Síndrome de burnout e ansiedade em trabalhadores em saúde mental: enfrentando uma realidade silenciosa / Burnout syndrome and anxiety in mental health workers: facing a silent reality / Síndrome de burnout y ansiedad en los trabajadores de salud mental: enfrentando una realidad silenciosa

Introdução:Os trabalhadores em saúde mental são expostos a situações adversas e estressantes, agravadas por um constante estado de excitabilidade e atenção, sendo conhecido aumento na incidência da Sídrome de Burnout e de ansiedade nesse grupo.Objetivo:avaliar a prevalência da Síndrome na amostra e suas correlações com outras variáveis.Metodologia:Estudo transversal, observacional, onde 142 trabalhadores de um hospital psiquiátrico foram entrevistados por meio de três questionários: sociocultural, Maslach Burnout Inventory eBeck Anxiety Inventory. Os dados foram tabulados e analisados por meio do teste de qui-quadrado, com valor de p significativo <0,05.Resultados:na amostra, a maioria era mulher, com média de idade 50 anos e média de 14 anos de trabalho nesse hospital. 55 trabalhadores apresentaram Burnout (pelo menos um critério comprometido), sendo 18 com diminuição da esfera de realização pessoal, 41 com exaustão emocionale 23 sofrendo de despersonalização. Foi encontrada uma relação da Síndrome de Burnout com elevados níveis de ansiedade (p=0.0008). Conclusões:O grupo com maiores níveis de ansiedade mostraram pior estados emocional e de saúde mental, associado à incidência da Síndrome de Burnout (AU).

Introduction:Mental health workers are exposed to adverse and stressful situations, aggravated by a constant state of excitability and attention, with an increase in the incidence of Burnout Syndrome and anxiety in this group.Objective:to evaluate the prevalence of the Syndromein the sample and its correlations with other variables.Methodology:Cross-sectional, observational study, where 142 workers from a psychiatric hospital were interviewed using three questionnaires: sociocultural, Maslach Burnout Inventory and Beck Anxiety Inventory. The data were tabulated and analyzed using the chi-square test, with a significant p-value <0.05.Results:in the sample, most were women, with an average age of 50 years and an average of 14 years of work at this hospital. 55 workers had Burnout (at least one compromised criterion), 18 with reduced personal achievement, 41 with emotional exhaustion and 23 suffering from depersonalization. A relationship between Burnout Syndrome and high levels of anxiety was found (p = 0.0008). Conclusions:The group with the highest levels of anxiety showed worse emotional and mental health states, associated with the incidence of Burnout Syndrome (AU).

Introducción: Los trabajadores de salud mental están expuestos a situaciones adversas y estresantes, agravadas por un estado constante de excitabilidad y atención, con un aumento de la incidencia del Síndrome de Burnout y ansiedad en este grupo.Objetivo: evaluar la prevalencia de la Síndromeen la muestra y sus correlaciones con otras variables. Metodología: Estudio observacional transversal, en el que se entrevistó a 142 trabajadores de un hospital psiquiátrico mediante tres cuestionarios: sociocultural, Maslach Burnout Inventory y Beck Anxiety Inventory. Los datos se tabularon y analizaron mediante la prueba de chi-cuadrado, con un valor de p significativo <0,05. Resultados: en la muestra, la mayoría eran mujeres, con una edad media de 50 años y una media de 14 años de trabajo en este hospital. 55 trabajadores tenían Burnout (al menos un criterio comprometido), 18 con logro personal reducido, 41 con agotamiento emocional y 23 con despersonalización. Se encontró relación entre el Síndrome de Burnout y altos niveles de ansiedad (p = 0,0008). Conclusiones: El grupo con mayores niveles de ansiedad presentó peoresestados emocionales y de salud mental, asociados a la incidencia del Síndrome de Burnout (AU).

Mobile applications for sexual encounters accessed by men who have sex with men: Information on sexually transmitted infection.

We evaluated existing mobile applications (apps) on both Android and iOS (Apple) platforms that are used by men who have sex with men (MSM) to obtain sexual encounters. The word "gay" was used to search for apps in the Apple and Google Play virtual stores. The 10 most downloaded apps were analysed concerning safe sexual practices (SSP) messages. Out of 245 apps selected, 213 were evaluated - 102 for Android and 111 for iOS. Mostly social networks were accessed by MSM of which 112 allow access to people aged 14 and over. Most of the apps could be downloaded in more than two languages. Of the 10 most downloaded and evaluated apps, 5 had no HIV/STI and SSP messages, only 3 contained HIV/STI and SSP messages, and 2 had information about one or the other. Several social networking apps are available, however, there is no information on HIV/STI in the most accessed apps.

Multivariate analysis reveals differentially expressed genes among distinct subtypes of diffuse astrocytic gliomas: diagnostic implications.

Diagnosis and classification of gliomas mostly relies on histopathology and a few genetic markers. Here we interrogated microarray gene expression profiles (GEP) of 268 diffuse astrocytic gliomas-33 diffuse astrocytomas (DA), 52 anaplastic astrocytomas (AA) and 183 primary glioblastoma (GBM)-based on multivariate analysis, to identify discriminatory GEP that might support precise histopathological tumor stratification, particularly among inconclusive cases with II-III grade diagnosed, which have different prognosis and treatment strategies. Microarrays based GEP was analyzed on 155 diffuse astrocytic gliomas (discovery cohort) and validated in another 113 tumors (validation set) via sequential univariate analysis (pairwise comparison) for discriminatory gene selection, followed by nonnegative matrix factorization and canonical biplot for identification of discriminatory GEP among the distinct histological tumor subtypes. GEP data analysis identified a set of 27 genes capable of differentiating among distinct subtypes of gliomas that might support current histological classification. DA + AA showed similar molecular profiles with only a few discriminatory genes overexpressed (FSTL5 and SFRP2) and underexpressed (XIST, TOP2A and SHOX2) in DA vs AA and GBM. Compared to DA + AA, GBM displayed underexpression of ETNPPL, SH3GL2, GABRG2, SPX, DPP10, GABRB2 and CNTN3 and overexpression of CHI3L1, IGFBP3, COL1A1 and VEGFA, among other differentially expressed genes.

Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival.

BACKGROUND: The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial. METHODS: We investigated the RNA gene expression profile of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), murine doble minute 4 (MDM4), and platelet derived growth factor receptor alpha (PDGFRA) in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in EGFR and PDGFRA, were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied. RESULTS: At the RNA level, CDK4 was the most frequently overexpressed gene (90%) followed by EGFR (58%) and PDGFRA (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with EGFR gene expression levels. In turn, intragenic EGFR deletions were found in 39 patients (47%), including EGFRvIII (46%) in association with EGFRvIVa (4%), EGFRvII (2%) or other EGFR deletions (3%) and PDGFRA deletion of exons 8-9 was found in only two tumors (2%). CONCLUSIONS: Overall, none of the gene expression profiles and/or intragenic EGFR deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM.

Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles.

Several classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region - either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management.

Correlação entre vaginose bacteriana e desfechos obstétricos desfavoráveis em mulheres brasileiras / Correlation between bacterial vaginosis and adverse obstetric outcomes in Brazilian women

Infecções vaginais e mudanças na flora vaginal são prevalentes durante a gravidez e têm sido associadas com desfechos obstétricos adversos, tais como trabalho de parto prematuro, amniorrexe prematura e baixo peso ao nascer. Objetivos: Correlacionar a presença de vaginose bacteriana (VB) com desfecho obstétrico desfavorável em mulheres brasileiras com gravidez no terceiro trimestre. Métodos: O estudo prospectivo observacional foi conduzido avaliando microbiota vaginal por bacterioscopia (a fresco e Gram) usando swab vaginal obtido de mulheres grávidas entre a 26 e a 32a semanas de gestação. As mulheres foram monitoradas até o parto, e os dados de seu seguimento e os demográficos foram coletados por meio de um questionário autoaplicável. Resultados: Foi diagnosticada VB, com base nos critérios de Amsel e de Nugent, em 77 mulheres entre as 190, demonstrando prevalência de 42.5%. VB foi significativamente associada com maior risco de parto prematuro (risk ratio [RR], 2.89; 95% intervalo de confiança [IC], 2.35­3.56) e de baixo peso ao nascer (RR, 2.17; 95%IC, 1.61­2.92). A rotura prematura das membranas não foi associada com VB. Conclusão: Foi constatada alta frequência de VB entre as mulheres brasileiras grávidas no terceiro trimestre, e a BV correlacionou-se com piores prognósticos da gravidez. O rastreio rotineiro de mulheres grávidas pode permitir um tratamento precoce e a prevenção de algumas complicações obstétricas

Vaginal infections and modifications in the vaginal flora are very prevalent during pregnancy and have been associated with adverse obstetric outcomes, such as preterm labor, preterm premature rupture of membranes and low birth weight. Objective: To evaluate the prevalence and associations of bacterial vaginosis (BV) and pregnancy outcomes among Brazilian pregnant women in the third trimester. Methods: A prospective observational study was conducted assessing vaginal microbiota on bacterioscopy (wet mount and Gram stain), using vaginal swabs obtained from pregnant women between 26 and 32 weeks' gestation. The women were monitored until delivery, and their pregnancy outcome and demographic data were collected using an interviewer-administered questionnaire. Results: BV was assessed using both Amsel's criteria and Nugent's score in 77 of 190 women, resulting in the prevalence of 42.5%. BV was significantly associated with preterm labor (risk ratio [RR], 2.89; 95% confidence interval [CI], 2.35­3.56) and low birth weight (RR, 2.17; 95%CI, 1.61­2.92). Premature rupture of membranes was not associated with BV. Conclusion: BV was found to be very frequent among Brazilian pregnant women in the third trimester and correlated to unfortunate pregnancy outcomes. Regular screening of pregnant women may allow for early treatment and prevention of some obstetric complications.

Amplified and homozygously deleted genes in glioblastoma: impact on gene expression levels.

BACKGROUND: Glioblastoma multiforme (GBM) displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown. METHODOLOGY: Single-nucleotide polymorphism (SNP)-arrays were used to determine the frequency of recurrent amplicons and homozygous deletions in GBM (n = 46), and to evaluate the impact of copy number alterations (CNA) on mRNA levels of the genes involved. PRINCIPAL FINDINGS: Recurrent amplicons were detected for chromosomes 7 (50%), 12 (22%), 1 (11%), 4 (9%), 11 (4%), and 17 (4%), whereas homozygous deletions involved chromosomes 9p21 (52%) and 10q (22%). Most genes that displayed a high correlation between DNA CNA and mRNA levels were coded in the amplified chromosomes. For some amplicons the impact of DNA CNA on mRNA expression was restricted to a single gene (e.g., EGFR at 7p11.2), while for others it involved multiple genes (e.g., 11 and 5 genes at 12q14.1-q15 and 4q12, respectively). Despite homozygous del(9p21) and del(10q23.31) included multiple genes, association between these DNA CNA and RNA expression was restricted to the MTAP gene. CONCLUSIONS: Overall, our results showed a high frequency of amplicons and homozygous deletions in GBM with variable impact on the expression of the genes involved, and they contributed to the identification of other potentially relevant genes.

Detailed characterization of alterations of chromosomes 7, 9, and 10 in glioblastomas as assessed by single-nucleotide polymorphism arrays.

Glioblastomas are cytogenetically heterogeneous tumors that frequently display alterations of chromosomes 7, 9p, and 10q. We used high-density (500K) single-nucleotide polymorphism arrays to investigate genome-wide copy number alterations and loss of heterozygosity in 35 primary glioblastomas. We focused on the identification and detailed characterization of alterations involving the most frequently altered chromosomes (chromosomes 7, 9, and 10), the identification of distinct prognostic subgroups of glioblastomas based on the cytogenetic patterns of alteration for these chromosomes, and validation of their prognostic impact in a larger series of tumors from public databases. Gains of chromosome 7 (97%), with or without epidermal growth factor receptor (EGFR) amplification, and losses of chromosomes 9p (83%) and 10 (91%) were the most frequent alterations. Such alterations defined five different cytogenetic groups with a significant effect on patient survival; notably, EGFR amplification (29%) was associated with a better survival among older patients, as confirmed by multivariate analysis of a larger series of glioblastomas from the literature. In addition, our results provide further evidence about the relevance of other genes (eg, EGFR, CDKN2A/B, MTAP) in the pathogenesis of glioblastomas. Altogether, our results confirm the cytogenetic heterogeneity of glioblastomas and suggest that their stratification based on combined assessment of cytogenetic alterations involving chromosomes 7, 9, and 10 may contribute to the prognostic evaluation of glioblastomas.

Gene expression profiles of human glioblastomas are associated with both tumor cytogenetics and histopathology.

Despite the increasing knowledge about the genetic alterations and molecular pathways involved in gliomas, few studies have investigated the association between the gene expression profiles (GEP) and both cytogenetics and histopathology of gliomas. Here, we analyzed the GEP (U133Plus2.0 chip) of 40 gliomas (35 astrocytic tumors, 3 oligodendrogliomas, and 2 mixed tumors) and their association with tumor cytogenetics and histopathology. Unsupervised and supervised analyses showed significantly different GEP in low- vs high-grade gliomas, the most discriminating genes including genes involved in the regulation of cell proliferation, apoptosis, DNA repair, and signal transduction. In turn, among glioblastoma multiforme (GBM), 3 subgroups of tumors were identified according to their GEP, which were closely associated with the cytogenetic profile of their ancestral tumor cell clones: (i) EGFR amplification, (ii) isolated trisomy 7, and (iii) more complex karyotypes. In summary, our results show a clear association between the GEP of gliomas and tumor histopathology; additionally, among grade IV astrocytoma, GEP are significantly associated with the cytogenetic profile of the ancestral tumor cell clone. Further studies in larger series of patients are necessary to confirm our observations.

Intratumoral patterns of clonal evolution in gliomas.

Few studies have explored the patterns of clonal evolution in gliomas. Here, we investigate the cytogenetic patterns of intratumoral clonal evolution of gliomas and their impact on tumor histopathology and patient survival. Cytogenetic analysis of 90 gliomas was performed in individual tumor cells (>200 cells/tumor) using multicolor (N = 16 probes) interphase-FISH. Overall, chromosome gains were more frequent than chromosome losses. Gains of chromosome 7 and/or EGFR amplification were detected in 91% of the cases, whereas del(9p21) (77%) and del(10q23) (78%) were the most frequent chromosome losses. Virtually, all cases (99%) showed >or=2 tumor cell clones, with higher numbers among high- versus low-grade gliomas (p = 0.001). Nine different cytogenetic patterns were found in the ancestral tumor clones. In most gliomas, ancestral clones showed abnormalities of chromosome 7, 9p, and/or 10q and cytogenetic evolution consisted of acquisition of additional abnormalities followed by tetraploidization. Conversely, early tetraploidization was associated with low-grade astrocytomas-2/3 pilocytic and 3/6 grade II diffuse astrocytomas-and combined loss of 1p36/19q13 with oligodendrogliomas, respectively; both aberrations were associated with a better patient outcome (p = 0.03). Overall, our results support the existence of different pathways of intratumoral evolution in gliomas.

The sensitizers nickel sulfate and 2,4-dinitrofluorobenzene increase CD40 and IL-12 receptor expression in a fetal skin dendritic cell line.

Dendritic cells (DCs) are antigen-presenting cells (APCs) capable of capturing haptens and to process and present them to T lymphocytes. In order to sensitize T cells for contact hypersensitivity (CHS), skin DCs suffer a maturation process with modifications on their surface molecules. The aim of this work was to evaluate changes induced by two contact sensitizers, 2,4-dinitrofluorobenzene (DNFB) and nickel sulfate (NiSO4), and a non-sensitizer 2,4-dichloronitrobenzene (DCNB), on the protein levels of two activation markers, CD40 and IL-12 receptor (IL-12R), in a mouse skin dendritic cell line (FSDC). The expression of CD40 and IL-12R proteins was evaluated by western blot assay and direct immunofluorescence microscopy. The results showed that CD40 and IL-12R expression increased significantly after cell exposure to NiSO4 and DNFB, although DNFB exhibited a stronger activity. There was no effect with DCNB. The epidermal cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), also used in the experiments, slightly increased the expression of both CD40 and IL-12R and when tested together with the sensitizers the effect was partially additive. The results suggest that the sensitizers DNFB and NiSO4 are directly involved on the changes of the surface markers CD40 and IL-12R in skin DCs, during the sensitization phase of CHS, and this effect may be enhanced by GM-CSF. In contrast, no effect was observed with DCNB.

Dexamethasone prevents granulocyte-macrophage colony-stimulating factor-induced nuclear factor-kappaB activation, inducible nitric oxide synthase expression and nitric oxide production in a skin dendritic cell line.

AIMS: Nitric oxide (NO) has been increasingly implicated in inflammatory skin diseases, namely in allergic contact dermatitis. In this work, we investigated the effect of dexamethasone on NO production induced by the epidermal cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in a mouse fetal skin dendritic cell line. METHODS: NO production was assessed by the method of Griess. Expression of the inducible isoform of nitric oxide synthase (iNOS) protein was evaluated by western blot analysis and immunofluorescence microscopy. Western blot analysis was also performed to evaluate cytosolic IkappaB-alpha (IkappaB-alpha) protein levels. The electrophoretic mobility shift assay was used to evaluate the activation or inhibition of nuclear factor kappa B (NF-kappaB). RESULTS: GM-CSF induced iNOS expression and NO production, and activated the transcription factor NF-kappaB. Dexamethasone inhibited, in a dose-dependent manner, NO production induced by GM-CSF. Addition of dexamethasone to the culture, 30 min before GM-CSF stimulation, significantly inhibited the cellular expression of iNOS. Dexamethasone also inhibited GM-CSF-induced NF-kappaB activation by preventing a significant decrease on the IkappaB-alpha protein levels, thus blocking NF-kappaB migration to the nucleus. CONCLUSIONS: The corticosteroid dexamethasone inhibits GM-CSF-induced NF-kappaB activation, iNOS protein expression and NO production. These results suggest that dexamethasone is a potent inhibitor of intracellular events that are involved on NO synthesis, in skin dendritic cells.