Cholinergic responses in cloned human TE671/RD tumour cells

The cholinergic responses of the human tumour cell line TE671/RD were examined using digital Ca²⁺ imaging fluorescence microscopy and patch-clamp measurements. In response to stimulation of the muscarinic acetylcholine (ACh) receptor (mAChR), the intracellular concentration of Ca²⁺ ([Ca²⁺]_i) rose about two-fold, in parallel with inositol 1,4,5-trisphosphate accumulation, measured by chromatographic techniques. By contrast, there was no increment of [Ca²⁺]_i upon stimulation of the nicotinic ACh receptor (nAChR), nor after caffeine application. Electrophysiological experiments showed that TE671/RD cells lack functional voltage-activated Ca²⁺ channels. The stimulation of the nAChR induced transient whole-cell currents (I _ACh). Little or no current was detected in isotonic extracellular Ca²⁺, with Cs⁺ in the patch pipette. Cell pretreatment with muscarine reduced I _ACh by about 20%, without consistent modifications of current kinetics. Muscarine applied to the extra-patch membrane under the cell-attached configuration had no obvious effect on ACh-evoked unitary events. In conclusion, in human TE671/ RD cells, muscarinic stimulation increases [Ca²⁺]_i, while nicotinic stimulation does not. In addition, the nAChR exhibits peculiar ion permeability properties and is not functionally regulated by the breakdown of phosphoinositides.     

RNA interference against enterovirus 71 infection

Enterovirus 71 (EV71) is a highly infectious major causative agent of hand, foot, and mouth disease (HFMD) which could lead to severe neurological complications. There is currently no effective therapy against EV71. In this study, RNA interference (RNAi) is employed as a therapeutic approach for specific viral inhibition. Various regions of the EV71 genome were targeted for inhibition by chemically synthesized siRNAs. Transfection of rhabdomyosarcoma (RD) cells with siRNA targeting the 3'UTR, 2C, 3C, or 3D region significantly alleviated cytopathic effects of EV71. The inhibitory effect was dosage-dependent with a corresponding decrease in viral RNA, viral proteins, and plaque formations by EV71. Viral inhibition of siRNA transfected RD cells was still evident after 48 h. In addition, no significant adverse off-target silencing effects were observed. These results demonstrated the potential and feasibility for the use of siRNA as an antiviral therapy for EV71 infections.     

The aged, the dying, the dead: Medical-legal considerations

Some of the special considerations involved in medical care of the aged and dying, along with the medical-legal problems that may arise, are discussed. Legal cases involving the rights of the dying and their families are reviewed, and precautions given for avoiding difficulties.     

武汉市颗粒物污染对呼吸系统健康影响及经济损失分析

目的评估颗粒物(particulate matter,PM)污染对呼吸系统疾病(respiratory disease,RD)住院人数的影响,估计降低PM水平可避免的经济损失,为评估空气污染治理的成本-效益提供依据。方法收集武汉市2015—2019年两家三甲医院RD住院患者资料、同期武汉市PM浓度和气象数据。采用广义相加模型(generalized additive model,GAM)估计PM对RD住院人数的影响,采用疾病成本法(cost of illness approach,COI)估算PM浓度降低带来的可避免经济损失。结果PM污染造成RD住院人数增加,PM_(2.5)和PM_(10)浓度每上升10μg/m^(3),分别导致RD住院人数上升1.71%和0.71%。其中男性和0~14岁人群受影响较大,PM_(2.5)浓度每上升10μg/m^(3),男性和0~14岁住院人数分别上升1.97%和2.65%;PM_(10)浓度每上升10μg/m^(3),男性和0~14岁住院人数分别上升0.87%和0.88%。2015—2019年PM污染造成武汉市6.33万人住院和12.14亿元经济损失。若PM浓度降低至同期世界卫生组织建议值,武汉市每年可避免1.94亿元经济损失和1.01万人住院。结论PM暴露可导致沉重的疾病负担和经济损失,采取有效的措施控制PM浓度,将带来较大的经济效益。     

Effects of malnutrition on the acute phase response of plasma proteins in patients undergoing total gastrectomy

The serum level of six acute phase proteins (APP) has been evaluated preoperatively and for a few days in the postoperative period. Thirty patients undergoing total gastrectomy for gastric cancer have been studied in two subgroups according to their nutritional status. Those with gastric cancer had significantly higher baseline serum levels of alpha 1 acid glycoprotein (alpha1AGP) and C-reactive protein (CRP) than a control group. Malnourished patients also had reduced acute phase response for alpha1AGP and alpha 1 antitrypsin (alpha1AT) a higher increase of CRP and fibrinogen, and a lower decrease for transferrin and retinol binding protein (RBP).     

A note on calculating asymptotic confidence intervals for the adjusted risk difference and number needed to treat in the Cox regression model

Recently, Laubender and Bender (Stat. Med. 2010; 29: 851–859) applied the average risk difference (RD) approach to estimate adjusted RD and corresponding number needed to treat measures in the Cox proportional hazards model. We calculated standard errors and confidence intervals by using bootstrap techniques. In this paper, we develop asymptotic variance estimates of the adjusted RD measures and corresponding asymptotic confidence intervals within the counting process theory and evaluated them in a simulation study. We illustrate the use of the asymptotic confidence intervals by means of data of the Düsseldorf Obesity Mortality Study. Copyright © 2013 John Wiley & Sons, Ltd.     

A Group Randomized Intervention Trial Increases Participation in the School Breakfast Program in 16 Rural High Schools in Minnesota

BackgroundBreakfast consumption is associated with better diet quality and healthier weights, yet many adolescents miss breakfast. Nationally, 17.1% of students participate in the School Breakfast Program (SBP). Only 10% of high school students participate.ObjectiveOur aim was to evaluate an environmental intervention to increase SBP participation in high schools.DesignA group randomized trial was carried out from 2012 to 2015.Participants/settingNinth- and 10th-grade students enrolled in 16 rural schools in Minnesota (median 387 students) were randomized to intervention or control condition.InterventionA school-based intervention that included two key components was implemented over a 12-month period. One component focused on increasing SBP participation by increasing student access to school breakfast through changes in school breakfast service practices (eg, serving breakfast from a grab-n-go cart in the atrium; expanding breakfast service times). The other component focused on promoting school breakfast through student-directed marketing campaigns.Main outcome measureChange in school-level participation in the SBP was assessed between baseline (among ninth and tenth graders) and follow-up (among tenth and eleventh graders). School meal and attendance records were used to assess change in school-level participation rates in the SBP.Statistical analysesThe Wilcoxon test was used for analysis of difference in change in mean SBP participation rate by experimental group.ResultsThe median change in SBP participation rate between baseline and follow-up was 3% (interquartile range=13.5%) among the eight schools in the intervention group and 0.5% (interquartile range=0.7%) among the eight schools in the control group. This difference in change between groups was statistically significant (Wilcoxon test, P=0.03). The intervention effect increased throughout the intervention period, with change in mean SBP participation rate by the end of the school year reaching 10.3% (95% CI 3.0 to 17.6). However, among the intervention schools, the change in mean SBP participation rates was highly variable (range=–0.8% to 24.8%).ConclusionsInterventions designed to improve access to the SBP by reducing environmental and social barriers have potential to increase participation among high school students.