hypertensive disorders of pregnancy, and 1% (540 of 45 890) had GDM/IGT. PTD incidence was higher in Black (4145 of 20 288 [20%]) compared with White (1941 of 19 963 [10%]) participants. The following were associated with all-cause mortality: preterm spontaneous labor (aHR, 1.07 [95% CI, 1.03-1.1]); preterm premature rupture of membranes (aHR, 1.23 [1.05-1.44]); preterm induced labor (aHR, 1.31 [1.03-1.66]); preterm prelabor cesarean delivery (aHR, 2.09 [1.75-2.48]) compared with full-term delivery; gestational hypertension (aHR, 1.09 [0.97-1.22]); preeclampsia or eclampsia (aHR, 1.14 [0.99-1.32]) and superimposed preeclampsia or eclampsia (aHR, 1.32 [1.20-1.46]) compared with normotensive; and GDM/IGT (aHR, 1.14 [1.00-1.30]) compared with normoglycemic. P values for effect modification between Black and White participants for PTD, hypertensive disorders of pregnancy, and GDM/IGT were 0.009, 0.05, and 0.92, respectively. Preterm induced labor was associated with greater mortality risk among Black (aHR, 1.64 [1.10-2.46]) compared with White (aHR, 1.29 [0.97-1.73]) participants, while preterm prelabor cesarean delivery was higher in White (aHR, 2.34 [1.90-2.90]) compared with Black (aHR, 1.40 [1.00-1.96]) participants. CONCLUSIONS: In this large, diverse US cohort, pregnancy complications were associated with higher mortality nearly 50 years later. Higher incidence of some complications in Black individuals and differential associations with mortality risk suggest that disparities in pregnancy health may have life-long implications for earlier mortality.

Genome-wide epigenetic signatures facilitated the variant classification of the PURA gene and uncovered the pathomechanism of PURA-related neurodevelopmental disorders.

PURPOSE: Rare genetic variants in the PURA gene cause the PURA-related neurodevelopmental disorder (PURA-NDD), characterized by neonatal abnormalities and developmental delay. Using genome-wide DNA methylation analysis on patients with PURA variants, we aim to establish a PURA-NDD-specific methylation profile and provide further insights on the molecular basis of the PURA-NDD. METHODS: Twenty three individuals (including 12 unpublished) carrying PURA variants were enrolled. We conducted the Illumina Infinium EPIC microarray analysis in 17 PURA-NDD individuals. In vitro experiments were performed to examine how PURA variants affect Pur-a expression. RESULTS: Additional phenotypes in 12 newly identified patients were described in this study. Genome-wide DNA methylation analysis unveiled distinctive methylation profiles to PURA-NDD, and the established classifier can reclassify PURA variants of uncertain significance. Patients bearing PURA hapoloinsufficient and missense variants have comparable DNA methylation profiles, and cells expressing these PURA variants showed consistent Pur-a downregulation, suggesting a haploinsufficiency mechanism. CONCLUSION: Patients with PURA-NDD exhibit a specific episignature, which has potential to aid identification and diagnosis of PURA-NDD patients and offer implications for further functional investigations.

More than sleep problems? Testing five key health behaviors as reasons for quality of life issues among shift workers.

BACKGROUND: The shift work schedule is a common work arrangement that can disrupt typical sleep-wake rhythms and lead to negative health consequences. The present study aims to examine the effect of shift work on health-related quality of life (QoL) and explore potential behaviorial mediators (i.e., sleep, eating, exercise, smoking, drinking). METHODS: A cross-sectional survey was conducted among 4,449 petroleum workers in southwest China. Data on shift work status, health behaviors, and physical and mental health QoL were collected. We tested our model using path analysis and the Monte Carlo approach among 2,129 included participants. RESULTS: After adjusting for covariates, shift work did not exhibit a significant direct association with QoL. However, shift work indirectly related to poorer physical health quality of life via less frequent healthy food consumption; shift work also indirectly related to poorer mental health QoL via both less frequent healthy food consumption and physical exercise. No significant indirect effects were found via sleeping, smoking, or drinking. CONCLUSIONS: Results suggest that shift work presents a challenge for QoL among Chinese petroleum workers due to their lesser engagement in two specific health behaviors: healthy eating and physical exercise. Healthy eating and exercise may present an even more prominent threat to shift workers' QoL than sleep and substance use. Strategies targeting shift work schedule as well as eating and exercise behaviors may help protect against poor QoL and adverse physical and mental health outcomes in this vulnerable group.

Genomic epidemiology reveals multiple mechanisms of linezolid resistance in clinical enterococci in China.

BACKGROUND: Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022. METHODS: Enterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis. RESULTS: The optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains. CONCLUSIONS: Our study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China.

HDAC6 inhibitor promotes reactive oxygen species-meditated clearance of Staphylococcus aureus in macrophage.

Staphylococcus aureus (S. aureus) pneumonia has become an increasingly important public health problem. Recent evidence suggests that epigenetic modifications are critical in the host immune defence against pathogen infection. In this study, we found that S. aureus infection induces the expression of histone deacetylase 6 (HDAC6) in a dose-dependent manner. Furthermore, by using a S. aureus pneumonia mouse model, we showed that the HDAC6 inhibitor, tubastatin A, demonstrates a protective effect in S. aureus pneumonia, decreasing the mortality and destruction of lung architecture, reducing the bacterial burden in the lungs and inhibiting inflammatory responses. Mechanistic studies in primary bone marrow-derived macrophages demonstrated that the HDAC6 inhibitors, tubastatin A and tubacin, reduced the intracellular bacterial load by promoting bacterial clearance rather than regulating phagocytosis. Finally, N-acetyl-L- cysteine, a widely used reactive oxygen species (ROS) scavenger, antagonized ROS production and significantly inhibited tubastatin A-induced S. aureus clearance. These findings demonstrate that HDAC6 inhibitors promote the bactericidal activity of macrophages by inducing ROS, an important host factor for S. aureus clearance and production. Our study identified HDAC6 as a suitable epigenetic modification target for preventing S. aureus infection, and tubastatin A as a useful compound in treating S. aureus pneumonia.

[Multidimensional Social Deprivation Impacts on Frailty in the Elderly: The Mediating Effect of Depression]. / 多维社会剥夺感对老年人衰弱的影响−抑郁的中介效应分析.

Objective: To investigate the mediating role of depression in the association between multidimensional social deprivation and frailty among the elderly. Methods: A total of 533 elderly individuals were enrolled from a district in Chengdu using a convenience sampling method. The participants responded to a questionnaire survey. Spearman rank correlation coefficient was employed to assess the correlations among social deprivation, depression, and frailty. MacKinnon's product-of-coefficients method was used to test the significance of the mediating effect of depression between social deprivation and frailty. Results: Among the participants, the average score for social deprivation among the participants was 48.9±7.1, the depression detection rate was 12.8%, and the frailty incidence rate was 8.4%. Social deprivation was positively correlated with frailty (r=0.212, P<0.001) and depression (r=0.399, P<0.001), while depression was positively correlated with frailty (r=0.248, P<0.001). The results of the mediation analysis showed that depression partially mediated the relationship between social deprivation and frailty (P<0.05), accounting for 64.95% of the mediation effect. Specifically, depression partially mediated the relationship between socio-economic status, comprehensive feeling, and frailty (P<0.05), accounting for 70.30% and 64.76% of the mediating effect, respectively. Depression fully mediated the relationship between family and social support, political and social participation dimensions, and frailty (P<0.05). Conclusion: Social deprivation can influence frailty in elderly people, with depression partially mediating this association.

An imputation approach for a time-to-event analysis subject to missing outcomes due to noncoverage in disease registries.

Disease incidence data in a national-based cohort study would ideally be obtained through a national disease registry. Unfortunately, no such registry currently exists in the United States. Instead, the results from individual state registries need to be combined to ascertain certain disease diagnoses in the United States. The National Cancer Institute has initiated a program to assemble all state registries to provide a complete assessment of all cancers in the United States. Unfortunately, not all registries have agreed to participate. In this article, we develop an imputation-based approach that uses self-reported cancer diagnosis from longitudinally collected questionnaires to impute cancer incidence not covered by the combined registry. We propose a two-step procedure, where in the first step a mover-stayer model is used to impute a participant's registry coverage status when it is only reported at the time of the questionnaires given at 10-year intervals and the time of the last-alive vital status and death. In the second step, we propose a semiparametric working model, fit using an imputed coverage area sample identified from the mover-stayer model, to impute registry-based survival outcomes for participants in areas not covered by the registry. The simulation studies show the approach performs well as compared with alternative ad hoc approaches for dealing with this problem. We illustrate the methodology with an analysis that links the United States Radiologic Technologists study cohort with the combined registry that includes 32 of the 50 states.

Absolute and relative risk estimation in the presence of outcome ascertainment gaps and competing risks.

Incomplete coverage by cancer registries can lead to an underreporting of cancers and a resulting bias in risk estimates. When registries are defined by geographic region, gaps in observation can arise for individuals who reside outside of or migrate from the total registry catchment area. Moreover, the exact periods of non-observation for an individual may be unknown due to intermittent reporting of residential histories. The motivating example for this work is the U.S. Radiologic Technologist (USRT) study which ascertained cancer outcomes for a national cohort through 43 state/regional registries; similar gaps in outcome ascertainment can appear in other registry or electronic health record- based cohort studies. We propose a two-step procedure for estimating relative and absolute risk in these settings. First, using a mover stayer model fitted to individuals' known residential history, we obtain individual posterior probabilities of residing outside the registry catchment area each year. Second, we incorporate these probabilities in the survival data likelihood for competing risks to account for unobserved events. We assess the performance of the proposed method in extensive simulation studies. Compared to several simple alternative approaches, the proposed method reduces bias and improves efficiency. Finally, we apply the proposed method to a study of first primary lung cancers in the USRT cohort.

Clinical performance of 0/1 h cardiac troponin algorithm for diagnosing non-STEMI in an emergency setting.

BACKGROUND: Non-ST-segment elevation myocardial infarction (NSTEMI) is a common form of acute myocardial infarction and rapid and accurate diagnosis is crucial for timely treatment. Current guidelines recommend using high-sensitivity cardiac troponin (hs-cTn) assays to determine circulating cTnI or cTnT levels. While the accuracy of the 0 h/1 h algorithm for diagnosing NSTEMI in different regions and patient populations remains controversial. Additionally, point-of-care testing (POCT) cTn assays have the potential to provide troponin readings to physicians within 15 min, but their accuracy in diagnosing NSTEMI in the emergency department (ED) requires further investigation. METHODS: A single-center prospective observational cohort study was conducted at Shaanxi Provincial People's Hospital to assess the analytical and diagnostic performance of the laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm with Radiometer AQT90-flex POCT cTnT assay in undifferentiated chest pain patients presenting to the ED. Whole-blood samples were collected and hs-cTnT and POCT cTnI were measured simultaneously at baseline and after 1 h. RESULTS: The study results showed that the POCT cTnT assay using the 0 h/1 h algorithm had comparable diagnostic accuracy to the laboratory-based Roche Modular E170 hs-cTnT assay in diagnosing NSTEMI in patients with chest pain. CONCLUSION: The laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm is reliable and accurate method for diagnosing NSTEMI in undifferentiated chest pain patients presenting to the ED. POCT cTnT assay has comparable diagnostic accuracy to the hs-cTnT assay and its rapid turnaround time makes it a valuable tool in expediting the diagnostic workup of chest pain patients.

Ascertainment of Incident Cancer by US Population-Based Cancer Registries Versus Self-Reports and Death Certificates in a Nationwide Cohort Study, the US Radiologic Technologists Study.

Follow-up of US cohort members for incident cancer is time-consuming, is costly, and often results in underascertainment when the traditional methods of self-reporting and/or medical record validation are used. We conducted one of the first large-scale investigations to assess the feasibility, methods, and benefits of linking participants in the US Radiologic Technologists (USRT) Study (n = 146,022) with the majority of US state or regional cancer registries. Follow-up of this cohort has relied primarily on questionnaires (mailed approximately every 10 years) and linkage with the National Death Index. We compared the level of agreement and completeness of questionnaire/death-certificate-based information with that of registry-based (43 registries) incident cancer follow-up in the USRT cohort. Using registry-identified first primary cancers from 1999-2012 as the gold standard, the overall sensitivity was 46.5% for self-reports only and 63.0% for both self-reports and death certificates. Among the 37.0% false-negative reports, 27.8% were due to dropout, while 9.2% were due to misreporting. The USRT cancer reporting patterns differed by cancer type. Our study indicates that linkage to state cancer registries would greatly improve completeness and accuracy of cancer follow-up in comparison with questionnaire self-reporting. These findings support ongoing development of a national US virtual pooled registry with which to streamline cohort linkages.

Marginal, conditional, and pseudo likelihood ratio approaches for biomarker combination to predict a binary disease outcome.

It is a common practice in public health research that multiple biomarkers are collected to diagnose or predict a disease outcome. A natural question is how to combine multiple biomarkers to improve the diagnostic accuracy. It has been shown by Neyman-Pearson lemma that the likelihood ratio statistic achieves the optimal AUC in theory. However, practical difficulty often lies in the estimation of the multivariate density functions. We propose three novel methods for the biomarker combination, with the idea of breaking down the joint densities to a series of univariate densities. The marginal likelihood ratio approach only assumes the marginal distribution of each biomarker. While the conditional likelihood ratio (CLR) and pseudo likelihood ratio (PLR) approaches assume the conditional distributions of a marker given others, and hence make use of the correlation structure to estimate the combination rules. The proposed methods make it much easier to assume and validate the univariate distributions of a biomarker than making multivariate distributional assumptions. Extensive simulation studies demonstrate that the CLR and the PLR approaches outperform many existing methods, and are therefore recommended for practical use. The proposed methods are motivated by and applied to a biomarker study to diagnose childhood autism/autism spectrum disorder.

Perceptions of social norms played an important role in the occurrence of casual sex among Yi minority residents in China: a population-based study.

BACKGROUND: Liangshan is one of the areas severely affected by both HIV and poverty in China. We investigated associations between perceptions of social norms related to casual sex and the occurrence of casual sex in lifetime among Yi minority people. Participants were Yi minority people aged 15-49 years old living in Liangshan. Of the participants, 11.8% were confirmed to be HIV-positive. About half of the participants (46.6%) had engaged in casual sex in their lifetime. All six perceptions of social norms were significantly associated with the presence of casual sex in lifetime. They were acceptable of belife: (1) casual sex in general (OR: 15.03), (2) not to use condom during casual sex (OR: 1.58), (3) a Yi woman to have more than one sex partner(OR: 4.54), (4) a Yi man to have more than one sex partner(OR: 4.51), (5) premarital sex with casual sex partner (OR: 4.29), and (6) extra-marital sex with casual sex partner (OR: 3.23). Casual sex may play an important role in facilitating HIV transmission among Yi minority people. Future interventions should consider making use of the Yi clan system to change perceptions of social norms related to casual sex.

Paracrine effects of adipose-derived stem cells in cutaneous wound healing in streptozotocin-induced diabetic rats.

OBJECTIVE: The purpose of this study was to explore the paracrine effects of adipose-derived stem cells (ASCs) on cutaneous wound healing in diabetic rats. METHOD: The ASCs were isolated and identified by immunofluorescent staining. The ASCs-conditioned medium (ASCs-CM) was harvested. Cell counting kit (CCK)-8 assay, scratch experiments, western blot and quantitative polymerase chain reaction (qPCR) were performed to observe the effects of ASCs-CM on fibroblasts. A full-thickness skin wound diabetic rat model was prepared, using 34 male, Sprague Dawley rats. ASCs-CM or negative-control medium (N-CM) was injected around the wound surface. The existing wound area was measured on days 4, 8, 12 and 16 after the postoperative day, and the wound tissues were collected for immunohistochemical staining and qPCR quantitative study. RESULTS: In this experiment, the isolated cells were characterised as ASCs. The results of CCK-8 assay, cell scratch test, western blot and qPCR showed ASCs-CM could significantly promote the proliferation, migration and differentiation of fibroblasts. Simultaneously, the healing rate of full-thickness skin wounds in diabetic rats was significantly higher in the ASCs-CM group than the N-CM group on days 4, 8, 12 and 16. Immunohistochemical staining and qPCR results showed that the expression of vascular endothelial growth factor (VEGF, days 4 and 8), α-smooth muscle actin (SMA) (days 4 and 16), transforming growth factor (TGF)-ß1 (days 4, 8 and 12) were higher in the ASCs-CM group than that of the N-CM group (p<0.05). CONCLUSION: This experiment demonstrated that ASCs-CM may accelerate wound healing in diabetic rats by promoting the secretion of TGF-ß1, VEGF and the proliferation, migration and differentiation of fibroblasts.

Joint modeling of longitudinal data with informative cluster size adjusted for zero-inflation and a dependent terminal event.

Repeated measures are often collected in longitudinal follow-up from clinical trials and observational studies. In many situations, these measures are adherent to some specific event and are only available when it occurs; an example is serum creatinine from laboratory tests for hospitalized acute kidney injuries. The frequency of event recurrences is potentially correlated with overall health condition and hence may influence the distribution of the outcome measure of interest, leading to informative cluster size. In particular, there may be a large portion of subjects without any events, thus no longitudinal measures are available, which may be due to insusceptibility to such events or censoring before any events, and this zero-inflation nature of the data needs to be taken into account. On the other hand, there often exists a terminal event that may be correlated with the recurrent events. Previous work in this area suffered from the limitation that not all these issues were handled simultaneously. To address this deficiency, we propose a novel joint modeling approach for longitudinal data adjusting for zero-inflated and informative cluster size as well as a terminal event. A three-stage semiparametric likelihood-based approach is applied for parameter estimation and inference. Extensive simulations are conducted to evaluate the performance of our proposal. Finally, we utilize the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study for illustration.

Prevalence and risk factors of metabolic associated fatty liver disease among people living with HIV in China.

BACKGROUND AND AIM: The new definition for metabolic associated fatty liver disease (MAFLD), formerly named non-alcoholic fatty liver disease (NAFLD), would undoubtedly have significant influence on diagnosis, epidemiology, and new drug research. We investigated the prevalence and risk factors of MAFLD among people living with HIV (PLWH). METHODS: In this cross-sectional study, transient elastography was performed in PLWH without significant alcohol intake and hepatitis B virus and hepatitis C virus infection. NAFLD was diagnosed as controlled attenuation parameter (CAP) ≥ 248 dB/m by transient elastography, and MAFLD was defined according to the 2020 international consensus. Advanced fibrosis was defined as liver stiffness measurement (LSM) ≥ 10 kPa. RESULTS: Among the 361 PLWH enrolled, the prevalence of NAFLD and MAFLD were 37.67% and 34.90%, respectively. Compared with the non-MAFLD group, the prevalence of elevated alanine aminotransferase (ALT) level (44.44% vs 16.17%, P < 0.001) and advanced fibrosis (19.05% vs 2.55%, P < 0.001) were significantly higher in the MAFLD group. A positive correlation between LSM and CAP values was found in the MAFLD group (rs  = 0.350, P < 0.001) but not in the non-MAFLD group. In multivariate analysis, independent risk predictors for MAFLD were higher ALT level (odds ratio [OR] 1.015, 95% confidence interval [CI] 1.003-1.028, P = 0.018), higher uric acid (OR 1.005, 95% CI 1.002-1.009, P = 0.003), higher total cholesterol (OR 1.406, 95% CI 1.029-1.921, P = 0.032), and greater waist-height ratio (OR 1.291, 95% CI 1.196-1.393, P < 0.001). CONCLUSIONS: A third of PLWH had MAFLD, which was highly accordant with the prevalence of NAFLD. Routine screening for MAFLD is necessary in PLWH.

Pesticide use and kidney function among farmers in the Biomarkers of Exposure and Effect in Agriculture study.

BACKGROUND: Pesticides have been reported to be associated with malignant and non-malignant kidney disease. Few studies have examined the relationship between individual pesticides and kidney dysfunction. OBJECTIVE: We evaluated the associations of pesticide use with measured kidney function among male pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study, a subcohort in the Agricultural Health Study. METHODS: Serum creatinine was measured in 1545 BEEA participants and estimated glomerular filtration rate (eGFR) was calculated with the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Using reported information on lifetime use of 41 pesticides, multivariable linear and logistic regression was used to examine associations with eGFR modeled continuously and with CKD (eGFR <60 mL/min/1.73 m2), respectively. Models were adjusted for possible confounding factors related to kidney function and correlated pesticides. RESULTS: Lower eGFR was observed among pesticide applicators who ever used the herbicides pendimethalin (-3.7%, 95% confidence interval (CI): 5.8%, -1.5%), atrazine (-3.7%, 95% CI: 6.9%, -0.4%), and dicamba (-2.8%, 95% CI: 5.3%, -0.2%) compared with never users of each pesticide. Ever use of pendimethalin (odds ratio (OR)=1.6, 95% CI: 1.1, 2.2) and atrazine (OR=1.8, 95% CI: 1.0, 3.0) was also associated with elevated odds of CKD, with an exposure-response association between intensity-weighted lifetime days of pendimethalin use and CKD among active farmers (N=1302; ptrend=0.04). Atrazine use within the last year was associated with lower eGFR and elevated odds of CKD when compared with never users, and we observed exposure-response associations with intensity-weighted lifetime days among recent users. Use of several other pesticides was associated with higher eGFR. DISCUSSION: These results suggest that two widely used herbicides, pendimethalin and atrazine, may be associated with altered kidney function among pesticide applicators. Our findings for these herbicides are consistent with observed associations with end-stage renal disease in the Agricultural Health Study.

Social support and quality of life among rural family caregivers of persons with severe mental illness in Sichuan Province, China: mediating roles of care burden and loneliness.

OBJECTIVE: To explore the relationship between social support and quality of life (QoL) among family caregivers of persons with severe mental illness (SMI) and examine the mediating roles of care burden and loneliness. METHODS: A cross-sectional study was carried out between December 2017 and May 2018. A random sample of 256 family caregivers of persons with SMI in rural areas of Sichuan Province, China was recruited for participation. Survey data on socio-demographics, social support, care burden, loneliness, and QoL were collected via in-person interviews. Multiple linear regression analysis and structural equation modeling (SEM) were used to test the hypothesized relationships. RESULTS: The majority (72.7%) of family caregivers of persons with SMI in this study reported having low QoL. Social support was positively associated with QoL and negatively associated with care burden and loneliness. The findings suggested the mediating roles of care burden and loneliness on the association between social support and QoL. CONCLUSION: The hypothesized model was found to be a suitable model for predicting QoL among family caregivers of persons with SMI. The findings can help inform the design of future interventions aimed at enhancing social support, reducing care burden and loneliness, which may be helpful to improve caregivers' QoL. Future study is required to find a causal path to promote QoL among family caregivers of persons with SMI.

Family function fully mediates the relationship between social support and perinatal depression in rural Southwest China.

BACKGROUND: Perinatal depression is the most common complication of gestation and childbearing affecting women and their families, and good social support and family function are considered protective and modifiable factors. This study aimed to investigate depression status and explore inter-relationships between social support and perinatal depression considering the influence of family function in rural areas of Southwest China. METHODS: This is a cross-sectional study. The following instruments were used: the Edinburgh Postpartum Depression Scale, the APGAR Family Care Index Scale, and the Social Support Rate Scale. A structural equation modelling was used to test the hypothesis relationships among the variables. RESULTS: A total of 490 rural antenatal (N = 249) and postpartum (N = 241) women (mean age (standard deviation), 28.17 ± 5.12) participated. We found that the prevalence of depression symptoms was 10.4%. Path analysis showed that family function had a direct negative correlation with depression (ß = - 0.251, 95%CI: - 0.382 to - 0.118). Social support had a direct positive correlation with family function (ß =0.293, 95%CI: 0.147 to 0.434) and had an indirect negative correlation with depression (ß = - 0.074, 95%CI: - 0.139 to - 0.032), family function fully mediated the relationship between social support and depression. CONCLUSIONS: Findings of this study highlight that family function should be considered as the key target for interventions aiming to lower the prevalence of perinatal depression. Family members interventions are critical to reduce depression among antenatal and postpartum women.

Factors associated with self-medication in children and the decomposition of rural-urban disparities in China.

BACKGROUND: Self-medication in children is one of the greatest threats to children health in China. OBJECTIVES: The purpose of this study was to examine the potential factors associated with self-medication in children and explore rural-urban disparities. METHODS: A total of 2798 children enrolled in the study. Informed consent was obtained from each primary caregiver following a detail explanation about the purpose of the study. Multivariable logistic regression analysis and Oaxaca-Blinder decomposition analysis were used. RESULTS: The results showed that 38.2% primary caregivers of rural areas self-medicated their children, compared to 18.7% of those in urban areas. The urban primary caregivers with college or above education were more likely to self-medicate their children, while rural primary caregivers with college or above education were less likely to self-medicate their children. Children having unhealthy eating habits were more likely to have been self-medicated by their primary caregivers in urban and rural areas. Urban primary caregivers who spend more than 10 min from home to the nearest medical institution were more likely to self-medicate their children. In rural areas, children aged 3-6 years old, primary caregivers with monthly household income per capita of 1001-3000 Yuan, and children with chronic diseases are another set of enabling factors which impacted on self-medication. Unhealthy eating habits of children were the largest contributor to the rural-urban self-medication gap. CONCLUSIONS: Children's factors explained the largest portion of the rural-urban difference in self-medication among children. The evidence presented in this study suggests that public health policies addressing rural-urban differences in children' s factors could serve as an effective method for reducing rural-urban disparities in self-medication among children.