A comprehensive examination of mental health in patients with head and neck cancer: systematic review and meta-analysis.

BACKGROUND: Patients with head and neck cancer present particularly considerable levels of emotional distress. However, the actual rates of clinically relevant mental health symptoms and disorders among this population remain unknown. METHODS: A Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analyses of Observational Studies in Epidemiology-compliant systematic review and quantitative random-effects meta-analysis was performed to determine suicide incidence and the prevalence of depression, anxiety, distress, posttraumatic stress, and insomnia in this population. MEDLINE, Web of Science, Cochrane Central Register, KCI Korean Journal database, SciELO, Russian Science Citation Index, and Ovid-PsycINFO databases were searched from database inception to August 1, 2023 (PROSPERO: CRD42023441432). Subgroup analyses and meta-regressions were performed to investigate the effect of clinical, therapeutical, and methodological factors. RESULTS: A total of 208 studies (n = 654 413; median age = 60.7 years; 25.5% women) were identified. Among the patients, 19.5% reported depressive symptoms (95% confidence interval [CI] = 17% to 21%), 17.8% anxiety symptoms (95% CI = 14% to 21%), 34.3% distress (95% CI = 29% to 39%), 17.7% posttraumatic symptoms (95% CI = 6% to 41%), and 43.8% insomnia symptoms (95% CI = 35% to 52%). Diagnostic criteria assessments revealed lower prevalence of disorders: 10.3% depression (95% CI = 7% to 13%), 5.6% anxiety (95% CI = 2% to 10%), 9.6% insomnia (95% CI = 1% to 40%), and 1% posttraumatic stress (95% CI = 0% to 84.5%). Suicide pooled incidence was 161.16 per 100 000 individuals per year (95% CI = 82 to 239). Meta-regressions found a statistically significant higher prevalence of anxiety in patients undergoing primary chemoradiation compared with surgery and increased distress in smokers and advanced tumor staging. European samples exhibited lower prevalence of distress. CONCLUSIONS: Patients with head and neck cancer presented notable prevalence of mental health concerns in all domains. Suicide remains a highly relevant concern. The prevalence of criteria-meeting disorders is significantly lower than clinically relevant symptoms. Investigating the effectiveness of targeted assessments for disorders in highly symptomatic patients is essential.

HIV and AIDS in the state of Paraná, Brazil, 2007-2022: trends and spatiotemporal distribution / HIV e AIDS no Estado do Paraná, Brasil, 2007-2022: tendência e distribuição espaçotemporal

ABSTRACT Objective: The aim of this study was to analyze the spatiotemporal evolution of the incidence rates of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in the state of Paraná, Brazil. Methods: An ecological study with an analytical component of time series analysis was conducted in the state of Paraná from 2007 to 2022. The data source was the Notifiable Diseases Information System. To study the trend, the Prais-Winsten generalized linear regression model was used by decomposing the time series, and for spatial analysis, the Moran's index was applied. Results: The total sample consisted of 50,676 HIV/AIDS records. The incidence rate showed an increasing trend, with an average growth of 2.14% [95% confidence interval - 95%CI 1.16-3.13] per month. From 2007 to 2014 and from 2015 to 2022, the average number of cases in the state was 105.64 and 159.20 per 100,000 inhabitants, respectively, with significant variation among municipalities. Spatial clusters of high risk persisted in the metropolitan region, the capital, and coastal areas, and a new cluster was observed in the northern region of the state. Conclusion: The incidence rates of HIV/AIDS showed an upward trend over time. The number of cases varied considerably in some municipalities, especially in the coastal region. Spatial analysis revealed geospatial patterns of high risk in the main metropolitan areas of Paraná: Curitiba (including the coastal area), Londrina, and Maringá, which share characteristics such as a high degree of urbanization and ongoing economic development.

RESUMO Objetivo: Este estudo teve como objetivo analisar a evolução espaçotemporal das taxas de incidência do vírus da imunodeficiência humana (HIV) e da síndrome da imunodeficiência adquirida (AIDS) no estado do Paraná, Brasil. Métodos: Foi realizado um estudo ecológico com componente analítico de séries temporais e análise espacial no estado do Paraná, de 2007 a 2022. A fonte de dados foi o Sistema de Informação de Agravos de Notificação. Para estudar a tendência, foi utilizado o modelo de regressão linear generalizada de Prais-Winsten por meio da decomposição de séries temporais e, para a análise espacial, foi aplicado o Índice de Moran. Resultados: A amostra total foi composta de 50.676 registros de HIV/AIDS. A taxa de incidência apresentou tendência crescente, com crescimento médio de 2,14% (intervalo de confiança de 95% — IC95% 1,16-3,13) ao mês. Nos períodos de 2007 a 2014 e 2015 a 2022, a média de casos no estado foi de 105,64 e 159,20 a cada 100 mil habitantes, respectivamente, com importantes variações entre os municípios. Agrupamentos espaciais de alto risco permaneceram na região metropolitana à capital e litoral e um novo agrupamento foi observado à região norte do estado. Conclusão: As taxas de incidência do HIV/AIDS apresentaram tendência temporal crescente. O número de casos variou substancialmente em alguns municípios, principalmente naqueles localizados na região litorânea. A análise espacial revelou padrões geoespaciais de alto risco nas principais regiões metropolitanas do Paraná: Curitiba (abrange o litoral), Londrina e Maringá, as quais compartilham características como elevado grau de urbanização e constante desenvolvimento econômico.

Substance use during pregnancy and risk of postpartum depression: a systematic review and meta-analysis.

Introduction: Postpartum depression (PPD) is a prevalent mental health condition affecting women globally within the first year following childbirth. Substance use during pregnancy has been associated with an increased risk of developing PPD, but the evidence remains inconclusive. This meta-analysis aims to comprehensively assess the effects of different substances on PPD risk, exploring potential modifiers and confounding factors. Objectives: To examine the proportion of PPD among substance users during pregnancy, compared to non-users, and investigate the specific risk associated with different substances (tobacco, alcohol, and non-specified substance use/multiple substance use). Methods: A systematic literature search was conducted from inception to November 2022 using the Web of Science database (Clarivate Analytics), incorporating Web of Science Core Collection, the BIOSIS Citation Index, the KCI-Korean Journal Database, MEDLINE®, the Russian Science Citation Index, the SciELO Citation Index, and the Cochrane Central Register of Reviews, and Ovid/PsycINFO databases. Inclusion criteria comprised original studies with pregnant women, using validated depression scales and substance use reporting. Results: Among the 26 included studies, encompassing 514,441 women, the pooled prevalence of PPD among substance users during pregnancy was 29% (95% CI 25-33). Meta-analyzes revealed an overall odds ratio (OR) of 3.67 (95% CI 2.31-5.85, p < 0.01) indicating a significantly higher risk of PPD among substance users compared to non-users. Subgroup analyzes demonstrated a higher risk for women with non-specified or multiple substance use (OR 4.67, 95% CI 2.59-8.41; p < 0.01) and tobacco use (OR 4.01, 95% CI 2.23-7.20; p < 0.01). Alcohol use showed a trend toward higher risk that did not reach statistical significance (OR 1.88, 95% CI 1.00-3.55; p = 0.051). Conclusion: This meta-analysis provides evidence of an increased risk of PPD among pregnant substance users, particularly those using multiple substances or tobacco. However, caution is needed in interpreting the association with alcohol use due to its non-significant result. Systematic review registration: This study protocol was registered at PROSPERO (registration number: CCRD42022375500).

Digital health for treatment adherence in people with tuberculosis: a systematic review / Saúde digital para a adesão ao tratamento da pessoa com tuberculose: uma revisão sistemática / Salud digital para la adherencia al tratamiento en personas con tuberculosis: una revisión sistemática

Justifications and Objectives: the use of digital health, among people diagnosed with tuberculosis, can be an effective strategy, combined with health services, to increase adherence to treatment and impact the disease's epidemiological data in the country. As this topic has been widely discussed and improved in recent years, it is necessary to further investigate the research available on scientific bases. The objective of this study was to describe the use of digital health technologies to assist with adherence to tuberculosis treatment. Methods: this is a systematic literature review with a rapid review approach, following the PRISMA guidelines and the Cochrane guide. Evidence quality was assessed using the Mixed Methods Appraisal Tool. The studies were identified in PubMed, VHL, CINAHL, Cochrane Trial, SciELO, Scopus and Embase. Experimental, quasi-experimental studies and clinical trials were included, without language restrictions, published between 2020 and 2022. Content: nine studies were selected, which demonstrated that the implementation of digital technologies improved adherence rates to medication treatment and cure rates. Applications use strategies such as synchronous and asynchronous video, voice calls and text messages. Among the studies, only two technology/application names were mentioned. Conclusion: digital technologies have had a positive impact on the treatment of people diagnosed with tuberculosis.(AU)

Justificativas e Objetivos: a utilização da saúde digital, junto às pessoas diagnosticadas com a tuberculose, pode ser uma estratégia eficaz, aliada dos serviços de saúde, para aumentar a adesão ao tratamento e impactar os dados epidemiológicos da doença no país. Como esse tema tem sido amplamente discutido e aprimorado nos últimos anos, é necessário investigar mais a fundo as pesquisas disponíveis nas bases científicas. O objetivo deste estudo foi descrever o uso de tecnologias em saúde digital para auxiliar na adesão ao tratamento da tuberculose. Método: trata-se de revisão sistemática da literatura com abordagem de revisão rápida, seguindo as diretrizes do PRISMA e o guia da Cochrane. A qualidade das evidências foi realizada utilizando a ferramenta Mixed Methods Appraisal Tool. Os estudos foram identificados nas bases de dados PubMed, BVS, CINAHL, Cochrane Trial, SciELO, Scopus e Embase. Foram incluídos estudos experimentais, quase-experimentais e ensaios clínicos, sem restrição de idioma, publicados entre 2020 e 2022. Conteúdo: foram selecionados nove estudos, que demonstraram que a implementação de tecnologias digitais melhorou as taxas de adesão ao tratamento medicamentoso e as taxas de cura. Os aplicativos utilizam estratégias como vídeo síncrono e assíncrono, chamadas de voz e mensagens de texto. Entre os estudos, apenas dois nomes de tecnologia/aplicativo foram mencionados. Conclusão: as tecnologias digitais têm impactado de forma positiva no tratamento das pessoas com diagnóstico de tuberculose.(AU)

Justificaciones y objetivos: el uso de la salud digital entre las personas diagnosticadas con tuberculosis puede ser una estrategia eficaz y aliada de los servicios de salud para aumentar la adherencia al tratamiento e impactar los datos epidemiológicos de la enfermedad en el país. 3. Método: se realizó una revisión sistemática de la literatura con un enfoque de revisión rápida, siguiendo las pautas de PRISMA y la guía de Cochrane. La calidad de la evidencia se evaluó utilizando la herramienta Mixed Methods Appraisal Tool. Los estudios se identificaron en las siguientes bases de datos: PubMed, BVS, CINAHL, Cochrane Trial, SciELO, Scopus y Embase. Se incluyeron estudios experimentales, cuasiexperimentales y ensayos clínicos, sin restricciones de idioma, publicados entre 2020 y 2022. Contenido: se seleccionaron nueve estudios que demostraron que la implementación de tecnologías digitales mejoró las tasas de adherencia al tratamiento con medicamentos y las tasas de curación. Las aplicaciones utilizan estrategias como video sincrónico y asincrónico, llamadas de voz y mensajes de texto. Entre los estudios, sólo se mencionaron dos nombres de tecnologías/aplicaciones. Conclusión: las tecnologías digitales han tenido un impacto positivo en el tratamiento de personas diagnosticadas con tuberculosis.(AU)

Systematic Reviews to Strengthen Evidence-based Nursing Practice / Revisiones sistemáticas para el fortalecimiento de la práctica de enfermería basada en evidencias / Revisões sistemáticas para fortalecer a prática de enfermagem baseada em evidências

Systematic reviews are essential to developing evidence-based nursing practice. The JBI, formerly known as the Joanna Briggs Institute, has contributed significantly to research through technical training on reviews. Cochrane Living Systematic Reviews and Systematic Reviews of Measurement Instruments have been approaches recently used by the scientific community. The purpose of Living Systematic Reviews is to continuously update priority issues, while Systematic Reviews of Measurement Instruments condense evidence on the validity of measurement instruments. This article overviews the JBI Systematic Review approaches and provides critical information about Cochrane Living Systematic Reviews and Systematic Reviews of Measurement Instruments. The use of these new approaches is necessary to maintain the evidence-based nursing practice and advance nursing knowledge.

Las revisiones sistemáticas son esenciales para el desarrollo de la práctica de enfermería basada en la evidencia. El JBI, conocido anteriormente como Joanna Briggs Institute, ha contribuido significativamente al desarrollo de la investigación mediante el entrenamiento técnico sobre revisiones. Las Revisiones Sistemáticas Vivas Cochrane y las Revisiones Sistemáticas de Instrumentos de Medición han sido enfoques recientemente utilizados por la comunidad científica. Las Revisiones Sistemáticas Vivas tienen como propósito generar actualizaciones continuas de temas prioritarios y las Revisiones Sistemáticas de Instrumentos de Medición aportan síntesis de evidencias relacionadas con la validez de los instrumentos de medida. Este artículo es una overview, que tiene como objetivo proporcionar una visión general sobre los abordajes de Revisiones Sistemáticas del JBI y brindar informaciones claves acerca de las Revisiones Sistemáticas Vivas Cochrane y las Revisiones Sistemáticas de Instrumentos de Medición. La utilización de estos nuevos abordajes es necesaria para mantener la práctica de enfermería basada en la evidencia y aportar al desarrollo del conocimiento enfermero.

As revisões sistemáticas são essenciais para o desenvolvimento da prática de enfermagem baseada em evidências. O JBI, conhecido anteriormente como Jhoanna Briggs Institute, contribuiu significativamente para o desenvolvimento da pesquisa mediante o treinamento técnico sobre revisões. As Revisões Sistemáticas Vivas Cochrane e as Revisões Sistemáticas de Instrumentos de Medição vêm sendo abordagens recentemente utilizadas pela comunidade científica. As Revisões Sistemáticas Vivas têm como objetivo gerar atualizações contínuas de temas prioritários e as Revisões Sistemáticas de Instrumentos de Medição contribuem com sínteses de evidências relacionadas com a validade dos instrumentos de medida. Este artigo é um overview, que tem como objetivo proporcionar uma visão geral sobre as abordagens de Revisões Sistemáticas do JBI e oferecer informações-chave sobre as Revisões Sistemáticas Vivas Cochrane e as Revisões Sistemáticas de Instrumentos de Medição. A utilização dessas novas abordagens é necessária para manter a prática de enfermagem baseada em evidências e contribuir para o desenvolvimento do conhecimento em enfermagem.

Serum Th17 and TNF-α distinguish between patients with occult hepatitis B infection, chronic hepatitis B infection and healthy individuals.

Chronic hepatitis B (CHB) is classified into five phases based on virus-host interactions: immune tolerance, immune clearance, inactive carrier state, reactive phase and occult hepatitis B infection (OBI). OBI is an uncommon asymptomatic phase of CHB that can be reactivated when the immune system is compromised, occasionally giving rise to severe liver disease. Host immune factors play essential roles in all phases of the CHB infection. Cytokines may alter infection course, influencing the propensity for and the progression of CHB and thus warrant study. Three clinical groups were studied: 48 healthy individuals (HI), 28 patients with persistent positive anti-HBc serological markers and negative HBsAg over time, who were diagnosed as OBI and 12 patients with active CHB. OBI patients were defined by three independent detections of the hepatitis B virus genome through nested PCR and real-time PCR. Quantitative measurement of 20 Th1, Th2 and Th17 human cytokines was performed in the sera of HI, OBI and CHB patients. Levels of IFN-γ, TNF-ß, IL-28A, IL-4, IL-5, IL-13, IL-1ß, IL-6, IL-21, IL-22, IL-23, GM-CSF and MIP-3α were similar between groups. IL-2, IL-12p70, IL-10, IL-17F and TGF-ß1 were similar in HI and OBI, but higher in CHB. TNF-α and the IL-17A:IL-17F ratio were significantly different between the three groups. TNF-α was progressively higher in HI, OBI and CHB (P = 0.004), while the IL-17A:IL-17F ratio was 1.1 in HI, 3.4 in OBI and 0.4 in CHB. Detection and levels of these pro-inflammatory cytokines in OBI patients suggest that they are undergoing a silent hepatic inflammatory process.

Modulation of aqueous humor melatonin levels by yellow-filter and its protective effect on lens.

Melatonin is mainly secreted by the pineal gland, and it is also produced by various ocular structures such as the lens. It has been recently demonstrated that melatonin ocular synthesis can be induced by blocking the blue component of white light by means of filters. Melatonin exhibits antioxidant properties that can be useful to face light-induced oxidative stress as well as oxidative events associated to ocular pathologies like cataracts. Moreover, as oxidative stress is a main event in cataract development, changes in melatonin levels could happen and be relevant in the progression of this pathology, a subject that remains uncertain. The goal of this work was to analyze the ability of a short wavelength light blocking (yellow) filter to modulate endogenous melatonin concentration and the antioxidant and cytoprotective actions induced by yellow filter's use in lens. Furthermore, we evaluated the potential changes in aqueous humor melatonin concentration from patients with cataracts. In human lens epithelial cells, white light-emitting diode (LED) light challenge reduced melatonin secretion, protein levels of the enzymes involved in melatonin synthesis (hydroxyindole-O-methyltransferase and unphosphorylated and phosphorylated forms of arylalkylamine N-acetyltransferase) and cell viability whereas increased reactive oxygen species production. Yellow filter exposure precluded melatonin secretion reduction and protected cells from oxidative damage. Consistent with cataract patient's results, significantly lower levels of melatonin were observed in aqueous humor of alloxan-induced diabetic cataract rabbits as compared to those of control rabbits. In contrast, aqueous humor melatonin levels of diabetic cataract animals maintaining in cages covered with a yellow filter resembled control values. This recovery seems to be mediated by the induction of melatonin biosynthetic enzymes protein expression. Yellow filter also preserved Nrf2 lens protein expression and superoxide dismutase protein levels and activity in diabetic animals. Modulation of endogenous ocular melatonin concentration using blocking filters might be a promising approach to prevent premature lens opacification.

Oncogenic role of PinX1 in prostate cancer cells through androgen receptor dependent and independent mechanisms.

Coregulators play an important role in prostate cancer (PCa), modulating androgen receptor (AR) action and representing a possible cause of androgen deprivation therapy failure. Pin2-interacting protein X1 (PinX1) is a nucleolar protein described as a steroid hormone receptor coregulator in breast cancer cell lines. In this work, we studied the effect of PinX1 on AR action in PCa. Our results demonstrate that PinX1 acts as an AR coactivator, increasing its transcriptional activity and target gene expression, as well as proliferation, migration and colony formation in PCa cell lines. These effects are observed in the presence and absence of AR agonist and antagonists, suggesting a possible androgen independent pathway for PinX1. We present the first oncogenic roles described for PinX1, acting as a coactivator of the AR.

Phospho-Tau Protein Expression in the Cell Cycle of SH-SY5Y Neuroblastoma Cells: A Morphological Study.

It has been reported that the main function of tau protein is to stabilize microtubules and promote the movement of organelles through the axon in neurons. In Alzheimer's disease, tau protein is the major constituent of the paired helical filament, and it undergoes post-translational modifications including hyperphosphorylation and truncation. Whether other functions of tau protein are involved in Alzheimer's disease is less clear. We used SH-SY5Y human neuroblastoma cells as an in vitro model to further study the functions of tau protein. We detected phosphorylated tau protein as small dense dots in the cell nucleus, which strongly colocalize with intranuclear speckle structures that were also labelled with an antibody to SC35, a protein involved in nuclear RNA splicing. We have shown further that tau protein, phosphorylated at the sites recognized by pT231, TG-3, and AD2 antibodies, is closely associated with cell division. Different functions may be characteristic of phosphorylation at specific sites. Our findings suggest that the presence of tau protein is involved in separation of sister chromatids in anaphase, and that tau protein also participates in maintaining the integrity of the DNA (pT231, prophase) and chromosomes during cell division (TG-3).

Quantitative phosphoproteomic analysis reveals common regulatory mechanisms between effector- and PAMP-triggered immunity in plants.

Plant immunity consists of two arms: pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), induced by surface-localized receptors, and effector-triggered immunity (ETI), induced by intracellular receptors. Despite the little structural similarity, both receptor types activate similar responses with different dynamics. To better understand phosphorylation events during ETI, we employed a phosphoproteomic screen using an inducible expression system of the bacterial effector avrRpt2 in Arabidopsis thaliana, and identified 109 differentially phosphorylated residues of membrane-associated proteins on activation of the intracellular RPS2 receptor. Interestingly, several RPS2-regulated phosphosites overlap with sites that are regulated during PTI, suggesting that these phosphosites may be convergent points of both signaling arms. Moreover, some of these sites are residues of important defense components, including the NADPH oxidase RBOHD, ABC-transporter PEN3, calcium-ATPase ACA8, noncanonical Gα protein XLG2 and H+ -ATPases. In particular, we found that S343 and S347 of RBOHD are common phosphorylation targets during PTI and ETI. Our mutational analyses showed that these sites are required for the production of reactive oxygen species during both PTI and ETI, and immunity against avirulent bacteria and a virulent necrotrophic fungus. We provide, for the first time, large-scale phosphoproteomic data of ETI, thereby suggesting crucial roles of common phosphosites in plant immunity.

Fibrillar Amyloid-ß Accumulation Triggers an Inflammatory Mechanism Leading to Hyperphosphorylation of the Carboxyl-Terminal End of Tau Polypeptide in the Hippocampal Formation of the 3×Tg-AD Transgenic Mouse.

Alzheimer's disease (AD) is a degenerative and irreversible disorder whose progressiveness is dependent on age. It is histopathologically characterized by the massive accumulation of insoluble forms of tau and amyloid-ß (Aß) asneurofibrillary tangles and neuritic plaques, respectively. Many studies have documented that these two polypeptides suffer several posttranslational modifications employing postmortem tissue sections from brains of patients with AD. In order to elucidate the molecular mechanisms underlying the posttranslational modifications of key players in this disease, including Aß and tau, several transgenic mouse models have been developed. One of these models is the 3×Tg-AD transgenic mouse, carrying three transgenes encoding APPSWE, S1M146V, and TauP301L proteins. To further characterize this transgenicmouse, we determined the accumulation of fibrillar Aß as a function of age in relation to the hyperphosphorylation patterns of TauP301L at both its N- and C-terminus in the hippocampal formation by immunofluorescence and confocal microscopy. Moreover, we searched for the expression of activated protein kinases and mediators of inflammation by western blot of wholeprotein extracts from hippocampal tissue sections since 3 to 28 months as well. Our results indicate that the presence of fibrillar Aß deposits correlates with a significant activation of astrocytes and microglia in subiculum and CA1 regions of hippocampus. Accordingly, we also observed a significant increase in the expression of TNF-α associated to neuritic plaques and glial cells. Importantly, there is an overexpression of the stress activated protein kinases SAPK/JNK and Cdk-5 in pyramidal neurons, which might phosphorylate several residues at the C-terminus of TauP301L. Therefore, the accumulation of Aß oligomers results in an inflammatory environment that upregulates kinases involved in hyperphosphorylation of TauP301L polypeptide.

Depresión y cáncer: una revisión orientada a la práctica clínica / Depression and cancer: a review oriented to clinical practice

La depresión es una entidad que afecta a una proporción del 15-25% de los pacientes con cáncer. A pesar de su elevada incidencia, es un trastorno habitualmente infradiagnosticado y que no recibe tratamiento adecuado. Este hecho conduce a una mala calidad de vida, una inadecuada adherencia al tratamiento y una menor tasa de supervivencia en esta población médica. Existe evidencia sobre la eficacia de abordajes tanto farmacológicos como psicoterapéuticos en pacientes oncológicos con depresión. El objetivo de este artículo es aportar una visión sobre aquellas intervenciones con demostrada eficacia que permiten a los pacientes con cáncer desarrollar un mejor afrontamiento de su enfermedad y lograr una mejor calidad de vida.

Depression is an entity that concerns about the15-25% of the patients with cancer. In spite of his high incident, it is habitually an under diagnosed disorder and do not receive adequate treatment. This fact drives to a worse quality of life, a worse adherence to the treatment and a minor rate of survival. There is evidence of the efficiency of pharmacological and psychological boardings in the patients with cancer and depression. The aim of this paper is to have a vision on those interventions with demonstrated efficiency. This treatment allows to the patients with cancer to develop a better confrontation of his disease and to achieve a better quality of life.

Novel role for PINX1 as a coregulator of nuclear hormone receptors.

Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process influenced by coactivator and corepressor proteins. This work shows that Pin2 interacting protein 1 (PINX1) interacts with the N-terminal domain of ERα and functions as a corepressor of ERα. Furthermore, it represses both AF-1 and AF-2 transcriptional activities. Chromatin immunoprecipitation assays verified that the interaction between ERα and PINX1 occurs on E2 regulated promoters and enhanced expression of PINX1 deregulates the expression of a number of genes that have a role in cell growth and proliferation in breast cancer. PINX1 overexpression decreases estrogen mediated proliferation of breast cancer cell lines, while its depletion shows the opposite effect. Taken together, these data show a novel molecular mechanism for PINX1 as an attenuator of estrogen receptor activity in breast cancer cell lines, furthering its role as a tumor suppressor gene in breast cancer.

Resultados post operatorios por tratamiento quirúrgico de prolapso genital del compartimiento medio con implante de malla-IVS posterior, en el Hospital Dos de Mayo 2011 - 2012 / Results post operative for surgical treatment of genital prolapse of the middle compartment with mesh implant-IVS posterior at the Hospital Dos de Mayo 2011-2012

Determinar los resultados post operatorios por tratamiento quirúrgico de prolapso genital del compartimiento medio con implante de Malla-IVS posterior, en el Hospital Dos de Mayo 2011-2012. Metodología: Estudio observacional, descriptivo, retrospectivo. Se estudió a 43 pacientes con tratamiento quirúrgico de prolapso genital del compartimiento medio con implante de Malla-IVS posterior. Para describir las variables numéricas se utilizó medida de tendencia central y de dispersión, para las variables cualitativas se usó frecuencias absolutas y relativas. En el análisis bivariado se utilizó la prueba Chi-cuadrado con un nivel de confianza del 95 por ciento. Resultados: La edad de las pacientes estuvo comprendida entre 35 a 85 años con una media de 56.7 años, el estado civil más frecuente fue "casada" (53.5 por ciento), el nivel de educación en su mayoría fue secundaria (51.2 por ciento). En las características obstétricas se observó mayor porcentaje de pacientes con gesta > a 3 y > a 3 partos. Respecto a la seguridad del implante de malla IVS posterior solo se observó hematoma vulvar en el 4.7 por ciento de las pacientes mas no se observó otras complicaciones. En la evaluación de la actividad sexual: ninguna paciente presentó disfunción sexual, en el 81.4 por ciento se resolvió la dispareunia y el 18.6 por ciento tuvo dispareunia persistente. Los resultados que evaluaron mejora de la alteración de la micción y evacuación se observó en el 79.1 por ciento incontinencia urinaria de esfuerzo "resuelta", la urgencia urinaria se resolvió en el 93 por ciento y solo se encontró un caso de incontinencia fecal. La duración del tiempo quirúrgico fue < a 2 horas en el 65.1 por ciento y > a 2 horas en 34.9 por ciento, donde la estancia hospitalaria fue de 2 a 4 días en mayor proporción (51.2 por ciento). Además de realizar la técnica IVS posterior algunas pacientes requirieron técnicas de corrección adicionales como Nazta TC (23 por ciento)...

To determine the postoperative results for surgical treatment of genital prolapse of middle compartment with implant posterior IVS-mesh in Dos de Mayo Hospital 2011-2012. Methodology: Observational, descriptive, transversal and retrospective study. The sample was 43 patients with surgical treatment of genital prolapse middle compartment with implant posterior IVS-mesh. To describe numerical variables, measure of central tendency and dispersion was used; for qualitative variables, absolute and relative frequencies. The Chi-square test with a confidence level of 95 per cent was used in the bivariate analysis. Results: The age of patients ranged from 35-85 years with a mean of 56.7 years, the most frequent marital status was "married" (53.5 per cent), level of education was mostly secondary (51.2 per cent). In obstetric characteristics was observed higher percentage of patients with gestation >3 and >3 births. Regarding safety of implant IVS-mesh was observed only vulvar hematoma in 4.7 per cent of patients but no other complications were observed. In the evaluation of sexual activity: no patient had sexual dysfunction, 81.4 per cent dyspareunia resolved and 18.6 per cent had persistent dyspareunia. The results that evaluated improvement of urination and evacuation alteration was observed in 79.1 per cent effort urinary incontinence "resolved", urinary urgency was resolved in 93 per cent and only one case of fecal incontinence. The operative time was <2 hours in 65.1 per cent and >2 hours in 34.9 per cent, where the hospital stay was 2-4 days in greater proportion (51.2 per cent). In addition to performing the IVS posterior technique some patients required additional correction techniques as Nazta TC (23 per cent), Sleep TOT (7 per cent), Sleep TOT and Peregre (7 per cent); and to relate these techniques to the frequency of complications or patient cure rate was no observed significant relationship between these variables. In evaluating...

Identifying at-risk states beyond positive symptoms: a brief task assessing how neurocognitive impairments impact on misrepresentation of the social world through blunted emotional appraisal / Identificando estados de risco para além dos sintomas positivos: um teste breve que avalia o impacto de disfunções neurocognitivas sobre a interpretação errônea do mundo social resultante de avaliação emocional embotada

OBJECTIVE: Neurocognitive impairments observed in psychotic disorder may impact on emotion recognition and theory of mind, resulting in altered understanding of the social world. Early intervention efforts would be served by further elucidation of this mechanism. METHOD: Patients with a psychotic disorder (n=30) and a reference control group (n=310) were asked to offer emotional appraisals of images of social situations (EASS task). The degree to which case-control differences in appraisals were mediated by neurocognitive alterations was analyzed. RESULTS: The EASS task displayed convergent and discriminant validity. Compared to controls, patients displayed blunted emotional appraisal of social situations (B=0.52, 95 percent CI: 0.30, 0.74, P<0.001; adjusted for age, sex and number of years of education: B=0.44, 95 percent CI: 0.20, 0.68, P<0.001), a difference of 0.88 (adjusted: 0.75) standard deviation. After adjustment for neurocognitive variables, the case-control difference was reduced by nearly 75 percent and was non-significant (B=0.12, 95 percent CI: -0.14, 0.39, P=0.37). CONCLUSIONS: Neurocognitive impairments observed in patients with psychotic disorder may underlie misrepresentation of the social world, mediated by altered emotion recognition. A task assessing the social impact of cognitive alterations in clinical practice may be useful in detecting key alterations very early in the course of psychotic illness.

OBJETIVO: Melhoras neurocognitivas observadas no transtorno psicótico podem ter impacto no reconhecimento de emoções e na teoria da mente, resultando numa alteração na compreensão do mundo social. Esforços para uma intervenção precoce poderiam se beneficiar de uma maior elucidação deste mecanismo. MÉTODO: Pacientes com transtornos psicóticos (n=30) e um grupo controle de referência (n=310) foram convidados a realizar avaliações emocionais de imagens de situações sociais (teste AESS). A relação das diferenças entre casos e controles com as alterações neurocognitivas foi analisada. RESULTADOS: O teste AESS apresentou validade convergente e discriminatória. Quando comparados aos controles, os pacientes apresentaram avaliação emocional embotada das situações sociais (B=0,52, 95 por cento CI: 0,30, 0,74, P<0,001; ajustado para a idade, sexo e número de anos de educação: B=0,44, 95 por cento CI: 0,20, 0,68, P<0001), uma diferença de 0,88 (ajustado: 0,75) desvio-padrão. Após o ajuste para as variáveis neurocognitivas, as diferenças no estudo caso-controle foram reduzidas em quase 75 por cento e deixaram de ser significativas (B=0,12, 95 por cento CI: -0,14, 0.39, P=0,37). CONCLUSÕES: Disfunções neurocognitivas observadas em pacientes com transtornos psicóticos podem ser subjacentes a uma distorção do mundo social, mediada pela alteração no reconhecimento de emoções. Um teste que avalie o impacto social de alterações cognitivas na prática clínica pode ser útil para a detecção das principais alterações nos primeiros estágios de transtornos psicóticos.

Subcellular localization and regulation of StarD4 protein in macrophages and fibroblasts.

StarD4 is a member of the StarD4 subfamily of START domain proteins with a characteristic lipid binding pocket specific for cholesterol. The objective of this study was to define StarD4 subcellular localization, regulation, and function. Immunobloting showed that StarD4 is highly expressed in the mouse fibroblast cell line 3T3-L1, in human THP-1 macrophages, Kupffer cells (liver macrophages), and hepatocytes. In 3T3-L1 cells and THP-1 macrophages, StarD4 protein appeared localized to the cytoplasm and the endoplasmic reticulum (ER). More specifically, in THP-1 macrophages StarD4 co-localized to areas of the ER enriched in Acyl-CoA:cholesterol acyltransferase-1 (ACAT-1), and was closely associated with budding lipid droplets. The addition of purified StarD4 recombinant protein to an in vitro assay increased ACAT activity 2-fold, indicating that StarD4 serves as a rate-limiting step in cholesteryl ester formation by delivering cholesterol to ACAT-1-enriched ER. In addition, StarD4 protein was found to be highly regulated and to redistribute in response to sterol levels. In summary, these observations, together with our previous findings demonstrating the ability of increased StarD4 expression to increase bile acid synthesis and cholesteryl ester formation, provide strong evidence for StarD4 as a highly regulated, non-vesicular, directional, intracellular transporter of cholesterol which plays a key role in the maintenance of intracellular cholesterol homeostasis.

Arabidopsis gp91phox homologues AtrbohD and AtrbohF are required for accumulation of reactive oxygen intermediates in the plant defense response.

Reactive oxygen intermediates (ROI) are strongly associated with plant defense responses. The origin of these ROI has been controversial. Arabidopsis respiratory burst oxidase homologues (rboh genes) have been proposed to play a role in ROI generation. We analyzed lines carrying dSpm insertions in the highly expressed AtrbohD and AtrbohF genes. Both are required for full ROI production observed during incompatible interactions with the bacterial pathogen Pseudomonas syringae pv. tomato DC3000(avrRpm1) and the oomycete parasite Peronospora parasitica. We also observed reduced cell death, visualized by trypan blue stain and reduced electrolyte leakage, in the Atrboh mutants after DC3000(avrRpm1) inoculation. However, enhanced cell death is observed after infection of mutant lines with P. parasitica. Paradoxically, although atrbohD mutation eliminated the majority of total ROI production, atrbohF mutation exhibited the strongest effect on cell death.