Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition. We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy. The results obtained from testing at least 1281 genes were provided to the reproductive couples. We aimed to ascertain the psychosocial effects on participants, the acceptability of screening to all participants, and the reproductive choices of persons identified as having an increased chance of having a child with a condition for which we screened. Among 10,038 reproductive couples enrolled in the study, 9107 (90.7%) completed screening, and 175 (1.9%) were newly identified as having an increased chance of having a child with a genetic condition for which we screened. These conditions involved pathogenic variants in 90 different genes; 74.3% of the conditions were autosomal recessive. Three months after receiving the results, 76.6% of the couples with a newly identified increased chance had used or planned to use reproductive interventions to avoid having an affected child. Those newly identified as having an increased chance had greater anxiety than those with a low chance. The median level of decisional regret was low in all result groups, and 98.9% of participants perceived screening to be acceptable. Couple-based reproductive genetic carrier screening was largely acceptable to participants and was used to inform reproductive decision making. The delivery of screening to a diverse and geographically dispersed population was feasible. (Funded by the Medical Research Future Fund of the Australian government; ClinicalTrials.gov number, NCT04157595.).

The misalignment between the circadian clock and behavioral cycles has been implicated in pathogenesis of many diseases. The main purpose of this study is to examine the association between rotating night shift work, exposure to light at night, and glomerular filtration rate among steelworkers in north China. A total of 6869 steelworkers, aged 22 to 60 years, were included in this study. Multivariable logistic regression was used to examine the association between night shift work, the brightness of bedroom ambient light at night (LAN), and estimated glomerular filtration rate (eGFR), with adjustment for potential confounders. Mediation analysis was performed to examine the mediation effect of potential mediators on the association of duration of night shifts and eGFR. Long duration of night shift work (≥29 years) had elevated odds of decreased eGFR (≤89 mL/min/1.73 m²) (odds ratio (OR), 1.37, 95% confidence interval (CI) 1.09–1.73) compared with day work after adjustment for potential confounders. The association between duration of night shifts and eGFR (continuous) was partially modified by diastolic blood pressure (average causal mediation effect (ACME), –0.077, 95% CI –0.134 to −0.030, p < 0.001). No significant associations were observed among the different brightness of bedroom ambient light levels: middle level (OR, 0.90, 95% CI 0.77–1.05), lightest level (OR, 0.94, 95% CI 0.75–1.18), and decreased eGFR compared with the darkest level. Long-term night-shift work, rather than the brightness of bedroom ambient LAN, is associated with early stage of renal dysfunction in steelworkers, and blood pressure may mediate the relationship between night shift work and decreased eGFR.

Silicosis is a chronic occupational lung disease caused by long-term inhalation of crystalline silica particulates. We created a rat model that closely approximates the exposure and development of silicosis in humans. Isobaric tags for relative and absolute quantitation (iTRAQ) technologies we used to identify proteins differentially expressed in activated rat lung tissue. We constructed three lentiviral knockdown vectors and an overexpression vector for the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene to achieve stable long-term expression. A total of 471 proteins were differentially expressed in the silicosis group compared with controls. Twenty upregulated, and eight downregulated proteins exhibited a ≥1.5-fold change relative to controls. We next found that the PTPN2, Factor B, and VRK1 concentrations in silicotic rats silicosis and SiO₂-stimulated MLE-12 cells were significantly higher than control groups. More importantly, we found that overexpression of PTPN2 simultaneously decreased the expression of phospho–signal transducer and activator of transcription 3 (p-STAT3) and Vimentin, while increasing E-cadherin expression. The opposite pattern was observed for PTPN2-gene silencing. We identified three proteins with substantially enhanced expression in silicosis. Our study also showed that PTPN2 can inhibit epithelial-mesenchymal transition by dephosphorylating STAT3 in silicosis fibrosis.

Although Kolmogorov-Smirnov (KS) statistic is a widely used method, some weaknesses exist in investigating abrupt Change Point (CP) problems, e.g. it is time-consuming and invalid sometimes. To detect abrupt change from time series fast, a novel method is proposed based on Haar Wavelet (HW) and KS statistic (HWKS). First, the two Binary Search Trees (BSTs), termed TcA and TcD, are constructed by multi-level HW from a diagnosed time series; the framework of HWKS method is implemented by introducing a modified KS statistic and two search rules based on the two BSTs; and then fast CP detection is implemented by two HWKS-based algorithms. Second, the performance of HWKS is evaluated by simulated time series dataset. The simulations show that HWKS is faster, more sensitive and efficient than KS, HW, and T methods. Last, HWKS is applied to analyze the electrocardiogram (ECG) time series, the experiment results show that the proposed method can find abrupt change from ECG segment with maximal data fluctuation more quickly and efficiently, and it is very helpful to inspect and diagnose the different state of health from a patient's ECG signal.

Objective To examine the associations of rotating night shift work with hyperhomocysteinaemia (HHcy) odds by different exposure metrics. Design Cross-sectional study. Setting Occupational physical examination centre for steel production workers, Tangshan, China. Participants A total of 6846 steelworkers, aged 22–60 years, from the baseline survey of a Chinese occupational cohort. Primary and secondary outcome measures Different exposure metrics of night shift work, including current shift status, duration of night shifts (years), cumulative number of night shifts (nights), cumulative length of night shifts (hours), average frequency of night shifts (nights/month), average length of night shifts (hours/night) and percentage of hours on night shifts, were used to examine the effects of past and current night shift work on HHcy odds. The total homocysteine concentration in the plasma above 15 µmol/L was defined as HHcy. Results Compared with those who never worked night shifts, current night shift workers had elevated odds of HHcy (OR 1.23, 95% CI 1.06 to 1.44). Considering a person’s lifetime work schedule and compared with individuals who never worked night shifts, duration of night shifts >28 years (OR 1.35, 95% CI 1.12 to 1.61), average frequency of night shifts >7 nights/month (OR 1.25, 95% CI 1.07 to 1.47) and percentage of hours on night shifts >30% (OR 1.23, 95% CI 1.05 to 1.43) were associated with higher HHcy odds. The duration of night shifts >20 years and the average frequency of night shifts >7 nights/month could significantly increase the odds of HHcy regardless of whether the average length of night shifts was greater than 8 hours/night. After stratification by sex, no significant association was found in female workers between different exposure metrics of night shift work and HHcy. Conclusions Long duration and high frequency of night shift work are associated with higher HHcy odds among male steelworkers.