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BACKGROUND: Opitz GBBB syndrome (GBBB) is an X-linked disease characterized by midline defects, including congenital heart defects. We present our diagnostic approach to the identification of GBBB in a consanguineous family in which two males siblings were concordant for a total anomalous connection of pulmonary veins and minor facial dysmorphias. METHODS: Targeted exome sequencing analysis of a 380-gene panel associated with cardiovascular disease was performed on the propositus. Interpretative analysis of the exome results was conducted, and 3D models of the protein changes were generated. RESULTS: We identified a NM_000381.4:c.608G>A;p.(Arg203Gln) change in MID1, affecting the conformation of the B-box 2 domain of the protein, with a zinc finger structure and associated protein interactions. This clinical phenotype is consistent with GBBB; however, the type of congenital heart disease observed in this case has not been previously reported. CONCLUSION: A new likely pathogenic variant on MID1 c.608G>A was found to be associated with Opitz GBBB syndrome.
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Doenças Genéticas Ligadas ao Cromossomo X , Hipertelorismo , Hipospadia , Humanos , Masculino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Hipertelorismo/genética , Hipospadia/genéticaRESUMO
Objetivo: conhecer as vivências e demandas de pessoas transexuais ao buscar serviços de Atenção Primária à Saúde. Método: pesquisa descritiva com abordagem qualitativa, realizada com pessoas autodeclaradas transexuais que utilizam os serviços de Atenção Primária à Saúde. A coleta de dados se deu por meio de questionário on-line, esses foram submetidos à análise através de software livre para dados qualitativos e o corpus textual de pesquisa passou pela análise do tipo temático-categorial. Resultados: com a análise dos dados, foi criada a categoria: vivências e demandas no atendimento na Atenção Primária à Saúde, que representou 51,6% das Unidades de Registro. Conclusão: no cenário atual, a população trans ainda padece com dificuldades de acesso aos serviços de saúde e, portanto de terem seus direitos garantidos
Objectives: to know the experiences and demands of transgender people when seeking primary health care services. Method: descriptive research with a qualitative approach, conducted with self-declared transsexual scare people who use primary health care services. Data collection was performed through an online questionnaire, which were submitted to analysis through free software for qualitative data and the textual corpus of research was analyzed by thematic-category analysis. Results: with data analysis, two categories were created: experiences in primary health care, which represented 51.6% of the Registry Units. Conclusion: in the current scenario, the trans population still suffers from difficulties in accessing health services and therefore having their rights guaranteed
Objetivos: conocer las experiencias y demandas de las personas transgénero a la hora de buscar servicios de atención primaria de salud. Método: investigación descriptiva con enfoque cualitativo, realizada con personas autodeclaradas transexuales que utilizan los servicios de atención primaria de salud. La recolección de datos se realizó a través de un cuestionario en línea, que se sometió a análisis a través de software libre para obtener datos cualitativos y el corpus textual de investigación se analizó mediante análisis de categoría temática. Resultados: con el análisis de datos se crearon dos categorías: experiencias en atención primaria de salud, que representaron el 51,6% de las Unidades de Registro. Conclusión: en el escenario actual, la población trans aún sufre dificultades para acceder a los servicios de salud y, por lo tanto, tener garantizados sus derechos
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Transexualidade , Pessoas Transgênero , Acessibilidade aos Serviços de SaúdeRESUMO
BACKGROUND: Opioid anesthetic agents can modulate the impaired immune response in obese patients through mechanisms that involve the expression and release of cytokines. For this reason, anesthetic care for obese patients remains controversial. Therefore, the aim of the study was to compare the effect of opioid-containing anesthesia (OCA) vs opioid-free anesthesia (OFA) using the Cortínez-Sepúlveda model on IL-6, IL-1ß and TNF-α serum levels before and after surgery in obese patients undergoing bypass surgery. METHODS: This randomized cross-sectional study conducted among 40 unrelated obese adults was performed in the Civil Hospital of Guadalajara "Dr. Juan I. Menchaca". Before undergoing laparoscopic Roux-en-Y gastric bypass, patients were randomly assigned to two anesthesia groups: OCA (n = 20) or OFA (n = 20). Fentanyl was the opioid used in the OCA group. The Cortínez-Sepúlveda pharmacokinetic model was used to characterize the disposition of intravenous propofol for the target-controlled infusion technique in obese patients. Body mass was determined to the nearest 0.05 kg using a balance scale (Seca 703; Seca, Hamburg, Germany). Blood samples were taken before and immediately after surgery and cytokine concentrations were determined by ELISA. Pain was assessed using a numerical pain rating scale. Adverse effects were collected within the first 24 h after surgery. RESULTS: A total of 6 men and 34 women were included (37.9 ± 10.6 years). Pre-surgery IL-6 and TNF-α serum levels were not detected in study subjects. However, IL-1ß levels significantly decreased after surgery (49.58 pg/mL (18.50-112.20)-before surgery vs 13 pg/mL (5.43-22)-after surgery, p = 0.019). IL-6 concentrations were significantly higher in subjects who received OCA (with fentanyl) compared to subjects with OFA (224.5 pg/mL (186.3-262.8) vs 99.5 pg/mL (60.8-138.2), respectively, p < 0.001; adjusted by age, gender, and BMI). In addition, the use of opioids confers an increased risk for higher IL-6 levels in obese patients (OR = 2.95, 95% CI: 1.2-7.2, p = 0.010). A linear regression model showed that the operative time (in hours) of bypass surgery and anesthetic technique were positively correlated with IL-6 levels. CONCLUSION: Anesthesia with opioids correlated positively with IL-6 serum levels in obese patients undergoing bypass surgery. This finding could have clinical relevance when an appropriate anesthetic management plan is selected for bariatric surgical patients. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov Identification Number: NCT04854252, date 22/04/2021.
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Anestesia , Derivação Gástrica , Propofol , Adulto , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Citocinas , Feminino , Fentanila/uso terapêutico , Derivação Gástrica/métodos , Humanos , Interleucina-6 , Masculino , Obesidade/cirurgia , Dor/tratamento farmacológico , Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: Hyperbaric oxygen (HBO2) therapy has been proposed to treat hypoxaemia and reduce inflammation in COVID-19. Our objective was to analyse safety and efficacy of HBO2 in treatment of hypoxaemia in patients with COVID-19 and evaluate time to hypoxaemia correction. METHODS: This was a multicentre, open-label randomised controlled trial conducted in Buenos Aires, Argentina, between July and November 2020. Patients with COVID-19 and severe hypoxaemia (SpO2 ≤90% despite oxygen supplementation) were assigned to receive either HBO2 treatment or the standard treatment for respiratory symptoms for 7 days. HBO2 treatment was planned for ≥5 sessions (1 /day) for 90 min at 1.45 atmosphere absolute (ATA). Outcomes were time to normalise oxygen requirement to SpO2 ≥93%, need for mechanical respiratory assistance, development of acute respiratory distress syndrome and mortality within 30 days. A sample size of 80 patients was estimated, with a planned interim analysis after determining outcomes on 50% of patients. RESULTS: The trial was stopped after the interim analysis. 40 patients were randomised, 20 in each group, age was 55.2±9.2 years. At admission, frequent symptoms were dyspnoea, fever and odynophagia; SpO2 was 85.1%±4.3% for the whole group. Patients in the treatment group received an average of 6.2±1.2 HBO2 sessions. Time to correct hypoxaemia was shorter in treatment group versus control group; median 3 days (IQR 1.0-4.5) versus median 9 days (IQR 5.5-12.5), respectively (p<0.010). OR for recovery from hypoxaemia in the HBO2 group at day 3 compared with the control group was 23.2 (95% CI 1.6 to 329.6; p=0.001) Treatment had no statistically significant effect on acute respiratory distress syndrome, mechanical ventilation or death within 30 days after admission. CONCLUSION: Our findings support the safety and efficacy of HBO2 in the treatment of COVID-19 and severe hypoxaemia. TRIAL REGISTRATION NUMBER: NCT04477954.
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COVID-19 , Oxigenoterapia Hiperbárica , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Pessoa de Meia-Idade , Oxigênio , SARS-CoV-2RESUMO
Hematologic malignancies such as leukemias and lymphomas are among the leading causes of pediatric cancer death worldwide, and although survival rates have improved with conventional treatments, the development of drug-resistant cancer cells may lead to patient relapse and limited possibilities of a cure. Drug-resistant cancer cells in these hematologic neoplasms are induced by overexpression of the antiapoptotic B-cell lymphoma 2 (Bcl-2) protein families, such as Bcl-XL, Bcl-2, and Mcl-1. We have previously shown that peptides from the BH3 domain of the proapoptotic Bax protein that also belongs to the Bcl-2 family may antagonize the antiapoptotic activity of the Bcl-2 family proteins, restore apoptosis, and induce chemosensitization of tumor cells. Furthermore, cell-permeable Bax BH3 peptides also elicit antitumor activity and extend survival in a murine xenograft model of human B non-Hodgkin's lymphoma. However, the activity of the BH3 peptides of the proapoptotic Bak protein of the Bcl-2 family against these hematologic malignant cells requires further characterization. In this study, we report the ability of the cell-permeable Bak BH3 peptide to restore apoptosis and induce chemosensitization of acute lymphoblastic leukemia and non-Hodgkin's lymphoma cell lines, and this event is enhanced with the coadministration of cell-permeable Bax BH3 peptide and represents an attractive approach to improve the patient outcomes with relapsed or refractory hematological malignant cells.
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OBJECTIVE: to reflect on the challenges and power of the nursing care process in Primary Health Care in the face of the New Coronavirus, COVID-19, in the Brazilian scenario. METHOD: reflective study, based on the discursive formulation in the context of COVID-19 in Primary Health Care, based on theoretical foundations and practical effects of neoliberal policy, the care process, and Nursing. RESULTS: in Brazil, COVID-19, has caused the need for challenges for strengthening primary care in the face of neoliberal policy, but it presents the potential of dialogue with communities and the (re)creation of the nursing care process through solidary collaborative networks. FINAL CONSIDERATIONS: reflecting on the nursing care process in primary care restores the strength present in the cooperation between health teams and community solidarity networks to change social and health circumstances, despite the challenge imposed by underfunding aggravated by neoliberalism.
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Betacoronavirus , Infecções por Coronavirus/enfermagem , Processo de Enfermagem/organização & administração , Pneumonia Viral/enfermagem , Política , Atenção Primária à Saúde/economia , Brasil/epidemiologia , COVID-19 , Infecções por Coronavirus/epidemiologia , Saúde Global , Humanos , Processo de Enfermagem/economia , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Fatores SocioeconômicosRESUMO
ABSTRACT Objective: to reflect on the challenges and power of the nursing care process in Primary Health Care in the face of the New Coronavirus, COVID-19, in the Brazilian scenario. Method: reflective study, based on the discursive formulation in the context of COVID-19 in Primary Health Care, based on theoretical foundations and practical effects of neoliberal policy, the care process, and Nursing. Results: in Brazil, COVID-19, has caused the need for challenges for strengthening primary care in the face of neoliberal policy, but it presents the potential of dialogue with communities and the (re)creation of the nursing care process through solidary collaborative networks. Final considerations: reflecting on the nursing care process in primary care restores the strength present in the cooperation between health teams and community solidarity networks to change social and health circumstances, despite the challenge imposed by underfunding aggravated by neoliberalism.
RESUMEN Objetivo: Hacer una reflexión sobre los desafíos y potencias del proceso de cuidado de Enfermería en la Atención Primaria de Salud frente al nuevo Coronavirus, COVID-19, en el escenario brasileño. Método: Estudio reflexivo, fundamentado en la formulación discursiva de la COVID-19 en la Atención Primaria de Salud, con base en fundamentos teóricos y efectos prácticos de la política neoliberal sobre el proceso de cuidado de Enfermería. Resultados: La COVID-19 en Brasil ha impuesto desafíos para la Atención Primaria en razón de la política neoliberal, pero trae como potencia un mayor diálogo con las comunidades y la (re)creación del proceso de cuidado de Enfermería, a través de redes colaborativas solidarias. Consideraciones Finales: Esta reflexión fortalece la cooperación entre equipos de salud y redes solidarias comunitarias, en la búsqueda de mejorías en lo social y en la salud, ante los desafíos impuestos por la política neoliberal.
RESUMO Objetivo: refletir sobre desafios e potências do processo de cuidado de enfermagem na Atenção Primária à Saúde diante do Novo Coronavírus, COVID-19, no contexto brasileiro. Método: estudo reflexivo, fundamentado na formulação discursiva no contexto da COVID-19 na Atenção Primária à Saúde, com base em fundamentos teóricos e efeitos práticos da política neoliberal, do processo de cuidado e da Enfermagem. Resultados e Discussão: a COVID-19, no Brasil, tem imposto os desafios do fortalecimento da atenção primária em face à política neoliberal, mas apresenta como potência o diálogo com as comunidades e a (re)criação do processo de cuidado de enfermagem por meio das redes colaborativas solidárias. Considerações finais: refletir sobre o processo de cuidado de enfermagem na atenção primária restabelece a força presente na cooperação entre equipes de saúde e redes solidárias comunitárias para mudar situações sociais e de saúde, a despeito do desafio imposto pelo subfinanciamento agravado pelo neoliberalismo.
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Humanos , Pneumonia Viral/enfermagem , Política , Atenção Primária à Saúde/economia , Infecções por Coronavirus/enfermagem , Betacoronavirus , Processo de Enfermagem/organização & administração , Pneumonia Viral/epidemiologia , Fatores Socioeconômicos , Brasil/epidemiologia , Saúde Global , Infecções por Coronavirus/epidemiologia , Pandemias , Processo de Enfermagem/economiaRESUMO
The survival of patients with non-Hodgkin's lymphoma (NHL) has substantially improved with current treatments. Nevertheless, the appearance of drug-resistant cancer cells leads to patient relapse. It is therefore necessary to find new antitumor therapies that can completely eradicate transformed cells. Chemotherapy-resistant cancer cells are characterized by the overexpression of members of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein family, such as Bcl-XL, Bcl-2, and Mcl-1. We have recently shown that peptides derived from the BH3 domain of the pro-apoptotic Bax protein may antagonize the anti-apoptotic activity of the Bcl-2 family proteins, restore apoptosis, and induce chemosensitization of tumor cells. In this study, we investigated the feasibility of releasing this peptide into the tumor microenvironment using live attenuated Salmonella enterica, which has proven to be an ally in cancer therapy due to its high affinity for tumor tissue, its ability to activate the innate and adaptive antitumor immune responses, and its potential use as a delivery system of heterologous molecules. Thus, we expressed and released the cell-permeable Bax BH3 peptide from the surface of Salmonella enterica serovar Typhimurium SL3261 through the MisL autotransporter system. We demonstrated that this recombinant bacterium significantly decreased the viability and increased the apoptosis of Ramos cells, a human B NHL cell line. Indeed, the intravenous administration of this recombinant Salmonella enterica elicited antitumor activity and extended survival in a xenograft NHL murine model. This antitumor activity was mediated by apoptosis and an inflammatory response. Our approach may represent an eventual alternative to treat relapsing or refractory NHL.
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Proteínas de Bactérias , Vacinas Anticâncer/imunologia , Sistemas de Liberação de Medicamentos , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/patologia , Proteínas de Membrana Transportadoras , Fragmentos de Peptídeos/imunologia , Proteínas Proto-Oncogênicas/imunologia , Salmonella enterica/imunologia , Proteína X Associada a bcl-2/imunologia , Animais , Apoptose/efeitos dos fármacos , Proteínas de Bactérias/química , Vacinas Anticâncer/administração & dosagem , Linhagem Celular , Permeabilidade da Membrana Celular , Sobrevivência Celular , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Proteínas de Membrana Transportadoras/química , Camundongos , Modelos Moleculares , Oligonucleotídeos/química , Fragmentos de Peptídeos/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Recombinantes , Salmonella enterica/genética , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/química , Proteína X Associada a bcl-2/genéticaRESUMO
Group B Streptococcus (GBS), is a leading cause of neonatal death and an emerging pathogen in adults. Additionally, GBS is a bovine pathogen causing intramammary infections. The likelihood of GBS interspecies transmission is largely unknown. We explored the potential transmission of GBS between cattle and people on dairy farms in Colombia and compared the antimicrobial resistance (AMR) profiles of isolates from both host species. Across 33 farms, throat swabs and rectal swabs were collected from 191 people, and rectal swabs and composite milk samples from 2092 cattle, yielding 60 human isolates and 301 bovine isolates. The majority (64%) of isolates belonged to shared sequence types (ST). Sequence type (ST) 1 was the most common strain in both host species, suggesting that interspecies transmission may be possible. Two members of the bovine-specific clonal complex 61/67 were detected in human samples (ST718 and ST1175), providing evidence for the lack of genuine species barriers. Apparent prevalence of penicillin resistance was surprisingly high in human and bovine isolates. Further investigation of this phenomenon is needed and could lead to modification of standard testing and treatment recommendations in human and veterinary medicine.