Resetting proteostasis with ISRIB promotes epithelial differentiation to attenuate pulmonary fibrosis.

Pulmonary fibrosis is a relentlessly progressive and often fatal disease with a paucity of available therapies. Genetic evidence implicates disordered epithelial repair, which is normally achieved by the differentiation of small cuboidal alveolar type 2 (AT2) cells into large, flattened alveolar type 1 (AT1) cells as an initiating event in pulmonary fibrosis pathogenesis. Using models of pulmonary fibrosis in young adult and old mice and a model of adult alveologenesis after pneumonectomy, we show that administration of ISRIB, a small molecule that restores protein translation by EIF2B during activation of the integrated stress response (ISR), accelerated the differentiation of AT2 into AT1 cells. Accelerated epithelial repair reduced the recruitment of profibrotic monocyte-derived alveolar macrophages and ameliorated lung fibrosis. These findings suggest a dysfunctional role for the ISR in regeneration of the alveolar epithelium after injury with implications for therapy.

The Relationship between Lifetime Exposure to Potentially Traumatic Events, Peritraumatic Dissociation, and PTSD in a Sample of Sexually Assaulted Women in Sao Paulo, Brazil.

Sexually assaulted women represent a particularly high-risk group for developing post-traumatic stress disorder (PTSD). Potentially traumatic events (PTEs) and peritraumatic dissociation (PD) are known risk factors for PTSD. However, little is known about how previous trauma affects PD and how this relationship affects PTSD. We aimed to investigate whether PD acts as a mediator between PTEs and PTSD severity in a sample of recently sexually assaulted women in Sao Paulo, Brazil. Seventy-four sexually assaulted women aged 18-44 completed questionnaires and structured interviews on PTSD, PD, and PTEs. We examined direct and indirect effects of variables using causal mediation analysis. Lifetime exposure to PTEs was a risk factor for PD, but PD was not a risk factor for PTSD symptom severity. Also, PD was not a mediator between PTEs and PTSD severity. We provided recommendations on how to further explore the relationship between lifetime traumatic exposure, PTSD, and peritraumatic dissociation.

Delayed resolution of bleomycin-induced pulmonary fibrosis in absence of MMP13 (collagenase 3).

Matrix metalloprotease 13 (MMP13) deficiency in pulmonary fibrosis has described contradictory phenotypes on inflammatory and fibrotic responses after lung injury, and its role during lung fibrosis resolution is still undefined. MMP13 has been considered the main collagenase in rodents, and the remodeling of fibrillar collagen is widely attributed to the action of this enzyme. In this study we aimed to explore the role of MMP13 during lung fibrosis progression and resolution. Lung fibrosis was induced by intratracheal instillation, and inflammatory, fibrotic, and resolution stages were evaluated in Mmp13-null and wild-type (WT) mice. Bronchoalveolar lavage fluid was taken for cytokine array analysis and activity of gelatinases. Our results showed that MMP13 is upregulated mainly during two stages after lung injury, inflammation and resolution of fibrosis, and it is mainly expressed by alveolar and interstitial macrophages. Mmp13-null mice exhibited more extensive inflammation at 7 days after bleomycin treatment, and it was characterized by increased macrophage infiltration and significant alterations in proinflammatory cytokines. We also documented that Mmp13-deficient mice experienced more severe and prolonged lung fibrosis compared with WT mice. Delayed resolution in Mmp13-deficient lungs was characterized by a decreased overall collagenolytic activity and persistent fibrotic foci associated with emphysema-like areas. Together, our findings indicate that MMP13 plays an antifibrotic role and its activity is crucial in lung repair and restoration of tissue integrity during fibrosis resolution.

Mental health of children who work on the streets in Brazil after enrollment in a psychosocial program.

PURPOSE: To evaluate the mental health status of children working on the streets in Sao Paulo City, Brazil, two years after their participation in a psychosocial program, and to identify factors associated with their mental health status. METHODS: From a total sample of 126 children working on the streets, 107 (85%) were re-evaluated two years after the initiation of a psychosocial program which aimed to cease their work on the streets. The focus was the presence of mental health problems, defined based on a screening instrument (Strengths and Difficulties Questionnaire). Logistic regression models tested factors related to the probability that a child would not present mental health problems at follow-up. RESULTS: The likelihood of a child presenting mental health problems was higher at baseline compared to the two-year follow-up (67.5 and 56.1%, respectively). Absence of mental health problems two years after a psychosocial intervention was significantly correlated with the following baseline factors: lower level of caregiver's psychiatric symptoms as measured by the SRQ (Self-Report Questionnaire) (AOR = 0.84, p = 0.0065), absence of child physical neglect (AOR = 0.38, p = 0.0705) and parental Protestant religion affiliation, compared to other religions (AOR = 4.06; p = 0.0107). CONCLUSIONS: Different factors are related to the absence of mental health problems of children working on the streets after enrollment in a two-year psychosocial program. Our findings suggest that interventions that aim to improve child mental health should consider the detection of psychiatric symptoms in caregivers, provide treatment when it is needed, and also assess other problems such as neglect in the family setting.

Children working on the streets in Brazil: predictors of mental health problems.

The objective of this study was to determine which factors predict higher risk for mental health problems in children working on the streets. We studied a sample of families that had at least one child working on the streets, from October 2008 to March 2009. The instruments applied were the parent version strengths and difficulties questionnaire (SDQ), the childhood trauma questionnaire (CTQ) for children and caregivers, the WorldSAFE core questionnaire, the global assessment of relational functioning scale (GARF), the schedule for affective disorders and schizophrenia for school-age children (K-SADS), and a socio-demographic questionnaire. 191 children between 7 and 14 years of age were analyzed; 126 (66%) were working on the streets, and 65 were siblings who did not work on the streets. Multivariate analysis showed that mental health problems in the caregivers, violent behaviors of the caregivers toward the children, absence of a partner living in the house, and lower levels of family functioning increased the risk of mental health problems in the children. Caregivers reported severe forms of physical punishment against their children in 62% of cases. Caregivers who had suffered sexual abuse and emotional negligence in childhood were more violent with their children. Factors that increased risk for mental health symptoms in these children were caregivers' psychopathology, physical punishment at home, single-parent structure, and poor family functioning. Work on the streets did not influence the children's mental health, when multiple risk factors were considered; family characteristics were the most significant in this sample.

Changes in attachment dimensions during the treatment of acute post-traumatic stress disorder in sexually assaulted Brazilian women.

Introduction: Attachment patterns are established during early childhood; however, extreme experiences throughout life may change this structure, either toward attachment security or insecurity. We analyzed changes in attachment dimensions in women with acute post-traumatic stress disorder (PTSD) following sexual assault, that were randomized to a 14-week treatment with either the medication sertraline or Interpersonal Psychotherapy. Methods: Seventy-four adult women who presented significant reduction in PTSD symptoms across the trial responded to the Revised Adult Attachment Scale at baseline, on week 8 of treatment, and at the end of the trial, on week 14. We fitted a generalized linear model to explain the attachment anxiety and avoidance scores at baseline. A generalized linear mixed model investigated how attachment dimensions changed over time. Socioeconomic data, treatment type, history of childhood trauma, and PTSD severity over the 14-week period were the considered covariates. Results: At baseline, attachment anxiety was associated with a history of early trauma. Attachment anxiety remained stable during the follow-up. Attachment avoidance, on the other hand, significantly increased from baseline to week 14. Higher avoidance was observed in patients with higher total PTSD scores and on the cluster of hyperarousal symptoms. Races other than White (black, mixed-race, or Asian) and younger age were associated with higher attachment avoidance. Discussion: Contrary to our expectations, attachment avoidance increased during follow-up, indicating changes in the interpersonal realm beyond the symptoms of PTSD.

Interpersonal psychotherapy versus sertraline for women with posttraumatic stress disorder following recent sexual assault: a randomized clinical trial.

Background: Sexual assault often triggers posttraumatic stress disorder (PTSD), a potentially chronic severe mental disorder. Most guidelines recommend selective serotonin reuptake inhibitors (SSRIs) and trauma-focused psychotherapies as treatment options. Interpersonal Psychotherapy (IPT), adapted for PTSD (IPT-PTSD), focuses on interpersonal consequences of trauma rather than confronting the trauma itself. Studies have found IPT-PTSD efficaciously reduced PTSD symptoms with limited attrition. No efficacy trials have compared IPT-PTSD and SSRI. We hypothesized IPT would reduce PTSD, anxiety, and depressive symptoms more than sertraline among women with PTSD following a recent sexual assault. Objectives: To compare the efficacy of IPT-PTSD to SSRI sertraline in a 14-week randomized clinical trial for women with PTSD following a recent sexual assault. Methods: Seventy-four women with PTSD who had suffered sexual assault in the last six months were randomly assigned to 14 weeks of IPT-PTSD (n = 39) or sertraline (n = 35). Instruments assessed PTSD, anxiety, and depressive symptoms. This randomized clinical trial was conducted in São Paulo, Brazil, using the Clinician-Administered PTSD Scale-5 (CAPS-5) as the primary outcome measure. Results: Both treatments significantly reduced PTSD, anxiety, and depressive symptoms, without between-group outcome differences. CAPS-5 mean decreased from 42.5 (SD = 9.4) to 27.1 (SD = 15.9) with sertraline and from 42.6 (SD = 9.1) to 29.1 (SD = 15.5) with IPT-PTSD. Attrition was high in both arms (p = .40). Conclusions: This trial showed within-group improvements without differences between IPT-PTSD and sertraline treatment of PTSD. Our findings suggest that non-exposure-based psychotherapies may benefit patients with PTSD, although we did not directly compare these treatments to an exposure therapy. Brazilian Clinical Trials Registry RBR-3z474z.

Antecedentes: La agresión sexual con frecuencia gatilla un trastorno de estrés postraumático (TEPT), un trastorno mental severo potencialmente crónico. La mayoría de las guías clínicas recomiendan los inhibidores selectivos de la receptación de serotonina (ISRSs) y psicoterapias focalizadas en trauma como opciones de tratamiento. La Psicoterapia Interpersonal (PIP), adaptada para TEPT (PIP-TEPT), se focaliza en las consecuencias interpersonales del trauma en lugar de confrontar el trauma en sí. Los estudios han encontrado que la PIP-TEPT eficazmente redujo los síntomas de TEPT con una deserción limitada. Ningún ensayo de eficacia ha comparado PIP-TEPT e ISRS. Hipotetizamos que la PIP-TEPT puede reducir los síntomas de TEPT, ansiedad y depresión más que la sertralina entre las mujeres con TEPT después de una agresión sexual reciente.Objetivos: Comparar la eficacia de la PIP-TEPT con sertralina, un ISRS en un ensayo clínico aleatorizado de 14 semanas para mujeres con TEPT después de una agresión sexual reciente.Métodos: Setenta y cuatro mujeres con TEPT que habían sufrido de una agresión sexual en los últimos seis meses fueron asignadas aleatoriamente a 14 semanas de PIP-TEPT (n = 39) o sertralina (n = 35). Los instrumentos evaluaron síntomas de TEPT, ansiedad y depresión. Este ensayo clínico aleatorizado se realizó en San Pablo, Brasil, utilizando la Escala de TEPT administrada por el clínico (CAPS-5, por sus siglas en inglés) como medida de resultado primaria.Resultados: Ambos tratamientos redujeron significativamente los síntomas de TEPT, ansiedad y depresión, sin diferencias de resultados entre los grupos. La media del CAPS-5 se redujo de 42.5 (DE = 9.4) a 27.1 (DE = 15.9) con sertralina y de 42.6 (DE = 9.1) a 29.1 (DE = 15.5) con la PIP-TEPT. La deserción fue alta en ambos tratamientos (p = .40).Conclusiones: Este ensayo mostro mejoría entre grupos sin diferencias entre la PIP-TEPT y sertralina en el tratamiento del TEPT. Nuestros hallazgos sugieren que las psicoterapias no basadas en la exposición pueden beneficiar a los pacientes con TEPT, aunque no comparamos directamente estos tratamientos con una terapia de exposición.Registro Brasileño de Ensayos Clínicos RBR-3z474z.

Validation of the Brazilian-Portuguese Version of the Clinician Administered Post Traumatic Stress Disorder Scale-5.

Objectives: The aim of this study was to validate CAPS-5 for the Brazilian-Portuguese language on a sample of 128 individuals from two centers (from the cities of São Paulo and Porto Alegre) who have been recently exposed to a traumatic event. Methods: We performed a reliability analysis between interviewers (with a subset of 32 individuals), an internal consistency analysis, and a confirmatory factorial analysis for the validation study. Results: The inter-rater reliability of the total PTSD symptom severity score was high [intraclass correlation coefficient =0.994, 95% CI (0.987-0.997), p < 0.001]. Cohen's Kappa for individual items ranged between 0.759 and 1. Cronbach's alpha coefficients indicated high internal consistency for the CAPS-5 full scale (α = 0.826) and an acceptable level of internal consistency for the four symptom clusters. The confirmatory factorial analysis for the 20-item original CAPS-5 did not fit the data well. A 15-item model with better results was then established by excluding the following CAPS-5 items: dissociative amnesia, recklessness, distorted cognitions, irritability, and hypervigilance. Conclusion: Despite the limitation of the predominance of female victims, and the high number of sexually assaulted women in our sample, the model with only 15 items provided a good fit to the data with high internal consistency (α = 0.835).

Identification of Autophagy-related Proteins in Lungs From Hypersensitivity Pneumonitis Patients.

Autophagy has been involved in the pathogenesis of various lung diseases. However, it is not yet known whether autophagy plays a role in hypersensitivity pneumonitis (HP). HP is an interstitial lung disease resulting from exposure to a wide variety of antigens that provoke an exaggerated immune response in susceptible individuals. The aim of this study was to explore the localization of autophagy key proteins in lungs from HP patients and controls by immunohistochemistry and analyze their expression levels by immunoblot. Macrophages and epithelial cells were strongly positive for the autophagosome biomarker LC3B (microtubule-associated protein light chain 3 beta) in HP lungs compared with controls. A similar pattern was found for the autophagy receptor p62 and the enzyme ATG4B. Unexpectedly, nuclear p62 signal was also noticed in macrophages from HP lungs. Regarding ATG5 and ATG7 localization, we observed positive staining in neutrophils, vascular smooth muscle cells, and endothelial cells. Our findings provide for the first time evidence that proteins from the autophagy machinery are highly expressed in the lungs of HP patients and describe the specific cellular and subcellular localization of LC3B, p62, ATG4B, ATG5, and ATG7 in HP lungs.

Posttraumatic Stress Disorder and Neuroprogression in Women Following Sexual Assault: Protocol for a Randomized Clinical Trial Evaluating Allostatic Load and Aging Process Acceleration.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent, chronic, and severe disorder related to traumatic events. Women are disproportionately affected by PTSD than men and are more at risk in the occurrence of sexual assault victimization. Estimates suggest that 50% of women develop PTSD following sexual assault and successful clinical management can be challenging. Growing evidence has implicated neural, immune, and endocrine alterations underpinning PTSD, but only few studies have assessed the evolution of acute PTSD in women. OBJECTIVE: This study aims to measure whether the onset of PTSD is associated with accelerated aging in women following sexual assault. We hypothesize that the increase of allostatic load caused by PTSD leads to neuroprogression. We will implement a randomized clinical trial to compare responses to treatment with either interpersonal psychotherapy adapted for PTSD (IPT-PTSD) or the selective serotonin reuptake inhibitor sertraline. METHODS: We will include women between 18 and 45 years of age, who experienced sexual assault from 1 to 6 months before the initial evaluation, and present with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnosis of PTSD. Baseline evaluation will comprise clinical and psychometric assessments, structural and functional magnetic resonance imaging, neuropsychological testing, polysomnography, evaluation of immune and endocrine parameters, and genetic analyses. Age-matched female healthy controls will be included and subjected to the same evaluation. Patients will be randomized for treatment in 1 of the 2 arms of the study for 14 weeks; follow-up will continue until 1 year after inclusion via treatment as usual. The researchers will collect clinical and laboratory data during periodic clinical assessments up to 1-year follow-up. RESULTS: Data collection started in early 2016 and will be completed by the end of the first semester of 2020. Analyses will be performed soon afterward, followed by the elaboration of several articles. Articles will be submitted in early 2021. This research project has obtained a grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2014/12559-5). CONCLUSIONS: We expect to provide insight into the consequences of recent sexual assault exposure in women by investigating the degree of neuroprogression developing from an early stage of PTSD. We also expect to provide important evidence on the efficacy of a non-exposure psychotherapy (IPT-PTSD) to mitigate PTSD symptoms in recently sexually assaulted women. Further, we aim to obtain evidence on how treatment outcomes are associated with neuroprogression measures. TRIAL REGISTRATION: Brazilian Clinical Trials Registry RBR-3z474z; http://www.ensaiosclinicos.gov.br/rg/RBR-3z474z/. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19162.

Preclinical studies indicate that INFLATIV, an herbal medicine cream containing Pereskia aculeata, presents potential to be marketed as a topical anti-inflammatory agent and as adjuvant in psoriasis therapy.

OBJECTIVES: A previous study reported that the hexane fraction (HF) obtained from Pereskia aculeata leaves showed promising topical anti-inflammatory activity. Intending its future use in clinical practice, a herbal medicine cream named INFLATIV was developed. Its anti-inflammatory and antipsoriatic potential were investigated. INFLATIV was subjected to preliminary accelerated stability tests and to a degradation profile assessment. METHODS: INFLATIV was prepared at 6% and 12%. The anti-inflammatory activity was assessed by croton oil single and multiple application challenge in mice. Mouse tail test was used for antipsoriatic potential investigation. Cutaneous atrophy test was performed. Preliminary accelerated stability tests were performed together with a degradation profile by GC-MS analysis. KEY FINDINGS: The anti-inflammatory activity shown by INFLATIV was comparable to dexamethasone. However, the skin atrophy caused by that drug was not observed. INFLATIV modified skin parakeratotic differentiation into orthokeratosis, which revealed its antipsoriatic potential. The ingredients used were suitable to carry the bioactives as they were well permeated by the skin. The preliminary accelerated stability tests indicated that INFLATIV 6% is more stable than 12%. CONCLUSIONS: The results demonstrated the relevant therapeutic and marketing potentials of INFLATIV, which is likely to be further evaluated in clinical trials for drug registration process with regulatory agencies.

Attrition in Interpersonal Psychotherapy Among Women With Post-traumatic Stress Disorder Following Sexual Assault.

BACKGROUND: An estimated 16.9% of adult Brazilian women experience sexual assault in their lifetime. Almost half of women who suffer such trauma develop post-traumatic stress disorder (PTSD). Markowitz et al. (2015) found that an affect-focused non-exposure therapy, Interpersonal Psychotherapy (IPT), adapted to treat PTSD (IPT-PTSD) had similar efficacy to and lower dropout rates than Prolonged Exposure (PE), the "gold standard," most studied exposure therapy for PTSD. OBJECTIVE: To assess attrition rates in IPT of sexually assaulted women recently diagnosed with PTSD. METHODS: The current study derives from a two-arm, randomized controlled clinical trial of sexually assaulted women with PTSD who received 14 weeks of standardized treatment with either IPT-PTSD or sertraline. Sample: The 32 patients in the IPT treatment arm were analyzed. RESULTS: Overall attrition was 29%. One patient was withdrawn because of suicidal risk; four dropped out pre-treatment, and five dropped out during IPT-PTSD. If the excluded patient is considered a dropout, the rate increases to 31%. DISCUSSION: This is the first formal study of IPT for PTSD specifically due to sexual assault. IPT attrition approximated dropout rates in PE studies, which are often around 30%, and to the sertraline group in our study (34.5%). Further research should compare IPT and PE among sexually assaulted women to clarify our hypothesis that IPT could be an attractive alternative approach for this patient group.

Impaired autophagic activity and ATG4B deficiency are associated with increased endoplasmic reticulum stress-induced lung injury.

Aging is the main risk factor for the development of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal lung disorder. Although the pathogenic mechanisms are uncertain, endoplasmic reticulum (ER) stress and impaired proteostasis that have been linked with aging are strongly associated with the pathogenesis of IPF. Using the Atg4b-deficient mice as a model, that partially reproduces the autophagy deficient conditions reported in aging and IPF lungs, we show for the first time how autophagy impairment and ER stress induction, contribute simultaneously to development of lung fibrosis in vivo. Increased expression of ER stress markers, inflammation and apoptosis of alveolar epithelial cells were observed in Atg4b-deficient mice compared to WT mice, when treated with the ER stress inducer tunicamycin. After tunicamycin treatment, Atg4b null lungs showed accumulation of its substrate LC3-I, demonstrating that these mice failed to induce autophagy despite the ER stress conditions. We also showed that compromised autophagy in lungs from Atg4b null mice is associated with exacerbated lung damage, epithelial apoptosis and the development of lung fibrosis at 21 days after tunicamycin treatment. Our findings indicate that ATG4B protein and autophagy are essential to mitigate ER stress and to prevent tunicamycin-induced epithelial apoptosis and lung fibrosis.

Quality of life of mothers whose children work on the streets of São Paulo, Brazil.

The present study evaluated the perceived quality of life of the mothers of street children and investigated the association with their history of childhood violence, the occurrence of current domestic violence, their current mental states and that of their children, and family functioning. The applied instruments were as follows: Strengths and Difficulties Questionnaire, WorldSAFECore Questionnaire, Instrument for the Assessment of Quality of Life of the WHO, Global Assessment of Relational Functioning Scale, Childhood Trauma Questionnaire and a socio-demographic questionnaire. The sample of convenience consisted of 79 low-income mothers who raised their children alone, and most of whom had a positive screening for mental illness. The multiple regression analysis showed that the perception of quality of life of these women was associated with the presence of psychopathology either in themselves or their children and family dysfunction. Thus any program aimed at improving the quality of life of such mothers should consider addressing their mental problems as well as those of their children, besides offering educational and psychotherapeutic approaches to these families to improve the social environment.

Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis.

Autophagy is a critical cellular homeostatic process that controls the turnover of damaged organelles and proteins. Impaired autophagic activity is involved in a number of diseases, including idiopathic pulmonary fibrosis suggesting that altered autophagy may contribute to fibrogenesis. However, the specific role of autophagy in lung fibrosis is still undefined. In this study, we show for the first time, how autophagy disruption contributes to bleomycin-induced lung fibrosis in vivo using an Atg4b-deficient mouse as a model. Atg4b-deficient mice displayed a significantly higher inflammatory response at 7 d after bleomycin treatment associated with increased neutrophilic infiltration and significant alterations in proinflammatory cytokines. Likewise, we found that Atg4b disruption resulted in augmented apoptosis affecting predominantly alveolar and bronchiolar epithelial cells. At 28 d post-bleomycin instillation Atg4b-deficient mice exhibited more extensive and severe fibrosis with increased collagen accumulation and deregulated extracellular matrix-related gene expression. Together, our findings indicate that the ATG4B protease and autophagy play a crucial role protecting epithelial cells against bleomycin-induced stress and apoptosis, and in the regulation of the inflammatory and fibrotic responses.

Factors related to the cortisol awakening response of children working on the streets and siblings, before and after 2 years of a psychosocial intervention.

The study objective was to observe the cortisol awakening response (CAR) pattern before and after a psychosocial intervention with children from dysfunctional families who had at least one child working on the streets, and to verify factors related to it. Two hundred and eleven children between 7 and 14 years old were selected and 191 were included, 178 were re-evaluated 2 years after, of whom 113 had cortisol measures completed. Besides cortisol, they were evaluated at baseline and at end point regarding: abuse/neglect, mental health symptoms, exposure to urban violence and family environment. There was no significant difference between the CAR area under the curve (AUC) before and after the intervention. Two regression analysis models were built to evaluate factors related to the CAR before and after intervention. Before the intervention, working on the streets (vs. not) was related to a greater cortisol increase after awakening, at follow-up, having suffered physical punishment (vs. not) was related to a flattened cortisol response. The intervention was not associated with changes in the magnitude of the CAR AUC, though the CAR was associated with psychosocial stressors pre- and post-intervention. Effective interventions for children at risk that might shape a physiological cortisol response are still needed.

Lack of association between the 5-HTTLPR and positive screening for mental disorders among children exposed to urban violence and maltreatment.

OBJECTIVE: To ascertain whether genetic variations in the serotonin transporter gene (5-HTTLPR 44-bp insertion/deletion polymorphism) influence an increase in depressive and anxiety symptoms in children and adolescents exposed to high levels of violence. METHODS: Saliva samples were collected from a group of children who were working on the streets and from their siblings who did not work on the streets. DNA was extracted from the saliva samples and analyzed for 5-HTTLPR polymorphism genotypes. RESULTS: One hundred and seventy-seven children between the ages of 7 and 14 years were analyzed (114 child workers and 63 siblings). Data on socioeconomic conditions, mental symptoms, and presence and severity of maltreatment and urban violence were collected using a sociodemographic inventory and clinical instruments. There was no positive correlation between the 5-HTTLPR polymorphism and presence of mental symptoms in our sample, although the children were exposed to high levels of abuse, neglect, and urban violence. CONCLUSIONS: Despite previous studies that associated adult psychiatric disorders with the 5-HTTLPR polymorphism and a history of childhood maltreatment, no such association was found in this sample of children at risk.

Exposure to maltreatment and urban violence in children working on the streets in São Paulo, Brazil: factors associated with street work.

OBJECTIVE: To quantitatively study the exposure to childhood maltreatment and urban violence in children from families with at least one child working on the streets and to investigate the relationship between these factors and street work. METHODS: Families who participated in a nongovernmental organization (NGO) program to eliminate child labor were included. Data concerning sociodemographic characteristics, punishment methods used in the family environment against the children, five types of abuse and neglect perpetrated by the caregivers, urban violence exposure and family functioning were collected. RESULTS: The sample included 126 children who were working on the streets and 65 siblings who were not working on the streets. Caregivers reported high levels of severe physical punishment. The children reported high levels of abuse and neglect, and high levels of urban violence exposure. The families showed a predominance of dysfunctional and unsatisfactory relationships. A multiple logistic regression model showed that age older than 12 years and severe physical punishment at home were associated with street work. CONCLUSION: Interventions to decrease the risk of child street work should be family-focused and should aim to reduce violence in the family environment.

A associação de técnicas de equilíbrio e condicionamento cardiorrespiratório diminui o risco de quedas e melhora a capacidade funcional em mulheres / La asociación de ejercicios de equilibrio con el acondicionamiento cardiorrespiratorio disminuye el riesgo de caídas y mejora la capacidad funcional de mujeres / Association of balance and cardiorespiratory conditioning techniques reduces risk of falls and improves functional capacity in women

RESUMO Verificou-se a efetividade da associação do treino de equilíbrio no solo com o treino cardiorrespiratório na água sobre a capacidade funcional e o risco de quedas em mulheres adultas. Esse ensaio clínico não controlado unicego foi composto por 24 mulheres (60,79±5,51), submetidas a três meses de treinamento. Instrumentos: Short Physical Performance Battery (SPPB), Quick Screen Clinical Falls Risk Assessment (QSCFRA) e Teste de Caminhada de Seis Minutos (TC6). Houve melhora dos índices de equilíbrio, mas sem significância estatística. Ocorreu melhora significativa para o risco de quedas (p<0,001) e TC6 (p=0,049), com aumento médio de 39,58±95,5 m na distância percorrida. Houve correlações significativas entre TC6 e SPPB pré-treinamento (r=0,56, p=0,008), idade e QSCFRA (r=0,538, p=0,012) e comorbidades e QSCFRA (r=0,696; p=0,006). Verificou-se efetividade na associação dos treinos propostos sobre a diminuição do risco de quedas e melhora da capacidade funcional.

RESUMEN Se estudia si hay eficacia la asociación de los ejercicios de equilibrio en el suelo con el acondicionamiento cardiorrespiratorio en el agua en la capacidad funcional y en el riesgo de caídas de mujeres mayores. De este estudio clínico no aleatorizado a ciegas participaron 24 mujeres (60,79±5,51), evaluadas durante tres meses. Se emplearon las siguientes: Short Physical Performance Battery (SPPB), Quick Screen Clinical Falls Risk Assessment (QSCFRA) y la Prueba de Caminata de 6 minutos (PC6). Aunque los índices de equilibrio presentaron mejoras, no fueron estadísticamente significantes. El riesgo de caídas (p<0,001) y la PC6 (p=0,049) tuvieron mejoras significativas, con un promedio de aumento de 39,58±95,5 m en la distancia cumplida. Presentaron correlaciones significativas la PC6 y la SPPB preejercicio (r=0,56; p=0,008), la edad y la QSCFRA (r=0,538; p=0,012) y las comorbilidades y la QSCFRA (r=0,696; p=0,006). Se concluye que la relación entre los ejercicios propuestos es eficaz para disminuir caídas y mejorar la capacidad funcional.

ABSTRACT This study aimed to test the effectiveness of the association of balance training on the ground with cardiorespiratory training in the water on the functional capacity and risk of falls on adult women. This single-blind uncontrolled clinical trial was formed by 24 women (60.79±5.51), subjected to three months of training. Instruments: Short Physical Performance Battery (SPPB), QuickScreen Clinical Falls Risk Assessment (QSCFRA) and Six-Minute Walk Test (6mwt). Balance improvement was noticed, although without statistical significance. Significant improvement occurred for risk of falls (p<0.001) and 6mwt (p=0.049), with a 39.58±95.5 mean increase of distance covered. Significant correlations happened between 6mwt and pre-training SPPB (r=0.56, p=0.008), age and QSCFRA (r=0.538, p=0.012), and comorbidities and QSCFRA (r=0.696; p=0.006). Effectiveness was observed in association with the proposed training on reduction of risk of falls and functional capacity improvement.

Quality of life of mothers whose children work on the streets of São Paulo, Brazil / Qualidade de vida de mães de crianças trabalhadoras de rua da cidade de São Paulo, Brasil / La calidad de vida de las madres de niños trabajadores en las calles de São Paulo, Brasil

The present study evaluated the perceived quality of life of the mothers of street children and investigated the association with their history of childhood violence, the occurrence of current domestic violence, their current mental states and that of their children, and family functioning. The applied instruments were as follows: Strengths and Difficulties Questionnaire, WorldSAFECore Questionnaire, Instrument for the Assessment of Quality of Life of the WHO, Global Assessment of Relational Functioning Scale, Childhood Trauma Questionnaire and a socio-demographic questionnaire. The sample of convenience consisted of 79 low-income mothers who raised their children alone, and most of whom had a positive screening for mental illness. The multiple regression analysis showed that the perception of quality of life of these women was associated with the presence of psychopathology either in themselves or their children and family dysfunction. Thus any program aimed at improving the quality of life of such mothers should consider addressing their mental problems as well as those of their children, besides offering educational and psychotherapeutic approaches to these families to improve the social environment.

Avaliamos a percepção da qualidade de vida de mães de crianças em situação de rua e investigamos a sua possível associação com os antecedentes maternos de abuso e violência na infância e vitimização atual, sintomas emocionais delas e de seus filhos e com o funcionamento familiar. Foram aplicados os seguintes instrumentos: Instrumento para a Avaliação da Qualidade de Vida da OMS - versão abreviada, Questionário de Capacidades e Dificuldades, WorldSAFECore Questionnaire, Escala de Avaliação Global de Funcionamento nas Relações Familiares, Childhood Trauma Questionnaire e um questionário sociodemográfico. Nossa amostra de conveniência foi constituída por 79 mães, a maioria delas com rastreamento positivo para doença mental. Aplicamos um modelo de regressão múltipla que encontrou associação entre a percepção de pior qualidade de vida com a presença de psicopatologia nelas e em seus filhos e com pior funcionamento familiar. Dessa forma, qualquer programa voltado para a melhora da qualidade de vida de mães nessa condição deve considerar a abordagem de problemas mentais nelas e em seus filhos, além de oferecer recursos educacionais e psicoterapêuticos para as famílias, visando à melhora das condições socioambientais.

Se presenta aquí una evaluación de la calidad de vida percibida por madres de niños en las calles, y se investigó la posible asociación con antecedentes maternos de abuso y violencia en la infancia y victimización actual, los síntomas emocionales de ellos y de sus hijos y el funcionamiento familiar. Se aplicaron los Instrumentos para la Evaluación de la Calidad de Vida de la OMS - versión abreviada, Cuestionario de Capacidades y Dificultades, WorldSAFECore Questionnaire, Escala de Evaluación Global de Funcionamiento en las Relaciones Familiares, Childhood Trauma Questionnaire y un cuestionario sociodemográfico. La muestra incluyó a 79 madres, la mayoría de ellas con una detección positiva para la enfermedad mental. La percepción de calidad de vida se asoció con la presencia de psicopatología en ellos y sus hijos y el funcionamiento familiar. Por lo tanto, cualquier programa destinado a mejorar la calidad de vida de las madres en esta condición debe considerar el enfoque de los problemas mentales en ellos y sus hijos y ofrecer trabajo educativo y terapéutico a esas familias.