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A theoretical study of the reported photocatalytic systems based on Zr-based MOF (UiO-67) with biphenyl-4,4'-dicarboxylic acid (bpdc) and 2,2'-bipyridine-5,5'-dicarboxylic acid (bpydc) as linkers was performed. Quantum chemical calculations were carried out to understand the optical properties of the materials and to facilitate the rational design of new UiO-67 derivatives with potentially improved features as photocatalysts under ambient conditions. Hence, the effect of the structural modifications on the optical properties was studied considering different designs based on the nature of the linkers: in 1 only the bpdc linker was considered, or the mixture 1 : 1 between bpdc and bpydc linkers (labeled as 1A). Also, substituents R, -NH2, and -SH, were included in the 1A MOF only over the bpdc linker (labeled as 1A-bpdc-R) and on both bpdc and bpydc linkers (labeled as 1A-R). Thus a family of six isoreticular UiO-67 derivatives was theoretically characterized using Density Functional Theory (DFT) calculations on the ground singlet (S0) and first excited states (singlet and triplet) using Time-Dependent Density Functional Theory (TD-DFT), multiconfigurational post-Hartree-Fock method via Complete Active Space Self-Consistent Field (CASSCF). In addition, the use of periodic DFT calculations suggest that the energy transfer (ET) channel between bpdc and bpydc linkers might generate more luminescence quenching of 1A when compare to 1. Besides, the results suggest that the 1A-R (R: -SH and NH2) can be used under ambient conditions; however, the ET exhibited by 1A, cannot take place in the same magnitude in these systems. These ET can favor the photocatalytic reduction of a potential metal ion, that can coordinate with the bpydc ligand, via LMCT transition. Consequently, the MOF might be photocatalytically active against molecules of interest (such as H2, N2, CO2, among others) with photo-reduced metal ions. These theoretical results serve as a useful tool to guide experimental efforts in the design of new photocatalytic MOF-based systems.
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Oncology patients presenting for outpatient evaluation of a respiratory tract infection (RTI) are often tested for a variety of viruses with a respiratory pathogen panel (RPP) in addition to influenza and SARS-CoV-2. This triad of testing is expensive and uncomfortable because it requires 2 nasal swabs. Little evidence supports the use of an RPP in outpatient settings, but it is routinely ordered. This retrospective chart review analyzed 183 RPPs performed at Jefferson between April 2020 and November 2021 in outpatient oncology patients presenting with RTI. Data collected included patient demographics, symptoms, and exam findings at time of RPP, additional testing completed, results of RPP, antibiotic and antiviral use before and after RPP results, and patient outcomes 30 days after RPP. Descriptive statistics were calculated. Of the 183 RPPs analyzed, 16.9% (31) were positive for at least 1 respiratory virus. Fifty-two patients (28.4%) started antibiotics before results of the RPP. Of those, 2 patients (3.8%) had a change in antibiotic plan after RPP results returned. Zero patients were started on antiviral medication before results of the RPP. One patient started antiviral treatment after RPP results returned. In total, only 3 patients (1.6%) had an RPP-driven change in medication management. This study suggests limited utility in use of RPPs for oncology patients presenting to the office with RTI symptoms. Targeted testing with a single nasal swab for influenza, RSV, and SARS-CoV-2 may be more clinically relevant. The authors hope to use these data to implement a quality improvement initiative to reduce RPP utilization in this population.
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Influenza Humana , Neoplasias , Infecções Respiratórias , Humanos , Pacientes Ambulatoriais , Estudos Retrospectivos , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia , SARS-CoV-2 , Antivirais/uso terapêutico , Neoplasias/tratamento farmacológico , Antibacterianos/uso terapêuticoRESUMO
Colorado issued a month long statewide lockdown on March 26, 2020, during the initial surge of the COVID-19 pandemic. The impact of this mandate on non-COVID-19 ICU admission rates and outcomes is unclear. DESIGN: We performed a retrospective analysis of all medical ICU admissions in the University of Colorado Health System in four predefined periods: 1) prepandemic (2 mo prior to lockdown period 1); 2) mandated lockdown from March 26 to April 26, 2020 (period 2); 3) between surges (period 3); and 4) nonmandated lockdown surge (between November 1, 2020, and March 31, 2021, period 4). SETTING: Nonsurgical ICU admissions at the University of Colorado Health Systems, including 10 hospitals throughout Colorado. SUBJECTS: All ICU admissions in four predefined time periods. MEASUREMENTS AND MAIN RESULTS: We included 13,787 patients who were admitted during the four study periods. The 28-day mortality rates for non-COVID-19 ICU admissions following index ICU admission were 13.6%, 18.0%, 13.5%, and 16.0% across periods 1-4, respectively. However, the increased odds in non-COVID-19 ICU mortality during the mandated lockdown period relative to prepandemic 1 (odds ratio [OR], 1.39; 95% CI, 1.11-1.72; p = 0.0.04) was attenuated and nonsignificant after adjustment for demographics, comorbidities, diagnosis flags, and severity (OR, 1.15; 95% CI, 0.89-1.48; p = 0.27). Similar results were found in time-to-event analyses. The most common diagnosis in each time period was acute respiratory failure (ARF), and we found it to have increased during lockdown (p < 0.001), whereas sepsis admissions increased during and decreased after lockdown (p = 0.004). Admissions for alcohol withdrawal syndrome (AWS) increased during lockdown and 6 months afterwards (p = 0.005). CONCLUSIONS: For non-COVID-19-related ICU admissions, mortality rate was similar before, during, and after Colorado's month long lockdown after confounder adjustment, including typical ICU admission flags. Primary admission diagnoses shifted throughout the predefined study periods with more admissions for severe critical diagnoses (i.e., ARF, sepsis, AWS) occurring during the mandated lockdown and nonmandated lockdown periods compared with the prepandemic and between surge period. This would suggest that the perceived increase in mortality during the lockdown for non-COVID-19 ICU admissions may be related to a shift inpatient demographics.
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The optical properties and transduction mechanisms in three reported optical chemosensors based on crown ether with selectivity turn-on luminescence toward Na+ over K+ , were investigated using Density Functional Theory/Time-Dependent Density Functional Theory (DFT/TD-DFT). The analysis of the structural stability of the conformers enables us to understand the optical properties of the sensors and their selectivity toward Na+ . The UV-Vis absorption and the radiative channels of the adiabatic S1 excited state were assessed. In these reported sensors, the Photoinduced Electron Transfer (PET) from the nitrogen and the oxygen (O-atoms of the substituted N-phenylaza group) lone pairs to fluorophore groups lead to a nonradiative deactivation process in the fluorophore to p-conjugated anilino-1,2,3-triazol ionophore. This Intramolecular Charge Transfer (ICT) deactivation produced the luminescence quenching in the free sensors and K+ /C1 complexes. The Na+ /sensor interaction produced a Chelation Enhanced Fluorescence (CHEF) due to the inhibition of the PET and ICT, which was confirmed via the calculated oscillator strength of the emission process. The K+ /sensor interaction displayed the possibility of PET in C3; however, this fact was inconclusive to affirm the quenching of luminescence, the CHEF in C2 and C3 and the selectivity toward Na+ over K+ in these systems. For this reason, simulation of the absorption and emissions spectra (calculated oscillator strength), calculation of the kinetic parameters (in charge transfers and radiative deactivations process), analysis of the metal-ligand interaction character, and the analysis of the structural stability of the conformers were determinant factors to understand the selectivity and the optical properties of these chemosensors. The results suggest that these theoretical tools can also be used to predict the optical properties and Na+ /K+ selectivity of optical chemosensors.
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Éteres de Coroa , Éteres de Coroa/química , Corantes Fluorescentes/química , Íons/química , Sódio , Espectrometria de FluorescênciaRESUMO
We have performed theoretical calculations with 70 drugs that have been considered in 231 clinical trials as possible candidates to repurpose drugs for schizophrenia based on their interactions with the dopaminergic system. A hypothesis of shared pharmacophore features was formulated to support our calculations. To do so, we have used the crystal structure of the D2-like dopamine receptor in complex with risperidone, eticlopride, and nemonapride. Linagliptin, citalopram, flunarizine, sildenafil, minocycline, and duloxetine were the drugs that best fit with our model. Molecular docking calculations, molecular dynamics outcomes, blood-brain barrier penetration, and human intestinal absorption were studied and compared with the results. From the six drugs selected in the shared pharmacophore features input, flunarizine showed the best docking score with D2, D3, and D4 dopamine receptors and had high stability during molecular dynamics simulations. Flunarizine is a frequently used medication to treat migraines and vertigo. However, its antipsychotic properties have been previously hypothesized, particularly because of its possible ability to block the D2 dopamine receptors.
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Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory disease caused by orthohantaviruses in the Americas with a fatality rate as high as 35%. In South America, Andes orthohantavirus (Hantaviridae, Orthohantavirus, ANDV) is a major cause of HCPS, particularly in Chile and Argentina, where thousands of cases have been reported since the virus was discovered. Two strains of ANDV that are classically used for experimental studies of the virus are Chile-9717869, isolated from the natural reservoir, the long-tailed pygmy rice rat, and CHI-7913, an isolate from a lethal human case of HCPS. An important animal model for studying pathogenesis of HCPS is the lethal Syrian golden hamster model of ANDV infection. In this model, ANDV strain Chile-9717869 is uniformly lethal and has been used extensively for pathogenesis, vaccination, and therapeutic studies. Here we show that the CHI-7913 strain, despite having high sequence similarity with Chile-9717869, does not cause lethal disease in Syrian hamsters. CHI-7913, while being able to infect hamsters and replicate to moderate levels, showed a reduced ability to replicate within the tissues compared with Chile-9717869. Hamsters infected with CHI-7913 had reduced expression of cytokines IL-4, IL-6, and IFN-γ compared with Chile-9717869 infected animals, suggesting potentially limited immune-mediated pathology. These results demonstrate that certain ANDV strains may not be lethal in the classical Syrian hamster model of infection, and further exploration into the differences between lethal and non-lethal strains provide important insights into molecular determinants of pathogenic hantavirus infection.Importance:Andes orthohantavirus (ANDV) is a New World hantavirus that is a major cause of hantavirus cardiopulmonary syndrome (HCPS, also referred to as hantavirus pulmonary syndrome) in South America, particularly in Chile and Argentina. ANDV is one of the few hantaviruses for which there is a reliable animal model, the Syrian hamster model, which recapitulates important aspects of human disease. Here we infected hamsters with a human isolate of ANDV, CHI-7913, to assess its pathogenicity compared with the classical lethal Chile-9717869 strain. CHI-7913 had 22 amino acid differences compared with Chile-9717869, did not cause lethal disease in hamsters, and showed reduced ability to replicate in vivo Our data indicate potentially important molecular signatures for pathogenesis of ANDV infection in hamsters and may lead to insights into what drives pathogenesis of certain hantaviruses in humans.
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The bacterium Escherichia coli is still considered the first option as a microbial cell factory for recombinant protein production, and affinity chromatography is by far the preferred technique for initial purification after protein expression and cell lysis. In this chapter, we describe the methodology to express and purify recombinant proteins in E. coli tagged with the first two metal-binding proteins proposed as fusion partners. They are the small metal-binding protein SmbP and a mutant of the copper resistance protein CusF3H+. There are several advantages of using them as protein tags: they prevent the formation of inclusion bodies by increasing solubility of the target proteins, they enable purification by immobilized metal-affinity chromatography using Ni(II) ions with high purity, and because of their low molecular weights, excellent final yields are obtained for the target proteins after cleavage and removal of the protein tag. Here we also describe the protocol for the production of proteins in the periplasm of E. coli tagged with two SmbP variants that include the PelB or the TorA signal sequences for transport via the Sec or the Tat pathway, respectively. Based on these methods, we consider CusF3H+ and SmbP excellent alternatives as fusion proteins for the production of recombinant proteins in E. coli.
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Cromatografia de Afinidade , Proteínas de Transporte de Cobre , Proteínas de Escherichia coli , Escherichia coli/química , Níquel/química , Periplasma/química , Proteínas de Transporte de Cobre/química , Proteínas de Transporte de Cobre/genética , Escherichia coli/genética , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Periplasma/genética , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificaçãoRESUMO
Abstract The Comparative Agendas Project (CAP) collects, organizes, and makes freely available millions of bits of information concerning the objects of government attention over long periods of time (often back to the Second World War) for more than 25 political systems, worldwide. As researchers affiliated with the CAP expand their projects into Latin America, they confront some challenges similar to those from other regions, and some unique to their national political systems. In this introductory essay, we explore the background of the CAP and the opportunities posed by its expansion into Latin American political systems.
Resumen: El Comparative Agendas Project (CAP, por sus siglas en inglés) recopila, organiza y pone a disposición de forma gratuita millones de datos sobre los temas que han sido priorizados por parte de políticos y gobernantes en más de 25 sistemas políticos de todo el mundo. Estas bases de datos abarcan un período de tiempo largo, que en la mayoría de casos comienza tras el fin de la Segunda Guerra Mundial). Los investigadores que desarrollan proyectos siguiendo la metodología del CAP en América Latina tienen que hacer frente a los desafíos comunes que los investigadores han encontrado al analizar la agenda política, a otros exclusivos de los sistemas políticos de los países de esta región. En este ensayo introductorio, exploramos los antecedentes del CAP y las oportunidades que se presentan con su expansión a los sistemas políticos latinoamericanos.
Resumo O Comparative Agendas Project (CAP) coleta, organiza e disponibiliza gratuitamente milhões de dados sobre os temas que têm chamado a atenção de governos em mais de 25 sistemas políticos de todo mundo. Os dados disponíveis compreendem um longo período desde a Segunda Guerra Mundial. Na expansão de seus projetos para a América Latina, os pesquisadores ligados ao CAP enfrentam, além de desafios comuns aqueles encontrados globalmente, outras adversidades particulares dos sistemas políticos adotados nas nações da região. Neste ensaio introdutório, exploramos os antecedentes do CAP e as oportunidades que se apresentam com sua expansão aos sistemas políticos latino-americanos.
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Humanos , Masculino , Feminino , Sistemas Políticos , Política Pública , Governança em Saúde , América LatinaRESUMO
Abstract This Thematic Special Issue on Policy Change and Policy Dynamics has as its main objective to present and discuss agenda setting, one of the most important issues for the study of public policies and the policy process. The agenda setting approach proposes an analytical approach on pre-decision processes to understand broader developments in public policy. To achieve that, it places the attention at the center of political action and relies on the fact that it is the change in attention that would cause, consequently, change in public policy. One of the most relevant aspects on the studies of policy agendas and policy change considers the diffusion occurred in the years 2000 with the application of its theoretical and methodological approaches to different societies and political systems beyond the United States. Consequently, another important achievement in the studies of agenda setting and policy change must be highlighted: studies of public policies in comparative perspective. Although agenda-setting studies have grown significantly in the international academic community, there are still some important points to be better explored. The intent of this Themed Special Issue of RAP is to contribute with the growing agenda-setting studies by highlighting the processes of policy changes and policy dynamics.
Resumen Este artículo es una breve presentación del número Temático Especial sobre Cambio y Dinámica de las Políticas Públicas, cuyo principal objetivo es plantear y discutir los conceptos involucrados en el proceso de establecimiento de la agenda (agenda-setting), uno de los temas más importantes para el estudio de las políticas públicas y de su proceso (policy process). Los modelos de agenda-setting proponen enfoques analíticos de los procesos predecisorios para el análisis y comprensión de aspectos más amplios en la construcción de problemas y soluciones en las políticas públicas. Para ello, pone la atención ‒un recurso escaso‒ en el centro de la acción política, indicando que es el cambio de atención lo que, en consecuencia, provocaría cambios en las políticas públicas. Uno de los aspectos más relevantes en los estudios de agenda-setting y cambios en las políticas públicas considera la difusión global de sus estudios que se dio en la década del 2000 con la aplicación de enfoques teóricos y metodológicos a diferentes países y sistemas políticos, más allá de Estados Unidos, donde dichos modelos y teorías surgieron en las décadas de 1980 y 1990. Consecuentemente, cabe destacar otro logro importante en los estudios de establecimiento de agenda y cambio de políticas: los estudios de políticas públicas en perspectiva comparada. Aunque los estudios de establecimiento de agendas han crecido significativamente en la comunidad académica internacional, todavía quedan algunos puntos importantes por explorar más a fondo. La intención de este Número Especial es contribuir a los crecientes estudios sobre agenda-setting, destacando los procesos de cambio y la dinámica de las políticas públicas.
Resumo Esse artigo é uma breve apresentação do número Especial Temático sobre Mudança e Dinâmicas de Políticas Públicas, que tem como objetivo principal apresentar e discutir os conceitos envolvidos no processo de agenda-setting, um dos temas mais importantes para o estudo das políticas públicas e do processo de políticas públicas (policy process). Os modelos de definição de agenda (agenda-setting) propõem abordagens analíticas sobre os processos pré-decisórios para a análise e compreensão de aspectos mais amplos na construção de problemas e soluções em políticas públicas. Para tanto, coloca a atenção, um recurso escasso, no centro da ação política, indicando que é a mudança de atenção que ocasionaria, consequentemente, mudanças em políticas públicas. Um dos aspectos mais relevantes nos estudos de agenda-setting e mudanças em políticas públicas considera a difusão global de seus estudos ocorrida nos anos 2000 com a aplicação de abordagens teóricas e metodológicas a diferentes países e sistemas políticos, para além Estados Unidos, de onde tais modelos e teorias surgiram nos anos 1980 e 1990. Consequentemente, outra conquista importante nos estudos de definição de agenda e mudança de políticas deve ser destacada: os estudos de políticas públicas em perspectiva comparada. Embora os estudos de definição de agendas tenham crescido significativamente na comunidade acadêmica internacional, ainda existem alguns pontos importantes a serem mais bem explorados. A intenção deste Número Especial, é o de contribuir com os crescentes estudos sobre agenda-setting, destacando os processos de mudanças e as dinâmicas das políticas públicas.
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Humanos , Masculino , Feminino , Sistemas Políticos , Política Pública , Gestão de MudançaRESUMO
Zika virus (ZIKV) has gained a lot of attention in the past few years due to its rapid spread worldwide and its close association to severe neurological outcomes, such as microcephaly and Guillain-Barre syndrome. In this study, the in vitro and in vivo anti-ZIKV activity of 7-deaza-7-fluoro-2'-C-methyl-adenosine (DFMA) was evaluated. In vitro, using primary mouse neuronal cells and human neural stem cells infected by ZIKV, treatment with DFMA resulted in impaired viral replication and protection against virus-induced cell death. In vivo, when administrated prior to infection, DFMA prevented lethality and markedly reduced viral loads and neuroinflammation, including microgliosis and overall brain damage. Additionally, as an early therapeutic treatment, DFMA increased survival rates in mice. Collectively, these findings demonstrate that the nucleoside analog DFMA inhibits ZIKV infection and viral-induced neuroinflammation in vitro and in vivo without apparent untoward effects, suggesting it may be useful in individuals infected with ZIKV.
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Adenosina/análogos & derivados , Antivirais/farmacologia , Inflamação/virologia , Doenças do Sistema Nervoso/virologia , Infecção por Zika virus/complicações , Adenosina/farmacologia , Adenosina/uso terapêutico , Animais , Antivirais/uso terapêutico , Linhagem Celular , Células Cultivadas , Chlorocebus aethiops , Culicidae/citologia , Humanos , Inflamação/tratamento farmacológico , Camundongos , Doenças do Sistema Nervoso/tratamento farmacológico , Células-Tronco Neurais , Células Vero , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Zika virus , Infecção por Zika virus/tratamento farmacológicoRESUMO
We have previously shown that the small metal-binding protein (SmbP) extracted from the gram-negative bacterium Nitrosomonas europaea can be employed as a fusion protein for the expression and purification of recombinant proteins in Escherichia coli. With the goal of increasing the amounts of SmbP-tagged proteins produced in the E. coli periplasm, we replaced the native SmbP signal peptide with three different signal sequences: two were from the proteins CusF and PelB, for transport via the Sec pathway, and one was the signal peptide from TorA, for transport via the Tat pathway. Expression of SmbP-tagged Red Fluorescent Protein (RFP) using these three alternative signal peptides individually showed a considerable increase in protein levels in the periplasm of E. coli as compared to its level using the SmbP signal sequence. Therefore, for routine periplasmic expression and purification of recombinant proteins in E. coli, we highly recommend the use of the fusion proteins PelB-SmbP or CusF-SmbP, since these signal sequences increase periplasmic production considerably as compared to the wild-type. Our work, finally, demonstrates that periplasmic expression for SmbP-tagged proteins is not limited to the Sec pathway, in that the TorA-SmbP construct can export reasonable quantities of folded proteins to the periplasm. Although the Sec route has been the most widely used, sometimes, depending on the nature of the protein of interest, for example, if it contains cofactors, it is more appropriate to consider using the Tat route over the Sec. SmbP therefore can be recommended in terms of its particular versatility when combined with signal peptides for the two different routes.
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Proteínas de Bactérias/genética , Clonagem Molecular/métodos , Nitrosomonas europaea/genética , Periplasma/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas de Bactérias/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cobre , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Expressão Gênica , Genes Reporter , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Proteínas de Ligação ao Ferro/genética , Proteínas de Ligação ao Ferro/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Nitrosomonas europaea/metabolismo , Oxirredutases N-Desmetilantes/genética , Oxirredutases N-Desmetilantes/metabolismo , Periplasma/química , Polissacarídeo-Liases/genética , Polissacarídeo-Liases/metabolismo , Sinais Direcionadores de Proteínas , Transporte Proteico , Proteínas Recombinantes de Fusão/metabolismo , Proteína Vermelha FluorescenteRESUMO
BACKGROUND: We analyzed whether the total hospital cost in a 90-day bundled payment period for ceramic-on-polyethylene (C-PE) and ceramic-on-ceramic (COC) total hip arthroplasty (THA) bearings was changing over time, and whether the cost differential between ceramic bearings and metal-on-polyethylene (M-PE) bearings was approaching the previously published tipping point for cost-effectiveness of US$325. METHODS: A total of 245,077 elderly Medicare patients (65+) who underwent primary THA between 2010 and 2015 were identified from the United States Medicare 100% national administrative hospital claims database. The total inpatient cost, calculated up to 90 days after index discharge, was computed using cost-to-charge ratios, and hospital payment was analyzed. The differential total inpatient cost of C-PE and COC bearings, compared to metal-on-polyethylene (M-PE), was evaluated using parametric and nonparametric models. RESULTS: After adjustment for patient and clinical factors, and the year of surgery, the mean hospital cost up to 90 days for primary THA with C-PE or COC was within ±1% of the cost for primary THA with M-PE bearings (P < .001). From the nonparametric analysis, the median total hospital cost was US$296-US$353 more for C-PE and COC than M-PE. Cost differentials were found to decrease significantly over time (P < .001). CONCLUSION: Patient and clinical factors had a far greater impact on the total cost of inpatient THA surgery than bearing selection, even when including readmission costs up to 90 days after discharge. Our findings indicate that the cost-effectiveness thresholds for ceramic bearings relative to M-PE are changing over time and increasingly achievable for the Medicare population.
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Artroplastia de Quadril/economia , Artroplastia de Quadril/instrumentação , Cerâmica , Análise Custo-Benefício , Prótese de Quadril/economia , Desenho de Prótese/economia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Medicare , Metais , Polietileno/economia , Mecanismo de Reembolso , Reoperação/economia , Estados UnidosRESUMO
BACKGROUND: In an era of innovation in surgical approaches for total hip arthroplasty (THA), there is concern for increasing trends of early failure. The purpose of this study is to evaluate the incidence of early failure of primary THA stratified by surgical approach. METHODS: A retrospective review was performed on consecutive primary THAs completed from 2007 to 2014 at a high-volume center. THAs were stratified by surgical approach. Only the direct anterior (DAA) and posterior approaches (PA) were included. The primary outcome measure was early revision (<5 years). Descriptive statistics were performed using SAS software. RESULTS: In total, 6894 primary THAs performed between 2007 and 2014 were included. Across 2431 DAA THAs and 4463 PA THAs, there were 103 revisions overall. There was no difference in the overall revision rate for DAA THAs (1.69%) compared to PA THAs (1.39%) (P = .33). The DAA had a higher rate of early revisions for femoral component loosening compared to the PA (P = .0003). About 35.7% of DAA THAs were revised for femoral loosening compared to 8% for the PA (P = .0003). Early failure by femoral loosening occurred more often via the DAA in Dorr A bone (P = .03). The PA had a higher incidence of revision for instability (P = .04). There was no difference in modes of failure with regards to time to failure, acetabular loosening, early periprosthetic fracture, or infection. CONCLUSION: The DAA had a higher incidence of femoral loosening while PA had a higher mode of failure due to instability. Overall revision rates were not statistically different between approaches.
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Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Prótese de Quadril/efeitos adversos , Falha de Prótese/etiologia , Acetábulo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fêmur , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas Periprotéticas/etiologia , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. We have previously shown that hepatic reticuloendothelial system (RES) iron deposition is associated with an advanced degree of nonalcoholic steatohepatitis (NASH) in humans. In this study, we aimed to determine differentially expressed genes related to iron overload, inflammation and oxidative stress pathways, with the goal of identifying factors associated with NASH progression. Seventy five patients with NAFLD were evaluated for their biochemical parameters and their liver tissue analyzed for NASH histological characteristics. Gene expression analysis of pathways related to iron homeostasis, inflammation and oxidative stress was performed using real-time PCR. Gene expression was compared between subjects based on disease status and presence of hepatic iron staining. We observed increased gene expression of hepcidin (HAMP) (2.3 fold, p = 0.027), transmembrane serine proteinase 6 (TMPRSS6) (8.4 fold, p = 0.003), signal transducer and activator of transcription 3 (STAT3) (5.5 fold, p = 0.004), proinflammatory cytokines; IL-1β (2.7 fold, p = 0.046) and TNF-α (3.8 fold, p = 0.001) in patients with NASH. TMPRSS6, a negative regulator of HAMP, is overexpressed in patients with NASH and HIF1α (hypoxia inducible factor-1) is downregulated. NAFLD patients with hepatic iron deposition exhibited higher hepcidin expression (3.1 fold, p = 0.04) but lower expression of cytokines. In conclusion, we observed elevated hepatic HAMP expression in patients with NASH and in NAFLD patients who had hepatic iron deposition, while proinflammatory cytokines displayed elevated expression only in patients with NASH, suggesting a regulatory role for hepcidin in NAFL to NASH transition and in mitigating inflammatory responses.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Sobrecarga de Ferro/genética , Hepatopatia Gordurosa não Alcoólica/genética , Inflamação/genética , Ferro/análise , Fígado/química , Serina Endopeptidases/genética , Regulação da Expressão Gênica , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/sangue , Mediadores da Inflamação/sangue , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/sangue , Fator de Transcrição STAT3/genética , Interleucina-1beta/genética , Interleucina-1beta/sangue , Reação em Cadeia da Polimerase em Tempo Real , Hepcidinas/genética , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/sangue , Inflamação/diagnóstico , Inflamação/sangue , Fígado/patologia , Proteínas de Membrana/genéticaRESUMO
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. We have previously shown that hepatic reticuloendothelial system (RES) iron deposition is associated with an advanced degree of nonalcoholic steatohepatitis (NASH) in humans. In this study, we aimed to determine differentially expressed genes related to iron overload, inflammation and oxidative stress pathways, with the goal of identifying factors associated with NASH progression. Seventy five patients with NAFLD were evaluated for their biochemical parameters and their liver tissue analyzed for NASH histological characteristics. Gene expression analysis of pathways related to iron homeostasis, inflammation and oxidative stress was performed using real-time PCR. Gene expression was compared between subjects based on disease status and presence of hepatic iron staining. We observed increased gene expression of hepcidin (HAMP) (2.3 fold, p = 0.027), transmembrane serine proteinase 6 (TMPRSS6) (8.4 fold, p = 0.003), signal transducer and activator of transcription 3 (STAT3) (5.5 fold, p = 0.004), proinflammatory cytokines; IL-1? (2.7 fold, p = 0.046) and TNF-? (3.8 fold, p = 0.001) in patients with NASH. TMPRSS6, a negative regulator of HAMP, is overexpressed in patients with NASH and HIF1? (hypoxia inducible factor-1) is downregulated. NAFLD patients with hepatic iron deposition exhibited higher hepcidin expression (3.1 fold, p = 0.04) but lower expression of cytokines. In conclusion, we observed elevated hepatic HAMP expression in patients with NASH and in NAFLD patients who had hepatic iron deposition, while proinflammatory cytokines displayed elevated expression only in patients with NASH, suggesting a regulatory role for hepcidin in NAFL to NASH transition and in mitigating inflammatory responses.
Assuntos
Inflamação/genética , Sobrecarga de Ferro/genética , Ferro/análise , Fígado/química , Hepatopatia Gordurosa não Alcoólica/genética , Estresse Oxidativo/genética , Adulto , Feminino , Regulação da Expressão Gênica , Hepcidinas/genética , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Mediadores da Inflamação/sangue , Interleucina-1beta/sangue , Interleucina-1beta/genética , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/diagnóstico , Fígado/patologia , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Fator de Transcrição STAT3/genética , Serina Endopeptidases/genética , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genéticaRESUMO
Global warming poses a threat to many ectothermic organisms because of the harmful effects that elevated temperatures can have on resting metabolic rate (RMR) and body size. This study evaluated the thermal sensitivity of Trinidadian guppies (Poecilia reticulata) by describing the effects of developmental temperature on mass, burst speed and RMR, and investigated whether these tropical fish can developmentally acclimate to their thermal conditions. These traits were measured following exposure to one of three treatments: 70 days at 23, 25, 28 or 30°C (acclimated groups); 6 h at 23, 28 or 30°C following 70 days at 25°C (unacclimated groups); or 6 h at 25°C following 70 days in another 25°C tank (control group). Body mass was lower in warmer temperatures, particularly amongst females and individuals reared at 30°C. The burst speed of fish acclimated to each temperature did not differ and was marginally higher than that of unacclimated fish, indicative of complete compensation. Conversely, acclimated and unacclimated fish did not differ in their RMR at each temperature. Amongst the acclimated groups, RMR was significantly higher at 30°C, indicating that guppies may become thermally limited at this temperature as a result of less energy being available for growth, reproduction and locomotion. Like other tropical ectotherms, guppies appear to be unable to adjust their RMR through physiological acclimation and may consequently be susceptible to rising temperatures. Also, because larger females have higher fecundity, our data suggest that fecundity will be reduced in a warmer climate, potentially decreasing the viability of guppy populations.
Assuntos
Aclimatação/fisiologia , Locomoção/fisiologia , Poecilia/metabolismo , Poecilia/fisiologia , Caracteres Sexuais , Temperatura , Animais , Peso Corporal/fisiologia , Feminino , Masculino , Consumo de Oxigênio/fisiologia , Poecilia/crescimento & desenvolvimento , Descanso/fisiologia , Trinidad e TobagoRESUMO
BACKGROUND: There is an ongoing clinical need for novel methods to measure hepatic iron content (HIC) noninvasively. Both magnetic resonance imaging (MRI) and superconducting quantum interference device (SQUID) methods have previously shown promise for estimation of HIC, but these methods can be expensive and are not widely available. Room-temperature susceptometry (RTS) represents an inexpensive alternative and was previously found to be strongly correlated with HIC estimated by SQUID measurements among patients with transfusional iron overload related to thalassemia. AIM: The goal of the current study was to examine the relationship between RTS and biochemical HIC measured in liver biopsy specimens in a more varied patient cohort. MATERIAL AND METHODS: Susceptometry was performed in a diverse group of patients with hyperferritinemia due to hereditary hemochromatosis (HHC) (n = 2), secondary iron overload (n = 3), nonalcoholic fatty liver disease (NAFLD) (n = 2), and chronic viral hepatitis (n = 3) within one month of liver biopsy in the absence of iron depletion therapy. RESULTS: The correlation coefficient between HIC estimated by susceptometry and by biochemical iron measurement in liver tissue was 0.71 (p = 0.022). Variance between liver iron measurement and susceptometry measurement was primarily related to reliance on the patient's body-mass index (BMI) to estimate the magnetic susceptibility of tissue overlying the liver. CONCLUSIONS: We believe RTS holds promise for noninvasive measurement of HIC. Improved measurement techniques, including more accurate overlayer correction, may further improve the accuracy of liver susceptometry in patients with liver disease.
Assuntos
Técnicas e Procedimentos Diagnósticos/instrumentação , Ferritinas/sangue , Ferro/metabolismo , Fígado/metabolismo , Fígado/patologia , Campos Magnéticos , Temperatura , Adulto , Idoso , Biópsia , Estudos de Coortes , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Feminino , Hemocromatose/metabolismo , Hemocromatose/patologia , Hepatite Crônica/metabolismo , Hepatite Crônica/patologia , Humanos , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Valor Preditivo dos TestesRESUMO
Understanding genetic diversity in natural populations is a fundamental objective of evolutionary biology. The immune genes of the major histocompatibility complex (MHC) are excellent candidates to study such diversity because they are highly polymorphic in populations. Although balancing selection may be responsible for maintaining diversity at these functionally important loci, temporal variation in selection pressure has rarely been examined. We examine temporal variation in MHC class IIB diversity in nine guppy (Poecilia reticulata) populations over two years. We found that five of the populations changed significantly more at the MHC than at neutral (microsatellite) loci as measured by F(ST), which suggests that the change at the MHC was due to selection and not neutral processes. Additionally, pairwise population differentiation measures at the MHC were higher in 2007 than in 2006, with the signature of selection changing from homogenizing to diversifying selection or neutral evolution. Interestingly, within the populations the magnitude of the change at the MHC between years was related to the change in the proportion of individuals infected by a common parasite, indicating a link between genetic structure and the parasite. Our data thereby implicate temporal variation in selective pressure as an important mechanism maintaining diversity at the MHC in wild populations.
Assuntos
Genes MHC da Classe II/genética , Variação Genética , Genética Populacional , Poecilia/genética , Seleção Genética , Análise de Variância , Animais , Primers do DNA/genética , Frequência do Gene , Repetições de Microssatélites/genética , Análise de Sequência de DNA , Especificidade da Espécie , Fatores de Tempo , Trinidad e TobagoRESUMO
O objetivo deste estudo foi comparar as alterações dentoesqueléticas decorrentes do tratamento exclusivo com o aparelho extrabucal de tração occipital em pacientes com más-oclusões de Classe II, Divisão I, com um grupo controle com o mesmo tipo de má-oclusão. O grupo experimental compreendeu 25 pacientes (dez meninos e 15 meninas), com média de idade inicial e final de 10,28 e 1 1,82 anos, respectivamente e período médio de tratamento de 1,54 anos. O grupo controle consistiu de 31 indivíduos (22 meninos e nove meninas), com média de idade inicial e final de 9,08 e 12,11 anos, respectivamente. Utilizaram-se telerradiografias de todos os indivíduos, obtidas antes e após a colocação do aparelho e do período de observação. O test "t" pareado foi utilizado na comparação intragrupos e o test "t" na comparação intergrupos. A tendência de deslocamento anterior da maxila foi alterada,'apresentando melhora na relação maxilomandibular e na convexidade facial. O comportamento vertical maxilar foi equilibrado e o desenvolvimento dos molares superiores no sentido vertical e sagital foi restringido. Concluiu-seque o uso do aparelho extrabucal de tração occipital é eficiente na correção das más-oclusões de Classe II, Divisão I, sendo indicado para pacientes meso e dolicofaciais.
The aim of this prospective study was to compare the dentoskeletal alterations resulting from treatment exclusively with the Extraoral occipital fraction appliance in patients with Class II, Division I, malocclusions with a control group with the same type of malocclusion. The Experimental group comprised 25patients (ten boys and 15 girls), with initial and final mean ages of 10.28 and 11.82 years, respectively and a treatment mean period of 1.54 years. The Control group consisted of 31 individuals (22 boys and 9 girls). with initial and final mean ages of 9.08 and 12.11 years, respectively. Lateral cephalometric radiographs were taken before and after placement of the appliance and of the period of observation. The paired t-test was used in the intragroup comparison and the t-test in the intergroup comparison. The trend towards anterior displacement of the maxilla was altered, presenting improvement in the maxillomandibular relationship and in facial convexity. The vertical maxillary behavior was balanced and development of the maxillary molars in the vertical and sagittal directions was restricted. The use of the Extraoral occipital traction appliance is very efficient for correcting Class 11, Division I, malocclusions, being an excellent option of treatment.
Assuntos
Humanos , Masculino , Feminino , Criança , Aparelhos de Tração Extrabucal/efeitos adversos , Má Oclusão Classe II de Angle , Ortodontia , CefalometriaRESUMO
We use microsatellite loci to detail the multiple paternity patterns in broods from 10 wild populations of the guppy (Poecilia reticulata) found in Northern Trinidad. The populations span two major drainages comprising the Caroni and the Oropouche, and include sites that are characterized by either high or low predation. Across the populations the frequency of multiple paternity is high with 95% (range: 70%-100%) of broods having multiple sires. Broods have an average of 3.5 sires (range: 1-9) and a mixed-model analysis suggests that broods from high predation sites have marginally more sires than do those from low predation sites, but this is true only in the Oropouche drainage. There is no difference in sire number between predation sites in the Caroni drainage. Brood size, but not female body length, is correlated with the number of sires and the correlation cannot be attributed solely to the stochastic process associated with sperm competition and a 'fair raffle'. Within broods there is significant skew in reproductive success among males, which may reflect variation in sperm competitiveness or female choice. There is, however, no difference in the skew among populations from different predation regimes or drainages. Finally, high predation populations were characterized by increased genetic variability at the microsatellite loci, suggesting a larger effective population size. We discuss explanations for the high degree of multiple paternity but the general lack of any major differences among broods from ecologically different populations.