Is Ankyrin a genetic risk factor for psychiatric phenotypes?

Background Genome wide association studies reported two single nucleotide polymorphisms in ANK3 (rs9804190 and rs10994336) as independent genetic risk factors for bipolar disorder. Another SNP in ANK3 (rs10761482) was associated with schizophrenia in a large European sample. Within the debate on common susceptibility genes for schizophrenia and bipolar disorder, we tried to investigate common findings by analyzing association of ANK3 with schizophrenia, bipolar disorder and unipolar depression. Methods We genotyped three single nucleotide polymorphisms (SNPs) in ANK3 (rs9804190, rs10994336, and rs10761482) in a case-control sample of German descent including 920 patients with schizophrenia, 400 with bipolar affective disorder, 220 patients with unipolar depression according to ICD 10 and 480 healthy controls. Sample was further differentiated according to Leonhard's classification featuring disease entities with specific combination of bipolar and psychotic syndromes. Results We found no association of rs9804190 and rs10994336 with bipolar disorder, unipolar depression or schizophrenia. In contrast to previous findings rs10761482 was associated with bipolar disorder (p = 0.015) but not with schizophrenia or unipolar depression. We observed no association with disease entities according to Leonhard's classification. Conclusion Our results support a specific genetic contribution of ANK3 to bipolar disorder though we failed to replicate findings for schizophrenia. We cannot confirm ANK3 as a common risk factor for different diseases

The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time.</p> <p>Methods</p> <p>Ninety-nine patients with non-small cell lung cancer (NSCLC) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical staining for CD68 (marker for macrophages), CD83 (marker for mature dendritic cells), and CD8 (marker for cytotoxic T cells) was performed and evaluated in a blinded fashion. The numbers of immune cells in tumor islets and stroma, tumor islets, or tumor stroma were counted under a microscope. Correlation of the cell numbers and patient's survival time was analyzed using the Statistical Package for the Social Sciences (version 13.0).</p> <p>Results</p> <p>The numbers of macrophages, mature dendritic cells and cytotoxic T cells were significantly more in the tumor stroma than in the tumor islets. The number of macrophages in the tumor islets was positively associated with patient's survival time, whereas the number of macrophages in the tumor stroma was negatively associated with patient's survival time in both univariate and multivariate analyses. The number of mature dendritic cells in the tumor islets and stroma, tumor islets only, or tumor stroma only was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets and stroma was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets only or stroma only was not associated with patient's survival time.</p> <p>Conclusions</p> <p>The number of macrophages in the tumor islets or stroma is an independent predictor of survival time in NSCLC patients. Counting macrophages in the tumor islets or stroma is more useful in predicting patient's survival time than counting mature dendritic cells or cytotoxic T cells.</p

Treatment of post-traumatic degenerative changes of the radio-carpal and distal radio-ulnar joints by combining radius, scaphoid, and lunate (RSL) fusion with ulnar head replacement

Distal radial fractures are a common type of fracture. In the case of intra-articular fractures, they often result in post-traumatic arthrosis. The objective of this study is to describe a novel alternative to the established salvage techniques for the treatment of post-traumatic arthrosis of the radio-carpal and distal radio-ulnar joints (DRUJ). Six patients with radio-carpal and DRUJ arthrosis were treated with a combined radius, scaphoid, and lunate (RSL) arthrodesis and as a Herbert ulnar head prosthesis. Follow-up consisted of both radiographic and functional assessments. Functional measurements were noted both pre- and postoperatively. No non-union or pseudoarthrosis was seen; neither did any of the ulnar head prostheses show loosening. Clinical examination showed an improvement in strength, pain, and range of movement, as well as a decrease in disability. Combining RSL arthrodesis with a Herbert ulnar head prosthesis, which deals with pain while retaining partial wrist movement, can be an alternative to established salvage procedures

Long-term effects of tongue piercing — a case control study

The aim of this study was to evaluate tooth and periodontal damage in subjects wearing a tongue piercing (TP) in comparison to matched control subjects without tongue piercing. Members of the German Federal Armed Forces who had TP (group TP) and a matched control group (group C) volunteered to take part in the study. The time in situ, localization and material of TP were documented. Dental examinations included DMF-T, oral hygiene, enamel fissures (EF), enamel cracks (EC) and recessions. Statistical analysis was determined by χ2 test and the t test. Both groups had 46 male subjects (mean age 22.1 years). The piercings had been in situ for 3.8 ± 3.1 years. Subjects in the TP group had a total of 1,260 teeth. Twenty-nine subjects had 115 teeth (9.1%) with EF (67% lingual). In group C (1,243 teeth), 30 subjects had 60 teeth with EF (4.8%, 78% vestibular) (p < 0.01). Thirty-eight subjects belonging to group TP had EC in 186 teeth (15%). In group C, 26 subjects with 56 teeth (4.5%) were affected by EC (p < 0.001). Twenty-seven subjects in group TP had 97 teeth (7.7%) with recessions. Lingual surfaces of anterior teeth in the lower jaw were affected most frequently (74%). In group C, 8 subjects had 19 teeth (1.5%) with recessions (65% vestibular). Differences between the two groups were statistically significant (p < 0.001). Tongue piercing is correlated with an increased occurrence of enamel fissures, enamel cracks and lingual recessions. Patients need better information on the potential complications associated with tongue piercing

Tunable Chemokine Production by Antigen Presenting Dendritic Cells in Response to Changes in Regulatory T Cell Frequency in Mouse Reactive Lymph Nodes

BACKGROUND: Although evidence exists that regulatory T cells (Tregs) can suppress the effector phase of immune responses, it is clear that their major role is in suppressing T cell priming in secondary lymphoid organs. Recent experiments using two photon laser microscopy indicate that dendritic cells (DCs) are central to Treg cell function and that the in vivo mechanisms of T cell regulation are more complex than those described in vitro. PRINCIPAL FINDINGS: Here we have sought to determine whether and how modulation of Treg numbers modifies the lymph node (LN) microenvironment. We found that pro-inflammatory chemokines -- CCL2 (MCP-1) and CCL3 (MIP-la) -- are secreted in the LN early (24 h) after T cell activation, that this secretion is dependent on antigen-specific DC-T cell interactions, and that it was inversely related to the frequency of Tregs specific for the same antigen. Furthermore, we demonstrate that Tregs modify the chemoattractant properties of antigen-presenting DCs, which, as the frequency of Tregs increases, fail to produce CCL2 and CCL3 and to attract antigen-specific T cells. CONCLUSIONS: These results substantiate a major role of Tregs in LN patterning during antigen-specific immune responses

Regulatory T cells and their role in rheumatic diseases: a potential target for novel therapeutic development

Regulatory T cells have an important role in limiting immune reactions and are essential regulators of self-tolerance. Among them, CD4+CD25high regulatory T cells are the best-described subset. In this article, we summarize current knowledge on the phenotype, function, and development of CD4+CD25high regulatory T cells. We also review the literature on the role of these T cells in rheumatic diseases and discuss the potential for their use in immunotherapy

Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits

Background Over the last several years, it has become apparent that there are critical problems with the hypothesis that brain dopamine (DA) systems, particularly in the nucleus accumbens, directly mediate the rewarding or primary motivational characteristics of natural stimuli such as food. Hypotheses related to DA function are undergoing a substantial restructuring, such that the classic emphasis on hedonia and primary reward is giving way to diverse lines of research that focus on aspects of instrumental learning, reward prediction, incentive motivation, and behavioral activation. Objective The present review discusses dopaminergic involvement in behavioral activation and, in particular, emphasizes the effort-related functions of nucleus accumbens DA and associated forebrain circuitry. Results The effects of accumbens DA depletions on food-seeking behavior are critically dependent upon the work requirements of the task. Lever pressing schedules that have minimal work requirements are largely unaffected by accumbens DA depletions, whereas reinforcement schedules that have high work (e.g., ratio) requirements are substantially impaired by accumbens DA depletions. Moreover, interference with accumbens DA transmission exerts a powerful influence over effort-related decision making. Rats with accumbens DA depletions reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead, these rats select a less-effortful type of food-seeking behavior. Conclusions Along with prefrontal cortex and the amygdala, nucleus accumbens is a component of the brain circuitry regulating effort-related functions. Studies of the brain systems regulating effort-based processes may have implications for understanding drug abuse, as well as energy-related disorders such as psychomotor slowing, fatigue, or anergia in depression

Personality psychology: Lexical approaches, assessment methods, and trait concepts reveal only half of the story—Why it is time for a paradigm shift

This article develops a comprehensive philosophy-of-science for personality psychology that goes far beyond the scope of the lexical approaches, assessment methods, and trait concepts that currently prevail. One of the field’s most important guiding scientific assumptions, the lexical hypothesis, is analysed from meta-theoretical viewpoints to reveal that it explicitly describes two sets of phenomena that must be clearly differentiated: 1) lexical repertoires and the representations that they encode and 2) the kinds of phenomena that are represented. Thus far, personality psychologists largely explored only the former, but have seriously neglected studying the latter. Meta-theoretical analyses of these different kinds of phenomena and their distinct natures, commonalities, differences, and interrelations reveal that personality psychology’s focus on lexical approaches, assessment methods, and trait concepts entails a) erroneous meta-theoretical assumptions about what the phenomena being studied actually are, and thus how they can be analysed and interpreted, b) that contemporary personality psychology is largely based on everyday psychological knowledge, and c) a fundamental circularity in the scientific explanations used in trait psychology. These findings seriously challenge the widespread assumptions about the causal and universal status of the phenomena described by prominent personality models. The current state of knowledge about the lexical hypothesis is reviewed, and implications for personality psychology are discussed. Ten desiderata for future research are outlined to overcome the current paradigmatic fixations that are substantially hampering intellectual innovation and progress in the field