EBI2 contributes to the induction of thymic central tolerance in mice by promoting rapid motility of medullary thymocytes

Maturing thymocytes enter the thymic medulla, where they encounter numerous self‐antigens presented by antigen presenting cells (APCs). Those thymocytes that are strongly self‐reactive undergo either negative selection or diversion into the regulatory T‐cell lineage. Although the majority of the proteome is expressed in the medulla, many self‐antigens are expressed by only a minor fraction of medullary APCs; thus, thymocytes must efficiently enter the medulla and scan APCs to ensure central tolerance. Chemokine receptors promote lymphocyte migration, organization within tissues, and interactions with APCs in lymphoid organs. The chemokine receptor EBI2 governs localization of T cells, B cells, and dendritic cells (DCs) during immune responses in secondary lymphoid organs. However, the role of EBI2 in thymocyte development has not been elucidated. Here, we demonstrate that EBI2 is expressed by murine CD4⁺ single positive (CD4SP) thymocytes and thymic DCs. EBI2 deficiency alters the TCR repertoire, but does not grossly impact thymocyte cellularity or subset distribution. EBI2 deficiency also impairs negative selection of OT‐II TCR transgenic thymocytes responding to an endogenous self‐antigen. Two‐photon imaging revealed that EBI2 deficiency results in reduced migration and impaired medullary accumulation of CD4SP thymocytes. These data identify a role for EBI2 in promoting efficient thymic central tolerance.     

Substance use and depression in home visiting clients: Home visitor perspectives on addressing clients’ needs

Substance use and depression are prevalent among mothers enrolled in home visiting programs and are significant risk factors for child maltreatment, yet most home visiting programs are staffed by workers who lack the training and clinical skills to address these risks. Emanating from one state network's interest in advancing its practice in this area, the current study surveyed 159 home visitors on their current practices, training, knowledge, and perceived self‐efficacy, and perceived system‐ and client‐level barriers regarding client substance use and depression. Home visitors reported managing maternal depression more extensively than substance use, though overall management of both risk areas was low. More training was associated with more extensive management of both risk domains, as was greater home visitor knowledge and self‐efficacy. Implications for the development of strategies to improve home visitor management of client behavioral health risks, including enhanced skills‐based training and supervision, are discussed.     

基于代谢组学评价血液生物标志物对中枢神经系统肿瘤的诊断价值

目的 分析中枢神经系统肿瘤代谢组学图谱,评价小分子代谢物作为中枢神经系统肿瘤生物标志物的诊断价值.方法 本研究纳入126例中枢神经系统肿瘤患者和86例健康对照人群.通过液相色谱质谱联用技术(LC-MS/MS)检测血液中氨基酸和酰基肉碱,分析中枢神经系统肿瘤代谢组学图谱.用ROC曲线对小分子代谢物进行诊断效能分析.结果 中枢神经系统肿瘤代谢谱与健康人群有明显区别,19个指标有显著差异.肿瘤患者血液C2水平显著低于健康人群.Arg,C8和C18:2对中枢神经系统原发性肿瘤具有辅助诊断价值,ROC曲线下面积分别为0.868、0.895和0.756,灵敏度分别为82.6%、88.0%和60.9%,特异性分别为77.5%、80.8%和78.3%.结论 血液中小分子代谢物,包括氨基酸和酰基肉碱可作为中枢神经系统肿瘤辅助诊断新的生物标志物.     

阿片类药物呼吸抑制作用的机制研究进展

呼吸抑制是阿片类药物常见不良反应,其机制和治疗是目前临床中研究的重点。阿片类药物主要通过激动前包钦复合体和Kolliker-Fuse核(KF核)等处的μ阿片受体产生呼吸抑制作用。腺苷酸环化酶、G蛋白偶联内向整流钾通道(GIRK)以及电压门控钙通道等是阿片类药物影响呼吸的主要细胞信号传导机制。     

贝克抑郁量表第2版中文版在抑郁症患者中的信效度

目的:评估贝克抑郁量表第2版(Beck Depression Inventory-II,BDI-II)中文版的信度和效度。方法:方便选取142名复发性抑郁症患者完成BDI-II和汉密尔顿抑郁量表(HAMD)的测试,并随机抽取20名患者1周后进行BDI-II的重测。结果:BDI-II中文版的Cronbachα系数为0.94,各条目间的相关系数在0.18～0.71之间,各条目与BDI-II总分的相关系数在0.56～0.82之间,重测相关系数为0.55(P<0.05);BDI-II分与HAMD分呈正相关(r=0.67,P<0.01)。探索性因子分析显示BDI-II可提取躯体化-情感(13个条目)和认知(8个条目)2个因子。结论:贝克抑郁量表第2版中文版具有良好的信度与效度,能够作为自评工具用来评估抑郁症状严重度。     

穴位埋线配合文拉法辛治疗难治性抑郁症的对照研究

目的观察穴位埋线配合文拉法辛治疗难治性抑郁症的临床疗效。方法将80例抑郁症患者随机分成观察组(穴位埋线+药物)和对照组(药物),共观察6周,于治疗前、治疗后1,2,4,6周末采用汉密顿抑郁量表(HAMD),副反应量表(TESS)评定疗效及毒副反应。结果观察组与对照组治愈率比较,差异有显著性意义(χ2=5.05,P<0.05),两组HAMD评分,不良反应(TESS)评分比较,差异均有显著性意义(P<0.05)。结论埋线配合文拉法辛治疗难治性抑郁症是一种安全有效的方法,值得在临床上推广应用。     

Association between morningness‐eveningness,sleep duration,weekend catch‐up sleep and depression among Korean high‐school students

The present study aimed to examine the association between morningness‐eveningness preferences, sleep duration, weekend catch‐up sleep duration and depression among Korean high‐school students. A total of 8,655 high‐school students participated from 15 districts in South Korea and completed an online self‐report questionnaire. The following sleep characteristics were assessed: weekday and weekend sleep duration, weekend catch‐up sleep duration, morningness‐eveningness preference, perceived sufficiency of sleep, self‐reported snoring and sleep apnea, daytime sleepiness, and sleep environment. Age, gender, body mass index, number of private classes, proneness to internet addiction, and depressive mood were also evaluated. A logistic regression analysis was conducted to compute odds ratios for the association between depression and sleep characteristics, after controlling for relevant covariates. Eveningness preference was a significant predictor of depressive mood (adjusted OR, 1.71; 95% CI, 1.47–1.99). Weekend CUS durations that were ≥2 hr and enrollment in numerous private classes were associated with a lower risk for depression (0.68, 0.55–0.85; 0.76, 0.60–0.95; respectively). Female gender, underweight and obese body weight, short weekday sleep durations, excessive daytime sleepiness, perceived excessiveness and insufficiency of sleep, self‐reported snoring and sleep apnea, proneness to internet addiction and a non‐optimal sleep environment were associated with an increased risk for depression. Eveningness preference and insufficient weekday sleep duration were associated with an increased risk for depression. Weekend CUS duration ≥2 hr reduced the risk for depression. Diverse aspects, including sleeping habits and sleep‐related environmental factors, should be considered to reduce depressive symptoms in late adolescents.     

Dispositional optimism buffers combat veterans from the negative effects of warzone stress on mental health symptoms and work impairment

The study examined dispositional optimism s role in buffering the effect of warzone stress on mental health symptoms and mental health symptoms on work impairment. A total of 2,439 soldiers from an active-duty brigade combat team were surveyed following a 12-month deployment to Iraq. Posttraumatic stress disorder (PTSD) symptoms, depression symptoms, combat exposure, deployment demands, and work impairment were measured. Soldiers higher in dispositional optimism showed weaker relationships between combat exposure and PTSD symptoms, and between deployment demands and PTSD and depression symptoms. Dispositional optimism also buffered mental health symptom effects on work impairment. Dispositional optimism may protect soldiers from warzone stress and mental health symptoms. Potential mechanisms explaining how dispositional optimism may serve as a protective factor are discussed.     

Acceptability of a clinician-assisted computerized psychological intervention for comorbid mental health and substance use problems: treatment adherence data from a randomized controlled trial

Background

Computer-delivered psychological treatments have great potential, particularly for individuals who cannot access traditional approaches. Little is known about the acceptability of computer-delivered treatment, especially among those with comorbid mental health and substance use problems.

Objective

The objective of our study was to assess the acceptability of a clinician-assisted computer-based (CAC) psychological treatment (delivered on DVD in a clinic-setting) for comorbid depression and alcohol or cannabis use problems relative to a therapist-delivered equivalent and a brief intervention control.

Methods

We compared treatment acceptability, in terms of treatment dropout/participation and therapeutic alliance, of therapist-delivered versus CAC psychological treatment. We randomly assigned 97 participants with current depression and problematic alcohol/cannabis use to three conditions: brief intervention (BI, one individual session delivered face to face), therapist-delivered (one initial face-to-face session plus 9 individual sessions delivered by a therapist), and CAC interventions (one initial face-to-face session plus 9 individual CAC sessions). Randomization occurred following baseline and provision of the initial session, and therapeutic alliance ratings were obtained from participants following completion of the initial session, and at sessions 5 and 10 among the therapist-delivered and CAC conditions.

Results

Treatment retention and attendance rates were equal between therapist-delivered and CAC conditions, with 51% (34/67) completing all 10 treatment sessions. No significant differences existed between participants in therapist-delivered and CAC conditions at any point in therapy on the majority of therapeutic alliance subscales. However, relative to therapist-delivered treatment, the subscale of Client Initiative was rated significantly higher among participants allocated to the BI (F_2,54 = 4.86, P = .01) and CAC participants after session 5 (F_1,29 = 9.24, P = .005), and this domain was related to better alcohol outcomes. Linear regression modeled therapeutic alliance over all sessions, with treatment allocation, retention, other demographic factors, and baseline symptoms exhibiting no predictive value.

Conclusions

Participants in a trial of CAC versus therapist-delivered treatment were equally able to engage, bond, and commit to treatment, despite comorbidity typically being associated with increased treatment dropout, problematic engagement, and complexities in treatment planning. The extent to which a client feels that they are directing therapy (Client initiative) may be an important component of change in BI and CAC intervention, especially for hazardous alcohol use.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12607000437460; http://www.anzctr.org.au/trial_view.aspx?ID=82228 (Archived by WebCite at http://www.webcitation.org/5ubuRsULu)