Longitudinal treatment responsiveness on plasma neurofilament light chain and glial fibrillary acidic protein levels in neuromyelitis optica spectrum disorder.

BACKGROUND: Neurofilament light chain (NfL) and glial fibrilliary acidic protein (GFAP) have been suggested to be biomarkers of the pathophysiological process of neuromyelitis optica spectrum disorders (NMOSD), but the relationship between the plasma levels of these molecules with disease activity and treatment is incompletely understood. OBJECTIVE: To investigate the treatment effects of disease-modifying drugs on plasma neurofilament light chain (pNfL) and plasma glial fibrillary acidic protein (pGFAP) and explore the predictive value of pNfL and pGFAP in the activity of NMOSD. METHODS: pNfL and pGFAP levels were measured using single-molecule arrays in 72 patients with NMOSD and 38 healthy controls (HCs). Patients with NMOSD received tocilizumab (n = 29), rituximab (n = 23), oral prednisone (n = 16), and oral azathioprine or mycophenolate mofetil (n = 4). RESULTS: NMOSD patients had significantly higher pNfL and pGFAP levels than HCs (pNfL, 18.3 (11.2-39.3) versus 11.5 (7.0-23.3) pg/mL; p = 0.001; pGFAP, 149.7 (88.6-406.5) versus 68.7 (59.4-80.8) pg/mL; p < 0.001). Multivariable regression analyses indicated that baseline pNfL concentration was associated with age (p = 0.017), Expanded Disability Status Scale (EDSS) score (p = 0.002), and recent relapses (p < 0.001). Baseline pGFAP concentration was also associated with EDSS (p < 0.001) and recent relapses (p < 0.001). Compared with prednisone, tocilizumab and rituximab significantly reduced pNfL [tocilizumab, exp(ß), 0.65; 95% confidence interval (CI), 0.56-0.75; p < 0.001; rituximab, exp(ß), 0.79; 95% CI = 0.68-0.93; p = 0.005] and pGFAP levels [tocilizumab, exp(ß), 0.64; 95% CI, 0.51-0.80; p < 0.001; rituximab, exp(ß), 0.77; 95% CI, 0.61-0.98; p = 0.041] at the end of the study. The pNfL levels in the tocilizumab and rituximab groups were reduced to those of HCs [tocilizumab, 8.5 (7.06-17.90) pg/mL; p = 0.426; rituximab, 14.0 (9.94-21.80) pg/mL; p = 0.216]. However, the pGFAP levels did not decrease to those of HCs in NMOSD patients at the end of study [tocilizumab, 88.9 (63.4-131.8) pg/mL; p = 0.012; rituximab, 141.7 (90.8-192.7) pg/mL; p < 0.001]. CONCLUSION: pNfL and pGFAP may serve as biomarkers for NMOSD disease activity and treatment effects.

Maternal exposure to TCDD during gestation advanced sensory-motor development, but induced impairments of spatial learning and memory in adult male rat offspring.

2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) is an endocrine disrupting chemical (EDC) with high persistency. Even a low amount can pass the placental barrier during gestational exposure. Exposure to TCDD exposure can impair the development of the nervous system in children, leading to impaired learning ability in later-life. But the changes in neurobehavioral developments in infancy and childhood caused by TCDD are unknown. Pregnant Sprague-Dawley rats were given a consecutive daily dose of TCDD (200 or 800 ng/day/kg) or an equivalent volume of vehicle by gavage on gestational days 8-14 (GD 8-14) as the prenatal TCDD exposure model. In the offspring, early neurobehavioral development was assessed at postnatal day 5 (PND5) and eye-opening was monitored from PND10 onwards. Adult male offspring was tested by Morris Water Maze for spatial memory and learning ability evaluation. Hippocampus Nissl's staining and astrocyte GFAP immunohistochemistry were used to evaluate the activity of astrocytes. The results of the behavioral tests showed that gestational TCDD exposure induced premature motor activity and earlier eyes-opening, but lead to serious deficits of spatial memory and learning ability in the adult male offspring. Morphology and number of neurons in the hippocampus CA1 region was not affected, while the activity of astrocytes in the same region was significantly reduced. These data indicate that perinatal TCDD exposure induced premature neurobehavioral development but impaired the spatial learning and memory in adult male rat offspring. The decreased activity of astrocytes in the hippocampus may play a role in these adverse effects.

Psychological distress and dyslipidemia in chinese police officers: a 4-year follow-up study in Tianjin, China.

OBJECTIVE: This study aimed at investigating whether psychological distress in police officers was associated with dyslipidemia. METHODS: A survey was conducted to examine the psychological distress among 5867 police officers in Tianjin, China, from 2007 to 2011. Psychological distress was measured using the Symptom Check List-90-Revised. Cox proportional hazard regression was used to calculate the hazard ratios (HR) of the incidence of dyslipidemia predicted by psychological distress. RESULTS: Among the 3300 participants without dyslipidemia at baseline (2567 with dyslipidemia), 60.5% (n = 1829) developed incident dyslipidemia 2.61 years (median) later. The adjusted HR was 1.15 (95% confidence interval, 1.05 to 1.26) after the adjustment of police classifications and other variables. The adjusted HR for police officers in charge of traffic control was 1.30 (95% confidence interval, 1.09 to 1.56). CONCLUSIONS: Further investigations for associations of psychological factors with dyslipidemia and cardiovascular diseases are needed.

Levels of PCDDs, PCDFs and dl-PCBs in the blood of childbearing-aged women living in the vicinity of a chemical plant in Tianjin: a primary study.

Several studies have suggested that maternal exposure to Polychlorinated dibenzo-p-dioxins (PCDDs), poly-chlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (PCBs) may affect foetal growth and infant development. The aim of our study was to determine whether the childbearing-aged residents living near a chemical plant have a greater exposure risk. Concentrations of 17 PCDD/Fs congeners and 12 non-ortho and mono-ortho dioxin-like PCBs were measured using HRGC-HRMS in the blood of 30 non-occupational childbearing-aged women living near a chemical plant (Dagu) that had been producing chlorinated pesticides from 1958 to 2004. The factors that influenced the body burden were investigated based on responses to a questionnaire. Levels of PCDD/Fs+PCBs were in the range of 16.43-155.29pg WHO 2005-TEQg(-1) lipid. PCDDs and PCDFs contributed 56.72% and 34.44%, respectively, to the total TEQ value. Total WHO-TEQ was approximately tenfold higher in the participants living in the vicinity of the plant (distance: 1.52±0.148km) than in the groups living farther away (distance: 4.93±1.124km). A negative correlation between total WHO-TEQ and distance to Dagu was observed by multiple linear regression models. The data provide basic information for monitoring dioxin-like chemicals in the district and for the future study of the relationship between POPs and pregnancy outcomes.

[Research and realization of technique of intra-vehicular pressure garment].

OBJECTIVE: To study the technology of intra-vehicular pressure protection for manned space craft pressure emergency and to develop the pressure garment. METHOD: According to the requirements of manned spacecraft emergency, the research scheme was proposed. Then the realization method of the following techniques were studied: structure of the pressure suit, pressure control, ergonomics, ventilation and oxygen supply, vision support and anti-fog. The performance of the space suit was verified by research and environment experiment. RESULT: An intra-vehicular pressure garment system was realized. It could fulfil the requirements of pressure protection and ergonomics and has passed overall performance test, interface test, and environment test. CONCLUSION: The intra-vehicular pressure garment developed by us can meet the requirements of space transportation system during pressure emergency.

[Effects of head-down bedrest on surface temperature distribution and non-evaporative heat dissipation].

OBJECTIVE: To study effect of simulated weightlessness on non-evaporative heat dissipation from different parts of the human body. METHOD: Body surface temperature distribution of five subjects was measured under -6 degrees head down bedrest for 7 d with HR-II infrared thermography. Non-evaporative heat dissipation was calculated with the heat exchange equations based on surface temperature. RESULT: The temperature difference between torso and extremities increased during bed rest, and the largest was 6.7 degrees C higher than the control on the 3rd day of bed rest. The part of non-evaporative heat dissipation from the torso increased about 6% and that from head-neck increased 2%. At the same time, the parts of heat dissipation from the upper and lower extremities decreased about 3% and 5% respectively. CONCLUSION: The parts of non-evaporative heat dissipation from different areas of the human body changed during simulated weightlessness. This result provided a basis for the flow distribution design of liquid cooling garment of EVA suit.