A developmental in vivo 1H NMR study in mice with genetic redox dysregulation: an animal model with relevance to schizophrenia

Glutathione (GSH), a major redox regulator and anti-oxidant, is decreased in cerebrospinal fluid and prefrontal cortex of schizophrenia patients. The gene of the key GSH-synthesizing enzyme, glutamate-cysteine ligase, modifier (GCLM) subunit, is associated with schizophrenia, suggesting that the deficit in the GSH system is of genetic origin. Using the GCLM knock-out (KO) mouse model with 60% decreased brain GSH levels, we have shown that redox dysregulation results in abnormal brain morphology and function. Current theory holds that schizophrenia is a developmental disease involving progressive anatomical and functional brain pathology. Here, we used GCLM KO mice to investigate the impact of a genetically dysregulated redox system on the neurochemical profile of the developing brain. The anterior and posterior cortical neurochemical profile of male and female GCLM KO, heterozygous and wildtype mice was determined by localised in vivo 1H NMR spectroscopy at 14.1 T (Varian/Magnex spectrometer) on post-natal days 10, 20, 30, 60 and 90. We show, for the first time, (1) that high quality 1H NMR spectra can be acquired from early developing mouse brains and (2) that recurrent anaesthesia by itself when administered at the same developmental days has no adverse effects on brain metabolites nor on adult behaviour. (3) Most importantly, our results reveal genotype and age specific changes for a number of metabolites revealing insight into normal brain development and about the impact of genetic GSH dysregulation.

Délire temporel systématisé et trouble auditif d'origine corticale [Systematized temporal delusion and hearing disorders of cortical origin].

We report a case of delusion characterized by a time disorientation with a constant three days advance. Five years previously, the patient had suffered a left hemisphere stroke with aphasia. The delusional belief appeared at the same time as a cortical deafness following a second right hemisphere infarction. There was severe behaviour disturbances which lasted seven months, then cleared without any other change in the clinical picture. The lesions involved the left parietal lobe as well as the temporal and insular regions of both hemispheres.

Motive-oriented therapeutic relationship in brief psychodynamic intervention for patients with depression and personality disorders.

Motive-Oriented Therapeutic Relationship (MOTR, also called Complementary Therapeutic Relationship) has already shown itself to be related to therapeutic outcome in several studies. The present study aims to test MOTR in a 4-session Brief Psychodynamic Intervention for patients presenting with major depressive disorder (MDD) and comorbid personality disorder (PD). In total, N = 20 patients were selected; n = 10 had MDD, n = 10 had MDD with comorbid PD. The first therapy session was videotaped and analyzed by means of Plan Analysis and the MOTR scale. Results suggest a differential effect on outcome: only the nonverbal component of MOTR is related to symptomatic change in patients presenting with MDD and comorbid PD; no such effect was found for patients with MDD alone. These results are discussed in line with the generalization and refinement of the conclusions of previous findings on the MOTR. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1-11, 2011.

Obésite, troubles alimentaires et groupe de parole à l'adolescence [Obesity, eating disorders and the group approach for adolescents].

About a third of obese adolescents also suffer from some kind of eating disorders which have to be recognized and included in the therapeutic frame. Besides this co-morbidity, most of these patients also require a psychological support. The group approach represents an adequate response to these problems, in providing a space for exchanges and an opportunity for mutual support. The group approach may even prove more beneficial than an individual treatment. Involving the parents too reinforces the improvement that adolescents can get from their participation in such groups.

Identification of novel elements of the Drosophila blisterome sheds light on potential pathological mechanisms of several human diseases.

Main developmental programs are highly conserved among species of the animal kingdom. Improper execution of these programs often leads to progression of various diseases and disorders. Here we focused on Drosophila wing tissue morphogenesis, a fairly complex developmental program, one of the steps of which - apposition of the dorsal and ventral wing sheets during metamorphosis - is mediated by integrins. Disruption of this apposition leads to wing blistering which serves as an easily screenable phenotype for components regulating this process. By means of RNAi-silencing technique and the blister phenotype as readout, we identify numerous novel proteins potentially involved in wing sheet adhesion. Remarkably, our results reveal not only participants of the integrin-mediated machinery, but also components of other cellular processes, e.g. cell cycle, RNA splicing, and vesicular trafficking. With the use of bioinformatics tools, these data are assembled into a large blisterome network. Analysis of human orthologues of the Drosophila blisterome components shows that many disease-related genes may contribute to cell adhesion implementation, providing hints on possible mechanisms of these human pathologies.

Work-related stress according to the demand-control model and minor psychic disorders in nursing workers

This was a cross-sectional study that aimed to assess the association between work-related stress according to the Demand-Control Model, and the occurrence of Minor Psychic Disorder (MPD) in nursing workers. The participants were 335 professionals, out of which 245 were nursing technicians, aged predominantly between 20 and 40 years. Data were collected using the Job Stress Scale and the Self-Reporting Questionnaire-20. The analysis was performed using descriptive and analytical statistics. The prevalence of suspected MPD was 20.6%. Workers classified in the quadrants active job and high strain of the Demand-Control Model presented higher potential for developing MPD compared with those classified in the quadrant low strain. In conclusion, stress affects the mental health of workers and the aspects related to high psychological demands and high control still require further insight in order to understand their influence on the disease processes of nursing workers.

Neuronal autophagy as a mediator of life and death: contrasting roles in chronic neurodegenerative and acute neural disorders.

Autophagy is a cellular mechanism for degrading proteins and organelles. It was first described as a physiological process essential for cellular health and survival, and this is its role in most cells. However, it can also be a mediator of cell death, either by the triggering of apoptosis or by an independent "autophagic" cell death mechanism. This duality is important in the central nervous system, where the activation of autophagy has recently been shown to be protective in certain chronic neurodegenerative diseases but deleterious in acute neural disorders such as stroke and hypoxic/ischemic injury. The authors here discuss these distinct roles of autophagy in the nervous system with a focus on the role of autophagy in mediating neuronal death. The development of new therapeutic strategies based on the manipulation of autophagy will need to take into account these opposing roles of autophagy.

Hospitalizations leading causes for maternal disorders

Presenting the rates of obstetric admissions of women living in Paraná in 2010.Method: A descriptive study in which the admission information of the hospital system of the Unified Health System was analyzed. Data from women aged between 10 to 49 years available on the DATASUS website were analyzed, using percentage and according to primary diagnosis, age and Regional Health area.Results: The Rate of Obstetric Complications (RtOC) was 38%, increasing with the age of women. Complications of labor and delivery (10.5%), and pregnancy with abortive outcome (9.1%) were the diagnoses with highest RtOC. The RtOC ranged between 8.4% in Telêmaco Borba, until 62.6% in Ponta Grossa.Conclusion: The healthcare team should monitor the rates of admissions for obstetric complications as these indicate the quality of health care of women, mainly focused on labor, delivery and women of older age.


Genetic counseling for individuals with hemoglobin disorders and for their relatives: a systematic literature review

Objective: To identify genetic counseling programs that do not encourage therapeutic abortion for individuals with hemoglobin disorders and/or for their relatives. Method: Systematic literature review of articles published from 2001 to 2012 that are located in the PubMed, LILACS, SciELO and SCOPUS databases using keywords in Portuguese, English and Spanish and that met the inclusion and exclusion criteria described on a standardized form. Results: A total of 409 articles were located, but only eight (1.9%) were selected for analysis. Conclusion: Although seldom mentioned in the literature, educational/preventive programs targeting hemoglobinopathies are feasible and allow the affected individuals to acquire knowledge on the consequences of this condition and their odds of transmitting it.



Interdisciplinary intervention for work-related musculoskeletal disorders

The proposed research aims to address the work-related MSD management issue through an interdisciplinary intervention involving clinical and occupational health competencies (rheumatology, occupational medicine, ergonomics). Workers enduring MSD (especially back-pain) and absent from work are selected from volunteering companies (construction, hospitals, public transport, delivery networks). The workers are randomly placed into two groups : the control group benefits from an usual MSD management strategy and the intervention group benefits from a case-management strategy including workhardening treatment (work oriented reeducation) and ergonomic intervention in the workplace. The comparison of health and work-related variables prior and after intervention in the two groups will be used to assess the intervention efficiency and its economic benefits. We expect to produce new strategies for the management of MSD and workplace rehabilitation as well as guidelines for both authorities and companies.

Difficulties of familes in caring for children and adolescents with mental disorders: an integrative review

Objective To identify the difficulties of families with children and/or adolescents with mental disorder. Method This is an integrative review. In December 2013, an electronic search was performed on Latin American Caribbean Literature on Health Sciences databases (LILACS) and on Electronic Medicus Index of the National Library of Medicine (MEDLINE) indexed in the Health Virtual Library (BVS) using a combination of descriptors and boolean operators as follows: mental disorders and child or adolescent and caregivers and/not health staff. Results 557 studies were identified, of which 15 were selected for this study. The findings indicated difficulties related to the care for or to interaction with children/adolescents with mental disorder. Conclusion The studies revealed difficulties related to everyday practices of care and feelings expressed during care practices, as well as in relationships with children or adolescents with mental disorder.



Massage with aromatherapy: effectiveness on anxiety of users with personality disorders in psychiatric hospitalization

OBJECTIVE To investigate the effectiveness of aromatherapy massage using the essential oils (0.5%) of Lavandula angustifolia and Pelargonium graveolens for anxiety reduction in patients with personality disorders during psychiatric hospitalization. METHOD Uncontrolled clinical trial with 50 subjects submitted to six massages with aromatherapy, performed on alternate days, on the cervical and the posterior thoracic regions. Vital data (heart and respiratory rate) were collected before and after each session and an anxiety scale (Trait Anxiety Inventory-State) was applied at the beginning and end of the intervention. The results were statistically analyzed with the chi square test and paired t test. RESULTS There was a statistically significant decrease (p < 0.001) of the heart and respiratory mean rates after each intervention session, as well as in the inventory score. CONCLUSION Aromatherapy has demonstrated effectiveness in anxiety relief, considering the decrease of heart and respiratory rates in patients diagnosed with personality disorders during psychiatric hospitalization.

Violence, Burnout and Minor Psychiatric Disorders in Hospital Work

OBJECTIVE Identifying the violence suffered by the health team workers and their association with Burnout and minor psychiatric disorders. METHODS Cross-sectional study with 269 health team professionals of a public hospital in southern Brazil. Data were collected through the use of the Survey Questionnaire: Workplace Violence in the Health Sector, Maslach Inventory Burnout and Self-Report Questionnaire. RESULTS Workplace violence struck 63.2% of workers, prevailing mostly in women (p = 0.001), among nursing auxiliaries/technicians (p=0.014) and was associated with minor psychiatric disorders (p<0.05), as exposure to different forms of violence increased the chances of these disorders by 60% (CI 95%: 1.2-2.1). The three Burnout dimensions were also associated to violence at work (p<0.05). CONCLUSION Health workers experience violence in the workplace and this exposure is associated with Burnout symptoms and minor psychiatric disorders.

Developmental stage-specific expression of cyclic adenosine 3',5'-monophosphate response element-binding protein CREB during spermatogenesis involves alternative exon splicing.

Spermatogenesis is a temporally regulated developmental process by which the gonadotropin-responsive somatic Sertoli and Leydig cells act interdependently to direct the maturation of the germinal cells. The metabolism of Sertoli and Leydig cells is regulated by the pituitary gonadotropins FSH and LH, which, in turn, activate adenylate cyclase. Because the cAMP-second messenger pathway is activated by FSH and LH, we postulated that the cAMP-responsive element-binding protein (CREB) plays a physiological role in Sertoli and Leydig cells, respectively. Immunocytochemical analyses of rat testicular sections show a remarkably high expression of CREB in the haploid round spermatids and, to some extent, in pachytene spermatocytes and Sertoli cells. Although most of the CREB antigen is detected in the nuclei, some CREB antigen is also present in the cytoplasm. Remarkably, the cytoplasmic CREB results from the translation of a unique alternatively spliced transcript of the CREB gene that incorporates an exon containing multiple stop codons inserted immediately up-stream of the exons encoding the DNA-binding domain of CREB. Thus, the RNA containing the alternatively spliced exon encodes a truncated transcriptional transactivator protein lacking both the DNA-binding domain and nuclear translocation signal of CREB. Most of the CREB transcripts detected in the germinal cells contain the alternatively spliced exon, suggesting a function of the exon to modulate the synthesis of CREB. In the Sertoli cells we observed a striking cyclical (12-day periodicity) increase in the levels of CREB mRNA that coincides with the splicing out of the restrictive exon containing the stop codons. Because earlier studies established that FSH-stimulated cAMP levels in Sertoli cells are also cyclical, and the CREB gene promoter contains cAMP-responsive enhancers, we suggest that the alternative RNA splicing controls a positive autoregulation of CREB gene expression mediated by cAMP.

Copy number variation characteristics in subpopulations of patients with autism spectrum disorders.

Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic etiology. We used high-resolution whole genome array-based comparative genomic hybridization (array-CGH) to screen 223 ASD patients for gene dose alterations associated with susceptibility for autism. Clinically significant copy number variations (CNVs) were identified in 18 individuals (8%), of which 9 cases (4%) had de novo aberrations. In addition, 20 individuals (9%) were shown to have CNVs of unclear clinical relevance. Among these, 13 cases carried rare but inherited CNVs that may increase the risk for developing ASDs, while parental samples were unavailable in the remaining seven cases. Classification of all patients into different phenotypic and inheritance pattern groups indicated the presence of different CNV patterns in different patient groups. Clinically relevant CNVs were more common in syndromic cases compared to non-syndromic cases. Rare inherited CNVs were present in a higher proportion of ASD cases having first- or second-degree relatives with an ASD-related neuropsychiatric phenotype in comparison with cases without reported heredity (P = 0.0096). We conclude that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for the development of ASDs and related neuropsychiatric disorders giving us further insight into the complex genetics underlying ASDs.