Protein kinases as targets for interventive biogerontology: overview and perspectives

Protein kinases are enzymes that catalyze the transfer of γ phosphate from adenosine triphosphate to substrate proteins, and are important signal transduction mediators in a diversity of biological processes, ranging from apoptosis to energy metabolism. In this article, we will take this prominent class of proteins as an example to illustrate the involvement of proteins in modulation of aging and to highlight the prospects and challenges of protein-targeted interventions for anti-aging purposes. It is hoped that through this article, more empirical work on interventive gerontology will follow, and with collaborative endeavors among researchers, hurdles in anti-aging intervention development can be overcome in the near future.     

系统性红斑狼疮患者外周血白细胞双链RNA依赖蛋白激酶基因表达

 目的 通过检测系统性红斑狼疮（SLE）患者外周血白细胞双链RNA依赖蛋白激酶（PKR）基因表达水平,探讨其与SLE临床及病情活动的相关性。方法 分离100例SLE患者、40例非SLE患者、40例健康人外周血白细胞,抽提总RNA并逆转录成cDNA,实时定量PCR检测所有受试者PKR基因表达水平,并进行相关性分析。以2^-ΔCt代表PKR mRNA的起始拷贝量。结果 （1）SLE患者PKR mRNA起始拷贝量（14.69±7.62）高于非SLE患者（5.09±4.73;P=0.012）和健康人（4.79±3.49;P=0.005）,差异有统计学意义。（2）SLE疾病活动指数（SLEDAI）≥15分的SLE患者PKR mRNA起始拷贝量为22.57±2.61,明显高于SLEDAI≤4分（8.85±2.17;P=0.000）和SLEDAI 5～14分的SLE患者（12.94±2.41;P=0.000）。（3）有狼疮肾炎的SLE患者PKR mRNA起始拷贝量（16.85±7.32）高于无狼疮肾炎的SLE患者（8.35±2.04;P=0.034）。（4）SLE患者PKR mRNA起始拷贝量与SLEDAI、外周血白细胞计数、24 h尿蛋白、血清HDL-C呈正相关（r=0.32, P=0.000;r=0.46,P=0.000;r=0.21,P=0.000;r=0.21,P=0.022）,与Hb、抗核糖核蛋白（RNP）抗体水平呈负相关（r=-0.22,P=0.035;r_s=-0.21,P=0.025）。结论 SLE患者外周血白细胞PKR基因表达上调,且在重度SLE患者中更明显,提示PKR基因可能与狼疮的发病相关。     

S100B and schizophrenia

The research for peripheral biological markers of schizophrenia, although abundant, has been unfruitful. In the last 2 decades, the S100B protein has made its own room in this area of research. S100B is a calcium‐binding protein that has been proposed as a marker of astrocyte activation and brain dysfunction. Research results on S100B concentrations and schizophrenia clinical diagnosis are very consistent; patients with schizophrenia have higher S100B concentrations than healthy controls. The results regarding schizophrenia subtypes and clinical characteristics are not as conclusive. Age of patients, body mass index, illness duration and age at onset have been found to show no correlation, a positive correlation or a negative correlation with S100B levels. With respect to psychopathology, S100B data are inconclusive. Positive, negative and absence of correlation between S100B concentrations and positive and negative psychopathology have been reported. Methodological biases, such as day/night and seasonal variations, the use of anticoagulants to treat biological samples, the type of analytical technique to measure S100B and the different psychopathological scales to measure schizophrenia symptoms, are some of the factors that should be taken into account when researching into this area in order to reduce the variability of the reported results. The clinical implications of S100B changes in schizophrenia remain to be elucidated.     

What are the critical incidents that affect how people cope with being detained under Section 136 of the Mental Health Act (1983, 2007)?

Abstract

Purpose: Section 136 (S136) of the Mental Health Act (1983, 2007) provides legislative powers for police officers to detain those suspected of being ‘mentally disordered’ for a mental health assessment. Despite its increasing use, there is currently little qualitative research exploring detainee’s experiences.

Methodology: Participants recruited from NHS places of safety participated in a semi-structured interview. The novel application of Critical Incident Technique (CIT) within this study enabled the specific identification of critical incidents which mental health service users thought had either helped with, or worsened the S136 detention experience. A wish list of absent factors was also gathered.

Findings: Six categories of helpful critical incidents, seven categories of unhelpful critical incidents and five categories of wish-list items were identified. The importance of authentic relationships underpinned many categories, as well as challenging stigma, considering previous detentions; and receiving practical support.

Originality/value: The outlined study is the first of its kind to utilise CIT methodology to specifically identify critical incidents related to the process of S136 detention. These findings provide specific ways to improve the experience of detention informed directly by those who have been directly subjected to S136.

• Key points

• Take time to invest in meaningful relationships with those who are detained; asking about the individual’s life experience and their perception of its relationship to their current presenting difficulties.

• Identify the service user’s values -what’s important to them, and what gives meaning to their life – and discuss this in relation to what their worries, concerns or wishes may be for treatment.

• Discuss previous experiences of involuntary admission- this can support all parties involved to consider the impact of detention upon the individual, and services.

• Use problem-free discussions to normalise and help de-stigmatise mental health difficulties and support rapport building.

• Provide practical support, such as food, drink and routinely allow those who are detained to gather personal belongings such as a change of clothes or a book.

• Ensure advocacy services are always available and accessible for those who are detained under S136.

• Where possible, avoid the use of restrictive or stigmatising practices in front of the public where possible (e.g. use of handcuffs, police vehicles as transport) to minimise risk of increasing mental health stigma.

     

The Psychometric Properties and Correlates of the Reynolds' Suicide Ideation Questionnaire with Kuwaiti and American Students

In samples of Kuwaiti (n = 460) and American (n = 273) college students, the Reynolds Suicide Ideation Questionnaire (SIQ) proved to have good internal consistency and concurrent validity with measures of anxiety, optimism, pessimism, death obsession, obsession-compulsion, and ego-grasping. The SIQ was factorially complex in both samples, but the eight critical items showed a similar two-factor pattern in both samples. It is important to note that in spite of the great differences between Kuwait and US students and their cultures, the findings were quite similar. By and large, the psychological correlates of the SIQ may have cross-cultural generality.     

Ruthenium Red Colorimetric and Birefringent Staining of Amyloid-β Aggregates in Vitro and in Tg2576 Mice

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Tonic regulation of vascular permeability

Our major theme is that the layered structure of the endothelial barrier requires continuous activation of signalling pathways regulated by sphingosine‐1‐phosphate (S1P) and intracellular cAMP. These pathways modulate the adherens junction, continuity of tight junction strands, and the balance of synthesis and degradation of glycocalyx components. We evaluate recent evidence that baseline permeability is maintained by constant activity of mechanisms involving the small GTPases Rap1 and Rac1. In the basal state, the barrier is compromised when activities of the small GTPases are reduced by low S1P supply or delivery. With inflammatory stimulus, increased permeability can be understood in part as the action of signalling to reduce Rap1 and Rac1 activation. With the hypothesis that microvessel permeability and selectivity under both normal and inflammatory conditions are regulated by mechanisms that are continuously active, it follows that when S1P or intracellular cAMP are elevated at the time of inflammatory stimulus, they can buffer changes induced by inflammatory agents and maintain normal barrier stability. When endothelium is exposed to inflammatory conditions and subsequently exposed to elevated S1P or intracellular cAMP, the same processes restore the functional barrier by first re‐establishing the adherens junction, then modulating tight junctions and glycocalyx. In more extreme inflammatory conditions, loss of the inhibitory actions of Rac1‐dependent mechanisms may promote expression of more inflammatory endothelial phenotypes by contributing to the up‐regulation of RhoA‐dependent contractile mechanisms and the sustained loss of surface glycocalyx allowing access of inflammatory cells to the endothelium.     

The effect of two different bracket types on the salivary levels of S mutans and S sobrinus in the early phase of orthodontic treatment

Objective:To determine the difference in the levels of Streptococcus mutans and S sobrinus in stimulated saliva in orthodontic patients with different bracket types (stainless steel and esthetic brackets) using polymerase chain reaction and cultivation method.Materials and Methods:Thirty-two patients, aged 13 to 30 years, were selected following these criteria: 1) orthodontic treatment indication, 2) systemic health, and 3) no tobacco and antibiotic consummation for three months prior to the commencement of the study. Patients were divided into two groups according to the bracket type; 16 patients formed the conventional bracket group (stainless steel brackets), and 16 patients formed the esthetic bracket group (plastic brackets). The levels of S mutans and S sobrinus in stimulated whole saliva samples were collected prior to fixed orthodontic appliance placement (T1) and 12 weeks after placement (T2), as were the Decayed, Missing, and Filled Surface Index (DMFS) and Oral Hygiene Index-Simplified (OHI-S). Mann-Whitney, Wilcoxon, and chi-square tests were used for statistical analysis.Results:Statistical analysis (chi-square test) showed no difference in S mutans and S sobrinus counts among patients with different brackets at either T1 or T2. There was no difference in total bacteria counts after fixed orthodontic appliance placement.Conclusion:The number of colony-forming units of S mutans and S sobrinus in stimulated saliva samples does not seem to be significantly different between patients with stainless steel brackets and patients with plastic brackets.