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PURPOSE: To compare the DNA damage in granulosa cells (GCs) of women undergoing ovarian-stimulated cycles with four widely used recombinant human follicle-stimulating hormones (rhFSH) in in vitro fertilization (IVF) protocols (Corneumon®, Gonal-F®, Pergoveris® and Puregon®). METHODS: A randomized trial was carried out at a Mexican hospital. GCs were isolated from 18 women with infertility undergoing assisted reproductive techniques (ART). Four controlled ovarian stimulation (COS) protocols including Corneumon®, Gonal-F®, Pergoveris® or Puregon® were used. GCs DNA damage was assessed by the Comet assay. Two parameters were measured: comet tail length (CTL), and Olive tail moment (OTM, the percentage of DNA in the tail multiplied by the distance between the center of the tail and head). RESULTS: Use of the different hrFSH in COS caused variable and statistically significant levels of DNA damage in GCs of infertile women. CTL was similar in the Corneumon® and Pergoveris® groups (mean values of 48.73 and 55.18, respectively) and Corneumon® CTL was significantly lower compared to the Gonal-F® and Puregon® groups (mean values of 61.98 and 91.17, respectively). Mean OTM values were significantly lower in Corneumon® and Pergoveris® groups, compared to Gonal-F® and Puregon® groups (25.59, 27.35, 34.76, and 47.27, respectively). CONCLUSION: Use of Corneumon® and Pergoveris® in COS caused statistically significantly lower levels of DNA damage in GCs of infertile women undergoing ART, which could potentially correlate with better reproductive outcomes.
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Infertilidade Feminina , Hormônio Luteinizante , Feminino , Humanos , Dano ao DNA , Combinação de Medicamentos , Fertilização in vitro , Hormônio Foliculoestimulante , Hormônio Foliculoestimulante Humano , Células da Granulosa , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Proteínas RecombinantesRESUMO
In this retrospective study, we aimed to evaluate the effects of the neurotrophic compound Cerebrolysin on executive, cognitive, and functional performance in patients with traumatic brain injury (TBI) with a highly severe disability level. A total of 44 patients were included in the study, with 33 patients in the control group and 11 patients in the interventional group who received intravenous infusions of 30 mL Cerebrolysin. Both groups received standard rehabilitation therapy following the rehabilitation protocol for patients with TBI at Hospital Clínico Mutual de Seguridad. Functional and cognitive scales were evaluated at baseline, at four months, and at the endpoint of the intervention therapy at seven months (on average). The results revealed a significant improvement in the Cerebrolysin-treated group compared to the control group. Specifically, patients who received Cerebrolysin showed a moderate residual disability and a significant reduction in the need for care. Concerning the promising results and considering the limitations of the retrospective study design, we suggest that randomized controlled studies be initiated to corroborate the positive findings for Cerebrolysin in patients with moderate to severe brain trauma.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Humanos , Estudos Retrospectivos , Lesões Encefálicas/reabilitação , Lesões Encefálicas Traumáticas/tratamento farmacológico , Cognição , Recuperação de Função FisiológicaRESUMO
Background and purpose: The novel coronavirus, SARS-CoV-2, which was identified after the outbreak in Wuhan, China, in December 2019, has kept the whole world in tenterhooks due to its severe life-threatening nature of the infection. The World Health Organization (WHO) declared coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 a pandemic in 2020, an unprecedented challenge, having a high contagious life-threatening condition with unprecedented impacts for worldwide societies and health care systems. Neurologic symptoms related to SARS-CoV-2 have been described recently in the literature, and acute cerebrovascular disease is one of the most serious complications. The occurrence of large-vessel occlusion in young patients with COVID-19 infection has been exceedingly rare. In this article, we describe the profile of patients undergoing decompressive craniectomy for the treatment of intracranial hypertension by stroke associated with COVID-19 published so far. A narrative review of the central issue in focus was designed: decompressive craniectomy in a pandemic time.
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OBJECTIVE: Polymyalgia rheumatica (PMR) is the most common inflammatory disease in patients over 50 years. Information about the disease in Latin America (LATAM) is scarce. We aimed to evaluate a group of Colombian patients with PMR and to conduct a systematic review of PMR in LATAM. METHODS: A multicentric retrospective study was performed. Medical records of 256 PMR patients were evaluated. Patients were divided into two groups, those fulfilling the 2012 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for PMR and those who did not (i.e., clinical diagnosis). A systematic literature review and meta regression was performed comparing Colombian vs LATAM patients. RESULTS: From 256 patients, 145 (56.6%) fulfilled the 2012 EULAR/ACR criteria, and 111 (43.3%) were classified by clinical diagnosis. Inflammatory bilateral shoulder pain, pelvic girdle aching, morning stiffness >45 min, elevated erythrocyte sedimentation rate (ESR), and C-reactive protein (CPR), and Methotrexate (MTX) prescription were more common in the 2012 EULAR/ACR group. None of the included patients presented overt polyautoimmunity (PolyA), whereas up to 24% exhibited latent PolyA. In addition, these patients showed high frequency of malignancy (7.59%). In the meta regression analysis, Colombian patients exhibited lower ESR levels, and were less likely to develop giant cell arteritis (GCA) as compared to the rest of LATAM data. CONCLUSION: Patients with PMR in LATAM exhibit similar phenotypes from other cohorts worldwide. Malignancy, GCA and latent PolyA should be considered in the routine clinical follow-up of patients with PMR.
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OBJECTIVE: We sought to evaluate contractile function in single-ventricle patients before and after imposition of Fontan physiology. METHODS: Single right ventricle (SRV; n = 38) and single left ventricle (SLV; n = 11) patients underwent cardiac magnetic resonance imaging pre and post Fontan operation. Global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain were measured along with ejection fraction (EF) and atrioventricular valve regurgitation (AVVR). RESULTS: Age at cardiac magnetic resonance imaging before the Fontan operation was 3.1 ± 1.3 years and after the Fontan procedure was 5.8 ± 2.7 years. There were no significant EF differences between SRV and SLV patients before and after the Fontan procedure, and EF did not deteriorate significantly after the Fontan operation. GRS was significantly lower for SRV patients than for SLV patients before (24.3% vs 32.1%; P = .048) and after (21.8% vs 29.7%; P = .045) the Fontan procedure. GRS and GCS of the SRV patients deteriorated significantly after the Fontan operation (GRS, P = .01; GCS, P = .009). Strains showed positive correlations before and after the Fontan operation with positive correlations among each strain. Within all patients, strains correlated positively with EF. Strains and EF negatively correlated with AVVR (GRS P = .03, r = -0.22; GCS P = .03, r = -0.23; EF P < .001, r = -0.37). CONCLUSIONS: Strains were lower for SRV than for SLV patients before and after the Fontan operation and deteriorated after the Fontan operation. Our study suggests that strain measures might detect ventricular deterioration earlier than EF. Because strains before and after the Fontan operation were positively correlated, and negatively correlated with AVVR, the early institution of myocardial protective therapy including AVVR management, especially for SRV patients, might have benefit.
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Técnica de Fontan , Coração Univentricular/fisiopatologia , Coração Univentricular/cirurgia , Função Ventricular , Fenômenos Biomecânicos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Volume SistólicoRESUMO
Sex differences in the brain have prompted many researchers to investigate the underlying molecular actors, such as the glucocorticoid receptor (GR). This nuclear receptor controls gene expression, including microRNAs (miRNAs), in non-neuronal cells. Here, we investigated sex-biased effects of GR on hippocampal miRNA expression and neuronal morphology by generating a neuron-specific GR knockout mouse (Emx1-Nr3c1 -/-). The levels of 578 mature miRNAs were assessed using NanoString technology and, in contrast to males, female Emx1-Nr3c1 -/- mice showed a substantially higher number of differentially expressed miRNAs, confirming a sex-biased effect of GR ablation. Based on bioinformatic analyses we identified several transcription factors potentially involved in miRNA regulation. Functional enrichment analyses of the miRNA-mRNA interactions revealed pathways related to neuronal arborization and both spine morphology and density in both sexes. Two recognized regulators of dendritic morphology, CAMKII-α and GSK-3ß, increased their protein levels by GR ablation in female mice hippocampus, without changes in males. Additionally, sex-specific effects of GR deletion were observed on CA1 neuronal arborization and dendritic spine features. For instance, a reduced density of mushroom spines in apical dendrites was evidenced only in females, while a decreased length in basal dendrites was noted only in males. However, length and arborization of apical dendrites were reduced by GR ablation irrespective of the sex. Overall, our study provides new insights into the sex-biased GR actions, especially in terms of miRNAs expression and neuronal morphology in the hippocampus.
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IntroductionEmergency physicians are using bolus-dose vasopressors to temporize hypotensive patients until more definitive blood pressure support can be established. Despite a paucity of clinical outcome data, emergency department applications are expanding into the prehospital setting. This series presents two cases of field expedient vasopressor use by emergency medicine providers for preflight stabilization during aeromedical evacuation to a hospital ship as part of the United States Navy disaster response in Puerto Rico. A critical approach and review of the literature are discussed.Case ReportTwo critically ill patients were managed in an austere environment as a result of the devastation from Hurricane Maria (Yabucoa, Puerto Rico; 2017). They both exhibited signs of respiratory distress, hemodynamic instability, and distributive shock requiring definitive airway management and hemodynamic support prior to aeromedical evacuation.DiscussionThe novel use of field expedient vasopressors prior to induction for rapid sequence intubation was successfully and safely employed in both cases. Both patients had multiple risk factors for peri-induction cardiac arrest given their presenting hemodynamics. Despite their illness severity, both patients were induced, transported, and ultimately admitted to the intensive care unit (ICU) in stable condition following administration of the field expedient vasopressors.Conclusion:Field expedient vasopressors were safely and effectively employed in an austere field environment during a disaster response. This case series contributes to the growing body of literature of safe bolus-dose vasopressor use by emergency physicians to temporize hypotensive patients in resource-constrained situations. HardwickJM, MurnanSD, Morrison-PonceDP, DevlinJJ. Field expedient vasopressors during aeromedical evacuation: a case series from the Puerto Rico disaster response. Prehosp Disaster Med. 2018;33(6):668-672.
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Broncodilatadores/uso terapêutico , Tempestades Ciclônicas , Epinefrina/uso terapêutico , Síndrome do Desconforto Respiratório/terapia , Idoso , Resgate Aéreo , Broncodilatadores/administração & dosagem , Serviços Médicos de Emergência , Epinefrina/administração & dosagem , Feminino , Humanos , Intubação Intratraqueal , Porto RicoRESUMO
INTRODUCTION: Acquired brain injury (ABI) during childhood typically causes behavior problems in the child and high levels of stress in the family. The aims of this study are: (1) to investigate the effectiveness and feasibility of a parenting intervention in improving behavior and self-regulation in Mexican children with ABI compared to telephone support; (2) to investigate the effectiveness and feasibility of a parenting intervention in improving parenting skills, parent self-efficacy and decreasing parental stress in parents of children with ABI compared to telephone support. Our secondary aims are (1) to explore the impact that parent characteristics have on the intervention outcomes; (2) to investigate if changes are maintained 3 months after the intervention. METHODS: The research design is a blind randomized controlled trial (RCT). Eligible participants include children with a diagnosis of ABI, between 6 and 12 years of age, and their parents. Sixty-six children and their parents will be randomly allocated to either a parenting program group or telephone support group. The parenting program involves six face-to-face weekly group sessions of 2.5 h each. Participants in the control group receive an information sheet with behavioral strategies, and six weekly phone calls, in which strategies to improve academic skills are provided. Children and their parents are evaluated by blind assessors before the intervention, immediately after the intervention and 3-months post-intervention. DISCUSSION: This study will be the first to evaluate the efficacy and feasibility of a parenting program for Mexican parents of children with ABI. TRIAL IDENTIFIER: ACTRN12617000360314.
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Aging is a multifactorial process associated with an increased susceptibility to neurodegenerative disorders which can be related to chronic inflammation. Chronic inflammation, however, can be characterized by the persistent elevated glucocorticoid (GCs) levels, activation of the proinflammatory transcription factor NF-кB, as well as an increase in cytokines. Interestingly, both NF-кB and cytokines can be even modulated by Glycogen Synthase Kinase 3 beta (GSK-3ß) activity, which is a key protein that can intermediate inflammation and metabolism, once it has a critical role in AKT signaling pathway, and can also intermediate WNT/ß-CATENIN signaling pathway. The aim of this study was to verify age-related changes in inflammatory status, as well as in the AKT and WNT signaling pathways. Results showed an age-related increase in neuroinflammation as indicated by NF-кB activation, TNF-α and GCs increased levels, a decrease in AKT activation and an increase in GSK-3ß activity in both 12- and 24- month old animals. Aging also seems to induce a progressive decrease in canonical WNT/ß-CATENIN signaling pathway once there is a decrease in DVL-2 levels and in the transcription of Axin2 gene. Little is known about the DVL-2 regulation as well as its roles in WNT signaling pathway, but for the first time it was suggested that DVL-2 expression can be changed along aging.
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Envelhecimento/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Inflamação/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Regulação da Expressão Gênica no Desenvolvimento , Glucocorticoides , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta , Hipocampo/fisiologia , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Wnt/genéticaRESUMO
A indústria farmacêutica configura-se como um oligopólio, com produtos diferenciados em segmentos de classes terapêuticas específicas. As grandes farmacêuticas globais concentram seus esforços de pesquisa e de comercialização nas doenças degenerativas, que trazem maior retorno financeiro. No Brasil, destaca-se a presença de um conjunto de laboratórios públicos, os quais compõem a Rede Brasileira de Produção Pública de Medicamentos (RBPPM), voltados para as necessidades do Sistema Único de Saúde (SUS), em grande parte negligenciadas pelas Big Pharmas. O objetivo deste estudo é investigar o uso pelos laboratórios farmacêuticos oficiais brasileiros das contribuições derivadas das tecnologias da informação e comunicação (TIC), no sentido da integração da cadeia de suprimentos da RBPPM. Em sua primeira fase, a pesquisa de campo foi realizada por meio de uma abordagem quantitativa em todos os laboratórios oficiais afiliados à Associação de Laboratórios Farmacêuticos Oficiais Brasileiros (Alfob). Essa análise permitiu levantar questões que foram aprofundadas por meio da abordagem qualitativa em três laboratórios selecionados da fase anterior. As evidências coletadas permitem concluir que os objetivos descritos na criação da RBPPM, cujo alcance poderia ser facilitado pela adoção dos atributos da GCS pela rede capitaneada pelo Ministério da Saúde, ainda são incipientes e erráticos. O estudo demonstrou que, apesar das evidências teóricas e empíricas a respeito da capacidade das TIC de integrar processos, os laboratórios públicos brasileiros ainda fazem pouco uso das tecnologias estudadas na gestão de cadeias de suprimento (GCS), e o desempenho das poucas ferramentas encontradas revelou-se incipiente e insatisfatório. É bem provável que essa evidência seja uma decorrência natural do fato de que a RBPPM não utilizava uma abordagem de GCS na época em que esta pesquisa foi realizada.
The pharmaceutical industry is characterized as an oligopoly with differentiated products in segments of specific therapeutic classes. The global pharmaceutical companies focus their research and marketing efforts on degenerative diseases, as they bring bigger income as result. In Brazil, a distinctive feature is the presence of a set of public laboratories, which comprise the Brazilian Network of Public Production of Medicines (RBPPM), targeting the needs of the Unified Health System (SUS), in great part ignored by the Big Pharmas. The aim of this study is to investigate the use by Brazilian Official Pharmaceutical Laboratories of contributions derived from the Information and Communication Technologies (ICT), towards the integration of RBPPM ́s supply chain. In its first phase, the field research was carried out through a quantitative approach in all affiliated Alfob official laboratories. This analysis allowed to raise issues that have been deepened by qualitative approach in three laboratories selected from the previous phase. Collected evidences allowed to conclude that the objectives defined by the Health Department at the creation of RBPPM, that could be facilitated by the adoption of the attributes of the SCM network headed, are still incomplete and erratic. The study demonstrated that despite the theoretical and empirical evidences about the capacity of ICT to integrate processes, the Brazilian government labs still make little use of ICT supply chain management (SCM) technologies, and the performance the few tools found proved unsatisfactory and incipient. It is likely that this evidence is a natural consequence of the fact that RBPPM did not use an approach of SCM at the time this research was conducted.
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Humanos , Masculino , Feminino , Indústria Farmacêutica , Gestão da Informação em Saúde , Tecnologia da Informação , Comercialização de Medicamentos , Produção de Produtos , Sistema Único de Saúde , Armazenamento de Medicamentos , Laboratórios , Política Nacional de Medicamentos , Pesquisa QualitativaRESUMO
OBJECTIVES: Social isolation during the prepubertal period may have long-term effects on metabolism. The exposure to stressful events is associated with increased palatable food intake, constituting reward-based eating. However, palatable food consumption in early life may lead to metabolic alterations later in life. We investigated whether isolation stress during early life can lead to metabolic alterations in male and female rats with or without exposure to a palatable diet. METHODS: Animals were stressed by isolation during one week after weaning, with or without exposure to a palatable diet. RESULTS: Stress and palatable diet induced increased caloric consumption. In females, there was a potentiation of consumption in animals exposed to stress and palatable diet, reflected by increased weight gain and triacylglycerol levels in juveniles, as well as increased adiponectin levels. Most of the effects had disappeared in the adults. Different effects were observed in males: in juveniles, stress increased unacylated ghrelin levels, and hypothalamic neuropeptide Y (NPY). Subsequently, adult males that were exposed to a palatable diet during prepuberty showed increased body weight and retroperitoneal fat deposition, increased glycemia, and decreased plasma adiponectin and hypothalamic NPY. Exposure to stress during prepuberty led to increased adrenals during adulthood, decreased LDL-cholesterol and increased triacylglycerol levels. CONCLUSION: Isolation stress and consumption of palatable diet changes metabolism in a sex-specific manner. Prepuberty female rats were more prone to stress effects on food consumption, while males showed more long-lasting effects, being more susceptible to a metabolic programming after the consumption of a palatable diet.
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Ingestão de Alimentos , Maturidade Sexual/fisiologia , Isolamento Social , Estresse Psicológico/metabolismo , Adiponectina/sangue , Animais , Glicemia/análise , Feminino , Hipotálamo/química , Insulina/sangue , Masculino , Neuropeptídeo Y/análise , Ratos , Ratos Wistar , Caracteres Sexuais , Aumento de PesoRESUMO
El traumatismo craneoencefálico es el daño cerebral causado por una fuerza externa, que puede producir una alteración del estado de conciencia, resultando un deterioro del funcionamiento de las capacidades cognitivas y físicas. La Escala de Coma de Glasgow nos permite clasificar el grado de un Traumatismo Craneoencefálico, cuyo tratamiento debe iniciarse con una adecuada reanimación, según el protocolo del soporte vital avanzado al trauma. Métodos: Se estableció una secuencia estandarizada para la búsqueda de información en la base de datos electrónicas: PudMed, Scielo, Cuiden, Ciberindex, Cochrane BVS, y otras bases disponibles. La búsqueda fue limitada a 10 años a la fecha actual, en idioma inglés o español, de las cuales 10 fueron revisiones sistemáticas y 14 revisiones narrativas útiles para el desarrollo de esta guía. Resultados: El manejo inicial en todo paciente con traumatismo craneoencefálico debe estar respaldado por los principios de Soporte Vital Avanzado de Trauma (ATLS) si se genera un episodio de hipoxia aumenta su mortalidad en un 50%, en un episodio de hipotensión en un 100%. Todas las alteraciones a nivel de conciencia son emergencias letales hasta que las funciones vitales estén estabilizadas. Conclusión: La Guía de Práctica Clínica permite que el personal de enfermería estandarice y proporcione la práctica diaria en el cuidado y manejo del paciente con Traumatismo Craneoencefálico Grave y sirva de base para la toma de decisiones. Traumatismo Craneoencefálico Grave, Soporte Vital Avanzado, Escala de Glasgow, enfermería.
Introduction: Traumatic brain injury is defined as brain damage caused by an external force, and can produce an altered state of consciousness, resulting in deterioration of the functioning of cognitive and physical abilities. The Glasgow Coma Scale allows us to classify the degree of traumatic brain injury. Treatment should be initiated with appropriate resuscitation, according to the protocol advanced trauma life support. Method: PudMed, Scielo, Cuiden, Ciberindex, Cochrane VHL and other bases were used; standard sequence for finding information in electronic databases was established. The search was limited to 10 years from the current date, in English or Spanish language. 10 systematic and 14 narrative reviews were useful for the development of this guide. Results: The initial management in all patients with head trauma must be supported by the principles of Advanced Trauma Life Support (ATLS). If an episode of hypoxia is generated increase mortality by 50%; low blood pressure episode increases it by 100%. All alterations of consciousness are emergencies until vital functions are stabilized. Conclusion: Clinical Practice Guide allows nurses to standardize and give better service in the care and management of patients with severe head trauma. It serves as a basis for decision-making. Severe head trauma, Advanced Life Support, GCS, nursing.
Introdução: Lesão cerebral traumática é dano cerebral causado por uma força externa, que pode produzir um estado alterado de consciência, resultando em uma deterioração do funcionamento das habilidades cognitivas e físicas. A Escala de Coma de Glasgow nos permite classificar o grau de lesão cerebral traumática. Cujo tratamento deve ser iniciado com a reanimação adequado, de acordo com o suporte de vida trauma protocolo avançado. Métódo: PudMed, Scielo, CUIDEN, Ciberindex, Cochrane BVS e outras bases disponíveis: uma seqüência padrão para busca de informações em bases de dados electrónicas foi estabelecido. A busca foi limitada a 10 anos a partir da data atual, em Inglês ou espanhol. Dos quais 10 eram sistemática e narrativa avaliações 14 útil para o desenvolvimento deste Guia comentários. Resultados: A conduta inicial em todos os pacientes com traumatismo craniano deve ser apoiada pelos princípios do Advanced Trauma Life Support (ATLS) se um episódio de hipoxia é gerado mortalidade aumenta em 50%, um episódio hipotensivo 100%. Todas as alterações são de nível letal de emergências consciência até as funções vitais são estabilizadas. Conclusões: Guia Clinical Practice permite enfermeiros padroniza e fornece prática diária no cuidado e tratamento de pacientes com traumatismo craniano grave e servir como base para a tomada de decisões. traumatismo craniano grave, Suporte Avançado de Vida, GCS, de enfermagem.