External environmental agents influence telomere length and telomerase activity by modulating internal cellular processes: Implications in human aging

External environment affects cellular physiological processes and impact the stability of our genome. The most important structural components of our linear chromosomes which endure the impact by these agents, are the chromosomal ends called telomeres. Telomeres preserve the integrity of our genome by preventing end to end fusions and telomeric loss through by inhibiting DNA damage response (DDR) activation. This is accomplished by the presence of a six membered shelterin complex at telomeres. Further, telomeres cannot be replicated by normal DNA polymerase and require a special enzyme called telomerase which is expressed only in stem cells, few immune cells and germ cells. Telomeres are rich in guanine content and thus become extremely prone to damage arising due to physiological processes like oxidative stress and inflammation. External environmental factors which includes various physical, biological and chemical agents also affect telomere homeostasis by increasing oxidative stress and inflammation. In the present review, we highlight the effect of these external factors on telomerase activity and telomere length. We also discuss how the external agents affect the physiological processes, thus modulating telomere stability. Further, we describe its implication in the development of aging and its related pathologies.     

A computer-based expert system designs and analyzes a 2(k−p) fractional factorial design for the formulation optimization of novel multicomponent liposomes

A computer-based technique based on a 2^(k−p) fractional factorial design was applied for the optimization of recently described multicomponent protective liposomal formulations. These formulations contain sodium ascorbate (vitamin C) as a model drug sensitive to photochemical oxidation, as well as oil red O and/or oxybenzone as oil soluble light absorbers, incorporated into the lipid bilayers and sulisobenzone as a water soluble light absorber incorporated into the aqueous phase of liposomes. The three light absorbers (present or absent) incorporated in multilamellar liposomes and the drug in free or in complexed with α-cyclodextrin form comprised the four factors of the system. The stabilization ratio and the percentage entrapment in the liposomes of the vitamin were the two response variables of the system to be optimized. The entrapment values were calculated for all the materials either spectrophotometrically or by using second order derivative spectrophotometry. The response variables were predicted by multiple regression equations comprising combinations of the four formulation factors. Both the higher entrapment and the higher protection for the drug should characterize the optimum formulation.     

Elevated Rates of Restraint and Seclusion in Child and Adolescent Psychiatric Inpatients in China and Their Associated Factors

Child Psychiatry & Human Development - To investigate the rate of restraint and seclusion (R&S) use in child and adolescent psychiatric inpatients in China and to examine factors...     

Technological advances in psychotherapy: Implications for the assessment and treatment of obsessive compulsive disorder

Obsessive compulsive disorder (OCD) is a prevalent and costly condition that causes significant functional impairment and reduced quality of life. Although treatments with demonstrated efficacy for OCD, such as cognitive behavior therapy and antidepressants, have existed for over three decades, many patients remain inadequately treated or untreated. Challenges encountered in the treatment of OCD include problems with homework compliance, frequent relapse, difficulties in simulating the spontaneous nature of intrusive thoughts, and infrequent treatment sessions. Accumulated research now indicates that computerized assessment and therapy tools can significantly improve the cost/time-effectiveness of conventional psychotherapeutic interventions for anxiety disorders such as OCD without impairing therapeutic progress and outcome. In this paper we examine the potential of such technology, address current challenges in the assessment and treatment of OCD, and provide a rationale for future research in the field. We outline the general utility of computer technology in psychotherapeutic interventions, critically evaluate the existing literature on computer-assisted assessment and treatment specific to OCD, as well as discuss potential implications of portable technology for OCD treatment delivery and outcomes.     

Indoleamine 2,3-dioxygenase inhibition attenuates lipopolysaccharide induced persistent microglial activation and depressive-like complications in fractalkine receptor (CX3CR1)-deficient mice

An impaired ability to regulate the activation of microglia by fractalkine (CX₃CL1) leads to persistent neuroinflammation and behavioral alterations following lipopolysaccharide (LPS) challenge. While these responses are usually transient, LPS injection caused prolonged depressive-like behavior in fractalkine receptor deficient mice (CX₃CR1^−/−) that was associated with exaggerated microglial activation and induction of the tryptophan (TRP) degrading enzyme indoleamine 2,3-dioxygenase (IDO). IDO activation and subsequent generation of neuroactive kynurenine metabolites may have a pivotal role in the development of depression. Therefore, the purpose of this study was to determine the extent to which LPS-induced depressive-like behavior in CX₃CR1^−/− mice was dependent on IDO activation. CX₃CR1^−/− mice were implanted prior to LPS challenge with a slow release pellet of 1-methyl-tryptophan (1-MT), a competitive inhibitor of IDO. Here we show that the depressive-like behavior evident in CX₃CR1^−/− mice 72 h after LPS injection was abrogated by inhibition of IDO. LPS also decreased body weight and locomotor activity in CX₃CR1^−/− mice, but these effects were independent of 1-MT. Consistent with the increased metabolism of TRP by IDO, the ratio of 3-hydroxykynurenine (3-HK) to TRP was increased in the brain 72 h after LPS. Increased serotonin (5-HT) turnover was also evident in the brain. The LPS-associated increases in both 3-HK:TRP and 5-HIAA:5-HT ratios were prevented by the inhibition of IDO. Last, IDO blockade attenuated microglial activation in the prefrontal cortex and hippocampus 72 h after LPS. Collectively these data indicate that LPS-induced IDO activation contributes to persistent microglial activation and depressive-like behavior in CX₃CR1^−/− mice.     

131例神经梅毒患者临床特征及实验室检查结果分析

【摘要】 目的 深入了解神经梅毒在男女性之间以及有无神经症状患者之间的特征差异,为神经梅毒的防控、临床诊断与治疗提供依据。方法 回顾分析2015年6月至2019年12月安徽医科大学第一附属医院皮肤性病科131例神经梅毒住院患者的临床表现和实验室检查结果,根据性别以及神经/精神症状分组。组间比较采用独立双样本t检验或Mann?Whitney U检验,分类变量计数资料采用χ2检验和Fisher精确检验,比较不同组别之间临床特征及实验室指标差异。结果 131例患者中,无症状神经梅毒72例（无症状组）,有症状神经梅毒59例（有症状组）。有症状组的既往驱梅治疗比例（10.17%）显著低于无症状组（98.61%）（OR = 0.002,P < 0.001）。男性患者和有症状患者的首诊误诊率分别为50.00%和89.83%,分别高于女性患者（24.49%,OR = 3.08,P = 0.004）和无症状患者（0,OR = 13.00,P < 0.001）。男性有症状患者比例（57.32%）显著高于女性患者（14.64%）（OR = 4.14,P = 0.003）,脑脊液甲苯胺红不加热血清试验（TRUST）阳性率（52.44%）显著高于女性患者（26.54%）（OR = 3.05,P = 0.004）,脑脊液总蛋白含量升高（> 0.5 g/L）者的比例（79.27%）高于女性（59.18%）（OR = 2.64,P = 0.01）,脑脊液总蛋白含量［（0.76 ± 0.41） g/L］高于女性［（0.56 ± 0.25） g/L,P = 0.002］,并且男性脑部核磁共振成像异常检出率（72.22%）高于女性（44.90%）（OR = 2.13,P = 0.039）。有症状女性患者的确诊年龄［（50.82 ± 9.31）岁］大于无症状女性患者［（42.30 ± 12.18）岁］（P?=?0.038）。有症状神经梅毒患者脑脊液TRUST阳性率（55.93%）高于无症状患者（31.94%）（OR = 2.70,P = 0.006）,脑脊液总蛋白水平［（0.79 ± 0.46） g/L］显著高于无症状患者［（0.60 ± 0.24） g/L,P = 0.003］。结论 神经梅毒首诊误诊率高;男性患者病情较女性患者严重;既往驱梅治疗史、性别和年龄因素在神经梅毒病程发展过程中可能起一定作用。     

青少年抑郁障碍病人注意偏向特点

目的探讨青少年抑郁障碍病人对情绪面孔图片的注意偏向特点。方法选取65例符合ICD-10诊断标准的青少年抑郁障碍病人为抑郁组,以性别、年龄和受教育程度与之匹配的正常青少年55人作为对照组。采用点探测范式,对受试者进行注意偏向任务测评。结果抑郁组在中性、负性图片注意反应时均高于对照组(P<0.01), 抑郁组注意偏向值大于对照组(P<0.01),2组间注意反应准确率差异无统计学意义(P>0.05)。抑郁组中,负性注意反应时高于中性(P<0.05),对照组内两者反应时差异无统计学意义(P>0.05)。HAMD量表评分与抑郁组中性和负性注意反应时呈正相关关系(r=0.315, r=0.413, P<0.01)。结论青少年抑郁障碍病人对负性情绪图片存在注意偏向效应。     

Structural atlas-based spatial registration for functional near-infrared spectroscopy enabling inter-study data integration

ObjectiveThe use of functional near-infrared spectroscopy (fNIRS) is growing, leading to a need for methods to summarise data from multiple studies. However, this is difficult using the current channel-based methods when experiments do not share a common channel (CH) arrangement. Thus, we proposed and implemented a CH-independent analysis method for summarising fNIRS data.MethodsWe defined sub-regions as spatial bins to organise fNIRS data. Sub-regions were defined on the standard brain surface based on macro- and micro-structural information. After probabilistically estimating CH location in standard stereotaxic brain space, the CH-based data were reorganised into these spatial bins to evaluate sub-region-based activation.ResultsSub-regions with sizes corresponding to fNIRS spatial resolution were defined. We demonstrated this method by integrating data from two of our fNIRS studies that shared the same region of interest but used different channel arrangements.ConclusionsUsing this method, data from multiple fNIRS studies with different CH arrangements can be integrated in standard brain space, while keeping in mind the brain structure–function relationship.SignificanceThe current method will facilitate an effective use of accumulating fNIRS data by allowing integration of data from multiple studies.     

抑郁症病人睡眠结构特征与前瞻性记忆的相关性研究

目的探讨抑郁症病人睡眠结构特征及其与前瞻性记忆的相关性。方法选取 2017年 1月至 2020年 1月安徽省精神卫生中心 113例住院抑郁症病人作为抑郁组,同期该中心公开招募 47例健康者作为对照组,两组对象均行多导睡眠监测,评估汉密尔顿抑郁量表( HAMD)、汉密尔顿焦虑量表( HAMA)、基于事件的前瞻性记忆( EBPM)和基于时间的前瞻性记忆( TBPM),分析抑郁症病人睡眠结构与 EBPM和 TBPM的关系。结果相比于对照组,抑郁组快速眼动睡眠( REM)潜伏期( 235.52±83.65)min和卧床时间 507.00(49.25)min较对照组 REM潜伏期( 137.78±56.23)min和卧床时间 483.80(54.50)min长( P<0.05);抑郁组 EBPM评分 2.00(5.00)分和 TBPM评分 2.00(4.00)分较对照组的 EBPM 6.00(5.00)分和 TBPM 5.00(5.00)分少( P<0.05)。相关性分析显示,抑郁组 N2潜伏期与 TBPM呈正相关［ β=0.041,95%CI:(0.008,0.074)］,REM持续时间与 TBPM呈正相关［ β=0.024,95%CI:(0.010,0.039)］。模型加入性别、年龄、文化、体质量指数( BMI)、 HAMD、HAMA、病程等混杂因素后,多因素线性回归分析结果显示,抑郁组 REM持续时间仍与 TBPM呈正相关［ β=0.017,95%CI:(0.003,0.031)］;而 N2潜伏期与 TBPM的关联差异无统计学意义( P>0.05)。结论抑郁症病人存在睡眠结构异常和前瞻性记忆损害, TBPM与 REM持续时间呈正相关,且这种关联不受病人性别、年龄、文化、体质量指数、抑郁程度、焦虑程度和病程等的影响。