A study of the involvement of melanin-concentrating hormone receptor 1 (MCHR1) in murine models of depression.

BACKGROUND: Most antidepressant medications target central monoamine systems and are often characterized by limited efficacies and unwanted side effects. Thus, significant efforts are ongoing to identify novel targets for the treatment of depression. Growing evidence suggests that neuropeptides play a role in the pathophysiology of depression. The melanin-concentrating hormone (MCH) is one such neuropeptide, implicated in the modulation of many physiological responses. METHODS: We utilized an array of techniques including chronic mild stress (CMS) as a depression paradigm, neurobehavior, gene expression analysis, and knockout genetics to investigate the role of MCH receptor subtype 1 (MCHR1) in murine models of depression. RESULTS: We report here that following a 5-week exposure to repeated chronic mild stress (an ethologically relevant animal model of depression), C57Bl/6J mice have increased hippocampal gene expression of MCH receptor subtype 1 (MCHR1), the cognate melanin concentrating hormone receptor in mice. This increased gene expression is reversed by chronic fluoxetine hydrochloride (Prozac) treatment. Additionally, while female and male mice carrying a null mutation of the MCHR1 gene show comparable anxiolytic-like behavior on the open field, only female knockout mice exhibit antidepressant-like behavior, when tested on the forced swim and tail suspension tests. CONCLUSION: Taken together, we suggest that antagonism of the MCHR1 receptor may provide a novel approach for the treatment of affective disorders, including depression, with a potentially increased efficacy in women.     

结核定点医院医护人员感染预防控制效果研究

目的评估结核定点医院医务人员结核菌潜伏感染率,评价该医院在实施管理控制、环境控制、个人防护等结核菌感染控制预防措施的效果。方法选取2018年1~5月在福建省福州市肺科医院工作的呼吸科及结核病科工作人员101名,将研究对象分为两组:我院呼吸科医护人员56名(其中医生19名,护士37名)、我院结核科医护人员组45名(其中医生11名,护士34名),同时使用结核分枝杆菌感染T细胞斑点实验(T-SPOT.TB)及结核菌素皮肤试验(TST)对两组医护人员进行结核菌潜伏感染率调查,以上两组医护人员既往均无结核病史、无结核病症状,胸片正常。结果呼吸科及结核科医护人员T-SPOT.TB阳性率分别是26.78%、22.22%,两组比较差异无统计学意义(χ~2=0.279,P=0.597),呼吸科及结核科医护人员TST阳性率分别是48.21%、24.44%,两组比较差异有统计学意义(χ~2=6.007,P=0.014);进一步比较呼吸科及结核科医生T-SPOT.TB阳性率分别是31.58%、9.09%,用Fisher精确概率法比较两组差异无统计学意义(P=0.215),呼吸科及结核科医生TST阳性率分别是52.63%、9.09%,用Fisher精确概率法比较两组差异有统计学意义(P=0.023);45名结核科医护人员T-SPOT.TB阳性率及TST阳性率分别为22.22%、24.44%,均明显低于资料显示的我国医护人员结核菌感染率50%~70%。结论在肺结核病房实施管理控制、环境控制、个人防护等预防控制措施对降低医护人员结核菌潜伏感染率效果显著;呼吸科医护人员结核菌潜伏感染率有高于结核科医护人员的趋势。     

Comparison of QuantiFERON TB‐G‐test to TST for detecting latent tuberculosis infection in a high‐incidence area containing BCG‐vaccinated population

Objective Until recently, the only tool for detection of latent tuberculosis infection (LTBI) was the tuberculin skin test (TST). QuantiFERON‐TB Gold In‐Tube test (QFT) is a promising in vitro diagnostic test for LTBI that has potential advantages over the TST. In this study we aimed to compare QFT with TST for diagnosis of LTBI. Patients and methods A total of 186 BCG‐vaccinated subjects enrolled in study. They underwent TST and QFT assay. They divided in two groups. Group 1 includes individuals who were at low risk for exposure to M. tuberculosis (LRG) and Group 2 includes individuals who were likely to have been exposed to M. tuberculosis infections (HRG). Results Overall agreement between QFT and TST was 89.3% (kappa = 0.052). In LRG, agreement between the two tests was 52.6% (95% confidence interval, 44–60%) with κ‐values of 0.019. In HRG agreement between the two tests was 63.2% (95% confidence interval, 42–84%) with κ‐values of 0.28. Conclusion In conclusion, the QFT assay showed acceptable results for determining latent M. tuberculosis infection in vaccinated population. The decision to select QFT over TST will depend on the population, purpose of testing and resource availability.     

Labeling of neurons following intravenous injections of fluorescent tracers in mice

Several fluorescent tracers were injected intravenously in the tail veins of adult mice, and the distribution of these substances in the central nervous system and sensory and autonomic ganglia was investigated. Injections of the blue tracers Granular Blue, True Blue and Fast Blue resulted in labeling of the somatomotor and visceromotor nuclei of the brainstem and spinal cord, the paraventricular, supraoptic and arcuate nuclei of the hypothalamus, the area postrema and the sensory and sympathetic ganglia. Following i.v. injections of Nuclear Yellow, labeling occurred only in the median eminence, the area postrema and the sensory and sympathetic ganglia.     

Relationship between serum substance P levels and daytime sleepiness in obstructive sleep apnea syndrome

OBJECTIVE: We hypothesized that intermittent hypoxia might influence serum substance P levels, and that this effect might in turn contribute in excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea syndrome (OSAS). PATIENTS AND METHODS: Fifty-five patients with newly diagnosed OSAS and 15 age-matched nonapneic control subjects were enrolled in this study. Full polysomnography was performed in all patients. Single blood samples were drawn between 8:00 am and 9:00 am after the sleep study. Substance P levels were analyzed with a competitive enzyme immunoassay (substance P EIA kit; Cayman Chemical; Ann Arbor, MI). RESULTS: There were no significant differences in age, gender, body mass index, smoking habit, and snoring between the two groups. Serum substance P levels in the OSAS group were significantly lower than that in the control group (p < 0.0001). Serum substance P levels were positively correlated with rapid eye movement sleep (r = 0.330, p = 0.049) and slow-wave sleep (r = 0.324, p = 0.049) phases. Serum substance P levels were negatively correlated with Epworth sleepiness scale score (r = - 0.253, p = 0.048), number of total apneas during the night (r = - 0.247, p = 0.036), number of respiratory events during the night (r = - 0.266, p = 0.024), apnea-hypopnea index (r = - 0.287, p = 0.015), respiratory arousal index (r = - 0.267, p = 0.026), time spent in apnea and hypopnea (r = - 0.307, p = 0.01), average oxygen desaturation (r = - 0.265, p = 0.026), and oxygen desaturation index (r = - 0.254, p = 0.031). CONCLUSION: We concluded that EDS seen in some of the OSAS patients might be associated with various pathophysiologic mechanisms including substance P levels.     

Comparison of IGRA and TST in the diagnosis of latent tuberculosis among women of reproductive age in South India

BackgroundLatent tuberculosis infection (LTBI) is a mycobacterial infection defined on the basis of cellular immune response to mycobacterial antigens. The tuberculin skin test (TST) and the Interferon-Gamma Release Assay (IGRA) are the two tests currently used to establish the diagnosis of LTB. Literature suggests that a study regarding tuberculosis (TB) infection among women of reproductive age group is limited.MethodsFemale household contact, married, aged 18–49 years underwent written consent form and are screened for LTBI using the TST and IGRA. Participants are injected with TST [5 tuberculin unit (TU), purified protein derivative (PPD)] and IGRA [QuantiFERON®-TB Gold Plus kit (QFT-Plus)]. All the household contacts were followed-up for one year for incident TB cases. Statistical analysis was done using STATA version 14 (StataCorp., Texas, USA). Cohen's kappa test was used to determine the agreement between two tests.ResultsThe prevalence of LTBI was found to be 69% (either TST or IGRA positive). Positivity rate of IGRA was higher when compared to that of TST. Out of 139 participants, 68 (49%) tested positive for TST, 80 (57.6%) tested positive for IGRA and 52 (37.4%) tested positive for both. Discordant results were observed in about two fifth of the study population and there was poor agreement between the two tests.ConclusionLongitudinal studies are required to detect incident TB cases to evaluate the usefulness of these tests. The study was found that IGRA is more consistent to diagnosis of latent tuberculosis infection than the TST. Such studies can also be performed in varied settings among different populations which would help us to improve the diagnosis of LTBI and consequently help in TB control.     

三重磁刺激技术对上运动神经元损伤的评价作用

目的研究三重磁刺激技术(TST)的特点,探讨TST在评价运动神经元疾病患者上运动神经元(UMN)损害中的作用。方法选取肌萎缩侧索硬化(ALS)患者12例、下运动神经元综合征(LMNS)患者14例,分别进行双上肢小指展肌TST测定及运动诱发电位(MEP)潜伏期、中枢运动传导时间(CMCT)测定,并将TST波幅比与改良的医学研究委员会(MRC)评分、修订的肌萎缩侧索硬化功能评分量表(ALSFRS-R)评分、肺功能百分比、病程等进行相关性分析。结果 ALS患者12例均完成双侧TST检测,其尺神经TST波幅比为(55.8±32.6)%,较正常参考值下降(F=-3.448,P=0.002),TST波幅比阳性率为70.8%。LMNS患者共13例完成TST检测,其尺神经TST波幅比为(79.4±16.4)%,与正常参考值无统计学差异(F=0.215,P=0.832)。ALS组尺神经TST波幅比〔(55.8±32.6)%〕低于LMNS〔(79.4±16.4)%〕(F=-3.275,P=0.002)。TST波幅比评价UMN体征的敏感度76.5%,高于传统电生理指标;特异度为54.5%,低于传统电生理指标。TST波幅比与改良的MRC评分存在相关性(r=0.431,P=0.035),与ALSFRS-R评分、肺功能、病程、MEP潜伏期以及CMCT均无相关性。结论 TST可以发现亚临床UMN损害,其敏感性高于传统电生理观测指标。TST可以定量评估UMN受损程度,有可能用于ALS患者病情监测。     

Detection of proximal conduction blocks using a triple stimulation technique improves the early diagnosis of Guillain–Barré syndrome

Objective

Current diagnostic electrophysiological criteria can miss the early stages of Guillain–Barré syndrome (GBS). We evaluated the diagnostic efficiency of the triple stimulation technique (TST) in highlighting proximal conduction blocks (CBs) in patients who do not meet the electrophysiological criteria for GBS.