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BACKGROUND & AIMS: Despite the significant advances made in the diagnosis and treatment of Barrett's esophagus (BE), there is still a need for standardized definitions, appropriate recognition of endoscopic landmarks, and consistent use of classification systems. Current controversies in basic definitions of BE and the relative lack of anatomic knowledge are significant barriers to uniform documentation. We aimed to provide consensus-driven recommendations for uniform reporting and global application. METHODS: The World Endoscopy Organization Barrett's Esophagus Committee appointed leaders to develop an evidence-based Delphi study. A working group of 6 members identified and formulated 23 statements, and 30 internationally recognized experts from 18 countries participated in 3 rounds of voting. We defined consensus as agreement by ≥80% of experts for each statement and used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool to assess the quality of evidence and the strength of recommendations. RESULTS: After 3 rounds of voting, experts achieved consensus on 6 endoscopic landmarks (palisade vessels, gastroesophageal junction, squamocolumnar junction, lesion location, extraluminal compressions, and quadrant orientation), 13 definitions (BE, hiatus hernia, squamous islands, columnar islands, Barrett's endoscopic therapy, endoscopic resection, endoscopic ablation, systematic inspection, complete eradication of intestinal metaplasia, complete eradication of dysplasia, residual disease, recurrent disease, and failure of endoscopic therapy), and 4 classification systems (Prague, Los Angeles, Paris, and Barrett's International NBI Group). In round 1, 18 statements (78%) reached consensus, with 12 (67%) receiving strong agreement from more than half of the experts. In round 2, 4 of the remaining statements (80%) reached consensus, with 1 statement receiving strong agreement from 50% of the experts. In the third round, a consensus was reached on the remaining statement. CONCLUSIONS: We developed evidence-based, consensus-driven statements on endoscopic landmarks, definitions, and classifications of BE. These recommendations may facilitate global uniform reporting in BE.
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Esôfago de Barrett , Neoplasias Esofágicas , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/patologia , Esôfago de Barrett/terapia , Brasil , Consenso , Técnica Delphi , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Esofagoscopia , HumanosRESUMO
No disponible.
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COVID-19 , Transplante de Fígado , Vacinas Virais , Anticorpos Antivirais , Vacinas contra COVID-19 , Humanos , SARS-CoV-2RESUMO
We have previously shown that infectious pancreatic necrosis virus (IPNV) enters the embryo cell line CHSE-214 by macropinocytosis. In this study, we have extended our investigation into SHK-1 cells, a macrophage-like cell line derived from the head kidney of Atlantic salmon, the most economically important host of IPNV. We show that IPNV infection stimulated fluid uptake in SHK-1 cells above the constitutive macropinocytosis level. In addition, upon infection of SHK-1 cells, IPNV produced several changes in actin dynamics, such as protrusions and ruffles, which are important features of macropinocytosis. We also observed that the Na+/H+ pump inhibitor EIPA blocked IPNV infection. On the other hand, IPNV entry was independent of clathrin, a possibility that could not be ruled out in CHSE 214 cells. In order to determine the possible role of accessory factors on the macropinocytic process, we tested several inhibitors that affect components of transduction pathways. While pharmacological intervention of PKI3, PAK-1 and Rac1 did not affect IPNV infection, inhibition of Ras and Rho GTPases as well as Cdc42 resulted in a partial decrease in IPNV infection. Further studies will be required to determine the signalling pathway involved in the macropinocytosis-mediated entry of IPNV into its target cells.
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Vírus da Necrose Pancreática Infecciosa/fisiologia , Macrófagos/virologia , Pinocitose , Salmão/virologia , Internalização do Vírus , Actinas/metabolismo , Animais , Infecções por Birnaviridae/virologia , Linhagem Celular , Doenças dos Peixes/virologia , Rim Cefálico/virologia , Macrófagos/citologiaRESUMO
BACKGROUND: Stable insertion of the retroviral DNA genome into host chromatin requires the functional association between the intasome (integrase·viral DNA complex) and the nucleosome. The data from the literature suggest that direct protein-protein contacts between integrase and histones may be involved in anchoring the intasome to the nucleosome. Since histone tails are candidates for interactions with the incoming intasomes we have investigated whether they could participate in modulating the nucleosomal integration process. RESULTS: We show here that histone tails are required for an optimal association between HIV-1 integrase (IN) and the nucleosome for efficient integration. We also demonstrate direct interactions between IN and the amino-terminal tail of human histone H4 in vitro. Structure/function studies enabled us to identify amino acids in the carboxy-terminal domain of IN that are important for this interaction. Analysis of the nucleosome-binding properties of catalytically active mutated INs confirmed that their ability to engage the nucleosome for integration in vitro was affected. Pseudovirus particles bearing mutations that affect the IN/H4 association also showed impaired replication capacity due to altered integration and re-targeting of their insertion sites toward dynamic regions of the chromatin with lower nucleosome occupancy. CONCLUSIONS: Collectively, our data support a functional association between HIV-1 IN and histone tails that promotes anchoring of the intasome to nucleosomes and optimal integration into chromatin.
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Integrase de HIV/metabolismo , HIV-1/metabolismo , Histonas/metabolismo , Nucleossomos/metabolismo , Integração Viral , Linhagem Celular Transformada , Cromatina/virologia , DNA Viral/metabolismo , Células HEK293 , HIV-1/genética , Histonas/química , Interações Hospedeiro-Parasita/fisiologia , Humanos , Ligação ProteicaRESUMO
BACKGROUND: Retroviral integration depends on the interaction between intasomes, host chromatin and cellular targeting cofactors as LEDGF/p75 or BET proteins. Previous studies indicated that the retroviral integrase, by itself, may play a role in the local integration site selection within nucleosomal target DNA. We focused our study on this local association by analyzing the intrinsic properties of various retroviral intasomes to functionally accommodate different chromatin structures in the lack of other cofactors. RESULTS: Using in vitro conditions allowing the efficient catalysis of full site integration without these cofactors, we show that distinct retroviral integrases are not equally affected by chromatin compactness. Indeed, while PFV and MLV integration reactions are favored into dense and stable nucleosomes, HIV-1 and ASV concerted integration reactions are preferred into poorly dense chromatin regions of our nucleosomal acceptor templates. Predicted nucleosome occupancy around integration sites identified in infected cells suggests the presence of a nucleosome at the MLV and HIV-1 integration sites surrounded by differently dense chromatin. Further analyses of the relationships between the in vitro integration site selectivity and the structure of the inserted DNA indicate that structural constraints within intasomes could account for their ability to accommodate nucleosomal DNA and could dictate their capability to bind nucleosomes functionally in these specific chromatin contexts. CONCLUSIONS: Thus, both intasome architecture and compactness of the chromatin surrounding the targeted nucleosome appear important determinants of the retroviral integration site selectivity. This supports a mechanism involving a global targeting of the intasomes toward suitable chromatin regions followed by a local integration site selection modulated by the intrinsic structural constraints of the intasomes governing the target DNA bending and dictating their sensitivity toward suitable specific nucleosomal structures and density.
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Cromatina/virologia , Interações Hospedeiro-Patógeno , Nucleossomos/virologia , Retroviridae/fisiologia , Integração Viral , Cromatina/metabolismo , DNA/metabolismo , Humanos , Integrases/metabolismo , Nucleossomos/metabolismoRESUMO
BACKGROUND: The description of local seasonality patterns in respiratory syncytial virus (RSV) incidence is important to guide the timing of administration of RSV immunization products. METHODS: We characterized RSV seasonality in Guatemala using the moving epidemic method (MEM) with absolute counts of RSV-associated acute respiratory infections (ARI) from hospital surveillance in Santa Rosa and Quetzaltenango departments of Guatemala. RESULTS: From Week 17 of 2008 through Week 16 of 2018, 8487 ARI cases tested positive for RSV by rRT-PCR. Season onsets varied up to 5 months; early seasons starting in late May to early August and finishing in September to November were most common, but late seasons starting in October to November and finishing in March to April were also observed. Both epidemic patterns had similar durations ranging from 4 to 6 months. Epidemic thresholds (the levels of virus activity that signal the onset and end of a seasonal epidemic) calculated prospectively using previous seasons' data captured between 70% and 99% of annual RSV detections. Onset weeks differed by 2-10 weeks, and offset weeks differed by 2-16 weeks between the two surveillance sites. CONCLUSIONS: Variability in the timing of seasonal RSV epidemics in Guatemala demonstrates the difficulty in precisely predicting the timing of seasonal RSV epidemics based on onset weeks from past seasons and suggests that maximal reduction in RSV disease burden would be achieved through year-round vaccination and immunoprophylaxis administration to at-risk infants.
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Epidemias , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Estações do Ano , Guatemala/epidemiologia , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano/isolamento & purificação , Lactente , Pré-Escolar , Incidência , Feminino , Masculino , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , CriançaRESUMO
Current WHO guidelines for onchocerciasis elimination provide requirements for stopping mass drug administration of ivermectin and the verification of elimination of transmission. These guidelines also recommend post-elimination surveillance (PES) based on entomological surveys. Serological markers in humans could complement entomological PES once the longevity of anti-OV-16 antibody responses is better understood. In 2014-2015 we evaluated ELISA anti-OV-16 IgG4 antibody persistence among previously seropositive people from the central endemic zone of Guatemala. The country stopped all onchocerciasis program interventions in 2012 and was verified by WHO as having eliminated transmission of onchocerciasis in 2016. A total of 246 participants with prior OV-16 ELISA results from 2003, 2006, 2007, or 2009 were enrolled in a follow-up study. Of these, 77 people were previously OV-16 seropositive and 169 were previously seronegative. By 2014 and 2015, 56 (72.7%) previously seropositive individuals had sero-reverted, whereas all previous negatives remained seronegative. The progression of antibody responses over time was estimated using a mixed-effects linear regression model, using data from seropositive participants who had sero-reverted. The temporal variation showed a mean activity unit decay of 0.20 per year (95% credible interval [CrI]: 0.17, 0.23), corresponding to an estimated antibody response half-life of 3.3 years (95% CrI: 2.7, 4.1). These findings indicate that the majority of seropositive people will sero-revert over time.
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Anticorpos Anti-Helmínticos , Imunoglobulina G , Oncocercose , Humanos , Guatemala/epidemiologia , Oncocercose/epidemiologia , Oncocercose/transmissão , Oncocercose/imunologia , Oncocercose/prevenção & controle , Imunoglobulina G/sangue , Masculino , Feminino , Adulto , Anticorpos Anti-Helmínticos/sangue , Pessoa de Meia-Idade , Ivermectina/uso terapêutico , Ivermectina/administração & dosagem , Erradicação de Doenças/métodos , Doenças Endêmicas/prevenção & controle , Animais , Onchocerca volvulus/imunologia , Adulto Jovem , Adolescente , Ensaio de Imunoadsorção Enzimática , Administração Massiva de MedicamentosRESUMO
BACKGROUND: Retroviral integrases (INs) catalyze the integration of viral DNA in the chromosomal DNA of the infected cell. This reaction requires the multimerization of IN to coordinate a nucleophilic attack of the 3' ends of viral DNA at two staggered phosphodiester bonds on the recipient DNA. Several models indicate that a tetramer of IN would be required for two-end concerted integration. Complementation assays have shown that the N-terminal domain (NTD) of integrase is essential for concerted integration, contributing to the formation of a multimer through protein-protein interaction. The isolated NTD of Mo-MLV integrase behave as a dimer in solution however the structure of the dimer in solution is not known. RESULTS: In this work, crosslinking and mass spectrometry were used to identify regions involved in the dimerization of the isolated Mo-MLV NTD. The distances between the crosslinked lysines within the monomer are in agreement with the structure of the NTD monomer found in 3NNQ. The intermolecular crosslinked peptides corresponding to Lys 20-Lys 31, Lys 24-Lys 24 and Lys 68-Lys 88 were identified. The 3D coordinates of 3NNQ were used to derive a theoretical structure of the NTD dimer with the suite 3D-Dock, based on shape and electrostatics complementarity, and filtered with the distance restraints determined in the crosslinking experiments. CONCLUSIONS: The crosslinking results are consistent with the monomeric structure of NTD in 3NNQ, but for the dimer, in our model both polypeptides are oriented in parallel with each other and the contacting areas between the monomers would involve the interactions between helices 1 and helices 3 and 4.
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Integrases/química , Vírus da Leucemia Murina de Moloney/enzimologia , Proteínas Virais/química , Sequência de Aminoácidos , Animais , Cromatografia Líquida de Alta Pressão , Dimerização , Integrases/metabolismo , Espectrometria de Massas , Camundongos , Simulação de Acoplamento Molecular , Dados de Sequência Molecular , Peptídeos/análise , Estrutura Terciária de Proteína , Alinhamento de Sequência , Eletricidade Estática , Proteínas Virais/metabolismoRESUMO
Background: "Rendez-vous" (RV) technique is a mixed-technique which uses both laparoscopic and endoscopic skills; however, the evidence is contradictory regarding the implementation of this technique or the 2-step sequential technique (endoscopic retrograde cholangiopancreatography [ERCP] followed by laparoscopic cholecystectomy [LC]) in the management of cholecysto-choledocholitiasis. Objective: To estimate the association between the implementation of RV technique and the presence of post-surgical complications as primary outcome, using as comparator the 2-step sequential technique. Method: An observational, analytical, retrospective study was conducted, using as exposed cohort the medical records from patients with a diagnosis of cholelithiasis, cholecystitis, or mild biliary pancreatitis. The exposed cohort underwent RV technique, while the unexposed cohort were those which underwent two step technique. Results: There was a lower post-surgical complication rate in the RV group (0%) compared with the 10.1% (p = 0.3617) in the control group. Also, RV technique showed a lesser hospitalization time (p = 0.0377) and a lesser post-surgical hospitalization time (p < 0.0001). Conclusions: RV technique is superior when compared with the 2-step sequential technique (ERCP followed by LC), based on a better surgical success rate, a fewer complications rate and less hospitalization time.
Antecedentes: La técnica de «Rendez-vous¼ (RV) es una técnica mixta en la que se combinan las habilidades endoscópicas y laparoscópicas. La evidencia es contradictoria respecto al uso de RV frente a la técnica secuencial en dos tiempos (colangiopancreatografía retrógrada endoscópica [CPRE] seguida de colecistectomía laparoscópica [CL]) para el manejo de la colecisto-coledocolitiasis. Objetivo: Estimar la asociación entre el uso de la técnica RV y la presencia de complicaciones posquirúrgicas como desenlace primario, en comparación con la técnica secuencial. Método: Se realizó un estudio observacional analítico retrospectivo que tomó como cohorte expuesta las historias clínicas de pacientes con diagnóstico de colelitiasis, colecistitis o pancreatitis leve de origen biliar sometidos a la técnica RV, y se compararon con registros en los que se realizó la técnica de dos tiempos. Resultados: La tasa de complicaciones posquirúrgicas en el grupo de RV fue del 0%, frente al 10.1% (p = 0.3617) en el grupo control. Además, la RV presentó menor tiempo de hospitalización global (p = 0.0377) y posquirúrgica (p < 0.0001). Conclusiones: La técnica RV es superior a la técnica secuencial de CPRE seguida de CL, por su mayor tasa de éxito, menor tasa de complicaciones y menor tiempo hospitalario.
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Cooking and heating using solid fuels can result in dangerous levels of exposure to household air pollution (HAP). HAPIN is an ongoing randomized controlled trial assessing the impact of a liquified petroleum gas stove and fuel intervention on HAP exposure and health in Guatemala, India, Peru, and Rwanda among households that rely primarily on solid cooking fuels. Given the potential impacts of HAP exposure on cardiovascular outcomes during pregnancy, we seek to characterize the relationship between personal exposures to HAP and blood pressure among pregnant women at baseline (prior to intervention) in the study. We assessed associations between PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 µm), BC (black carbon), and CO (carbon monoxide) exposures and blood pressure at baseline, prior to intervention, among 3195 pregnant women between 9 and 19 weeks of gestation. We measured 24-hour personal exposure to PM2.5/BC/CO and gestational blood pressure. Multivariable linear regression models were used to evaluate associations between personal exposures to three air pollutants and blood pressure parameters. Trial-wide, we found moderate increases in systolic blood pressure (SBP) and decreases in diastolic blood pressure (DBP) as exposure to PM2.5, BC, and CO increased. None of these associations, however, were significant at the 0.05 level. HAP exposure and blood pressure associations were inconsistent in direction and magnitude within each country. We observed effect modification by body mass index (BMI) in India and Peru. Compared to women with normal weights, obese women in India and Peru (but not in Rwanda or Guatemala) had higher SBP per unit increase in log transformed PM2.5 and BC exposures. We did not find a cross-sectional association between HAP exposure and blood pressure in pregnant women; however, HAP may be associated with higher blood pressure in pregnant women who are obese, but this increase was not consistent across settings.
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In recent years there has been a significant increase in the consumption of dietary energy supplements (DES) associated with the parallel advertising against obesity and favoring high physical performance. We present the case and outcome of a young patient who developed acute mixed liver injury (hepatocellular and cholestatic) after ingestion of various "over the counter" products to increase muscle mass and physical performance (NO Xplode®, creatine, L-carnitine, and Growth Factor ATN®). The diagnosis was based on the exclusion of other diseases and liver biopsy findings. The dietary supplement and herbal multivitamins industry is one with the highest growth rates in the market, with annual revenues amounting to billions and constantly lacking scientific or reproducible evidence about the efficacy and/or safety of the offered products. Furthermore, and contrary to popular belief, different forms of injury associated with these natural substances have been documented particularly in the liver, supporting the need of a more strict regulation.
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Atletas , Desempenho Atlético , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colestase/induzido quimicamente , Suplementos Nutricionais/efeitos adversos , Fígado/efeitos dos fármacos , Medicamentos sem Prescrição/efeitos adversos , Substâncias para Melhoria do Desempenho/efeitos adversos , Doença Aguda , Adolescente , Biomarcadores/sangue , Biópsia , Carnitina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Colestase/sangue , Colestase/diagnóstico , Colestase/tratamento farmacológico , Creatina/efeitos adversos , Humanos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática , Imageamento por Ressonância Magnética , Masculino , UltrassonografiaRESUMO
Although there is abundant evidence supporting an active lifestyle, it is necessary to promote the practice of physical activity among the population. To understand this phenomenon, several studies have been conducted to describe the reasons why people participate in sports activities. The PALMS (Physical Activity and Leisure Motivation Scale) was created as a comprehensive tool to measure the reasons for practicing sports. This tool consists of 40 items related to sports and is designed for the young and adult population. Each of the subscales is formed of five items (mastery, enjoyment, psychological condition, physical condition, appearance, the expectations of others, affiliation, competition/ego) that reflect the possible reasons for practicing sports. This study sought to validate the PALMS in the cultural context of Spain, for the type of population for which it is designed. In total, 596 voluntary participants completed the study from Spain, aged 18 to 53, who regularly practice sports. The adequacy of the model obtained in the exploratory study was confirmed, since a model composed of eight factors and 40 indicators in total was obtained. The parameters were statistically significant (p < 0.05) and the factor loadings presented values greater than 0.5. Regarding internal consistency, the values of Cronbach's alpha and those of the composite reliability were above 0.8. In conclusion, the validation of the Spanish PALMS proved to be a valid and reliable measurement instrument for the evaluation of the reasons that lead the population to perform sports physical activity.
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Motivação , Esportes , Adulto , Exercício Físico/psicologia , Humanos , Atividades de Lazer , Psicometria , Reprodutibilidade dos Testes , Esportes/psicologia , Inquéritos e QuestionáriosRESUMO
Background: Cirrhosis is a public health threat associated with high mortality. Alcoholic Liver Disease (ALD) is the leading cause in Latin America and Metabolic Associated Fatty Liver Disease (MAFLD) in western countries. In Mexico, ALD and chronic Hepatitis C Virus infection (HCV) were the most frequent aetiologies during the past decades. We aimed to describe the trends in the aetiologies of cirrhosis in a middle-income country. Methods: We performed a retrospective cohort study including patients diagnosed with cirrhosis between 2000 and 2019 from six different tertiary care hospitals in central Mexico. We collected information regarding cirrhosis etiology, year of diagnosis, hepatocellular carcinoma development, liver transplantation, and death. We illustrated the change in the tendencies of cirrhosis aetiologies by displaying the proportional incidence of each etiology over time stratified by age and gender, and we compared these proportions over time using chi square tests. Findings: Overall, 4,584 patients were included. In 2019, MAFLD was the most frequent cirrhosis etiology (30%), followed by ALD (24%) and HCV (23%). During the study period, MAFLD became the leading etiology, ALD remained second, and HCV passed from first to fourth. When analysed by gender, ALD was the leading etiology for men and MAFLD for women. The annual incidence of HCC was 3·84 cases/100 persons-year, the median survival after diagnosis was 12·1 years, and seven percent underwent LT. Interpretation: Increased alcohol consumption and the obesity epidemic have caused a transition in the aetiologies of cirrhosis in Mexico. Public health policies must be tailored accordingly to mitigate the burden of alcohol and metabolic conditions in developing countries. Funding: None.
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A single polypeptide of the HIV-1 reverse transcriptase that reconstituted Mg(2+)-dependent RNase H activity has been made. Using molecular modeling, the construct was designed to encode the p51 subunit joined by a linker to the thumb (T), connection (C), and RNase H (R) domains of p66. This p51-G-TCR construct was purified from the soluble fraction of an Escherichia coli strain, MIC2067(DE3), lacking endogenous RNase HI and HII. The p51-G-TCR RNase H construct displayed Mg(2+)-dependent activity using a fluorescent nonspecific assay and showed the same cleavage pattern as HIV-1 reverse transcriptase (RT) on substrates that mimic the tRNA removal required for second-strand transfer reactions. The mutant E706Q (E478Q in RT) was purified under similar conditions and was not active. The RNase H of the p51-G-TCR RNase H construct and wild type HIV-1 RT had similar K(m)s for an RNA-DNA hybrid substrate and showed similar inhibition kinetics to two known inhibitors of the HIV-1 RT RNase H.
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Fármacos Anti-HIV/farmacologia , Transcriptase Reversa do HIV/metabolismo , HIV-1/enzimologia , Inibidores da Transcriptase Reversa/farmacologia , Ribonuclease H/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Avaliação Pré-Clínica de Medicamentos , Transcriptase Reversa do HIV/química , Transcriptase Reversa do HIV/genética , HIV-1/genética , HIV-1/metabolismo , Magnésio/metabolismo , Modelos Moleculares , RNA de Transferência/genética , Ribonuclease H/química , Ribonuclease H/genética , Análise de Sequência de RNARESUMO
AIM: The aim of this study was to establish the validity of an external measurement system (the Hawk goniometer). This is a digital device which measures joint ranges compared to the universal goniometer for the measurement of shoulder range of motion in healthy adults. MATERIAL AND METHODS: a correlational study with 157 healthy volunteers completed six shoulder movements (forward flexion, abduction, extension, adduction and internal and external rotation) with each shoulder. The degree of agreement between each goniometer and Hawk measurement was assessed using Intra-class Correlation Coefficients (ICC) and Bland-Altman 95% limits of agreement (LOA). RESULTS: the tests showed a very strong relationship between the readings of both devices (CI between 0.81 and 0.99) and there were no significant differences between the mean readings of both devices. An intraclass correlation coefficient (ICC) of above 0.9 was obtained, indicating a high intra-evaluator reliability of the Hawk goniometer in repeated measurements of shoulder range of motion. CONCLUSIONS: the Hawk goniometer is a valid and reliable element for the objective measurement of the range of motion at the shoulder joint.
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Falcões , Articulação do Ombro , Adulto , Animais , Artrometria Articular , Humanos , Amplitude de Movimento Articular , Reprodutibilidade dos Testes , OmbroRESUMO
ABSTRACT: As access to human immunodeficiency virus treatment expands in Low to Middle Income Countries, it becomes critical to develop and test strategies to improve adherence and ensure efficacy. Text messaging improves adherence to antiretroviral treatment antiretroviral treatment in some patient populations, but data surrounding the use of these tools is sparse in pediatric and adolescent patients in low to middle income countries. We evaluated if a text message intervention can improve antiretroviral treatment adherence while accounting for cell phone access, patterns of use, and willingness to receive text messages.We carried out a cross sectional study to understand willingness of receiving text message reminders, followed by a randomized controlled trial to assess effectiveness of text message intervention.Enrolled participants were randomized to receive standard care with regular clinic visits, or standard care plus short message service reminders. Adherence was measured 3 times during the study period using a 4-day Recall Questionnaire. Outcome was measured based on differences in the average adherence between the intervention and control group at each time point (baseline, 3âmonths, 6âmonths).Most respondents were willing to receive text message adherence reminders (81.1%, nâ=â53). Respondent literacy, travel time to clinic, cell phone access, and patterns of use were significantly associated with willingness. In the randomized trial the intervention group (nâ=â50) experienced a small but significant mean improvement in adherence over the six-month period (4%, Pâ<â.01) whereas the control group (nâ=â50) did not (mean improvement: 0.8%, Pâ=â.64).Text message interventions effectively support antiretroviral adherence in pediatric patients living with human immunodeficiency virus. Studies designed to assess the impact of text messaging interventions must examine local context for cellular phone infrastructure and use and must account for potential loss to follow up when patients miss appointments and study assessments.
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Fármacos Anti-HIV/uso terapêutico , Soropositividade para HIV/tratamento farmacológico , Adesão à Medicação , Envio de Mensagens de Texto , Adolescente , Criança , Custos e Análise de Custo , Estudos Transversais , Países em Desenvolvimento , Guatemala , Humanos , Envio de Mensagens de Texto/economia , Adulto JovemRESUMO
Epitheloid hemangioendothelioma is a very rare tumor, with a variable presentation and unpredictable clinical behavior. The etiology and the triggering risk factors have not been specified. Unlike other primary liver tumors, it does not arise in the background of chronic liver disease. The approach is challenging due to the spectrum of possibilities and the need for immunohistochemistry to establish the definitive diagnosis. The information available so far is limited due to the few published cases, this favors that the therapeutic options are few or that there is insufficient evidence to standardize them when the lesion is not resectable.
El hemangioendotelioma epiteloide es un tumor muy infrecuente, con una presentación variable y un comportamiento clínico impredecible. No se han precisado la etiología ni los factores de riesgo desencadenantes. A diferencia de otros tumores hepáticos primarios, no surge en el contexto de una enfermedad crónica del hígado. El abordaje es un reto debido al espectro de posibilidades y la necesidad de inmunohistoquímica para establecer el diagnóstico definitivo. La información disponible hasta el momento es limitada por los escasos casos publicados, lo que favorece que las opciones terapéuticas sean pocas o no exista la evidencia suficiente para estandarizarlas cuando la lesión no sea resecable.
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Hemangioendotelioma Epitelioide , Neoplasias Hepáticas , Neoplasias Vasculares , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/cirurgia , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/diagnósticoRESUMO
The Household Air Pollution Intervention Network trial is a multi-country study on the effects of a liquefied petroleum gas (LPG) stove and fuel distribution intervention on women's and children's health. There is limited data on exposure reductions achieved by switching from solid to clean cooking fuels in rural settings across multiple countries. As formative research in 2017, we recruited pregnant women and characterized the impact of the intervention on personal exposures and kitchen levels of fine particulate matter (PM2.5) in Guatemala, India, and Rwanda. Forty pregnant women were enrolled in each site. We measured cooking area concentrations of and personal exposures to PM2.5 for 24 or 48 h using gravimetric-based PM2.5 samplers at baseline and two follow-ups over two months after delivery of an LPG cookstove and free fuel supply. Mixed models were used to estimate PM2.5 reductions. Median kitchen PM2.5 concentrations were 296 µg/m3 at baseline (interquartile range, IQR: 158-507), 24 µg/m3 at first follow-up (IQR: 18-37), and 23 µg/m3 at second follow-up (IQR: 14-37). Median personal exposures to PM2.5 were 134 µg/m3 at baseline (IQR: 71-224), 35 µg/m3 at first follow-up (IQR: 23-51), and 32 µg/m3 at second follow-up (IQR: 23-47). Overall, the LPG intervention was associated with a 92% (95% confidence interval (CI): 90-94%) reduction in kitchen PM2.5 concentrations and a 74% (95% CI: 70-79%) reduction in personal PM2.5 exposures. Results were similar for each site. CONCLUSIONS: The intervention was associated with substantial reductions in kitchen and personal PM2.5 overall and in all sites. Results suggest LPG interventions in these rural settings may lower exposures to the WHO annual interim target-1 of 35 µg/m3. The range of exposure contrasts falls on steep sections of estimated exposure-response curves for birthweight, blood pressure, and acute lower respiratory infections, implying potentially important health benefits when transitioning from solid fuels to LPG.
Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Petróleo , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Criança , Saúde da Criança , Culinária , Feminino , Humanos , Material Particulado/análise , Gravidez , Gestantes , População Rural , Saúde da MulherRESUMO
X-ray diffraction data on a few retroviral integrases show a flexible loop near the active site. By sequence alignment, the peptide region 207-218 of Mo-MLV IN appears to correspond to this flexible loop. In this study, residues H208, Y211, R212, Q214, S215 and S216 of Mo-MLV IN were mutated to determine their role on enzyme activity. We found that Y211A, R212A, R212K and Q214A decreased integration activity, while disintegration and 3'-processing were not significantly affected. By contrast H208A was completely inactive in all the assays. The core domain of Mo-MLV integrase was modeled and the flexibility of the region 207-216 was analyzed. Substitutions with low integration activity showed a lower flexibility than wild type integrase. We propose that the peptide region 207-216 is a flexible loop and that H208, Y211, R212 and Q214 of this loop are involved in the correct assembly of the DNA-integrase complex during integration.
Assuntos
Integrases/genética , Integrases/metabolismo , Vírus da Leucemia Murina de Moloney/enzimologia , Sequência de Aminoácidos , Integrases/química , Modelos Moleculares , Vírus da Leucemia Murina de Moloney/genética , Mutagênese Sítio-Dirigida , Mutação , Estrutura Terciária de Proteína , Alinhamento de Sequência , Integração ViralRESUMO
A case of a 31-day-old infant patient with a Tessier 0-14 deformity related to multiple midline deformities is presented. Although Transnasal endoscopic surgery is the mainstay for the treatment of anterior and middle skull base meningoceles, there are complex cases in which a combined and multidisciplinary approach is necessary. The surgical decisions and techniques are described. To date, this is the first patient reported with Tessier 0-14 deformity treated with a combined endoscopic and external surgical approach.