�Ȼ�﮶���������ǻ��沿���������֪����Ӱ���о�

??Objective    To observe the effects of lithium chloride pretreatment on cognitive ability of aged rats after oral and maxillofacial surgery. Methods    A total of 48 aged male SD rats??18 ~ 20 months old??weight 550 ~ 700 g?? were bought from the Experimental Animal Center of China Medical University . These rats were randomly divided into three groups??including the normal control group??group C??n=16????surgery and anesthesia group??group O??n=16????and lithium chloride preconditioning group??group L??n=16??.Rats in each group were randomly divided into two parts??one part was given Morris water maze test three days after the surgery and its characteristics of behavior tested. Another part was decapitated 24 h after the surgery and extracted and the hippocampus brain separated at the same time. Test expression content of IL-1β GSK-3β p-GSK-3β??ser9??in the hippocampus by Elisa and Western blotting detection method respectively. Results    Morris water maze test showed that??the first day after surgery??latencies of group L and O were significantly longer than group C??compared with group C in swimming distance?? latency and swim distances of group L were shorter than group O. With the comparison of multiple analysis of variance??differences were statistically significant??P??0.05??. Groups L and O in the second day were slightly shortened compared to the first day??on the third day after surgery it has also improved over the second day. Space exploration experiments in rats showed that??the dwell time of group C was significantly longer in the platform quadrant and the frequency of crossing the platform also increased compared with groups L and O. In addition??group L and group O were higher in IL-β levels than group C??the difference being statistically significant by analysis of variance??P??0.05????but group L was significantly lower compared with group O??the difference being statistically significant??P??0.05??. The content of GSK-3β of three groups were of no significant difference??P > 0.05????but p-GSK-3β??ser9??content was significantly lower in group L and O than in group C. The content of GSK-3β of group L was higher than in group O??the difference being statistically significant??P??0.05??. Conclusion    Pretreatment with lithium chloride in postoperative aged rats can inhibit the expression of inflammatory cytokines and increase GSK-3β phosphorylation in the hippocampus cells??so p-GSK-3β??ser9??upregulates and inhibites  the apoptosis of brain cells??thereby improved cognitive abilities after the cavity and maxillofacial surgery.     

Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies

The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC₆₀) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity.     

Leading together towards a stronger ‘us’: An experimental test of the effectiveness of the 5R Shared Leadership Program (5RS) in basketball teams

ObjectivesLeadership has been suggested to be a key factor in gaining a competitive advantage as a team, with shared leadership being a better predictor of team functioning than vertical leadership. Although the benefits of shared leadership are well-documented, evidence about how to implement a shared leadership structure remains sparse. This leaves coaches with three key challenges: (1) identifying the best leaders; (2) defining what roles those leaders should fulfill; and (3) developing their leadership skills. Solutions to these challenges have been proposed in the 5R Shared Leadership Program (5R^S) — a leadership development program that seeks to implement an effective structure of shared leadership within sports teams.DesignTo test the effectiveness of 5R^S program, we conducted an experimental-comparison group intervention in which eight national-level basketball teams (N = 96) completed a questionnaire at two points in time (i.e., pre- and posttest). The teams in the intervention condition completed the 5R^S program, in which we identified the leadership structure in their teams (through Shared Leadership Mapping), appointed the best leaders in their leadership role, and then developed their identity leadership skills.ResultsThe results revealed that the 5R^S program was successful in strengthening athlete leaders’ identity leadership skills, and as a result also team members’ identification with their team. Furthermore, in contrast to athletes in the comparison condition, athletes in the 5R^S condition were able to maintain their levels of intrinsic motivation and commitment to team goals, while also reporting improved well-being.ConclusionsThe present study provides encouraging evidence that, by implementing a structure of shared leadership and by promoting athlete leaders’ identity leadership skills, the 5R^S program is able to improve the team’s functioning and the well-being of its members.     

丙泊酚麻醉对老龄大鼠认知功能和海马神经元γ-氨基丁酸A受体表达的影响

目的观察丙泊酚麻醉对老龄大鼠认知功能及海马神经元γ-氨基丁酸A(GABA)受体表达的影响。方法50只SD老年大鼠随机分为丙泊酚组和对照组,每组25只。丙泊酚组大鼠腹腔注射1%丙泊酚中/长链脂肪乳注射液6 mL/kg,对照组腹腔注射等体积的生理盐水。麻醉后1 d进行Morris水迷宫实验,分别采用HE染色和尼氏体染色观察海马区神经细胞及尼氏体(Nissl体)形态学变化,Western Blot检测GABA蛋白量表达。结果麻醉后,2组大鼠肛温、心率、呼吸频率、血氧饱和度比较,差异均无统计学意义(P>0.05)。随着实验时间的延长,2组大鼠逃逸潜伏期、总里程数逐渐减小,丙泊酚组大鼠各时间点逃逸潜伏期、总里程均高于对照组,差异有统计学意义(P<0.05)。丙泊酚组大鼠穿越平台区域次数、时间小于、短于对照组,差异有统计学意义(P<0.05)。对照组海马区Nissl体存在于细胞浆及树突,染色较深,神经细胞排列整齐,形态规则;丙泊酚组Nissl体消失,神经细胞数量减少,细胞核破裂、丢失。丙泊酚组大鼠海马GABA蛋白表达量低于对照组,差异有统计学意义(P<0.05)。结论丙泊酚对大鼠认知功能有影响,并与海马区GABA的表达相关。     

Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models,once tauopathy is initiated,by restoring the autophagic flux

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTau^P301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTau^P301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.     

Increased alpha suppression with age during involuntary memory retrieval

Recent work suggests that while voluntary episodic memory declines with age, involuntary episodic memory, which comes to mind spontaneously without intention, remains relatively intact. However, the neurophysiology underlying these differences has yet to be established. The current study used electroencephalography (EEG) to investigate voluntary and involuntary retrieval in older and younger adults. Participants first encoded sounds, half of which were paired with pictures, the other half unpaired. EEG was then recorded as they listened to the sounds, with participants in the involuntary group performing a sound localization cover task, and those in the voluntary group additionally attempting to recall the associated pictures. Participants later reported which sounds brought the paired picture to mind during the localization task. Reaction times on the localization task were slower for voluntary than involuntary retrieval and for paired than unpaired sounds, possibly reflecting increased attentional demands of voluntary retrieval and interference from reactivation of the associated pictures respectively. For the EEG analyses, young adults showed greater alpha event-related desynchronization (ERD) during voluntary than involuntary retrieval at frontal and occipital sites, while older adults showed pronounced alpha ERD regardless of intention. Additionally, older adults showed greater ERD for paired than unpaired sounds at occipital sites, likely reflecting visual reactivation of the associated pictures. Young adults did not show this alpha ERD memory effect. Taken together, these data suggest that involuntary memory is largely preserved with age, but this may be due to older adults' greater recruitment of top-down control even when demand for such control is limited.     

线性法测量皮质下缺血性血管病患者脑萎缩及其与认知损害的相关性分析

目的通过线性法测量皮质下缺血性血管病(SIVD)患者脑萎缩,分析其与认知功能损害的相关性。方法共纳入SIVD组50例,健康对照组50例。所有入组对象均完成一般情况评定、Mo CA量表评估认知功能、头颅MRI检查,线性法进行脑萎缩测量。结果 SIVD组代表脑室系统横径的测量值及脑沟测量值,除桥池宽度外,均较对照组显著增大(P 0. 05)。SIVD组的脑萎缩测量相对值除脑干指数外,均显著高于对照组(P 0. 05)。SIVD组双侧侧脑室两额角间最宽距离、双侧侧脑室额角两侧尾状核头间最小距离、第三脑室宽度、双侧侧脑室腰部外侧壁最小距离与Mo CA评分呈显著负相关(P 0. 05)。SIVD组脑萎缩测量相对值中的额角指数、尾状核指数、哈氏值、第三脑室宽度与视空间能力、计算力、延迟记忆和定向力均呈负相关(P 0. 05)。结论 SIVD患者存在明显的皮质和皮质下萎缩,并与认知功能损害相关。哈氏值、额角指数、尾状核指数、第三脑室宽度可作为SIVD患者脑萎缩的预测指标,提示执行功能/视空间及计算力、记忆力的损害。