Fatores causadores e estratégias terapêuticas para infertilidade em mulheres com síndrome dos ovários policísticos / Causers factors and therapies for infertility in women with polycystic ovarian syndrome

O trabalho teve por objetivo apresentar, a partir de uma revisão de literatura, quais os mecanismos que causam infertilidade na Síndrome dos Ovários Policísticos (SOP), assim como identificar os possíveis tratamentos disponíveis. Sabe-se que a SOP é o distúrbio endócrino mais comum na idade fértil, o qual acomete até 10% das mulheres, apresentando alterações hormonais, reprodutivas e metabólicas. Sendo assim, para seu diagnóstico são necessários pelo menos dois critérios: oligo-ovulação ou anovulação, hiperandrogenismo clínico e/ou laboratorial e ovários policísticos identificados ao exame ultrassonográfico. De acordo com a avaliação clínica de cada paciente, têm-se entre as opções terapêuticas mudanças nos hábitos de vida como primeira escolha, por exemplo, prática de atividade física e alimentação saudável, além da terapia farmacológica, uso de hormônios, fertilização e cirurgia. Entretanto, alguns efeitos colaterais no tratamento ainda causam preocupação, como o risco de gestação múltipla, o que sinaliza a necessidade de mais estudos que promovam melhoria no prognóstico dessas mulheres

Endotoxin-Induced Emphysema Exacerbation: A Novel Model of Chronic Obstructive Pulmonary Disease Exacerbations Causing Cardiopulmonary Impairment and Diaphragm Dysfunction

Chronic obstructive pulmonary disease (COPD) is a progressive disorder of the lung parenchyma which also involves extrapulmonary manifestations, such as cardiovascular impairment, diaphragm dysfunction, and frequent exacerbations. The development of animal models is important to elucidate the pathophysiology of COPD exacerbations and enable analysis of possible therapeutic approaches. We aimed to characterize a model of acute emphysema exacerbation and evaluate its consequences on the lung, heart, and diaphragm. Twenty-four Wistar rats were randomly assigned into one of two groups: control (C) or emphysema (ELA). In ELA group, animals received four intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals. The C group received saline under the same protocol. Five weeks after the last instillation, C and ELA animals received saline (SAL) or E. coli lipopolysaccharide (LPS) (200 μg in 200 μl) intratracheally. Twenty-four hours after saline or endotoxin administration, arterial blood gases, lung inflammation and morphometry, collagen fiber content, and lung mechanics were analyzed. Echocardiography, diaphragm ultrasonography (US), and computed tomography (CT) of the chest were done. ELA-LPS animals, compared to ELA-SAL, exhibited decreased arterial oxygenation; increases in alveolar collapse (p < 0.0001), relative neutrophil counts (p = 0.007), levels of cytokine-induced neutrophil chemoattractant-1, interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and vascular endothelial growth factor in lung tissue, collagen fiber deposition in alveolar septa, airways, and pulmonary vessel walls, and dynamic lung elastance (p < 0.0001); reduced pulmonary acceleration time/ejection time ratio, (an indirect index of pulmonary arterial hypertension); decreased diaphragm thickening fraction and excursion; and areas of emphysema associated with heterogeneous alveolar opacities on chest CT. In conclusion, we developed a model of endotoxin-induced emphysema exacerbation that affected not only the lungs but also the heart and diaphragm, thus resembling several features of human disease. This model of emphysema should allow preclinical testing of novel therapies with potential for translation into clinical practice

High anti-SARS-CoV-2 antibody seroconversion rates before the second wave in Manaus, Brazil, and the protective effect of social behaviour measures: results from the prospective DETECTCoV-19 cohort

Background: The city of Manaus, Brazil, has seen two collapses of the health system due to the COVID-19 pandemic. We report anti-SARS-CoV-2 nucleocapsid IgG antibody seroconversion rates and associated risk factors in Manaus residents before the second wave of the epidemic in Brazil. Methods: A convenience sample of adult (aged ≥18 years) residents of Manaus was recruited through online and university website advertising into the DETECTCoV-19 study cohort. The current analysis of seroconversion included a subgroup of DETECTCoV-19 participants who had at least two serum sample collections separated by at least 4 weeks between Aug 19 and Oct 2, 2020 (visit 1), and Oct 19 and Nov 27, 2020 (visit 2). Those who reported (or had no data on) having a COVID-19 diagnosis before visit 1, and who were positive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at visit 1 were excluded. Using an in-house ELISA, the reactivity index (RI; calculated as the optical density ratio of the sample to the negative control) for serum anti-SARS-CoV-2 nucleocapsid IgG antibodies was measured at both visits. We calculated the incidence of seroconversion (defined as RI values ≤1·5 at visit 1 and ≥1·5 at visit 2, and a ratio >2 between the visit 2 and visit 1 RI values) during the study period, as well as incidence rate ratios (IRRs) through cluster-corrected and adjusted Poisson regression models to analyse associations between seroconversion and variables related to sociodemographic characteristics, health access, comorbidities, COVID-19 exposure, protective behaviours, and symptoms. Findings: 2496 DETECTCoV-19 cohort participants returned for a follow-up visit between Oct 19 and Nov 27, 2020, of whom 204 reported having COVID-19 before the first visit and 24 had no data regarding previous disease status. 559 participants were seropositive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at baseline. Of the remaining 1709 participants who were seronegative at baseline, 71 did not meet the criteria for seroconversion and were excluded from the analyses. Among the remaining 1638 participants who were seronegative at baseline, 214 showed seroconversion at visit 2. The seroconversion incidence was 13·06% (95% CI 11·52–14·79) overall and 6·78% (5·61–8·10) for symptomatic seroconversion, over a median follow-up period of 57 days (IQR 54–61). 48·1% of seroconversion events were estimated to be asymptomatic. The sample had higher proportions of affluent and higher-educated people than those reported for the Manaus city population. In the fully adjusted and corrected model, risk factors for seroconversion before visit 2 were having a COVID-19 case in the household (IRR 1·49 [95% CI 1·21–1·83]), not wearing a mask during contact with a person with COVID-19 (1·25 [1·09–1·45]), relaxation of physical distancing (1·31 [1·05–1·64]), and having flu-like symptoms (1·79 [1·23–2·59]) or a COVID-19 diagnosis (3·57 [2·27–5·63]) between the first and second visits, whereas working remotely was associated with lower incidence (0·74 [0·56–0·97]). Interpretation: An intense infection transmission period preceded the second wave of COVID-19 in Manaus. Several modifiable behaviours increased the risk of seroconversion, including non-compliance with non-pharmaceutical interventions measures such as not wearing a mask during contact, relaxation of protective measures, and non-remote working. Increased testing in high-transmission areas is needed to provide timely information about ongoing transmission and aid appropriate implementation of transmission mitigation measures. Funding: Ministry of Education, Brazil; Fundação de Amparo à Pesquisa do Estado do Amazonas; Pan American Health Organization (PAHO)/WHO.World Health OrganizationRevisión por pare

Prevalêcia de incontinência urinária e fatores associados em mulheres no climatério em uma unidade de atenção primária à saúde

Objective: To estimate the prevalence of urinary incontinence (UI) and investigate the associated factors. Methods: This is a quantitative, cross-sectional and analytical study with 233 women going through climacteric, in the age range of 40-65 years, seen in a Primary Health Care Unit (PHU) developed in the period from December 2014 to June 2015. Sociodemographic and clinical (obstetrical and gynecological) data, comorbidities and urinary profile were assessed. The software SPSS 19.0 and the chi-square test were employed to evaluate the association between the variables. The significance level of 5% was adopted. Results: Complaint about UI was present in 41.2% (n=96) of women. Higher prevalence was observed in the age group of 40-45 years with 36.5% (n=35) (pObjetivo: Estimar la prevalencia de incontinencia urinaria (IU) en mujeres en el climaterio y investigar los factores asociados. Métodos: Se trata de un estudio cuantitativo del tipo transversal y analítico con 233 mujeres en el climaterio, en la franja de edad entre 40 y 65 años asistidas en la Unidad de Atención a la Salud (UAPS) desarrollado en el periodo de diciembre de 2014 a junio de 2015. Se recogieron datos sociodemográficos, de comorbidades, clínicos (obstétricos y ginecológicos) y del perfil urinario. Se utilizo el programa SPSS 19.0 y la prueba chi-cuadrado para analizar la asociación entre las variables. Se adoptó el nivel de significancia del 5%. Resultados: La queja de IU estuvo presente en el 41,2% (n=96) de las mujeres. Se verificó mayor prevalencia en la franja de edad entre 40-45 años en el 36,5% (n=35) (p=0,05), color pardo en el 21,9% (n=21) (p=0,002) y baja escolaridad (hasta el 1º ciclo fundamental completo) en el 39,6% (n=38) (p=0,627). Respecto las comorbidades autorreferidas, el 38,5% (n=37) de las mujeres con incontinencia presentaron hipertensión arterial sistémica (p=0,9’6), el 17,7% (n=17) diabetes (p=0,982) y el 28,1% (n=27) constipación intestinal (p=0,101). Sobre las características clínicas, el 41,7% (n=35) tuvieron solamente partos del tipo vaginal (p=0,087) y el 53,1% (n=51) estaban en la menopausia (p=0,113). Se verificó la IU de esfuerzo en el 85,4% (n=82) de las mujeres. Conclusión: Se encontró elevada prevalencia de IU en mujeres en el climaterio destacando mayor ocurrencia en las jóvenes de color pardo.Objetivo: Estimar a prevalência de incontinência urinária (IU) em mulheres no climatério e investigar os fatores associados. Métodos: Trata-se de um estudo quantitativo, do tipo transversal e analítico com 233 mulheres no climatério, na faixa etária de 40 a 65 anos, atendidas em uma Unidade de Atenção Primária a Saúde (UAPS), desenvolvido no período de dezembro de 2014 a junho de 2015. Coletaram-se os dados sociodemográficos, comorbidades, clínicos (obstétricos e ginecológicos) e perfil urinário. Utilizou-se o programa SPSS 19.0 e o teste de qui-quadrado para analisar associação entre as variáveis. Adotou-se nível de significância de 5%. Resultados: A queixa de IU esteve presente em 41,2% (n=96) das mulheres. Verificou-se maior prevalência na faixa etária de 40-45 anos com 36,5% (n=35) (p=0,05), cor parda com 21,9% (n=21) (p=0,002) e escolaridade baixa (até 1º ciclo fundamental completo) com 39,6% (n=38) (p=0,627). Quanto à comorbidades autorreferidas, 38,5% (n=37) das mulheres incontinentes apresentaram hipertensão arterial sistêmica (p=0,9’6), 17,7% (n=17) diabetes (p=0,982) e 28,1% (n=27) constipação intestinal (p=0,101). Sobre as características clínicas, 41,7% (n=35) tiveram apenas partos do tipo vaginal (p=0,087) e 53,1% (n=51) estavam na menopausa (p=0,113). Verificou-se a IU de esforço em 85,4% (n=82) das mulheres. Conclusão: Encontrou-se elevada prevalência de incontinência urinária em mulheres climatéricas, destacando maior ocorrência nas mais jovens e de cor parda

Ghrelin therapy improves lung and cardiovascular function in experimental emphysema

Abstract Background Emphysema is a progressive disease characterized by irreversible airspace enlargement followed by a decline in lung function. It also causes extrapulmonary effects, such as loss of body mass and cor pulmonale, which are associated with shorter survival and worse clinical outcomes. Ghrelin, a growth-hormone secretagogue, stimulates muscle anabolism, has anti-inflammatory effects, promotes vasodilation, and improves cardiac performance. Therefore, we hypothesized that ghrelin might reduce lung inflammation and remodelling as well as improve lung mechanics and cardiac function in experimental emphysema. Methods Forty female C57BL/6 mice were randomly assigned into two main groups: control (C) and emphysema (ELA). In the ELA group (n=20), animals received four intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals. C animals (n=20) received saline alone (50 μL) using the same protocol. Two weeks after the last instillation of saline or PPE, C and ELA animals received ghrelin or saline (n=10/group) intraperitoneally (i.p.) daily, during 3 weeks. Dual-energy X-ray absorptiometry (DEXA), echocardiography, lung mechanics, histology, and molecular biology were analysed. Results In elastase-induced emphysema, ghrelin treatment decreased alveolar hyperinflation and mean linear intercept, neutrophil infiltration, and collagen fibre content in the alveolar septa and pulmonary vessel wall; increased elastic fibre content; reduced M1-macrophage populations and increased M2 polarization; decreased levels of keratinocyte-derived chemokine (KC, a mouse analogue of interleukin-8), tumour necrosis factor-α, and transforming growth factor-β, but increased interleukin-10 in lung tissue; augmented static lung elastance; reduced arterial pulmonary hypertension and right ventricular hypertrophy on echocardiography; and increased lean mass. Conclusion In the elastase-induced emphysema model used herein, ghrelin not only reduced lung damage but also improved cardiac function and increased lean mass. These findings should prompt further studies to evaluate ghrelin as a potential therapy for emphysema