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BACKGROUND: Evidence-based medical therapy for heart failure with reduced ejection fraction (HFrEF) often entails substantial out-of-pocket costs that can vary appreciably between patients. This has raised concerns regarding financial toxicity, equity, and adherence to medical therapy. In spite of these concerns, cost discussions in the HFrEF population appear to be rare, partly because out-of-pocket costs are generally unavailable during clinical encounters. In this trial, out-of-pocket cost information is given to patients and clinicians during outpatient encounters with the aim to assess the impact of providing this information on medication discussions and decisions. HYPOTHESIS: Cost-informed decision-making will be facilitated by providing access to patient-specific out-of-pocket cost estimates at the time of clinical encounter. DESIGN: Integrating Cost into Shared Decision-Making for Heart Failure with Reduced Ejection Fraction (POCKET-COST-HF) is a multicenter trial based at Emory Healthcare and University of Colorado Health. Adapting an existing patient activation tool from the EPIC-HF trial, patients and clinicians are presented a checklist with medications approved for treatment of HFrEF with or without patient-specific out-of-pocket costs (obtained from a financial navigation firm). Clinical encounters are audio-recorded, and patients are surveyed about their experience. The trial utilizes a stepped-wedge cluster randomized design, allowing for each site to enroll control and intervention group patients while minimizing contamination of the control arm. DISCUSSION: This trial will elucidate the potential impact of robust cost disclosure efforts and key information regarding patient and clinician perspectives related to cost and cost communication. It also will reveal important challenges associated with providing out-of-pocket costs for medications during clinical encounters. Acquiring medication costs for this trial requires an involved process and outsourcing of work. In addition, costs may change throughout the year, raising questions regarding what specific information is most valuable. These data will represent an important step towards understanding the role of integrating cost discussions into heart failure care. GOV IDENTIFIER: NCT04793880.
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Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Humanos , Insuficiencia Cardíaca/terapia , Gastos en Salud , Volumen Sistólico , Atención a la SaludRESUMEN
Pompe disease (PD) is a neuromuscular disorder caused by acid α-glucosidase (GAA) deficiency. Reduced GAA activity leads to pathological glycogen accumulation in cardiac and skeletal muscles responsible for severe heart impairment, respiratory defects, and muscle weakness. Enzyme replacement therapy with recombinant human GAA (rhGAA) is the standard-of-care treatment for PD, however, its efficacy is limited due to poor uptake in muscle and the development of an immune response. Multiple clinical trials are ongoing in PD with adeno-associated virus (AAV) vectors based on liver- and muscle-targeting. Current gene therapy approaches are limited by liver proliferation, poor muscle targeting, and the potential immune response to the hGAA transgene. To generate a treatment tailored to infantile-onset PD, we took advantage of a novel AAV capsid able to increase skeletal muscle targeting compared to AAV9 while reducing liver overload. When combined with a liver-muscle tandem promoter (LiMP), and despite the extensive liver-detargeting, this vector had a limited immune response to the hGAA transgene. This combination of capsid and promoter with improved muscle expression and specificity allowed for glycogen clearance in cardiac and skeletal muscles of Gaa-/- adult mice. In neonate Gaa-/- , complete rescue of glycogen content and muscle strength was observed 6 months after AAV vector injection. Our work highlights the importance of residual liver expression to control the immune response toward a potentially immunogenic transgene expressed in muscle. In conclusion, the demonstration of the efficacy of a muscle-specific AAV capsid-promoter combination for the full rescue of PD manifestation in both neonate and adult Gaa-/- provides a potential therapeutic avenue for the infantile-onset form of this devastating disease.
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Dependovirus , Enfermedad del Almacenamiento de Glucógeno Tipo II , Ratones , Humanos , Animales , Recién Nacido , Dependovirus/genética , Dependovirus/metabolismo , Vectores Genéticos/genética , Ratones Noqueados , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Enfermedad del Almacenamiento de Glucógeno Tipo II/terapia , Enfermedad del Almacenamiento de Glucógeno Tipo II/patología , alfa-Glucosidasas/genética , alfa-Glucosidasas/uso terapéutico , Hígado/metabolismo , Músculo Esquelético/patología , Glucógeno/metabolismo , Terapia Genética , FenotipoRESUMEN
The advent of social media has changed numerous aspects of modern life, with users developing and maintaining personal and professional relationships, following and sharing breaking news and importantly, searching for and disseminating health information and medical research. In the present paper, we reviewed available literature to outline the potential uses, pitfalls and impacts of social media for providers, scientists and institutions involved in digestive health in the domains of patient care, research and professional development. We recommend that these groups become more active participants on social media platforms to combat misinformation, advocate for patients, and curate and disseminate valuable research and educational materials. We also recommend that societies such as NASPGHAN assist its members in accessing training on effective social media use and the creation and maintenance of public-facing profiles and that academic institutions incorporate substantive social media contributions into academic promotion processes.
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Gastroenterología , Medios de Comunicación Sociales , Niño , Humanos , Gastroenterología/educación , Sociedades Médicas , Atención al Paciente , América del NorteRESUMEN
Lung transplantation is a well-established treatment for advanced lung disease, improving survival and quality of life. Over the last 60 years all aspects of lung transplantation have evolved significantly and exponential growth in transplant volume. This has been particularly evident over the last decade with a substantial increase in lung transplant numbers as a result of innovations in donor utilization procurement, including the use donation after circulatory death and ex-vivo lung perfusion organs. Donor lungs have proved to be surprisingly robust, and therefore the donor pool is actually larger than previously thought. Parallel to this, lung transplant outcomes have continued to improve with improved acute management as well as microbiological and immunological insights and innovations. The management of lung transplant recipients continues to be complex and heavily dependent on a tertiary care multidisciplinary paradigm. Whilst long term outcomes continue to be limited by chronic lung allograft dysfunction improvements in diagnostics, mechanistic understanding and evolutions in treatment paradigms have all contributed to a median survival that in some centres approaches 10 years. As ongoing studies build on developing novel approaches to diagnosis and treatment of transplant complications and improvements in donor utilization more individuals will have the opportunity to benefit from lung transplantation. As has always been the case, early referral for transplant consideration is important to achieve best results.
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Trasplante de Pulmón , Trasplante de Pulmón/tendencias , Trasplante de Pulmón/métodos , Humanos , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos , Enfermedades Pulmonares/cirugía , Calidad de Vida , Resultado del TratamientoRESUMEN
Packed red blood cells (PRBC) are frequently ordered for cardiac catheterization procedures, which increases resource utilization and patient charges. We applied the Plan-Do-Study-Act (PDSA) principle in order to optimize the ordering of PRBC for pediatric cardiac procedures and reducing charges. Our primary aim was to increase adherence to ordering guidelines to greater than 97%, with a global aim to reduce resource utilization. The existing PRBC ordering guidelines were revised and procedure reports were updated to include administration of PRBC. The rate of pre-procedure PRBC orders, adherence to the new protocol guidelines, presence of documentation and rate of blood transfusion within 24 h post-procedure, frequency of emergency release blood during a procedure were monitored. During our study period, there was an increased adherence from 86 to 100% adherence following implementation of the updated guidelines. With improved adherence, we decreased PRBC ordering and hospital charges to the patient in low-risk cardiac catheterization procedures, without an increase in blood transfusions.
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Background: Maternal-fetal medicine (MFM) is a medical subspecialty that cares for patients with high-risk pregnancies. Methods: An IRB-approved survey was offered to patients in MFM offices of a tertiary health care system from March 2022 to May 2022. Demographics and responses to 15 statements about telemedicine were collected via a 5-point Likert scale. Exploratory factor analysis was performed to identify factors affecting patient perception of the telemedicine experience. We sought to examine perception of telemedicine in MFM, identify factors affecting perception, and identify whether specific demographics were associated with patients who view telemedicine appointments favorably. Results: Surveys were completed by 327 of 347 (94%) patients. A total of 233 (71%) patients felt that the telemedicine experience was equal in quality to in-person appointments, and 257 (79%) were open to telemedicine appointments in the future. Exploratory factor analysis yielded two factors: "physician attentiveness" and "technology comfort." Telemedicine was viewed favorably or neutrally for both factors. Education (lower) and marital status (single) were associated with a favorable perception of physician attentiveness. Ethnicity (Hispanic), employment status (employed), and prior telemedicine experience were associated with a favorable perception of technology comfort. Conclusion: Most patients felt the quality of telemedicine appointments was equal to those completed in person. Physician attentiveness and technology comfort affect telemedicine perception. Specific patient demographic characteristics were associated with differing perceptions of telemedicine in MFM. Our findings suggest that telemedicine is positively viewed for MFM and can be used for improving health care delivery efficiency in MFM.
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Obstetricia , Telemedicina , Embarazo , Femenino , Humanos , Perinatología , Atención a la Salud , PercepciónRESUMEN
Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis. In immunocompetent hosts, symptoms usually resolve within 3 days; however, in immunocompromised persons, HuNoV infection can become persistent, debilitating, and sometimes life-threatening. There are no licensed therapeutics for HuNoV due to a near half-century delay in its cultivation. Treatment for chronic HuNoV infection in immunosuppressed patients anecdotally includes nitazoxanide, a broad-spectrum antimicrobial licensed for treatment of parasite-induced gastroenteritis. Despite its off-label use for chronic HuNoV infection, nitazoxanide has not been clearly demonstrated to be an effective treatment. In this study, we standardized a pipeline for antiviral testing using multiple human small intestinal enteroid lines representing different intestinal segments and evaluated whether nitazoxanide inhibits replication of five HuNoV strains in vitro. Nitazoxanide did not exhibit high selective antiviral activity against any HuNoV strain tested, indicating it is not an effective antiviral for HuNoV infection. Human intestinal enteroids are further demonstrated as a model to serve as a preclinical platform to test antivirals against HuNoVs to treat gastrointestinal disease. Abstr.
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Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Humanos , Gastroenteritis/tratamiento farmacológico , Antivirales/farmacología , Antivirales/uso terapéutico , Estándares de Referencia , Infecciones por Caliciviridae/tratamiento farmacológico , Replicación ViralRESUMEN
Structural color is poorly known in plants relative to animals. In fruits, only a handful of cases have been described, including in Viburnum tinus where the blue color results from a disordered multilayered reflector made of lipid droplets. Here, we examine the broader evolutionary context of fruit structural color across the genus Viburnum. We obtained fresh and herbarium fruit material from 30 Viburnum species spanning the phylogeny and used transmission electron microscopy, optical simulations, and ancestral state reconstruction to identify the presence/absence of photonic structures in each species, understand the mechanism producing structural color in newly identified species, relate the development of cell wall structure to reflectance in Viburnum dentatum, and describe the evolution of cell wall architecture across Viburnum. We identify at least two (possibly three) origins of blue fruit color in Viburnum in species which produce large photonic structures made of lipid droplets embedded in the cell wall and which reflect blue light. Examining the full spectrum of mechanisms producing color in pl, including structural color as well as pigments, will yield further insights into the diversity, ecology, and evolution of fruit color.
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Adoxaceae , Viburnum , Animales , Frutas , Color , Lípidos/análisisRESUMEN
BACKGROUND: Short bowel syndrome is the most common cause of intestinal failure, with morbidity and mortality linked to remanent small intestine length. There is no current standard for noninvasive bowel length measurement. MATERIALS AND METHODS: The literature was systematically searched for articles describing measurements of small intestine length from radiographic studies. Inclusion required reporting intestinal length as an outcome and use of diagnostic imaging for length assessment compared to a ground truth. Two reviewers independently screened studies for inclusion, extracted data, and assessed study quality. RESULTS: Eleven studies met the inclusion criteria and reported small intestinal length measurement using four imaging modalities: barium follow-through, ultrasound, computed tomography, and magnetic resonance. Five barium follow-through studies reported variable correlations with intraoperative measurements (r = 0.43-0.93); most (3/5) reported underestimation of length. US studies (n = 2) did not correlate with ground truths. Two computed tomography studies reported moderate-to-strong correlations with pathologic (r = 0.76) and intraoperative measurements (r = 0.99). Five studies of magnetic resonance showed moderate-to-strong correlations with intraoperative or postmortem measurements (r = 0.70-0.90). Vascular imaging software was used in two studies, and a segmentation algorithm was used for measurements in one. CONCLUSIONS: Noninvasive measurement of small intestine length is challenging. Three-dimensional imaging modalities reduce the risk of length underestimation, which is common with two-dimensional techniques. However, they also require longer times to perform length measurements. Automated segmentation has been trialed for magnetic resonance enterography, but this method does not translate directly to standard diagnostic imaging. While three-dimensional images are most accurate for length measurement, they are limited in their ability to measure intestinal dysmotility, which is an important functional measure in patients with intestinal failure. Future work should validate automated segmentation and measurement software using standard diagnostic imaging protocols.
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Insuficiencia Intestinal , Síndrome del Intestino Corto , Humanos , Bario , Intestino Delgado/cirugía , Síndrome del Intestino Corto/cirugía , Imagen por Resonancia Magnética/métodosRESUMEN
Functional abdominal pain disorders (FAPDs) are common in the pediatric population and are associated with a significant reduction in quality of life. Bidirectional communication of the brain-gut axis plays an important role in pain generation and perception in FAPDs. There is a paucity of data on the best approach to treat this group of disorders, with no Food and Drug Administration (FDA)-approved drugs and scarce research to substantiate the use of most medications. Use of hypnosis in pediatric FAPDs is supported by evidence and has long-term benefits of up to at least 5 years beyond completion of treatment, highlighting the importance of incorporating this therapy into the care of these patients. The mechanisms by which clinical hypnosis is beneficial in the treatment of FAPDs is not completely understood, but there is growing evidence that it impacts functioning of the brain-gut axis, potentially through influence on central pain processing, visceral sensitivity, and motility. The lack of side effects or potential for significant harm and low cost makes it an attractive option compared to pharmacologic therapies. This review addresses current barriers to clinical hypnosis including misconceptions among patients and families, lack of trained clinicians, and questions around insurance reimbursement. The recent use of telemedicine and delivery of hypnosis via audio-visual modalities allow more patients to benefit from this treatment. As the evidence base for hypnosis grows, acceptance and training will likely increase as well. Further research is needed to understand how hypnosis works and to develop tools that predict who is most likely to respond to hypnosis. Studies on cost-effectiveness in comparing hypnosis to other therapies for FAPDs will increase evidence for appropriate healthcare utilization. Because hypnosis has applications beyond pain and is child-friendly with minimal to no risk, hypnosis could be an important therapeutic tool in the wider pediatric gastrointestinal population.
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Enfermedades Gastrointestinales , Hipnosis , Humanos , Niño , Calidad de Vida , Enfermedades Gastrointestinales/terapia , Dolor Abdominal/terapiaRESUMEN
INTRODUCTION: The importance of including people affected by research (e.g., community members, citizens or patient partners) is increasingly recognized across the breadth of institutions involved in connecting research with action. Yet, the increasing rhetoric of inclusion remains situated in research systems that tend to reward traditional dissemination and uphold power dynamics in ways that centre particular (privileged) voices over others. In research explicitly interested in doing research with those most affected by the issue or outcomes, research teams need to know how to advance meaningful inclusion. This study focused on listening to voices often excluded from research processes to understand what meaningful inclusion looks and feels like, and asked what contributes to being or feeling tokenized. METHODS: In this deliberative dialogue study, 16 participants with experience of navigating social exclusions and contributing to research activities reflected on what makes for meaningful experiences of inclusion. Using a co-production approach, with a diversely representative research team of 15 that included patient and community partners, we used critically reflective dialogue to guide an inclusive process to study design and implementation, from conceptualization of research questions through to writing. RESULTS: We heard that: research practices, partnerships and systems all contribute to experiences of inclusion or exclusion; the insufficiency or absence of standards for accountability amplifies the experience of exclusion; and inclusive practices require intention, planning, reflection and resources. CONCLUSIONS: We offer evidence-informed recommendations for the deeply relational work and practices for inclusivity, focused on promising practices for cultivating welcoming systems, spaces and relationships. PATIENT OR PUBLIC CONTRIBUTION: This work reflects a co-production approach, where people who use and are affected by research results actively partnered in the research process, including study design, data-generating activities, analysis and interpretation, and writing. Several of these partners are authors of this manuscript.
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Objective: Racial inequities in mental health care utilization (MHCU) are well documented. Marginalized racial groups are more likely to report psychosis-like experiences (PLEs) and are at elevated risk for racial discrimination and trauma, impacting PLE severity. Little is known about how factors associated with race impact treatment seeking among individuals reporting PLEs. The present study examined associations between race, trauma, discrimination, PLEs, and MHCU among people endorsing high levels of PLEs. Method: Participants were Asian/Asian American, Black/African American, or White/European American college students ages 18-25 years meeting PLE self-report measure cutoff scores (N = 177). Binary logistic and multiple linear regressions were used to examine associations between past, current, and prospective MHCU and race, potentially traumatic events, discrimination, and PLEs. Results: Participants endorsing more PLEs were more likely to report past and current treatment and to be considering future services. Asian/Asian American and Black/African American participants were less likely to endorse past, current, and prospective future mental health care. Potentially traumatic events predicted increased utilization of past treatment. Conclusions: Results suggest service differences among participants, such that Black/African American and Asian/Asian American young adults reporting PLEs were less likely than White/European American counterparts to seek treatment even when accounting for traumatic events and discrimination. These findings highlight the need to further elucidate MHCU among marginalized racial groups experiencing psychosis-like symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Microagresión , Aceptación de la Atención de Salud , Trastornos Psicóticos , Racismo , Trastornos Relacionados con Sustancias , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Asiático , Negro o Afroamericano , Disparidades en Atención de Salud , Trastornos Psicóticos/terapia , Trastornos Psicóticos/psicología , Racismo/psicología , Riesgo , Autoinforme , Trastornos Relacionados con Sustancias/psicología , Estados Unidos , Violencia/psicología , Blanco , Heridas y LesionesRESUMEN
Cell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility and usefulness has been demonstrated, several issues related to standardisation and technical validation must be addressed for its routine clinical application in cancer. In this regard, most cfDNA clinical applications are still limited to clinical trials, proving its value in several settings. In this paper, we review the current clinical trials involving cfDNA/ctDNA analysis and highlight those where it has been useful for patient stratification, treatment follow-up or development of novel approaches for early diagnosis. Our query included clinical trials, including the terms 'cfDNA', 'ctDNA', 'liquid biopsy' AND 'cancer OR neoplasm' in the FDA and EMA public databases. We identified 1370 clinical trials (FDA = 1129, EMA = 241) involving liquid-biopsy analysis in cancer. These clinical trials show promising results for the early detection of cancer and confirm cfDNA as a tool for real-time monitoring of acquired therapy resistance, accurate disease-progression surveillance and improvement of treatment, situations that result in a better quality of life and extended overall survival for cancer patients.
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Biomarcadores de Tumor/análisis , Ácidos Nucleicos Libres de Células/análisis , Ácidos Nucleicos Libres de Células/metabolismo , Ensayos Clínicos como Asunto/estadística & datos numéricos , Detección Precoz del Cáncer/métodos , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patología , Animales , Ácidos Nucleicos Libres de Células/genética , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Medicina de PrecisiónRESUMEN
Pyrethroids (PY) are synthetic pesticides used in many applications ranging from large-scale agriculture to household maintenance. Their classical mechanisms of action are associated with binding to the sodium channel of insect neurons, disrupting its inactivation, ensuring their use as insecticides. However, PY can also lead to toxicity in vertebrates, including humans. In most toxicological studies, the impact of PY on heart function is neglected. Acute exposure to a high dose of PY causes enhancement of the late sodium current (INaL), which impairs the action potential waveform and can cause severe cardiac arrhythmias. Moreover, long-term, low-dose exposure to PY displays oxidative stress in the heart, which could induce tissue remodeling and impairment. Isolated and preliminary evidence supports that, for acute exposure to PY, an antiarrhythmic therapy with ranolazine (an INaL blocker), can be a promising therapeutic approach. Besides, heart tissue remodeling associated with low doses and long-term exposure to PY seems to benefit from antioxidant therapy. Despite significant leaps in understanding the mechanical details of PY intoxication, currently, few studies are focusing on the heart. In this review, we present what is known and what are the gaps in the field of cardiotoxicity induced by PY.
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Cardiotoxicidad , Piretrinas , Animales , Humanos , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/metabolismo , Piretrinas/toxicidad , Ranolazina , Bloqueadores de los Canales de Sodio/farmacología , Canales de Sodio/metabolismoRESUMEN
The majority of plant colours are produced by anthocyanin and carotenoid pigments, but colouration obtained by nanostructured materials (i.e. structural colours) is increasingly reported in plants. Here, we identify a multilayer photonic structure in the fruits of Lantana strigocamara and compare it with a similar structure in Viburnum tinus fruits. We used a combination of transmission electron microscopy (EM), serial EM tomography, scanning force microscopy and optical simulations to characterise the photonic structure in L. strigocamara. We also examine the development of the structure during maturation. We found that the structural colour derives from a disordered, multilayered reflector consisting of lipid droplets of c.105 nm that form a plate-like structure in 3D. This structure begins to form early in development and reflects blue wavelengths of light with increasing intensity over time as the structure develops. The materials used are likely to be lipid polymers. Lantana strigocamara is the second origin of a lipid-based photonic structure, convergently evolved with the structure in Viburnum tinus. Chemical differences between the lipids in L. strigocamara and those of V. tinus suggest a distinct evolutionary trajectory with implications for the signalling function of structural colours in fruits.
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Lantana , Viburnum , Color , Frutas/química , Lantana/química , Lípidos/análisis , Viburnum/químicaRESUMEN
BACKGROUND: Resilience is dynamic and influenced by internal and external factors. In persons with chronic illness and/or disability, resilience is viewed as the ability to adapt to new life circumstances. Existing models of resilience typically focus on the absence of deficit and pathology in the individual, overlooking resources, well-being, and broader social impacts. Our proposed novel Relational, Intrapersonal, Social and Environmental (RISE) Model of resilience incorporates and describes the interconnection and influence of constructs that impact resilience and affect the quality of life. PURPOSE: The purpose of this study is to examine the fit of the RISE Model against original interview data obtained from persons with stroke and their partners. METHODS: This study is a secondary analysis of qualitative data collected from post-intervention interviews that were part of an intervention pilot study designed to promote resilience in couples coping with stroke. Interviews were coded to examine relationships between RISE Model constructs. RESULTS: The study included 36 interviews from 18 cohabitating couples; mean participant age was 53.33 years (SD ±14.70). Examples of each construct within the RISE Model appeared in transcribed interviews and common patterns of co-occurring constructs were identified. CONCLUSION: The constructs within the RISE Model were supported by the interviews. The impact of disability does not remain confined to a single individual and instead branches out into the broader social context, including close interpersonal relationships. A deeper understanding of resilience and its relationship with intrapersonal, interpersonal and socio-ecological constructs would add value to our understanding and fostering of resilience in persons with disabilities and/or chronic illness. CLINICAL TRIAL INFORMATION: NCT03335358.
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Personas con Discapacidad , Resiliencia Psicológica , Adaptación Psicológica , Adulto , Anciano , Humanos , Relaciones Interpersonales , Persona de Mediana Edad , Proyectos Piloto , Calidad de VidaRESUMEN
Chronic stress is associated with deleterious health outcomes and mortality risk. A potential mechanism by which stress affects healthspan and lifespan is acceleration of cellular aging. Biologic age prediction models, termed epigenetic clocks, have been developed to estimate biologic age differences among people with the same chronologic age. This study evaluates the simultaneous impact of perceived chronic stress and resilience on Grim Age acceleration. The perceived stress score (PSS) and Connor-Davidson Resilience Scale (CD-RISC) were used to measure chronic stress and resilience, respectively. DNA was extracted from whole blood and analyzed using the MethylationEPIC BeadChip. GrimAge estimates were calculated using the methylation age calculator. Forty-seven business executives were categorized by levels of high or low stress and resilience scores. Compared to participants with low stress and high resilience, those with low stress and low resilience demonstrated the strongest association with Grim Age acceleration (p = 0.044), after controlling for age and estimated cellular proportions. Interestingly, among participants with low resilience, those with high perceived stress had a weaker association with Grim Age acceleration than participants with low perceived stress. However, among participants with high resilience, low perceived stress had a weaker association with Grim Age acceleration than high perceived stress. Our findings suggest that the impact of perceived stress on epigenetic age acceleration may differ based on resilience capacity, with a potential paradoxical beneficial effect among those with low resilience.
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Productos Biológicos , Epigenómica , Envejecimiento/genética , Metilación de ADN , Epigénesis Genética , Humanos , Estrés PsicológicoRESUMEN
INTRODUCTION: Two-stage free functional muscle transfers for long-standing facial palsy can yield unpredictable results. Earlier studies have demonstrated incomplete regeneration across neurorrhaphies in native nerve and higher donor axonal counts correlating with improved outcomes but axonal count in nerve grafts have not been as thoroughly reviewed. To investigate the impact of varying axonal counts in autologous grafts on functional outcomes of repair. MATERIALS AND METHODS: Animals were allocated into three groups: Direct Nerve Repair (DNR, n = 50), Small Nerve Graft (SNG, n = 50), and Large Nerve Graft (LNG, n = 50). All grafts were inset into the Posterior Auricular Nerve with ear movement recovery (EMR) monitored as functional outcome. At various postoperative weeks (POWs), excised specimens were imaged with electron microscopy. Axonal counts were measured proximal to, distal (DAC) to, and within grafts. Total Success Ratio (TSR) was calculated. RESULTS: In DNR, DAC was significantly lower than proximal axonal counts at all POWs, with maximum TSR of 80%. TSR for LNG and SNG were significantly lower at all POWs when compared to DNR, with maximums of 56% and 38%, respectively. LNG had a significantly larger DAC than SNG at POW12 and beyond. A direct relationship was present between DAC and EMR for all values. CONCLUSIONS: Higher native axonal count of autologous nerve grafts resulted in higher percentage of regeneration across neurorrhaphies.
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Parálisis Facial , Regeneración Nerviosa , Animales , Axones/fisiología , Nervio Facial , Procedimientos Neuroquirúrgicos/métodosRESUMEN
INTRODUCTION: The Grammont-style reverse shoulder arthroplasty (RSA) relies on medialization and distalization of the shoulder center of rotation. Lateralized designs have recently gained popularity. The amount of lateralization, however, remains a controversial topic. The purpose of this study was to correlate the change in humeral offset (HO) with outcomes and complications following RSA. We hypothesized that a lateralized HO following RSA would be associated with improved range of motion (ROM), better patient-reported outcomes (PROs), and fewer complications. MATERIALS AND METHODS: A consecutive series of 104 patients (109 shoulders) was retrospectively evaluated. All patients underwent primary RSA by 2 shoulder and elbow fellowship-trained orthopedic surgeons at 2 different centers. Inclusion criteria was a primary RSA with at least 1-year follow-up. All patients had the HO measured on a preoperative and a postoperative Grashey radiograph, and the change in HO was calculated (ΔHO = PostHO-PreHO). A negative value was defined as a medialized HO and a positive value as a lateralized HO. ROM and primary outcomes, including forward elevation (FE), external rotation (ER), internal rotation (IR), Subjective Shoulder Value (SSV), and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score, were collected. Complications and revisions were also reported. RESULTS: The mean age was 72 years with a mean follow-up of 22.3 months. The average FE (92° vs. 148°), ER (34° vs. 44°), SSV (35% vs. 87%), and ASES score (37.2 vs. 81.2) increased significantly (all P < .01) compared with preoperative values. The HO was medialized postoperatively in 63 shoulders and lateralized in 46 shoulders. No statistically significant differences in the mean values for postoperative FE (147° vs. 146°, P = .892), ER (43° vs. 45°, P = .582), IR (L3 vs. L3, P = .852), SSV (88% vs. 85%, P = .476), and ASES score (81.3 vs. 81.1, P = .961) were found between the groups. However, there was significantly more improvement in ER in the lateralized HO cohort than the medialized cohort (16° vs. 7°, P = .033). Six shoulders, 5 medialized and 1 lateralized HO, demonstrated scapular notching and remained asymptomatic. Five shoulders, 4 medialized and 1 lateralized HO, experienced at least 1 instability incident, and 2 shoulders with medialized HO had an acromion/scapular spine fracture. Overall, 2 shoulders with medialized HO underwent revision surgery because of instability. CONCLUSIONS: Although RSA provides significant improvement in ROM and PROs regardless of postoperative HO, restoring baseline HO or lateralization beyond baseline may be favorable for improving ER and decreasing complications following RSA.
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Artroplastía de Reemplazo de Hombro , Fracturas del Hombro , Articulación del Hombro , Prótesis de Hombro , Anciano , Artroplastía de Reemplazo de Hombro/efectos adversos , Humanos , Húmero/cirugía , Rango del Movimiento Articular , Estudios Retrospectivos , Fracturas del Hombro/cirugía , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/cirugía , Resultado del TratamientoRESUMEN
Air pollution is a global challenge, and especially urban areas are particularly affected by acute episodes. Traditional approaches used to mitigate air pollution primarily consider the technical aspects of the problem but not the role of citizen behaviour and day-to-day practices. ClairCity, a Horizon 2020 funded project, created an impact assessment framework considering the role of citizen behaviour to create future scenarios, aiming to improve urban environments and the wellbeing and health of its inhabitants. This framework was applied to six pilot cases: Bristol, Amsterdam, Ljubljana, Sosnowiec, Aveiro Region and Liguria Region, considering three-time horizons: 2025, 2035 and 2050. The scenarios approach includes the Business As Usual (BAU) scenario and a Final Unified Policy Scenarios (FUPS) established by citizens, decision-makers, local planners and stakeholders based on data collected through a citizen and stakeholder co-creation process. Therefore, this paper aims to present the ClairCity outcomes, analysing the quantified impacts of selected measures in terms of emissions, air quality, population exposure, and health. Each case study has established a particular set of measures with different levels of ambition, therefore different levels of success were achieved towards the control and mitigation of their specific air pollution problems. The transport sector was the most addressed by the measures showing substantial improvements for NO2, already with the BAU scenarios, and overall, even better results when applying the citizen-led FUPS scenarios. In some cases, due to a lack of ambition for the residential and commercial sector, the results were not sufficient to fulfil the WHO guidelines. Overall, it was found in all cities that the co-created scenarios would lead to environmental improvements in terms of air quality and citizens' health compared to the baseline year of 2015. However, in some cases, the health impacts were lower than air quality due to the implementation of the measures not affecting the most densely populated areas. Benefits from the FUPS comparing to the BAU scenario were found to be highest in Amsterdam and Bristol, with further NO2 and PM10 emission reductions around 10%-16% by 2025 and 19%-28% by 2050, compared to BAU.