The proper timing of Atoh1 expression is pivotal for hair cell subtype differentiation and the establishment of inner ear function.

Atoh1 overexpression is essential for hair cell (HC) regeneration in the sensory epithelium of mammalian auditory and vestibular organs. However, Atoh1 overexpression alone cannot induce fully mature and functional HCs in the mammalian inner ear. In the current study, we investigated the effect of Atoh1 constitutive overexpression in native HCs by manipulating Atoh1 expression at different developmental stages. We demonstrated that constitutive overexpression of Atoh1 in native vestibular HCs did not affect cell survival but did impair vestibular function by interfering with the subtype differentiation of HCs and hair bundle development. In contrast, Atoh1 overexpression in cochlear HCs impeded their maturation, eventually leading to gradual HC loss in the cochlea and hearing dysfunction. Our study suggests that time-restricted Atoh1 expression is essential for the differentiation and survival of HCs in the inner ear, and this is pivotal for both hearing and vestibular function re-establishment through Atoh1 overexpression-induced HC regeneration strategies.

Effects of Short- And Medium-Term Exposures to Lower Air Temperature on 71 Novel Biomarkers of Subclinical Inflammation: Results from the KORA F4 Study.

Increasing evidence has revealed that exposure to low temperatures is linked to a higher risk of chronic diseases and death; however, the mechanisms underlying the observed associations are still poorly understood. We performed a cross-sectional analysis with 1115 participants from the population-based KORA F4 study, which was conducted in Augsburg, Germany, from 2006 to 2008. Seventy-one inflammation-related protein biomarkers were analyzed in serum using proximity extension assay technology. We employed generalized additive models to explore short- and medium-term effects of air temperature on biomarkers of subclinical inflammation at cumulative lags of 0-1 days, 2-6 days, 0-13 days, 0-27 days, and 0-55 days. We found that short- and medium-term exposures to lower air temperature were associated with higher levels in 64 biomarkers of subclinical inflammation, such as Protein S100-A12 (EN-RAGE), Interleukin-6 (IL-6), Interleukin-10 (IL-10), C-C motif chemokine 28 (CCL28), and Neurotrophin-3 (NT-3). More pronounced associations between lower air temperature and higher biomarker of subclinical inflammation were observed among older participants, people with cardiovascular disease or prediabetes/diabetes, and people exposed to higher levels of air pollution (PM2.5, NO2, and O3). Our findings provide intriguing insight into how low air temperature may cause adverse health effects by activating inflammatory pathways.

Associations between medium- and long-term exposure to air temperature and epigenetic age acceleration.

Climate change poses a serious threat to human health worldwide, while aging populations increase. However, no study has ever investigated the effects of air temperature on epigenetic age acceleration. This study involved 1,725 and 1,877 participants from the population-based KORA F4 (2006-2008) and follow-up FF4 (2013-2014) studies, respectively, conducted in Augsburg, Germany. The difference between epigenetic age and chronological age was referred to as epigenetic age acceleration and reflected by Horvath's epigenetic age acceleration (HorvathAA), Hannum's epigenetic age acceleration (HannumAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and Epigenetic Skin and Blood Age acceleration (SkinBloodAA). Daily air temperature was estimated using hybrid spatiotemporal regression-based models. To explore the medium- and long-term effects of air temperature modeled in time and space on epigenetic age acceleration, we applied generalized estimating equations (GEE) with distributed lag non-linear models, and GEE, respectively. We found that high temperature exposure based on the 8-week moving average air temperature (97.5th percentile of temperature compared to median temperature) was associated with increased HorvathAA, HannumAA, GrimAA, and SkinBloodAA: 1.83 (95% CI: 0.29-3.37), 11.71 (95% CI: 8.91-14.50), 2.26 (95% CI: 1.03-3.50), and 5.02 (95% CI: 3.42-6.63) years, respectively. Additionally, we found consistent results with high temperature exposure based on the 4-week moving average air temperature was associated with increased HannumAA, GrimAA, and SkinBloodAA: 9.18 (95% CI: 6.60-11.76), 1.78 (95% CI: 0.66-2.90), and 4.07 (95% CI: 2.56-5.57) years, respectively. For the spatial variation in annual average temperature, a 1 °C increase was associated with an increase in all five measures of epigenetic age acceleration (HorvathAA: 0.41 [95% CI: 0.24-0.57], HannumAA: 2.24 [95% CI: 1.95-2.53], PhenoAA: 0.32 [95% CI: 0.05-0.60], GrimAA: 0.24 [95%: 0.11-0.37], and SkinBloodAA: 1.17 [95% CI: 1.00-1.35] years). In conclusion, our results provide first evidence that medium- and long-term exposures to high air temperature affect increases in epigenetic age acceleration.

Air quality and health benefits of increasing carbon mitigation tech-innovation in China.

Most studies on the short-term local benefits of carbon mitigation technologies on air quality improvement and health focus on specific technologies such as biofuels or carbon sequestration technologies, while ignoring the overall role of the growing scale of low-carbon technologies. Based on STIRPAT model and EKC hypothesis, this paper takes 30 provinces in China from 2004 to 2016 as research samples. We builded the panel double fixed effect model to empirical analysis of climate change on carbon mitigation tech-innovation suppressing the influence of haze pollution, on this basis, the mediating effect model was used to explore the mediation function of industrial structure and energy structure. Meanwhile, we drawed on the existing studies on air quality and health benefits, and quantify the co-benefits of carbon mitigation tech-innovation on health through the equivalent substitution formula. It shows that a 1% increase in the number of low-carbon patent applications can reduce haze pollution by 0.066%. According to this estimate, to 2029, China's carbon mitigation tech-innovation could reduce PM2.5 concentration to 15 µg/m3 preventing 5.597 million premature deaths. Moreover, carbon mitigation tech-innovation can also indirectly inhibit haze pollution by triggering more systematic economic structure changes such as energy and industrial structure. Additionally, we found that the role of gray tech-innovation (GT) related to improving the efficiency of fossil energy is stronger than that of clean technology (CT) related to the use of renewable energy. This suggests that for a large economy such as China, where coal is still the dominant source of energy consumption, the short-term local benefits of improving air quality and health through the use of gray tech-innovation to improve energy and industrial structure are still important to balance the cost of carbon mitigation.

Higher Daily Air Temperature Is Associated with Shorter Leukocyte Telomere Length: KORA F3 and KORA F4.

Higher air temperature is associated with increased age-related morbidity and mortality. To date, short-term effects of air temperature on leukocyte telomere length have not been investigated in an adult population. We aimed to examine the short-term associations between air temperature and leukocyte telomere length in an adult population-based setting, including two independent cohorts. This population-based study involved 5864 participants from the KORA F3 (2004-2005) and F4 (2006-2008) cohort studies conducted in Augsburg, Germany. Leukocyte telomere length was assessed by a quantitative PCR-based method. We estimated air temperature at each participant's residential address through a highly resolved spatiotemporal model. We conducted cohort-specific generalized additive models to explore the short-term effects of air temperature on leukocyte telomere length at lags 0-1, 2-6, 0-6, and 0-13 days separately and pooled the estimates by fixed-effects meta-analysis. Our study found that between individuals, an interquartile range (IQR) increase in daily air temperature was associated with shorter leukocyte telomere length at lags 0-1, 2-6, 0-6, and 0-13 days (%change: -2.96 [-4.46; -1.43], -2.79 [-4.49; -1.07], -4.18 [-6.08; -2.25], and -6.69 [-9.04; -4.27], respectively). This meta-analysis of two cohort studies showed that between individuals, higher daily air temperature was associated with shorter leukocyte telomere length.

Economical and Efficient Protocol for Isolating and Culturing Bone Marrow-derived Dendritic Cells from Mice.

The demand for dendritic cells (DCs) is gradually increasing as immunology research advances. However, DCs are rare in all tissues. The traditional method for isolating DCs primarily involves inducing bone marrow (BM) differentiation into DCs by injecting large doses (>10 ng/mL) of granulocyte-macrophage colony-stimulating factor/interleukin-4 (GM-CSF/IL-4), making the procedure complex and expensive. In this protocol, using all BM cells cultured in 10 ng/mL GM-CSF/IL-4 medium, after 3-4 half-culture exchanges, up to 2.7 x 107 CD11c+ cells (DCs) per mouse (two femurs) were harvested with a purity of 80%-95%. After 10 days in culture, the expression of CD11c, CD80, and MHC II increased, whereas the number of cells decreased. The number of cells peaked after 7 days of culture. Moreover, this method only took 10 min to harvest all bone marrow cells, and a high number of DCs were obtained after 1 week of culture.

Short-term effects of cold spells on plasma viscosity: Results from the KORA cohort study in Augsburg, Germany.

As the underlying mechanisms of the adverse effects of cold spells on cardiac events are not well understood, we explored the effects of cold spells on plasma viscosity, a blood parameter linked to cardiovascular disease. This cross-sectional study involved 3622 participants from the KORA S1 Study (1984-1985), performed in Augsburg, Germany. Exposure data was obtained from the Bavarian State Office for the Environment. Cold spells were defined as two or more consecutive days with daily mean temperatures below the 3rd, 5th, or 10th percentile of the distribution. The effects of cold spells on plasma viscosity were explored by generalized additive models with distributed lag nonlinear models (DLNM). We estimated cumulative effects at lags 0-1, 0-6, 0-13, 0-20, and 0-27 days separately. Cold spells (mean temperature <3rd, <5th or <10th percentile) were significantly associated with an increase in plasma viscosity with a lag of 0-1 days [%change of geometric mean (95% confidence interval): 1.35 (0.06-2.68), 1.35 (0.06-2.68), and 2.49 (0.34-4.69), respectively], and a lag of 0-27 days [18.81 (8.97-29.54), 17.85 (8.29-28.25), and 7.41 (3.35-11.0), respectively]. For the analysis with mean temperature <3rd or 10th percentile, we also observed significant associations at lag 0-20 days [8.34 (0.43-16.88), and 4.96 (1.68, 8.35), respectively]. We found that cold spells had significant immediate and longer lagged effects on plasma viscosity. This finding supports the complex interplay of multiple mechanisms of cold on adverse cardiac events and enriches the knowledge about how cold exposure acts on the human body.

Rare earth elements in umbilical cord and risk for orofacial clefts.

Questions remain about the effects of rare earth elements (REEs) on reproductive health, and no study has explored in utero exposure to REEs and risk of orofacial clefts (OFCs). We recruited subjects from a case-control study conducted in Shanxi Province, China. Concentrations of fifteen REEs were quantified in umbilical cord samples by means of Inductively Coupled Plasma Mass Spectrometry measurements. We employed logistic regression and weighted quantile sum (WQS) regression models to estimate the association between REEs exposures and OFCs. Of 226 subjects included in our study, 34 were cleft lip only, 44 were cleft lip with cleft palate and 6 were cleft palate only. In the logistic regression model, concentrations above the median of all subjects were associated with an increased OFCs risk of 2.35-fold (95% CI: 1.22, 4.53) for Lanthanum and 2.12-fold for Neodymium (95% CI: 1.10, 4.10) adjusting for maternal age, BMI, gestational weeks, sex of infants and passive smoking. In WQS model, a quartile increase in the index resulting in an increase of 3.10 (95% CI: 1.38, 6.96) in the odds of OFC. Lanthanum and Neodymium were suggested to be important factors. The results were largely consistent for OFC subtypes. In conclusion, in utero exposure to mixtures of REEs increased the risk of OFCs. Lanthanum and Neodymium were likely to be important factors in the development of OFCs.

Association between selected alkaline earth elements concentrations in umbilical cord and risk for cleft lip with or without cleft palate.

The relationship between alkaline earth elements in utero exposure and the risk of cleft lip with or without cleft palate (CL ± P) remains unclear. We aimed to investigate the associations between the concentration of alkaline earth elements in umbilical cord and risk for CL ± P. A case-control study was carried out in this study, including 78 cases and 142 controls. Association between each metals and the risk of CL ± P were evaluated with conventional logistic regression, bayesian kernel machine regression and weighted quantile sum regression models. Logistic regression model indicated that in utero exposure to higher levels of Barium was associated with increasing risk for CL ± P (odds ratio = 2.79, 95% confidence interval, 1.22-6.38) and for cleft lip with cleft palate (odds ratio = 3.94, 95% confidence interval, 1.45-10.72). Bayesian kernel machine regression model showed the statistical association between the metals mixture and risk difference of CL ± P, and barium was associated with CL ± P risk when all other metals were held fixed at the 25th percentiles (risk difference = 1.07, 95% confidence interval, 1.01-1.14). In weighted quantile sum model, barium accounted for most of the weight index in the combined effect of the metals mixture. The weighted quantile sum index showed that a quartile increase in the index resulted in an increase odds of 1.69 (95% confidence interval, 1.16-2.46) for CL ± P and of 2.11 (95% confidence interval, 1.34-3.35) for CLP. No associations were found in the three statistical models between Calcium, Magnesium and Strontium and the risks of CL ± P. In conclusion, in utero exposure to mixtures of alkaline earth elements was associated with an increased risk for CL ± P, of which barium was likely to be important factors in the development.

DNA methylation-based biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4.

BACKGROUND: DNA methylation (DNAm) may play a role in age-related outcomes. It is not yet known which DNAm-based biomarkers of age acceleration (BoAA) has the strongest association with age-related endpoints. METHODS: We collected the blood samples from two independent cohorts: the Normative Ageing Study, and the Cooperative Health Research in the Region of Augsburg cohort. We measured epigenome-wide DNAm level, and generated five DNAm BoAA at baseline. We used Cox proportional hazards model to analyze the relationships between BoAA and all-cause death. We applied the Fine and Gray competing risk model to estimate the risk of BoAA on myocardial infarction (MI), stroke, and cancer, accounting for death of other reasons as the competing risks. We used random-effects meta-analyses to pool the individual results, with adjustment for multiple testing. FINDINGS: The mean chronological ages in the two cohorts were 74, and 61, respectively. Baseline GrimAgeAccel, and DNAm-related mortality risk score (DNAmRS) both had strong associations with all-cause death, MI, and stroke, independent from chronological age. For example, a one standard deviation (SD) increment in GrimAgeAccel was significantly associated with increased risk of all-cause death [hazard ratio (HR): 2.01; 95% confidence interval (CI), 1.15, 3.50], higher risk of MI (HR: 1.44; 95% CI, 1.16, 1.79), and elevated risk of stroke (HR: 1.42; 95% CI, 1.06, 1.91). There were no associations between any BoAA and cancer. INTERPRETATION: From the public health perspective, GrimAgeAccel is the most useful tool for identifying at-risk elderly, and evaluating the efficacy of anti-aging interventions. FUNDING: National Institute of Environmental Health Sciences of U.S., Harvard Chan-NIEHS Center for Environmental Health, German Federal Ministry of Education and Research, and the State of Bavaria in Germany.

Determination of organochlorine pesticides in human umbilical cord and association with orofacial clefts in offspring.

Studies based on questionnaires suggested that maternal exposure to pesticides increases the risk for orofacial clefts (OFCs). However, whether organochlorine pesticides (OCPs) exposure in vivo affects the occurrence of OFCs remains unclear. The aims of this study are to investigate the association of OCP exposure with the risk of OFCs by examining the concentrations of OCPs in human umbilical cords, and investigate the potential dietary sources of OCPs in umbilical cord tissues. A case-control study consisting of 89 OFC cases and 129 nonmalformed controls with available tissues of umbilical cord was conducted. Concentrations of twenty specific OCPs were determined in the umbilical cord by gas chromatograph-mass spectrometry, and seven OCPs with detection rate larger than 50% were included in analyses. The individual effect and joint effect of multiple OCPs in umbilical cords on the risk for OFCs were investigated using multivariate logistic models and Bayesian Kernel Machine Regression (BKMR). No difference was found in the median levels of ΣOCPs between cases (1.04 ng/g) and controls (1.03 ng/g). No significant associations were observed between levels of OCPs in umbilical cords and risk for OFCs in either multivariate logistic models or BKMR models. Maternal consumptions of beans or bean products were positively correlated with levels of ß-hexachlorocyclohexane, heptachlor epoxide, p,p'-DDE, and ∑OCPs in umbilical cord, respectively. In conclusion, we didn't find the association between in utero exposure to OCPs and the risk for OFCs. Maternal consumptions of beans or bean products may be a source of OCPs exposure.

Hypermethylation of WNT3A gene and non-syndromic cleft lip and/or palate in association with in utero exposure to lead: A mediation analysis.

OBJECTIVES: We aim to investigate association between WNT3A methylation and risk of non-syndromic cleft lip and/or palate (NSCL/P), and examine mediating effect of WNT3A methylation on the association of NSCL/P and lead (Pb) exposure in fetuses. METHODS: DNA methylation of WNT3A in umbilical cord blood was determined among 59 NSCL/P cases and 118 non-malformed controls. Mediation analysis was performed to evaluate the potential mediating effect of WNT3A methylation on association between concentrations of Pb in umbilical cord and risk for NSCL/P. Additionally, an animal experiment in which cleft palates were induced by lead acetate was conducted. RESULTS: The overall average methylation level of WNT3A was significant higher in NSCL/P cases as compared to controls. The risk for NSCL/P was increased by 1.90-fold with hypermethylation of WNT3A. Significant correlation was observed between concentrations of Pb in umbilical cord and methylation level of WNT3A. The hypermethylation of WNT3A had a mediating effect by 9.32% of total effect of Pb on NSCL/P risk. Gender-specific association between WNT3A methylation and NSCL/P was observed in male fetuses, and the percentage of the mediating effect increased to 14.28%. Animal experiment of mice showed that maternal oral exposure to lead acetate may result in cleft palate in offspring. CONCLUSION: Hypermethylation of WNT3A was associated with the risk for NSCL/P and may be partly explain the association between exposure to Pb and risk for NSCL/P. The teratogenic and fetotoxic effects of Pb were found in mice.

Level of physical activity among middle-aged and older Chinese people: evidence from the China health and retirement longitudinal study.

BACKGROUND: With data from different regions accumulated, physical inactivity (PI) was found to be pandemic worldwide. Using China Health and Retirement Longitudinal Study (CHARLS), a nationwide longitudinal survey data, we aimed to delineate the prevalence, incidence and risk factors of physical inactivity (PI) among Chinese people aged 45 years and older. METHODS: The CHARLS covered nearly all provinces, autonomous regions, municipalities of mainland China. With data from CHARLS, three cross-sectional analyses and a cohort analysis were conducted. In cross-sectional studies, we used surveys at 2011, 2013 and 2015 to examine the prevalence and its trend of PI. Multivariate generalized linear model was conducted in survey at 2011 to examine the risk factors for prevalent PI. Multiple imputation of missing values was used and results before and after imputation were compared. In cohort analysis, we identified people free of PI at 2011 and followed them up until 2015 to estimate the incidence of PI. Generalized estimating equation was used to examine the risk factors associated with incidence PI. In all analyses, PI was defined as insufficient physical activity according to the International Physical Activity Questionnaire (IPAQ) criterion. RESULTS: 6650, 5946 and 9389 participants were eligible for cross-sectional analyses, and 4525 participants were included for cohort analysis. The weighted prevalence of PI was 22.25% (95% CI: 20.63-23.95%) in 2011, 20.64% (95% CI: 19.22-22.14%) in 2013 and 19.31% (95% CI: 18.28-20.38%) in 2015. In multivariate analysis, PI was associated with older age, higher education, overweight, obesity and difficulties in daily living, and was negatively associated with working and higher level of expenditure. No material change was detected in results after multiple imputation. In cohort analysis, older age, abundant public facilities, difficulties in daily living were identified as risk factors of incidence PI, while urban areas, college and above education, and working were protective factors. CONCLUSIONS: PI is pandemic in 45 years and older people in China. People with older age, difficulties in daily living and people who are not working are at higher risk. More efforts should be paid in estimating and promoting leisure-time physical activities.

Toxic Effects of 3,3'-Iminodipropionitrile on Vestibular System in Adult C57BL/6J Mice In Vivo.

The utricle is one of the five sensory organs in the mammalian vestibular system, and while the utricle has a limited ability to repair itself, this is not sufficient for the recovery of vestibular function after hair cell (HC) loss induced by ototoxic drugs. In order to further explore the possible self-recovery mechanism of the adult mouse vestibular system, we established a reliable utricle epithelium injury model for studying the regeneration of HCs and examined the toxic effects of 3,3'-iminodiproprionitrile (IDPN) on the utricle in vivo in C57BL/6J mice, which is one of the most commonly used strains in inner ear research. This work focused on the epithelial cell loss, vestibular dysfunction, and spontaneous cell regeneration after IDPN administration. HC loss and supporting cell (SC) loss after IDPN treatment was dose-dependent and resulted in dysfunction of the vestibular system, as indicated by the swim test and the rotating vestibular ocular reflex (VOR) test. EdU-positive SCs were observed only in severely injured utricles wherein above 47% SCs were dead. No EdU-positive HCs were observed in either control or injured utricles. RT-qPCR showed transient upregulation of Hes5 and Hey1 and fluctuating upregulation of Axin2 and ß-catenin after IDPN administration. We conclude that a single intraperitoneal injection of IDPN is a practical way to establish an injured utricle model in adult C57BL/6J mice in vivo. We observed activation of Notch and Wnt signaling during the limited spontaneous HC regeneration after vestibular sensory epithelium damage, and such signaling might act as the promoting factors for tissue self-repair in the inner ear.

Uranium concentration in umbilical cord may increase the risk for orofacial clefts.

BACKGROUND: Orofacial clefts (OFCs) are common kind of congenital malformations. The teratogenicity of uranium (U) has been documented in animal study that maternal exposure to U can increase incidence of external malformations including cleft palate. However, there is limited evidence of the association of in utero exposure to U with OFCs risk in humans. OBJECTIVE: This study aimed to investigate the association between in utero exposure to U and the risk of OFCs and its subtypes. METHOD: All subjects were from a case-control study in Shanxi Province, northern China. Eighty-four OFCs cases and 142 healthy controls were included in this study. We used U concentration in umbilical cord as biomarkers to represent intrauterine exposure, which was detected by inductively coupled plasma mass spectrometry. Unconditional logistic regression was used to investigated the association between U level and the risk of OFCs and its subtypes. RESULTS: The median of U concentration in umbilical cord is 0.745 ng/g in case group and 0.455 ng/g in control group. When the U concentration was divided into two categories, high level of U exposure increased the risk of OFCs (OR: 2.08, 95% CI: 1.13-3.86) and its subtype cleft lip with cleft palate (CLP) (OR: 2.72, 95% CI: 1.21-6.14). When divided into three categories, high level of U elevated the risk for OFCs (OR: 2.40, 95% CI: 1.14-5.06) and CLP (OR: 3.04, 95% CI: 1.20-7.74). Meanwhile, a dose-response relationship between the U concentration and the risk of total OFCs (P for trend = 0.009) and CLP (P for trend = 0.007) was found. CONCLUSION: Our study found that in utero exposure to high level of U was associated with increased risk of OFCs and its subtype CLP.

Unidirectional and stage-dependent roles of Notch1 in Wnt-responsive Lgr5+ cells during mouse inner ear development.

Wnt and Notch signaling play crucial roles in the determination of the prosensory domain and in the differentiation of hair cells (HCs) and supporting cells during mouse inner ear development; however, the relationship between the two signaling pathways in the mouse cochlea remains largely unknown. Here, we investigated the interactions between Notch and Wnt signaling on the basis of the bidirectional regulation of Notch1 specifically in Wnt-responsive Lgr5+ progenitors during different cochlear development stages. We found that the downregulation of Notch1 in Lgr5+ cells from embryonic day (E) 14.5 to E18.5 can drive the quiescent Lgr5+ cells to re-enter the cell cycle and differentiate into extra HCs, whereas the upregulation of Notch1 expression did not affect the proliferation or differentiation of otic progenitor cells. No effect was observed on the upregulation or downregulation of Notch1 in Lgr5+ cells from E10.5 to E14.5. We concluded that the roles of Notch1 in Wnt-responsive Lgr5+ cells are unidirectional and stage dependent and Notch1 serves as a negative regulator for Lgr5+ progenitor activation during cochlear differentiation. Our findings improved the understanding of the interactions between Notch and Wnt signaling in cochlear development.

Gestational hypertension and pre-eclampsia and risk of spontaneous premature rupture of membranes: A population-based cohort study.

OBJECTIVE: To examine whether gestational hypertension and pre-eclampsia are associated with spontaneous premature rupture of membranes (PROM). METHODS: A retrospective, population-based cohort study was conducted in Hebei, Zhejiang, and Jiangsu provinces in China from 1993 to 1995. After excluding women with missing data of exposure and outcome, history of chronic hypertension, multiple births, and babies with major birth defects and ambiguous sex, this study comprised 199 231 singleton live births. Logistic regression was used to evaluate the association, adjusting for potential confounders. RESULTS: The incidence of PROM was 17.7% and 8.9% in women with gestational hypertension and pre-eclampsia, respectively, and 5.9% for the normotensive group. Compared with normotension, gestational hypertension was associated with an increase in the odds of PROM of 4.21 times (95% confidence interval [CI] 3.77-4.70), while pre-eclampsia had an increase of 2.27 times (95% CI 1.78-2.88). Additionally, women with hypertensive disorders of pregnancy had higher risks for term PROM (adjusted risk ratio [RR] 3.83, 95% CI 3.43-4.27) than preterm PROM (adjusted RR 3.10, 95% CI 2.18-4.41). Consistent results of the association were also observed in the sensitivity analyses. CONCLUSION: Gestational hypertension and pre-eclampsia were associated with an increased risk for PROM. Increased odds were observed for term PROM compared with preterm PROM.

Levels of polycyclic aromatic hydrocarbons in umbilical cord and risk of orofacial clefts.

Polycyclic aromatic hydrocarbons (PAHs), which are ubiquitous in the environment, have been found to cause orofacial clefts (OFCs) in mouse model. However, evidence from the human study with markers of intrauterine exposure is absent. We explored the associations between the levels of sixteen PAHs in umbilical cord tissue and risk for OFCs using multivariable logistic models and Bayesian Kernel Machine Regression (BKMR). This case-control study included 89 OFC cases and 129 controls without congenital malformations. Concentrations of PAHs in umbilical cord tissue were detected using gas chromatography coupled to triple quadrupole tandem mass spectrometry. The median levels of ΣPAHs, Σlow molecular weight polycyclic aromatic hydrocarbons, and Σhigh molecular weight polycyclic aromatic hydrocarbons were all higher in cases of total OFCs and its subtypes than in controls, although the differences were not statistically significant. No statistical associations between levels of PAHs in umbilical cord tissue and risk for OFCs were observed in either multivariable logistic models or BKMR models. Maternal using a stove for heating and lower frequency of ventilation in the bedroom/living room, and consumptions of fresh green vegetables were positively correlated with levels of PAHs in umbilical cord. In conclusion, our results did not suggest that in utero exposure to PAHs were associated with the risk for OFCs, in estimating whether single effect of PAHs or joint effects of multiple PAHs.

Cochlear Implantation and Rehabilitation.

Cochlear implant (CI) is currently the only medical treatment available to partially restore hearing to patients with profound-to-severe hearing loss. CI is fundamentally distinct from hearing aid (HA) use, as implants are surgically placed under the skin behind the ear where they bypass the normal sound-conducting mechanism, convert sound signals into electrical stimulation, and directly stimulate the residual auditory nerves. In recent years, CI has evolved into one of the most profound advances in modern medicine and provided hearing to more than 320,000 deaf patients. According to the time of onset, deafness is classified as prelingual and postlingual deafness, and the indications of cochlear implants vary slightly. The medical evaluation must be made before surgery, including the medical history, objective and subjective audiometry, imaging of the ear, as well as the genetic diagnostic. Here we reviewed the surgical approaches for cochlear implants as well as the complications.

Association between selected essential trace element concentrations in umbilical cord and risk for cleft lip with or without cleft palate: A case-control study.

A deficiency or excess of zinc (Zn), selenium (Se), cobalt (Co), molybdenum (Mo), or manganese (Mn) may interfere with fetal organogenesis. However, the impact of these essential trace elements on the occurrence of cleft lip with or without cleft palate (CL ±â€¯P) remains to be elucidated. We aimed to investigate the associations between the amounts of Zn, Se, Co, Mo, and Mn in umbilical cord tissue and risk for CL ±â€¯P. This case-control study included 200 controls without congenital malformations and 88 CL ±â€¯P cases. Zn, Se, Co, Mo, and Mn concentrations in the umbilical cord were determined using inductively coupled plasma mass spectrometry. Information was collected on demographics, lifestyle behaviors, and dietary intake. The median concentrations of Zn in cases of CL ±â€¯P and cleft lip with cleft palate (CLP), of Se in cases of CL ±â€¯P and cleft lip only (CLO), and of Co in cases of CLO were lower than in the controls. In utero exposure to higher levels of Zn was associated with reduced risk for CL ±â€¯P (OR = 0.44, 95% CI, 0.20-0.93) and for CLP (OR = 0.35, 95% CI, 0.14-0.86), and a higher level of Se was associated with reduced risk for CL ±â€¯P and CLO, with ORs of 0.47 (95% CI, 0.23-0.95) and 0.22 (95% CI, 0.08-0.67), respectively. By contrast, higher levels of Mo in the umbilical cord were associated with 2.52-fold (95% CI, 1.23-5.20) and 2.59-fold (95% CI, 1.12-5.95) higher risk for CL ±â€¯P and CLP, respectively. No association was found between Co or Mn and risk for CL ±â€¯P. In conclusion, in utero exposure to higher levels of Zn and Se was associated with reduced risk for CL ±â€¯P, but higher levels of Mo were associated with increased risk for CL ±â€¯P.