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1.
Artigo em Inglês | MEDLINE | ID: mdl-34657236

RESUMO

PURPOSE: Multiple morphological abnormalities in the sperm flagella (MMAF) comprise a severe phenotype of asthenoteratozoospermia with reduced or absent spermatozoa motility. Whereas dozens of candidate pathogenic genes for MMAF have been identified, the genetic cause in a large proportion of patients is unknown. We attempted to identify novel genetic explanations for MMAF. METHODS: We performed whole-exome sequencing of patients with MMAF to identify pathogenic variants. The phenotypes of spermatozoa in patients carrying DNAH10 variants were investigated using haematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy. The expression and location of DNAH10 and other spermatozoa structure-related proteins were analyzed using immunofluorescence assays. RESULTS: We found one homozygous frameshift DNAH10 variant (NM_207437: c.2514delG:p.L839*) and one compound heterozygous DNAH10 variant (NM_207437: c.10820 T > C:p.M3607T; c.12692C > T:p.T4231I) in two patients with MMAF. These variants were absent or rare in the general population. Haematoxylin and eosin staining and scanning electron microscopy revealed the significant disruption of sperm flagella in the patients. In addition, ultrastructural analysis by transmission electron microscopy showed significant inner dynein arm (IDA) deficiency in sperm flagella. Using immunofluorescence assays, we found a significant reduction in IDA-related proteins including DNAH10 and DNAH1. CONCLUSIONS: We identified putative novel pathogenic variants in DNAH10 for MMAF, which might advance the genetic diagnosis and clinical genetic counselling for male infertility.

2.
Psychoneuroendocrinology ; 134: 105435, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34649104

RESUMO

OBJECTIVE: To evaluate whether gestational diabetes mellitus (GDM) is associated with increased risks of autistic traits and attention deficit/hyperactivity disorder (ADHD) among offspring and whether placental inflammatory and oxidative stress cytokines play an intermediary role. METHODS: Based on a prospective cohort study from China, namely, the Ma'anshan Birth Cohort study (MABC), 3260 mother-child pairs were included. Autistic traits and ADHD symptoms among children were assessed at 18 months and 36 months, respectively. The mRNA expression levels of fourteen placental cytokines were determined using PCR. Logistic regression analysis was used to examine the associations between GDM and the risks of autistic traits or ADHD symptoms. Mediation analysis was used to assess the potential mediation effects of certain placental inflammatory factors. RESULTS: Of the 3260 children, 419 (12.85%) were exposed to GDM. The prevalence rates of autistic traits and ADHD symptoms were 13.86% and 6.4%, respectively. A 48.6% increased risk of autistic traits was observed among offspring born to mothers with GDM [odds ratio (OR) = 1.49, 95% confidence interval (95%CI): 1.11-2.00)], while no significant association was found in terms of ADHD symptoms. There were significant positive associations between GDM and IL-10 expression and between HIF1-α and CRP mRNA expression and a significant negative association between GDM and CD206 mRNA expression. The expression of MCP-1 mRNA was negatively associated with the risk of autistic traits [adjusted OR = 0.73 (95%CI: 0.73-0.55)]. The levels of TNF-α were positively associated with the risk of ADHD symptoms [OR = 2.11 (95%CI: 1.39-3.21)], while GRP78 was inversely associated with it [OR = 0.64 (95%CI: 0.44-0.94)]. However, none of the 14 placental cytokines was involved as a key mediator. CONCLUSION: Our findings suggest that GDM may act as a risk factor for autistic traits in offspring, while the biological mechanisms may not involve the 14 placental cytokines studied. No significant association between GDM and ADHD symptoms was observed.

3.
Clin Genet ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34595750

RESUMO

Non-obstructive azoospermia (NOA) represents one of the most serious forms of male infertility caused by spermatogenic failure. Despite multiple genes found to be associated with human NOA, the genetic basis of this idiopathic disease remains largely unknown. FBXO43 is a direct inhibitor of the anaphase-promoting complex/cyclosome (APC/C) E3 ligase and crucially important in mouse spermatogenesis. In this study, for the first time, we identified a homozygous nonsense mutation in FBXO43 c.1747C > T:p.Gln583X in two NOA brothers from a Chinese consanguineous family via whole-exome sequencing. FBXO43 was absent from testicular tissue of the proband, and FBXO43-immunostaining signals were invisible in the affected seminiferous tubules. Furthermore, in humans, FBXO43 defects cause meiotic arrest within early diplotene of prophase I. The results here demonstrate the pathogenicity of this loss-of-function mutation and confirmed that spermatocytes were unable to complete meiotic divisions without FBXO43 in humans. In mouse testicular protein extracts, three subunits of the APC/C, including ANAPC2, ANAPC8 and ANAPC10, were validated to interact directly with FBXO43, whereas no interactions were detected for FBXO43 and SKP1. This study furthers our understanding of the genetic basis of human NOA and provides insights into FBXO43 and male infertility.

4.
Chronobiol Int ; : 1-7, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632893

RESUMO

Modern lifestyles, and the popularization of artificial light at night, have led to maladjusted social time and internal circadian rhythm, so developing an instrument on biological rhythms is critical. A 36-item self-rated questionnaire assessing biological rhythm disorder in adolescents was developed according to the literature and expert evaluations. Based on a literature review, four dimensions, digital media use, sleep, eating habits, and activity, were determined. After preliminary item analysis, seven unqualified items were eliminated. A total of 1,152 college students and 8,082 middle school students were selected. Two independent sample t-tests, the Pearson correlations, and confirmatory factor analysis, were used to evaluate the reliability and validity of the questionnaire. The final questionnaire consisted of 4 dimensions covering 29 items, and the variance cumulative contribution was 62.65%. Cronbach's α for the total questionnaire was 0.950 and ranged from 0.817 to 0.904 for each dimension. The Pearson correlation coefficients between each item and the total score ranged from 0.360 to 0.755, and the Pearson correlation coefficient between each item and its dimension was between 0.575 and 0.841. Confirmatory factor analysis showed that the indices of CFI, TLI and RMSEA were 0.911, 0.901 and 0.043, respectively, which is a good degree of fit. The self-rating scale is consistent with the evaluation standard of psychometrics and can be used to evaluate the degree of biological rhythm disorder in adolescents.

5.
Front Public Health ; 9: 575315, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595146

RESUMO

Objective: The aim of this study is to analyze the latent class of basic reproduction number (R 0) trends of the 2019 novel coronavirus disease (COVID-19) in the major endemic areas of China. Methods: The provinces that reported more than 500 cases of COVID-19 till February 18, 2020 were selected as the major endemic areas. The Verhulst model was used to fit the growth rate of cumulative confirmed cases. The R 0 of COVID-19 was calculated using the parameters of severe acute respiratory syndrome (SARS) and COVID-19. The latent class of R 0 was analyzed using the latent profile analysis (LPA) model. Results: The median R 0 calculated from the SARS and COVID-19 parameters were 1.84-3.18 and 1.74-2.91, respectively. The R 0 calculated from the SARS parameters was greater than that calculated from the COVID-19 parameters (Z = -4.782 to -4.623, p < 0.01). Both R 0 can be divided into three latent classes. The initial value of R 0 in class 1 (Shandong Province, Sichuan Province, and Chongqing Municipality) was relatively low and decreased slowly. The initial value of R 0 in class 2 (Anhui Province, Hunan Province, Jiangxi Province, Henan Province, Zhejiang Province, Guangdong Province, and Jiangsu Province) was relatively high and decreased rapidly. Moreover, the initial R 0 value of class 3 (Hubei Province) was in the range between that of classes 1 and 2, but the higher R 0 level lasted longer and decreased slowly. Conclusion: The results indicated that the overall R 0 trend is decreased with the strengthening of comprehensive prevention and control measures of China for COVID-19, however, there are regional differences.


Assuntos
COVID-19 , SARS-CoV-2 , Número Básico de Reprodução , China/epidemiologia , Humanos , Incidência
6.
Clin Genet ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569065

RESUMO

Reduced generation of multiple motile cilia (RGMC) and the consequent primary ciliary dyskinesia (PCD) cause infertility due to a substantial reduction in the number of multiciliated cells (MCCs) in the efferent ducts (EDs)/oviducts. MCIDAS acts upstream of CCNO to regulate the biogenesis of basal bodies (BBs); therefore, both genes play a vital role in the multiciliogenesis of the reproductive tract epithelium. In this study, whole-exome sequencing was performed to identify the causative genes in ten unrelated infertile patients with PCD: seven males and three females. Notably, homozygous frameshift mutations in MCIDAS (c.186dupT, p.Pro63Serfs*22) and CCNO (c.262_263insGGCCC, p.Gln88Argfs*8) were identified in one male and one female participant from two unrelated consanguineous families. Haematoxylin-eosin staining/scanning electron microscopy revealed abnormal MCCs in the mutated EDs/oviducts. Furthermore, transmission electron microscopy revealed significantly reduced BBs. Immunofluorescence staining showed the absence of MCIDAS and CCNO signals in the affected tissues and confirmed that MCIDAS acts upstream of CCNO in the context of multiciliogenesis in the reproductive tract epithelium. In vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) was successful, with a positive pregnancy outcome in both MCIDAS- and CCNO-mutated patients. Our results support the use of IVF/ICSI interventions to treat infertility due to RGMC in couples.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34585354

RESUMO

The objective of this study is to investigate the mediating effect of placental inflammatory biomarkers on the relationship between prenatal phthalate coexposure and cognitive development in preschoolers. A subgroup of 1660 mother-child pairs from the Ma'anshan Birth Cohort study were included. We measured the levels of phthalate metabolites of dibutyl phthalate (DBP), butyl benzyl phthalate (BBzP), and di (2-ethylhexyl) phthalate (DEHP) in all the women included in the study from three urine samples collected in each of the trimesters. A potency-weighted sum of coexposure to DBP, BBzP, and DEHP (indicator: ∑PAE) was calculated. The mRNA of the proinflammatory cytokine IL-6 and the classically activated macrophage (M1) biomarker CD68 was analyzed using placental tissues. The Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition-Chinese was used to evaluate the full-scale intelligence quotient (FSIQ) of children aged 2.5-6 years. Average ∑PAEs and ∑PAEs in each trimester were associated with IL-6 and CD68. ∑PAE in the first trimester was positively associated with IL-6 (ß = 0.11, 95% CIs = 0.03-0.19) and CD68 (ß = 0.16, 95% CIs = 0.04-0.28), and negatively associated with FSIQ (ß =-0.06, 95% CIs = -0.11 to -0.02), verbal comprehension (ß =-0.06, 95% CIs = -0.11 to -0.01), and processing speed (ß =-0.07, 95% CIs = -0.12 to -0.01). Additionally, sex discrepancies were observed for the mediating effects of placental inflammation on the relationships between ∑PAE and children's cognitive development. For instance, the association between ∑PAE in early pregnancy and FSIQ was partially mediated by IL-6 (estimated proportion mediated: 21.85%) and CD68 (estimated proportion mediated: 16.2%). Gender-specific associations and trimester-specific relationships of prenatal multiple phthalate coexposure were revealed. ∑PAE in the first trimester of pregnancy was associated with increased of placental inflammation, and a decrease in preschoolers' cognitive development. In boys, placental IL-6 and CD68 elevation resulting from phthalates might be potential mechanisms of poor cognitive development.

8.
Ecotoxicol Environ Saf ; 226: 112829, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34592520

RESUMO

BACKGROUND: Previous studies have found associations between single toxic metals, such as arsenic and cadmium, and kidney function in adults with diabetes. However, studies with regards to other metals and metal mixtures are still limited. OBJECTIVE: Our study aimed to investigate the associations between urinary concentrations of 5 selected metals and metal mixtures and kidney function using a sample of older adults with diabetes mellitus in Chinese communities. METHODS: In a sample of older adults (n = 5186), 592 eligible subjects were included in this study. Urinary concentrations of 5 metals, i.e., arsenic (As), cadmium (Cd), vanadium (V), cobalt (Co), and thallium (Tl), were measured by inductively coupled plasma mass spectrometer (ICP-MS). Estimated glomerular filtration rate (eGFR) was calculated and dichotomized into indicator of chronic kidney disease (CKD). Logistic analysis and Bayesian kernel machine regression (BKMR) were used to explore the associations between single metals and metal mixtures and CKD, respectively. RESULTS: Urinary levels of As and V were positively correlated with CKD (OR=2.37, 95% CI: 1.31-4.30 for As; OR=2.24, 95% CI: 1.25-4.03 for V), when compared the 4th quartile with the 1st quartile. After adjustment for potential confounders, the significant association between As and CKD still existed (OR=2.73, 95% CI: 1.23-6.07). BKMR analyses showed strong linear positive associations between As and V and CKD. Higher urinary levels of the mixture were significantly associated with higher odds of CKD in a dose-response pattern. As and V showed the highest posterior inclusion probabilities. CONCLUSION: Urine As and V were positively associated with CKD in older adults with diabetes mellitus, separately and in a mixture. The metals mixture showed a linear dose-response association with the odds of CKD. The analyses of mixtures, rather than of single metals, may provide a real-world perspective on the relationship between metals and kidney function.

9.
JMIR Public Health Surveill ; 7(10): e26840, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34479184

RESUMO

BACKGROUND: The outbreak of COVID-19 in China occurred around the Chinese New Year (January 25, 2020), and infections decreased continuously afterward. General adoption of preventive measures during the Chinese New Year period was crucial in driving the decline. It is imperative to investigate preventive behaviors among Chinese university students, who could have spread COVID-19 when travelling home during the Chinese New Year break. OBJECTIVE: In this study, we investigated levels of COVID-19-related personal measures undertaken during the 7-day Chinese New Year holidays by university students in China, and associated COVID-19-related cognitive factors. METHODS: A cross-sectional anonymous web-based survey was conducted during the period from February 1 to 10, 2020. Data from 23,863 students (from 26 universities, 16 cities, 13 provincial-level regions) about personal measures (frequent face-mask wearing, frequent handwashing, frequent home staying, and an indicator that combined the 3 behaviors) were analyzed (overall response rate 70%). Multilevel multiple logistic regression analysis was performed. RESULTS: Only 28.0% of respondents (6684/23,863) had left home for >4 hours, and 49.3% (11,757/23,863) had never left home during the 7-day Chinese New Year period; 79.7% (19,026/23,863) always used face-masks in public areas. The frequency of handwashing with soap was relatively low (6424/23,863, 26.9% for >5 times/day); 72.4% (17,282/23,863) had frequently undertaken ≥2 of these 3 measures. COVID-19-related cognitive factors (perceptions on modes of transmission, permanent bodily damage, efficacy of personal or governmental preventive measures, nonavailability of vaccines and treatments) were significantly associated with preventive measures. Associations with frequent face-mask wearing were stronger than those with frequent home staying. CONCLUSIONS: University students had strong behavioral responses during the very early phase of the COVID-19 outbreak. Levels of personal prevention, especially frequent home staying and face-mask wearing, were high. Health promotion may modify cognitive factors. Some structural factors (eg, social distancing policy) might explain why the frequency of home staying was higher than that of handwashing. Other populations might have behaved similarly; however, such data were not available to us.

10.
PLoS Med ; 18(9): e1003805, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34582464

RESUMO

BACKGROUND: The prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades. Exposure to adverse intrauterine environment in fetal life may contribute to the elevated risk of early-onset CVD. Many studies have shown that maternal hypertensive disorders of pregnancy (HDP) are associated with increased risks of congenital heart disease, high blood pressure, increased BMI, and systemic vascular dysfunction in offspring. However, empirical evidence on the association between prenatal exposure to maternal HDP and early-onset CVD in childhood and adolescence remains limited. METHODS AND FINDINGS: We conducted a population-based cohort study using Danish national health registers, including 2,491,340 individuals born in Denmark from 1977 to 2018. Follow-up started at birth and ended at the first diagnosis of CVD, emigration, death, or 31 December 2018, whichever came first. Exposure of maternal HDP was categorized as preeclampsia or eclampsia (n = 68,387), gestational hypertension (n = 18,603), and pregestational hypertension (n = 15,062). Outcome was the diagnosis of early-onset CVD from birth to young adulthood (up to 40 years old). We performed Cox proportional hazards regression to evaluate the associations and whether the association differed by maternal history of CVD or diabetes before childbirth. We further assessed the association by timing of onset and severity of preeclampsia. The median follow-up time was 18.37 years, and 51.3% of the participants were males. A total of 4,532 offspring in the exposed group (2.47 per 1,000 person-years) and 94,457 in the unexposed group (2.03 per 1,000 person-years) were diagnosed with CVD. We found that exposure to maternal HDP was associated with an increased risk of early-onset CVD (hazard ratio [HR]: 1.23; 95% CI = 1.19 to 1.26; P < 0.001). The HRs for preeclampsia or eclampsia, gestational hypertension, and pregestational hypertension were 1.22 (95% CI, 1.18 to 1.26; P < 0.001), 1.25 (95% CI, 1.17 to 1.34; P < 0.001), and 1.28 (95% CI, 1.15 to 1.42; P < 0.001), respectively. We also observed increased risks for type-specific CVDs, in particular for hypertensive disease (HR, 2.11; 95% CI, 1.96 to 2.27; P < 0.001) and myocardial infarction (HR, 1.49; 95% CI, 1.12 to 1.98; P = 0.007). Strong associations were found among offspring of mothers with CVD history (HR, 1.67; 95% CI, 1.41 to 1.98; P < 0.001) or comorbid diabetes (HR, 1.56; 95% CI, 1.34 to 1.83; P < 0.001). When considering timing of onset and severity of preeclampsia on offspring CVD, the strongest association was observed for early-onset and severe preeclampsia (HR, 1.48, 95% CI, 1.30 to 1.67; P < 0.001). Study limitations include the lack of information on certain potential confounders (including smoking, physical activity, and alcohol consumption) and limited generalizability in other countries with varying disparities in healthcare. CONCLUSIONS: Offspring born to mothers with HDP, especially mothers with CVD or diabetes history, were at increased risks of overall and certain type-specific early-onset CVDs in their first decades of life. Further research is warranted to better understand the mechanisms underlying the relationship between maternal HDP and early-onset CVD in offspring.

11.
Ecotoxicol Environ Saf ; 225: 112736, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481356

RESUMO

BACKGROUND: Based on a medical record or questionnaire survey approach, previous epidemiological studies have investigated associations between maternal antibiotic exposure during pregnancy and childhood allergic diseases. However, biomonitoring studies on the prenatal low-dose antibiotic exposure, mainly from the environment and contaminated food, and in relation to children allergic diseases, are missing. OBJECTIVES: This research aimed to examine the associations between prenatal low-dose antibiotic exposure measured at multiple time points and children current allergic diseases at 4 years of age. METHODS: The current study including 2453 mother-child pairs was based on the Ma'anshan Birth Cohort study. Selected 41 antibiotics and their two metabolites, which including human antibiotics (HAs), preferred as human antibiotics (PHAs), veterinary antibiotics (VAs) and preferred as veterinary antibiotics (PVAs), in urine samples from 2453 pregnant women were biomonitored through liquid chromatography-triple quadrupole tandem mass spectrometry. Information on children current allergic diseases were collected via validated questionnaires. Generalized estimating equation were used to explore the associations between the repeated measurements of maternal urinary antibiotic over three trimesters and current allergic diseases in children. RESULTS: The detection rates of nine individual antibiotics in the three trimester during pregnancy are greater than 10%, and the 90th percentile concentration of the detected antibiotics ranges from 0.07 to 22.34 µg/g, and the 95th percentile concentration ranges from 0.17 to 59.57 µg/g. Among the participants, each one-unit concentration increment of sulfamethazine (adjusted OR=1.28, 95% CI: 1.10, 1.49, P-FDR=0.014) in the first trimester and ciprofloxacin (adjusted OR=1.17, 95% CI: 1.07, 1.28, P-FDR=0.008) in the second trimester were associated with an increased risk of current eczema in children. In the third trimester, each one-unit concentration increment of oxytetracycline (adjusted OR=1.90, 95% CI: 1.30, 2.78, P-FDR=0.014) was associated with an increased risk of current asthma in children. Gender-stratified analyses demonstrated that no gender differences were observed in the associations between prenatal antibiotic exposure and current allergic diseases in children. CONCLUSIONS: Maternal exposure to certain specific VAs or PVAs (sulfamethazine, ciprofloxacin and oxytetracycline) in different trimesters was associated with an increased risk of current asthma and current eczema in 4-year-old children. No gender differences were found in these associations. Further studies are warranted to confirm our findings and explore the potential mechanisms.


Assuntos
Antibacterianos , Exposição Materna , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Gravidez , Trimestres da Gravidez , Estudos Prospectivos
12.
Ecotoxicol Environ Saf ; 223: 112561, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34348191

RESUMO

Experimental animal studies and limited epidemiologic evidence among elder population suggest that exposure to light at night (LAN) may be obesogenic. Nevertheless, little is known about the possible impact of bedroom LAN exposure on subsequent adiposity and the distribution pattern of the accumulated fat, especially in younger population. Here, we estimated longitudinal associations of objectively assessed bedroom LAN exposure with general and abdominal adiposity among young adults. We measured 2-night bedroom LAN exposure using a portable illuminometer in a cohort of young adults (n = 482). Body composition using multifrequency bioelectrical impedance analysis was evaluated at baseline and 1-year follow-up visit. Significant increases in fat mass (2.4 kg, P = 0.015 in male; 1.9 kg, P < 0.001 in female), visceral fat area (10.7 cm2, P < 0.001 in male; 5.0 cm2, P = 0.01 in female), waist circumference (3.8 cm, P = 0.039 in male; 2.5 cm, P = 0.047 in female) and percentage of body fat (3.6%, P = 0.002 in male; 3.0%, P = 0.001 in female) were observed among individuals with bedroom LAN higher than 5 lx. Compared to the lowest quartile group of bedroom LAN exposure, the highest quartile group was associated with an increase of 0.64 kg/m2 in BMI (95% CI: 0.18-1.09 kg/m2; P = 0.006) and 1.22 kg increase in fat mass (95% CI: 0.10-2.34 kg; P = 0.025) among female participants, and 10.58 cm2 in visceral fat area (95% CI: 4.85-16.31 cm2; P = 0.001) and 2.59 cm in waist circumference (95% CI: 0.37-4.81 cm; P = 0.023) among male participants. In this cohort of Chinese young adults, significant associations were observed between bedroom LAN exposure and adiposity in a sex- and fat depot-specific fashion. Further intervention and longitudinal studies could help elucidate the actual effects and develop sex-specific strategies against lifetime obesity and related metabolic disorders.


Assuntos
Adiposidade , Doenças Metabólicas , Idoso , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Obesidade , Circunferência da Cintura , Adulto Jovem
13.
BMC Psychiatry ; 21(1): 407, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404392

RESUMO

BACKGROUND: Rapid socio-economic development makes China a unique laboratory for examining how lifestyle changes affect adolescent mental health. This study aims to identify joint trajectories of modifiable lifestyle indicators during pubertal transition and its associations with psychopathological outcomes. METHODS: A cohort of 1974 children aged 7-9 years were recruited in Anhui Province, China during March 2013. The assessment of lifestyle behaviors (screen time, physical activity, sleep duration and beverage intake) and depressive symptoms were conducted from Wave 1 to Wave 4 (2018). Suicide ideation, non-suicidal self-harm (NSSI) and alcohol use were self-reported at Wave 4. Longitudinal trajectories of lifestyle patterns were defined using group-based multi-trajectory models in 2019. RESULTS: Four lifestyle trajectories were identified: persistent healthy (39.9%), suboptimal healthy (25.3%), unhealthy mitigation (17.2%), and persistent unhealthy (17.7%). Compared with persistent healthy group, the risk of subsequent suicide ideation [odds ratio (OR): 2.86, 95%CI: 2.15-3.81], depressive symptoms (OR: 2.16, 95%CI: 1.39-3.35), alcohol use (OR: 2.53, 95%CI: 1.78-3.61) and non-suicidal self-harm (OR: 1.35, 95%CI: 1.09-1.67) was significantly higher in persistent unhealthy group. CONCLUSIONS: This study provided convincing evidence that unhealthy lifestyle trajectory during adolescence is associated with more than two-fold elevated odds for multiple domains of psychopathological outcomes over 5 years.


Assuntos
Transtornos Mentais , Comportamento Autodestrutivo , Adolescente , Criança , Humanos , Estilo de Vida , Psicopatologia , Fatores de Risco , Comportamento Autodestrutivo/epidemiologia , Ideação Suicida
14.
Brain Behav Immun ; 98: 257-262, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34454061

RESUMO

BACKGROUND: Prolonged parent-child separation is associated with a broad array of poor developmental outcomes. A potential pathway may be through changes in inflammatory processes. However, relatively little is known about the relationship between parent-child separation pattern (timing and duration) and inflammatory burden. The aim of this study was to investigate whether parent-child separation since birth is associated with inflammatory burden in adolescents. METHODS: A total of 574 adolescents (mean age 12.07 years, SD: 0.62) were enrolled from rural areas of Chizhou, Anhui Province, China. Parent-child separation was reported mainly by primary caregivers, and other adverse childhood adversities (ACEs) were derived from adolescents semi-structured interview or questionnaire. Blood samples were collected from venepuncture for C-reactive protein (CRP) as well as soluble urokinase plasminogen activator receptor (suPAR). RESULTS: Nearly 40% (232/574) participants experienced parent-child separation, among which more than 1 of 4 persistently separated from both parents since birth. Both CRP and suPAR levels were significantly higher among adolescents persistently separated from both parents, compared with those who did not separate from both parents (CRP: 1.75 vs. 1.36 mg/L, P < 0.001; suPAR: 2.85 ng/mL vs. 2.55 ng/mL, P < 0.001). After adjusted for demographic covariates, body mass index, ACEs as well as parental characteristics, persistent parent-child separation was associated with elevated suPAR (B = 0.30; 95% CI, 0.12-0.48) and CRP (B = 1.34; 95% CI, 1.02-1.75). No similar associations were observed between inflammatory burden with current or early childhood parent-child separation groups. Adolescents who exposed to persistent parent-child separation were more likely to have elevated suPAR levels even if they did not have elevated CRP levels (aOR, 4.26, 95% CI, 1.23-14.80; P = 0.022). CONCLUSION: Elevated inflammatory burden observed in persistent parent-child separation adolescents highlights the need to support children and adolescents undergoing separation from both parents in order to minimize the long-term impact on disease vulnerability.

15.
J Interpers Violence ; : 8862605211035869, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330168

RESUMO

This study aimed to examine the association between childhood maltreatment, parent-child relationship quality with psychological symptoms and to explore the moderating role of parent-child relationship quality in the association between childhood maltreatment and psychological symptoms among adolescents. It also probed to the role of gender differences in this effect. A representative sample of 14,500 middle school students in China were asked to complete a standard questionnaire on the details of childhood maltreatment, parent-child relationship quality, and psychological symptoms. All data were analyzed using SPSS 23.0. The PROCESS program was used to analyze whether parent-child relationship quality moderated the link between childhood maltreatment and psychological symptoms. The analyses revealed significant correlations between childhood maltreatment, parent-child relationship quality, and psychological symptoms (p < .001). Specifically, paternal relationship quality moderated the association between childhood maltreatment and psychological symptoms in the total sample (B = -0.01, p < .05) and the subgroup of girls (B = -0.01, p < .05), while maternal relationship quality moderated only the association between childhood maltreatment and psychological symptoms in the subgroup of boys (B = -0.01, p < .05). As the findings indicate, priority should be given to the quality of parent-child relationship and gender-specific methods employed to effectively reduce the psychological symptoms of adolescents with a history of childhood maltreatment.

16.
Endocr Pract ; 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34216800

RESUMO

OBJECTIVE: Agranulocytosis is a rare but serious adverse drug reaction (ADR) of thionamide antithyroid drugs (ATDs). We explored the characteristics of ADRs in patients with hyperthyroidism. METHODS: This retrospective study included 3558 inpatients with Graves disease treated in a Class A Grade 3 hospital between 2015 and 2019. The clinical presentation and laboratory workup of patients with antithyroid drug (ATD)-induced agranulocytosis was analyzed. RESULTS: Agranulocytosis was thought to be caused by ATDs in 36 patients. The hospital length of stay was 12 (10-16) days, and hospitalization costs were approximately $2810.89 ($2156.50-$4164.67). The median duration of ATD therapy prior to agranulocytosis development was 30 (20-40) days. Fever (83.33%) and sore throat (75%) were the most common symptoms as early signs of agranulocytosis. The lowest neutrophil counts were 0.01 (0.00-0.03) × 109/L and 0.14 (0.02-0.29) × 109/L in the methimazole and propylthiouracil groups, respectively (P = .037). The recovery times of agranulocytosis were 9.32 ± 2.89 days and 5.60 ± 4.10 days in the methimazole and propylthiouracil groups, respectively (P = .016). Patients with severe agranulocytosis required a longer time to recover (P < .001) and had closer to normal serum thyroxine and triiodothyronine levels. The interval between the first symptom of agranulocytosis and ATD withdrawal was 1 (0-3) day. CONCLUSIONS: Patients with agranulocytosis needed a long hospital length of stay and incurred high costs. Methimazole was prone to causing a more serious agranulocytosis than propylthiouracil. High thyroid hormone was unlikely to play a role in adverse drug reactions. Patient education is important.

17.
Hum Genet ; 140(9): 1367-1377, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34255152

RESUMO

Spermatozoa are polarized cells with a head and a flagellum joined together by the connecting piece. Flagellum integrity is critical for normal sperm function, and flagellum defects consistently lead to male infertility. Multiple morphological abnormalities of the flagella (MMAF) is a distinct sperm phenotype consistently leading to male infertility due to a reduced or absent sperm motility associated with severe morphological and ultrastructural flagellum defects. Despite numerous genes recently described to be recurrently associated with MMAF, more than half of the cases analyzed remain unresolved, suggesting that many yet uncharacterized gene defects account for this phenotype. By performing a retrospective exome analysis of the unsolved cases from our initial cohort of 167 infertile men with a MMAF phenotype, we identified one individual carrying a homozygous frameshift variant in CFAP206, a gene encoding a microtubule-docking adapter for radial spoke and inner dynein arm. Immunostaining experiments in the patient's sperm cells demonstrated the absence of WDR66 and RSPH1 proteins suggesting severe radial spokes and calmodulin and spoke-associated complex defects. Using the CRISPR-Cas9 technique, we generated homozygous Cfap206 knockout (KO) mice which presented with male infertility due to functional, structural and ultrastructural sperm flagellum defects associated with a very low rate of embryo development using ICSI. Overall, we showed that CFAP206 is essential for normal sperm flagellum structure and function in human and mouse and that bi-allelic mutations in CFAP206 cause male infertility in man and mouse by inducing morphological and functional defects of the sperm flagellum that may also cause ICSI failures.


Assuntos
Proteínas do Citoesqueleto , Mutação da Fase de Leitura , Homozigoto , Infertilidade Masculina , Cauda do Espermatozoide/metabolismo , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Masculino , Camundongos
18.
J Affect Disord ; 292: 255-260, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34134023

RESUMO

BACKGROUND: Increasing evidence has demonstrated that childhood adversity was a predictor of pain and hypothalamic-pituitary-adrenal (HPA) axis genetic variation is associated with pain risk. This study aims to explore possible effects of prolonged childhood separation from parents and HPA polygenic risk score (PRS) on pain among adolescents in rural China. METHOD: We used data from 219 adolescents in rural area of Fuyang city, Anhui province, China. Parent-child separation was collected through interview and pain intensity was reported using the 11-point Numerical Rating Scale. SNP genotyping was performed using an improved multiplex ligation detection reaction (iMLDR) technique. The PRS was computed based on 3 single nucleotide polymorphisms (SNPs) in 2 genes (FKBP5 and NR3C1) related to HPA-axis stress reactivity. RESULTS: Pain among adolescents separated from both parents scored higher compared to those without parent-child separation, however, this association was only observed in adolescents with moderate to high tertiles of PRS groups (parent-child separation in moderate group vs. no parent-child separation in moderate group: 3.07 vs. 1.57, P < 0.001; parent-child separation in highest group vs. no parent-child separation in highest group: 3.02 vs. 1.26, P < 0.001; parent-child separation in lowest group vs. no parent-child separation in lowest group: 2.34 vs. 1.25, P = 0.225). After controlled for demographic characteristics, psychopathological symptoms, adverse childhood experiences, parental warmth, prolonged childhood parent-child separation increased pain scores by 1.52 points (95% CI:0.72, 2.33) and 1.72 points (95% CI:1.13, 2.31) in moderate and high PRS groups, respectively. CONCLUSION: Our findings suggest that adolescents separated from both parents while carrying more risk alleles related to HPA-axis stress reactivity are at heightened risk of pain.


Assuntos
Separação da Família , Sistema Hipotálamo-Hipofisário , Dor/genética , Sistema Hipófise-Suprarrenal , Estresse Psicológico , Adolescente , China , Humanos , Hidrocortisona , Relações Pais-Filho , Polimorfismo de Nucleotídeo Único , Receptores de Glucocorticoides/genética , Estresse Psicológico/genética , Proteínas de Ligação a Tacrolimo/genética
19.
Brain Res ; 1767: 147562, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34144003

RESUMO

Increasing caesarean section (CS) rates are of global concern not only for health care providers but also from a more general public health point of view. Growing concern on the association between CS and offspring's neurodevelopmental outcomes have been raised in recent years, but the effect of CS on offspring's emotional development is rarely reported. By using mice models, we have set up two groups, ie. offspring born via CS and in-fostered by dams with vaginal delivery (VD), and offspring born via VD and in-fostered by their non-biological mothers. Depression-like behavioral was evaluated by sucrose preference test and forced swimming test, and anxiety-like behavioral was evaluated by open-field test and elevated plus maze test, respectively during offspring's adolescence and adulthood. Offspring's prefrontal cortex was collected for HE staining and assessment for DA, HVA, 5-HT, 5-HIAA. It was found that offspring born of CS have anxiety-like and depression-like behaviors in adolescence and adulthood. Male offspring was sensitive to be depressive and female offspring tended to be anxious. Although no significant sex difference was observed, there existed edema and nuclear retraction of neurons in the prefrontal cortex in offspring via CS during adolescence and adulthood. Compared with offspring born via VD, offspring through CS had shown higher DA and HVA levels while lower 5-HT and 5-HIAA levels in adolescence and adulthood, and this difference was observed in female offspring. The findings highlight the sex-specific effect of CS on offspring's emotional development. Variations in key neurotransmitters in the prefrontal cortex may partly explain the association between CS and offspring's emotional symptoms.

20.
Sleep Med ; 84: 165-172, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34153799

RESUMO

OBJECTIVE/BACKGROUND: School closure and home quarantine has been implemented worldwide during the coronavirus disease 2019 (COVID-19) outbreak. The study aims to assess the associations of circadian rhythm abnormalities (CRA) during the COVID-19 outbreak with mental health in Chinese undergraduates. METHODS: A nationwide cross-sectional university-based survey was conducted from 4th February to 12th, 2020. Based on different geographical locations and purposive sampling approach, 19 universities from 16 provinces or municipalities in the mainland of China were selected. A total of 14,789 participants were recruited by using multistage stratified random sampling. The data of CRA were collected by self-reported questionnaires consist of four items involved rest-activity cycle, diet rhythm, wake up rhythm and sleep rhythm. The Patient Health Questionnaire and the Generalized Anxiety Disorder were applied to evaluate the symptoms of depression and anxiety. Chi-square test and ordinal logistic regression models were used to describe the distributions and associations of CRA and mental health. RESULTS: A total of 11,787 students [female: 6731(57.1%)] aged 15-26 years old (M = 20.45, SD = 1.76) were analyzed (response rate: 79.7%). The results showed the percentage of CRA were 17.5-28.7%. The prevalence of depression and anxiety were significantly higher in students with single CRA. Students who reported the coexistence of four CRA were more likely to be with the symptoms of depression (OR: 4.43, 95% CI: 3.91-5.03) and anxiety (OR: 3.11, 95% CI: 2.70-3.60). Dose-response relationships were found between multiple CRA and mental problems. CONCLUSION: Circadian rhythm abnormalities are positively associated with mental health among university studies. Mental health care is needed for college students during the COVID-19 epidemic period.


Assuntos
COVID-19 , Universidades , Adolescente , Adulto , Ansiedade , China/epidemiologia , Ritmo Circadiano , Estudos Transversais , Depressão , Surtos de Doenças , Feminino , Humanos , Saúde Mental , SARS-CoV-2 , Inquéritos e Questionários , Adulto Jovem
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