脑出血继发损伤中沉默信息调节因子2的表达和炎症反应*

目的：探讨脑出血对酵母沉默信息调节因子2（Sirt2）和炎症的影响。方法：将胶原酶Ⅳ注入SD大鼠右侧 纹状体中建立脑出血模型，通过免疫印迹和ELISA 等方法测定大鼠脑出血后48 h 的Sirt2 的表达及炎症变化。利 用Hemin 诱导PC12 细胞损伤模拟体外脑出血模型，并检测Sirt2 及炎症变化；采用短发夹RNA（shRNA）-Sirt2 沉 默Sirt2 在PC12 细胞中的表达及对炎症的影响。结果：手术后48 h 脑出血行为学评分最低。脑出血组Sirt2 的表达 显著高于假手术组。脑出血组IL-6、IL-1β 表达显著升高。结论：脑出血可以促进Sirt2 的表达和炎症反应，降低 Sirt2 的表达可减缓炎症反应。 关键词 脑出血；沉默信息调节     

Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

Association of regional socioeconomic deprivation and rurality with global developmental delay in early childhood: Data from mandatory school entry examinations in Germany

BackgroundFrom birth to young adulthood, health and development of young people are strongly linked to their living situation, including their family’s socioeconomic position (SEP) and living environment. The impact of regional characteristics on development in early childhood beyond family SEP has been rarely investigated. This study aimed to identify regional predictors of global developmental delay at school entry taking family SEP into consideration.MethodWe used representative, population-based data from mandatory school entry examinations of the German federal state of Brandenburg in 2018/2019 with n=22,801 preschool children. By applying binary multilevel models, we hierarchically analyzed the effect of regional deprivation defined by the German Index of Socioeconomic Deprivation (GISD) and rurality operationalized as inverted population density of the children’s school district on global developmental delay (GDD) while adjusting for family SEP (low, medium and high).ResultsFamily SEP was significantly and strongly linked to GDD. Children with the highest family SEP showed a lower odds for GDD compared to a medium SEP (female: OR=4.26, male: OR=3.46) and low SEP (female: OR=16.58, male: OR=12.79). Furthermore, we discovered a smaller, but additional and independent effect of regional socioeconomic deprivation on GDD, with a higher odds for children from a more deprived school district (female: OR=1.35, male: OR=1.20). However, rurality did not show a significant link to GDD in preschool children beyond family SEP and regional deprivation.ConclusionFamily SEP and regional deprivation are risk factors for child development and of particular interest to promote health of children in early childhood and over the life course.     

Is neighbourhood deprivation a risk factor for gestational diabetes mellitus?

AIMS: To assess the relationship between neighbourhood deprivation and the rate of gestational diabetes mellitus (GDM) using routinely collected data from a clinical information system, in Plymouth, UK. METHODS: Between 1 January 1996 and 31 December 1997, 3933 women residing within the Plymouth Primary Care Trust (PCT) were screened for GDM using indices of neighbourhood deprivation and prevalence of GDM. Areas (n = 43) were classified according to the Townsend index, measuring material deprivation. Pregnant women with and without GDM were compared. RESULTS: The prevalence of GDM was 1.7%[95%, confidence interval (CI) 1.20, 2.11]. The prevalence of GDM ranged from 1.05% (95% CI 0.60, 1.70) in the most deprived to 2.10% (95%, CI 1.34, 3.13), in the least deprived neighbourhood. Crude rates decreased by 50%[relative prevalence (RP) (95% CI) 0.50 (0.27, 0.94); P = 0.06] amongst those living in the most-deprived compared with those living in the least-deprived areas. Using a stepwise binary logistic regression model, older age at delivery significantly increased the risk of developing GDM. [RP (95%, CI) 1.09, (1.04, 1.13)]. Townsend deprivation score had no significant independent association with GDM when other covariates were considered. CONCLUSION: These data suggest that the neighbourhood context in which women live has no impact on the risk of GDM. Diabet.     

Modified Epworth Sleepiness Scale in Chinese children with obstructive sleep apnea: a retrospective study

Background and objective  The purpose of this study is to assess whether Chinese children with high apnea–hypopnea index (AHI) are sleepier by a modified Epworth Sleepiness Scale (ESS). Materials and methods  Records were retrospectively reviewed. We included children who were between 3 and 12 years old, admitted for overnight polysomnogram because of suspected obstructive sleep apnea syndrome (OSAS). A modified ESS was used to assess excessive daytime sleepiness (EDS) of the children. Results  One hundred ninety-two Chinese children were included. Children with high AHI, defined as AHI > 5.0, were sleepier than children with AHI less than or equal to 5. After adjustment by age, gender, and obesity, children with high AHI remained significantly sleepier. Modified ESS was significantly correlated with AHI (rho = 0.124, 95% CI = 0.004–0.281). Modified ESS score of >8 was the best cutoff point with the sensitivity and specificity of 0.29 and 0.91, respectively. The odds ratio of children with modified ESS > 10 having high AHI was 4.231 (95%CI = 1.248 to 14.338) and children with modified ESS > 8 had the highest odds ratio, 4.295(95%CI = 1.66 to 11.1), of having high AHI. Conclusion   Chinese children with high AHI appear to be sleepier than children with low AHI. Children with suspected OSAS and high modified ESS, i.e., ESS > 8, had significantly higher odds ratio of having high AHI. Increased sleepiness is a specific but not a sensitive symptom in snoring children with high AHI. Screening for EDS in snoring children may help us identify those with high AHI and prioritize the management of those children. All authors worked and the study was carried out in Kwong Wah Hospital in Hong Kong. There was no conflict of interest and no specific source of funding for the study.     

Ill-health as a household norm: Evidence from other people's health problems

This paper proposes that an individual's self-assessed health (SAH) does not only suffer from systematic reporting bias and adaptation bias but is also biased owing to confounding health norm effects. Using 13 waves of the British Household Panel Survey covering the period 1991–2005, I show that, while there is a negative and statistically significant correlation between SAH and individuals' own health problem index, this negative effect reduces with the average number of health problems per (other) family member. The relative health bias is small, however, which implies that measures of SAH may not suffer seriously from systematic health norm bias. This is an important finding for researchers working with SAH data as it indicates that we do not have to worry too much about controlling for confounding influences from the health of other household members when estimating SAH regression equations.     

Regulation of local sweating in sleep-deprived exercising humans

Summary Thermoregulatory sweating [total body (m _sw,b), chest (m _sw,c) and thigh (m _sw,t) sweating], body temperatures [oesophageal (T _oes) and mean skin temperature (T _sk)] and heart rate were investigated in five sleep-deprived subjects (kept awake for 27 h) while exercising on a cycle (45 min at approximately 50% maximal oxygen consumption) in moderate heat (T _air andT _wall at 35° C. Them _sw,c andm _sw,t were measured under local thermal clamp (T _sk,1), set at 35.5° C. After sleep deprivation, neither the levels of body temperatures (T _oes,T _sk) nor the levels ofm _{sw, b},m _{sw, c} orm _{sw, t} differed from control at rest or during exercise steady state. During the transient phase of exercise (whenT _sk andT _sk,1 were unvarying), them _{sw, c} andm _{sw, t} changes were positively correlated with those ofT _oes. The slopes of them _{sw, c} versusT _oes, orm _{sw, t} versusT _oes relationships remained unchanged between control and sleep-loss experiments. Thus the slopes of the local sweating versusT _oes, relationships (m _{sw, c} andm _{sw, t} sweating data pooled which reached 1.05 (SEM 0.14) mg·cm^–2·min^–1°C^–1 and 1.14 (SEM 0.18) mg·cm^–2·min^–1·°C^–1 before and after sleep deprivation) respectively did not differ. However, in our experiment, sleep deprivation significantly increased theT _oes threshold for the onset of bothm _{sw, c} andm _{sw, t} (+0.3° C,P<0.001). From our investigations it would seem that the delayed core temperature for sweating onset in sleep-deprived humans, while exercising moderately in the heat, is likely to have been due to alterations occurring at the central level.