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Reduced skeletal muscle mass and oxidative capacity coexist in patients with pulmonary emphysema and are independently associated with higher mortality. If reduced cellular respiration contributes to muscle atrophy in that setting remains unknown. Using a mouse with genetically induced pulmonary emphysema that recapitulates muscle dysfunction, we found that reduced activity of succinate dehydrogenase (SDH) is a hallmark of its myopathic changes. We generated an inducible, muscle-specific SDH knockout mouse that demonstrates lower mitochondrial oxygen consumption, myofiber contractility, and exercise endurance. Respirometry analyses show that in vitro complex I respiration is unaffected by loss of SDH subunit C in muscle mitochondria, which is consistent with the pulmonary emphysema animal data. SDH knockout initially causes succinate accumulation associated with a down-regulated transcriptome but modest proteome effects. Muscle mass, myofiber type composition, and overall body mass constituents remain unaltered in the transgenic mice. Thus, while SDH regulates myofiber respiration in experimental pulmonary emphysema, it does not control muscle mass or other body constituents.
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Respiración de la Célula , Ratones Noqueados , Contracción Muscular , Músculo Esquelético , Enfisema Pulmonar , Succinato Deshidrogenasa , Animales , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/genética , Enfisema Pulmonar/patología , Enfisema Pulmonar/etiología , Succinato Deshidrogenasa/metabolismo , Succinato Deshidrogenasa/genética , Ratones , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Complejo II de Transporte de Electrones/metabolismo , Complejo II de Transporte de Electrones/genética , Modelos Animales de Enfermedad , Ratones Transgénicos , Mitocondrias Musculares/metabolismo , Mitocondrias Musculares/patología , Consumo de OxígenoRESUMEN
BACKGROUND & AIMS: Treatment outcomes for people living with autoimmune hepatitis (AIH) are limited by a lack of specific therapies, as well as limited well-validated prognostic tools and clinical trial endpoints. We sought to identify predictors of outcome for people living with AIH. METHODS: We evaluated the clinical course of people with AIH across 11 Canadian centres. Biochemical changes were analysed using linear mixed-effect and logistic regression. Clinical outcome was dynamically modelled using time-varying Cox proportional hazard modelling and landmark analysis. RESULTS: In 691 patients (median age 49 years, 75.4% female), with a median follow-up of 6 years (25th-75th percentile, 2.5-11), 118 clinical events occurred. Alanine aminotransferase (ALT) normalisation occurred in 63.8% of the cohort by 12 months. Older age at diagnosis (odd ratio [OR] 1.19, 95% CI 1.06-1.35) and female sex (OR 1.94, 95% CI 1.18-3.19) were associated with ALT normalisation at 6 months, whilst baseline cirrhosis status was associated with reduced chance of normalisation at 12 months (OR 0.52, 95% CI 0.33-0.82). Baseline total bilirubin, aminotransferases, and IgG values, as well as initial prednisone dose, did not predict average ALT reduction. At baseline, older age (hazard ratio [HR] 1.25, 95% CI 1.12-1.40), cirrhosis at diagnosis (HR 3.67, 95% CI 2.48-5.43), and elevated baseline total bilirubin (HR 1.36, 95% CI 1.17-1.58) increased the risk of clinical events. Prolonged elevations in ALT (HR 1.07, 95% CI 1.00-1.13) and aspartate aminotransferase (HR 1.13, 95% CI 1.06-1.21), but not IgG (HR 1.01, 95% CI 0.95-1.07), were associated with higher risk of clinical events. Higher ALT at 6 months was associated with worse clinical event-free survival. CONCLUSION: In people living with AIH, sustained elevated aminotransferase values, but not IgG, are associated with poorer long-term outcomes. Biochemical response and long-term survival are not associated with starting prednisone dose. IMPACT AND IMPLICATIONS: Using clinical data from multiple Canadian liver clinics treating autoimmune hepatitis (AIH), we evaluate treatment response and clinical outcomes. For the first time, we apply mixed-effect and time-varying survival statistical methods to rigorously examine treatment response and the impact of fluctuating liver biochemistry on clinical event-free survival. Key to the study impact, our data is 'real-world', represents a diverse population across Canada, and uses continuous measurements over follow-up. Our results challenge the role of IgG as a marker of treatment response and if normalisation of IgG should remain an important part of the definition of biochemical remission. Our analysis further highlights that baseline markers of disease severity may not prognosticate early treatment response. Additionally, the initial prednisone dose may be less relevant for achieving aminotransferase normalisation. This is important for patients and treating clinicians given the relevance and importance of side effects.
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Alanina Transaminasa , Hepatitis Autoinmune , Humanos , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/mortalidad , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Canadá/epidemiología , Adulto , Alanina Transaminasa/sangre , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Estudios de Cohortes , Resultado del Tratamiento , Pronóstico , Bilirrubina/sangre , Estudios de Seguimiento , Modelos de Riesgos Proporcionales , Inmunoglobulina G/sangreRESUMEN
BACKGROUND: Liver transplantation (LT) is indicated in patients with severe acute or chronic liver failure for which no other therapy is available. With the increasing number of LTs in recent years, liver centers worldwide must manage their patients according to their clinical situation and the expected waiting time for transplantation. The LT clinic at the Centre hospitalier de l'Université de Montréal (CHUM) is developing a new health care model across the entire continuum of pre-, peri-, and posttransplant care that features patient monitoring by an interdisciplinary team, including an accompanying patient; a digital platform to host a clinical plan; a learning program; and data collection from connected objects. OBJECTIVE: This study aims to (1) evaluate the outcomes following the implementation of a patient platform with connected devices and an accompanying patient, (2) identify implementation barriers and facilitators, (3) describe service outcomes in terms of health outcomes and the rates and nature of contact with the accompanying patient, (4) describe patient outcomes, and (5) assess the intervention's cost-effectiveness. METHODS: Six types of participants will be included in the study: (1) patients who received transplants and reached 1 year after transplantation before September 2023 (historical cohort or control group), (2) patients who will receive an LT between December 2023 and November 2024 (prospective cohort/intervention group), (3) relatives of those patients, (4) accompanying patients who have received an LT and are interested in supporting patients who will receive an LT, (5) health care professionals, and (6) decision makers. To describe the study sample and collect data to achieve all the objectives, a series of validated questionnaires, accompanying patient logbooks, transcripts of interviews and focus groups, and clinical indicators will be collected throughout the study. RESULTS: In total, 5 (steering, education, clinical-technological, nurse prescription, and accompanying patient) working committees have been established for the study. Recruitment of patients is expected to start in November 2023. All questionnaires and technological platforms have been prepared, and the clinicians, stakeholders, and accompanying patient personnel have been recruited. CONCLUSIONS: The implementation of this model in the trajectory of LT recipients at the CHUM may allow for better monitoring and health of patients undergoing transplantation, ultimately reducing the average length of hospital stay and promoting better use of medical resources. In the event of positive results, this model could be transposed to all transplant units at the CHUM and across Quebec (potentially affecting 888 patients per year) but could also be applied more widely to the monitoring of patients with other chronic diseases. The lessons learned from this project will be shared with decision makers and will serve as a model for other initiatives involving accompanying patients, connected objects, or digital platforms. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54440.
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Éxito Académico , Bachillerato en Enfermería , Estudiantes de Enfermería , Humanos , EstudiantesRESUMEN
A mission statement represents an organization's values, expectations, and priorities and guides its strategic decision-making. This article describes an innovative and iterative process for developing mission statements to reflect and guide the diversity, equity, and inclusion values of schools and colleges of nursing. The process began with extensive input from the faculty during the fall 2021 faculty retreat using a World Café approach. Following the retreat, members of the Equity and Inclusion Committee reviewed the information from the faculty about the college's values, goals, and vision for our tripartite mission. In drafting the mission statement, the Equity, and Inclusion Committee, which includes faculty, staff, and student representation from the college's multiple regional campuses, units, and departments, met to craft an initial draft collaboratively. The initial draft of the mission statement was then circulated to the Faculty Leadership Team, the Faculty Executive Committee, and individual departments within the college for feedback. Committee members used the input and suggested revisions to refine and finalize a proposed new mission statement. A survey was distributed to faculty, staff, and students to provide quantitative and qualitative feedback about the proposed mission statement (N = 125). Mean scores suggested agreement that the new mission statement reflected the values and future direction of the college (M = 7.91), aligned with personal values and career goals (M = 8.25), and its achievement would advance the discipline of nursing (M = 8.30). The level of support for adopting the new mission statement was strong (M = 7.83). Most of the faculty voted to adopt the new mission statement at a faculty meeting (N = 98, 85 %). The strategies described have implications for guiding the development of mission statements to speak to the issues of diversity, equity, and inclusion as core values and priorities of schools and colleges of nursing.
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Diversidad, Equidad e Inclusión , Docentes , HumanosRESUMEN
ADVERTISING AND PUBLIC INFORMATION: THE GAME HAS CHANGED FOR PHYSICIANS Until the decree of December 22, 2020, all advertising was forbidden to physicians. Jurisprudence was however uncertain due to the difficulty in differentiating between "advertising" and "information to the public". From now on, and in order to comply with European directives, communication to the public is authorized, in particular on the practitioner's website. However, and fortunately, it is part of a strong deontology and some prohibitions remain.
PUBLICITÉ ET INFORMATION DU PUBLIC : LA DONNE A CHANGÉ POUR LES MÉDECINS Jusqu'au décret du 22 décembre 2020, toute publicité était interdite aux médecins. La jurisprudence était pourtant aléatoire du fait de la difficulté à différencier "publicité" et "information du public". Désormais, et pour se conformer aux directives européennes, la communication au public est autorisée, notamment sur le site internet du praticien. Cependant et heureusement, elle s'inscrit dans le cadre d'une déontologie forte et certaines interdictions persistent.
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Comunicación , Médicos , HumanosRESUMEN
Immune checkpoint inhibitors (ICI) are being increasingly used to successfully treat several types of cancer. However, due to their mode of action, these treatments are associated with several immune-related adverse events (irAEs), including immune-mediated autoimmune-like hepatitis in 5 to 10% of cases. The specific immune mechanism responsible for the development of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI) is currently unknown. This review summarizes the current knowledge on hepatic irAEs during cancer immunotherapy. It also addresses the clinical management of ILICI and how it is becoming an increasingly important clinical issue. Clinical, histological, and laboratory features of autoimmune hepatitis (AIH) and ILICI are compared, and their shared and distinctive traits are discussed in an effort to better understand the development of hepatic irAEs. Finally, based on the current knowledge of liver immunology and AIH pathogenesis, we propose a series of events that could trigger the observed liver injury in ICI-treated patients. This model could be useful in the design of future studies aiming to identify the specific immune mechanism(s) at play in ILICI and improve immune checkpoint inhibitor cancer immunotherapy.
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Hepatitis Autoinmune , Neoplasias , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/terapia , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias/patologíaRESUMEN
The theory of planned behavior (TPB) has been widely used to guide research in cancer screening-related behavior, but no critique of the TPB's application in this domain has been published. We used Fawcett and DeSanto-Madeya's 2013 framework to analyze and evaluate the theory. The theory was developed on the basis of antecedent knowledge regarding human behavior, and its concepts and propositions are comprehensively delineated. The TPB shows adequate internal consistency and impressive social and theoretical significance. Methodologically sound studies are called for to further test some theory propositions and to evaluate its pragmatic adequacy for promoting cancer screening in nursing practice.
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Detección Precoz del Cáncer , Neoplasias , Humanos , Neoplasias/diagnósticoRESUMEN
Mitochondria are epicentres of eukaryotic metabolism and bioenergetics. Pioneering efforts in recent decades have established the core protein componentry of these organelles1 and have linked their dysfunction to more than 150 distinct disorders2,3. Still, hundreds of mitochondrial proteins lack clear functions4, and the underlying genetic basis for approximately 40% of mitochondrial disorders remains unresolved5. Here, to establish a more complete functional compendium of human mitochondrial proteins, we profiled more than 200 CRISPR-mediated HAP1 cell knockout lines using mass spectrometry-based multiomics analyses. This effort generated approximately 8.3 million distinct biomolecule measurements, providing a deep survey of the cellular responses to mitochondrial perturbations and laying a foundation for mechanistic investigations into protein function. Guided by these data, we discovered that PIGY upstream open reading frame (PYURF) is an S-adenosylmethionine-dependent methyltransferase chaperone that supports both complex I assembly and coenzyme Q biosynthesis and is disrupted in a previously unresolved multisystemic mitochondrial disorder. We further linked the putative zinc transporter SLC30A9 to mitochondrial ribosomes and OxPhos integrity and established RAB5IF as the second gene harbouring pathogenic variants that cause cerebrofaciothoracic dysplasia. Our data, which can be explored through the interactive online MITOMICS.app resource, suggest biological roles for many other orphan mitochondrial proteins that still lack robust functional characterization and define a rich cell signature of mitochondrial dysfunction that can support the genetic diagnosis of mitochondrial diseases.
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Mitocondrias , Proteínas Mitocondriales , Proteínas de Transporte de Catión , Proteínas de Ciclo Celular , Metabolismo Energético , Humanos , Espectrometría de Masas , Mitocondrias/genética , Mitocondrias/metabolismo , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Factores de Transcripción , Proteínas de Unión al GTP rab5RESUMEN
Patients with chronic obstructive pulmonary disease (COPD)-pulmonary emphysema often develop locomotor muscle dysfunction, which entails reduced muscle mass and force-generation capacity and is associated with worse outcomes, including higher mortality. Myogenesis contributes to adult muscle integrity during injury-repair cycles. Injurious events crucially occur in the skeletal muscles of patients with COPD in the setting of exacerbations and infections, which lead to acute decompensations for limited periods of time, after which patients typically fail to recover the baseline status they had before the acute event. Autophagy, which is dysregulated in muscles from patients with COPD, is a key regulator of muscle stem-satellite- cells activation and myogenesis, yet very little research has so far mechanistically investigated the role of autophagy dysregulation in COPD muscles. Using a genetically inducible interleukin-13-driven pulmonary emphysema model leading to muscle dysfunction, and confirmed with a second genetic animal model, we found a significant myogenic dysfunction associated with the reduced proliferative capacity of satellite cells. Transplantation experiments followed by lineage tracing suggest that an intrinsic defect in satellite cells, and not in the COPD environment, plays a dominant role in the observed myogenic dysfunction. RNA sequencing analysis and direct observation of COPD mice satellite cells suggest dysregulated autophagy. Moreover, while autophagy flux experiments with bafilomycin demonstrated deacceleration of autophagosome turnover in COPD mice satellite cells, spermidine-induced autophagy stimulation leads to a higher replication rate and myogenesis in these animals. Our data suggest that pulmonary emphysema causes disrupted myogenesis, which could be improved with stimulation of autophagy and satellite cells activation, leading to an attenuated muscle dysfunction.
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Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Animales , Autofagia , Humanos , Ratones , Desarrollo de Músculos , Músculo Esquelético , Enfisema Pulmonar/etiologíaRESUMEN
BACKGROUND AND AIMS: We investigated associations between ethnicity, survival, and disease severity in a diverse Canadian cohort of patients with primary biliary cholangitis (PBC). APPROACH AND RESULTS: Patients with PBC were included from the Canadian Network for Autoimmune Liver Disease. Ethnicity was defined using a modified list adopted from Statistics Canada, and ethnicities with small samples were grouped. Clinical events were defined as liver decompensation, HCC, liver transplantation, or death. Clinical event-free and liver transplantation-free survival were analyzed using Cox regression. Trajectories of serum liver function tests were assessed over time using mixed-effects regression. Health-related quality of life was assessed using the Short Form 36, the PBC-40 questionnaire, and the 5-D Itch scale and analyzed using mixed-effects regression. The cohort included 1538 patients with PBC from six sites and was comprised of 82% White, 4.7% Indigenous, 5.5% East Asian, 2.6% South Asian, and 5.1% miscellaneous ethnicities. Indigenous patients were the only ethnic group with impaired liver transplant-free and event-free survival compared to White patients (HR, 3.66; 95% CI, 2.23-6.01; HR, 3.09; 95% CI, 1.94-4.92). Indigenous patients were more likely to have a clinical event before diagnosis (10%) than all other ethnic groups despite similar age at diagnosis. Indigenous patients presented with higher alkaline phosphatase, total bilirubin, and GLOBE scores than White patients; and these relative elevations persisted during follow-up. CONCLUSIONS: Indigenous Canadians with PBC present with advanced disease and have worse long-term outcomes compared to White patients.
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Carcinoma Hepatocelular , Colangitis , Cirrosis Hepática Biliar , Neoplasias Hepáticas , Canadá/epidemiología , Etnicidad , Humanos , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Ácido UrsodesoxicólicoRESUMEN
PURPOSE: In this study, we examined the influence of interprofessional American Heart Association (AHA) resuscitation courses on pediatric health care professionals' (N = 218) self- reported collaborative practice behaviors (CPBs) and examined differences in CPBs between nursing, medicine, and respiratory therapy. DESIGN AND METHODS: A mixed methods explanatory design was utilized with a sample of pediatric nurses, nurse practitioners, physicians, and respiratory therapists. Data were collected using the Interprofessional Collaborative Competency Attainment Survey (ICCAS) and two open-ended questions. Data analysis included: exploratory factor analysis, paired t-tests, mixed effects modeling and directed content analysis. Inferences were made across quantitative and qualitative data. RESULTS: Statistically significant improvement in mean CPB scores was demonstrated by all professions (t (208) = -12.76; ρ < 0.001) immediately after the AHA courses. Qualitative responses indicated physicians identified roles and responsibilities (94%, n = 17) as the most important CPB. Communication was identified by nurses (78%, n = 76), nurse practitioners (100%, n = 11) and respiratory therapists (71%, n = 5) as most important. CONCLUSIONS: Participation in an interprofessional AHA course significantly increased mean self-reported CPB scores. Changes in mean CPB scores were sustained over 6 weeks upon return to clinical practice. PRACTICE IMPLICATIONS: Future research focused on CPBs of front-line health care professionals can provide an accurate portrayal of an interprofessional team and can inform how collaborative practice is established in everyday clinical practice.
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Relaciones Interprofesionales , Enfermeras Pediátricas , Actitud del Personal de Salud , Niño , Conducta Cooperativa , Humanos , Grupo de Atención al Paciente , Autoinforme , Encuestas y CuestionariosRESUMEN
Studies on pediatric patients with primary sclerosing cholangitis (PSC) have been limited by short follow-up and inconsistent classification of pediatric patients with autoimmune hepatitis-sclerosing cholangitis overlap (AIC). We conducted a retrospective study of patients diagnosed with AIC or PSC during childhood with extension of follow-up into adulthood. Methods: We reviewed records of patients followed for PSC or AIC between 1998 and 2019 at a pediatric referral center. Features at diagnosis, biochemical and liver-related outcomes (cholangitis, liver transplant, and cirrhosis) were compared. Results: Forty patients (27 PSC, 13 AIC) were followed for 92 months on average (standard deviation 79 months) with extension into adulthood in 52.5%; 70% had associated inflammatory bowel disease (IBD). The proportion of patients with significant fibrosis and abnormal baseline liver tests (serum bilirubin and transaminase levels) were similar in both groups. One year postdiagnosis, 55% (15/27) of PSC patients had normal liver tests versus only 15% (2/13) in the AIC group (P = 0.02). During follow-up, more liver-related events occurred in the AIC group (69% versus 27%, hazard ratio [HR] = 3.7 [95% confidence interval (CI): 1.4-10] P = 0.01). Baseline elevated serum bilirubin levels (HR = 5.3 [95% CI: 1.7-16.9] P = 0.005) and elevated transaminase levels at 1 year (HR = 9.09 [95% CI: 1.18-66.7) P = 0.03) were predictive of liver-related events, while having IBD was not (HR = 0.48 (95% CI: 0.15-1.5) P = 0.22). Conclusions: Pediatric patients with AIC and PSC presented at a similar fibrosis stage, however, with a more severe hepatitis in AIC. In this cohort, AIC was associated with more liver-related events, primarily driven by a higher rate of cirrhosis compared with PSC; transplant rates were similar.
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PURPOSE: Severe obesity, defined as a body mass index (BMI) ≥120th percent of the 95th BMI percentile for age and sex, is the fastest growing subcategory of obesity among youth, yet little is known about how this group understands and incorporates weight management strategies. The aims of this study were to explore how parents and adolescents understand severe obesity and incorporate management into their daily lives and evaluate the applicability of the Family Management Styles Framework (FMSF) to better understand the impact of severe obesity for adolescents. DESIGN AND METHODS: Directed content analysis grounded in a modified version of the FMSF was used to analyze one-time in-home face-to-face interviews with adolescents aged 12-17 years (N = 14) who received pediatric weight management care and a parent (N = 17). RESULTS: Both adolescents and parents described the day-to-day management as challenging and impactful to parent-child and sibling relationships. They described the need for sustained support and coaching in meeting daily physical activity requirements and related stories of weight stigma experienced. Further, parents' and adolescents' views were mostly congruent, except in their view of effectiveness of daily routines and how family attitudes and actions did or did not support the adolescent. CONCLUSIONS: The FMSF was successfully applied to understand family management of adolescents with severe obesity. These adolescents have complex physical and psychological needs impacting effective weight management and family life. PRACTICE IMPLICATIONS: Technology interventions should be considered to improve physiological and psychological outcomes for youth with severe obesity.
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Obesidad Mórbida , Obesidad Infantil , Adolescente , Índice de Masa Corporal , Humanos , Obesidad Mórbida/diagnóstico , Obesidad Mórbida/terapia , Padres , Obesidad Infantil/terapia , Estigma SocialRESUMEN
The Theory of Planned Behavior was developed to explain human behaviors. The theory has been broadly applied to health-related behaviors in nursing science but has not been examined in depth based on a critical nursing framework. This article systematically analyzes and evaluates the theory based on Fawcett and DeSanto-Madeya's 2013 framework. The theory reflects nursing metaparadigm concepts and has both social and theoretical significance as well as pragmatic adequacy, and its testability is supported by abundant empirical evidence. However, the theory's internal consistency and clarity could be improved with use of consistent terms for its concepts and relationships.
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BACKGROUND: There are no prior reports that compare differentially methylated regions of DNA in blood samples from COVID-19 patients to samples collected before the SARS-CoV-2 pandemic using a shared epigenotyping platform. We performed a genome-wide analysis of circulating blood DNA CpG methylation using the Infinium Human MethylationEPIC BeadChip on 124 blood samples from hospitalized COVID-19-positive and COVID-19-negative patients and compared these data with previously reported data from 39 healthy individuals collected before the pandemic. Prospective outcome measures such as COVID-19-GRAM risk-score and mortality were combined with methylation data. RESULTS: Global mean methylation levels did not differ between COVID-19 patients and healthy pre-pandemic controls. About 75% of acute illness-associated differentially methylated regions were located near gene promoter regions and were hypo-methylated in comparison with healthy pre-pandemic controls. Gene ontology analyses revealed terms associated with the immune response to viral infections and leukocyte activation; and disease ontology analyses revealed a predominance of autoimmune disorders. Among COVID-19-positive patients, worse outcomes were associated with a prevailing hyper-methylated status. Recursive feature elimination identified 77 differentially methylated positions predictive of COVID-19 severity measured by the GRAM-risk score. CONCLUSION: Our data contribute to the awareness that DNA methylation may influence the expression of genes that regulate COVID-19 progression and represent a targetable process in that setting.
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COVID-19/sangre , COVID-19/mortalidad , Metilación de ADN/fisiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , New York/epidemiología , Estudios Prospectivos , SARS-CoV-2RESUMEN
Patients with pulmonary emphysema often develop locomotor muscle dysfunction, which is independently associated with disability and higher mortality in that population. Muscle dysfunction entails reduced force generation capacity, which partially depends on fibers' oxidative potential, yet very little mechanistic research has focused on muscle respiration in pulmonary emphysema. Using a recently established animal model of pulmonary emphysema-driven skeletal muscle dysfunction, we found downregulation of SDHC (succinate dehydrogenase subunit C) in association with lower oxygen consumption and fatigue tolerance in locomotor muscles. Reduced SDH activity has been previously observed in muscles from patients with pulmonary emphysema, and we found that SDHC is required to support respiration in cultured muscle cells. Moreover, in vivo gain of SDH function in emphysema animals' muscles resulted in better oxygen consumption rate and fatigue tolerance. These changes correlated with a larger number of relatively more oxidative type 2-A and 2X fibers and a reduced amount of 2B fibers. Our data suggest that SDHC is a key regulator of respiration and fatigability in pulmonary emphysema-driven skeletal muscles, which could be impactful in developing strategies aimed at attenuating this comorbidity.
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Fatiga/enzimología , Proteínas de la Membrana/metabolismo , Músculo Esquelético/enzimología , Consumo de Oxígeno , Enfisema Pulmonar/enzimología , Animales , Modelos Animales de Enfermedad , Fatiga/genética , Fatiga/patología , Fatiga/fisiopatología , Proteínas de la Membrana/genética , Ratones , Ratones Transgénicos , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Enfisema Pulmonar/genética , Enfisema Pulmonar/patología , Enfisema Pulmonar/fisiopatologíaRESUMEN
BACKGROUND: Primary biliary cholangitis (PBC) frequently coexists with other autoimmune diseases, including celiac disease (CeD). Although the prevalence of CeD is high among cohorts with PBC, few studies have directly compared this prevalence to those among individuals with other liver diseases (OLD). AIM: To compare the prevalence of CeD between a cohort with PBC and a cohort with OLD. METHODS: Retrospective study from January 2013 to December 2016. All consecutive patients with an anti-transglutaminase (tTG) assay requested by a hepatologist and a diagnosis of chronic liver disease were included. CeD diagnosis was confirmed by duodenal biopsies. RESULTS: We included 399 consecutive patients (53.1 years SD 14.0, 54.1% women), notably 51 individuals with PBC and 348 individuals with OLD. PBC group included significantly more women (90.2% versus 48.9% P < 0.0001). The prevalence of CeD was higher in the group with PBC compared to the group with OLD (11.8 versus 2.9%, P < 0.003). In the OLD group, the prevalence of CeD was comparable regardless of the etiologic subgroup (nonalcoholic steatohepatitis 2.7% versus alcoholic liver disease 4.3%, versus viral 1.5% versus other autoimmune liver diseases 3.3%, NS). The presence of gastrointestinal symptoms at the time of the tTG assay was comparable between PBC and OLD groups (31.4 versus 29.6%, NS). CONCLUSION: There is a higher prevalence of CeD in the PBC group compared to other liver diseases.
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A detailed analysis of Symptom Management Theory (SMT) along with its extent of use and implications for adults with cancer as demonstrated in 20 oncology research studies is reported. SMT provides useful guidance for adult oncology research and nursing practice. Theory dimension most researched in cancer was symptom experience. Although theory assertions were demonstrated in 80% of the studies, it was used to an adequate extent only in 35% of them. Comparisons between cancer-related clinical outcomes with and without use of SMT, certain theory modifications, and future SMT-based studies involving longitudinal designs in this population are warranted.