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1.
Bioinformatics ; 40(1)2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38258418

RESUMEN

MOTIVATION: Scientific advances build on the findings of existing research. The 2001 publication of the human genome has led to the production of huge volumes of literature exploring the context-specific functions and interactions of genes. Technology is needed to perform large-scale text mining of research papers to extract the reported actions of genes in specific experimental contexts and cell states, such as cancer, thereby facilitating the design of new therapeutic strategies. RESULTS: We present a new corpus and Text Mining methodology that can accurately identify and extract the most important details of cancer genomics experiments from biomedical texts. We build a Named Entity Recognition model that accurately extracts relevant experiment details from PubMed abstract text, and a second model that identifies the relationships between them. This system outperforms earlier models and enables the analysis of gene function in diverse and dynamically evolving experimental contexts. AVAILABILITY AND IMPLEMENTATION: Code and data are available here: https://github.com/cambridgeltl/functional-genomics-ie.


Asunto(s)
Genómica , Neoplasias , Humanos , Neoplasias/genética , Minería de Datos/métodos , PubMed , Fenotipo
2.
J Ren Nutr ; 32(1): 39-50, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34649784

RESUMEN

OBJECTIVES: The aim of this study is to examine the effect of a telehealth intervention that used a dietary app, educational website, and weekly dietitian tele-counseling on sodium intake, diet quality, blood pressure, and albuminuria among individuals with diabetes and early-stage chronic kidney disease. DESIGN AND METHODS: We examined the effects of a dietary app-supported tele-counseling intervention in a single center, single arm study of 44 participants with type 2 diabetes and stage 1-3a chronic kidney disease. Participants recorded and shared dietary data via MyFitnessPal with registered dietitians, who used motivational interviewing to provide telephone counseling weekly for 8 weeks. After the 8-week intensive intervention, participants were followed at 6 and 12 months. Outcomes included 24-hour urine sodium (2 collections per timepoint), Healthy Eating Index 2015 score (three 24-hour dietary recalls per timepoint), 24-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP), and 24-hour urine albumin excretion. RESULTS: Out of 44 consented participants (mean age 60.3 ± 11.9 years, 43% female, 89% white, median estimated glomerular filtration rate was 78.5 mL/min/1.73 m2, median urine albumin excretion 52.9 mg/day, 84% hypertension), 32 (73%) completed 8-week follow-up, 27 (61%) completed 6-month follow-up, and 25 (57%) completed 12-month follow-up. Among participants who completed 12-month follow-up, reported sodium intake decreased by 638 mg/day from baseline of 2,919 mg/day (P < .001). The 24-hour mean urine sodium and albumin excretion did not decline over the study period. Healthy Eating Index 2015 score improved by 7.76 points at 12 months from a mean baseline of 54.6 (P < .001). Both 24-hour SBP and DBP declined at 12 months from baseline (SBP -5.7 mm Hg, 95% confidence interval -10.5 to -1.0, P = .02; DBP -4.1 mm Hg, 95% confidence interval -7.2 to -1.1, P = .01). CONCLUSIONS: Overall, this study demonstrates that a short, intensive, remotely delivered dietary intervention for adults with type 2 diabetes and early chronic kidney disease at high risk for disease progression and cardiovascular complications led to improvement in blood pressure and self-reported sodium intake and diet quality, but no improvement in albuminuria. Future research studies are needed to examine whether remotely delivered dietary interventions can ultimately improve kidney health over time.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipertensión , Aplicaciones Móviles , Insuficiencia Renal Crónica , Sodio en la Dieta , Anciano , Presión Sanguínea , Consejo , Diabetes Mellitus Tipo 2/complicaciones , Dieta Hiposódica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia
3.
Urban For Urban Green ; 70: 127543, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35291447

RESUMEN

This qualitative study explores the topic of mental health/wellbeing with reference to exposure to urban green space (UGS). It builds on previous research, which has highlighted the potential for green space interaction for supporting positive emotional and mental wellbeing, particularly in times of stress and uncertainty. Using this basis, the paper explores whether UGS interaction also helped to mitigate the negative mental health impacts brought about by the first COVID-19 lockdown. The specific focus is on students and expatriates living in Berlin, Germany as this population groupbecame increasingly vulnerable during this time as a result of uncertainty and restrictions in their daily lives brought about the enforced lockdown measures. More specifically, this paper investigates how a change in their daily routines created opportunities to interact with and experience UGS differently and how their emotional response and perception towards these spaces changed. Semi-structured interviews allowed for stories, experiences and emotions to unfold, which revealed that the participants' gained an appreciation for the potential of UGS to support their wellbeing during a stressful and isolating time. UGS interaction also allowed them to form tangible memories of summer 2020 as it provided a safe arena for them to maintain social contact with friends outdoors, or to escape their home environment and experience respite and relaxation in a natural setting. The findings demonstrate that for this sub-group of the population UGS became a reliable constant and a valuable public health resource, which may also help to mitigate the long-term adverse mental health impacts of the pandemic.

4.
J Ren Nutr ; 30(1): 53-60, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31078403

RESUMEN

OBJECTIVE(S): Although healthy dietary patterns are associated with decreased mortality in patients with chronic kidney disease (CKD), few patients receive dietitian counseling due to concerns such as dietitian availability, travel distance, and cost. Our objective was to determine the feasibility of dietary smartphone application-supported telecounseling to reduce sodium intake and improve dietary quality in patients with early CKD. METHODS: This was a pre-post, mixed methods feasibility study of 16 patients with Stage 1-3a CKD in central/northeast Pennsylvania. Patients recorded and shared dietary data via smartphone applications with registered dietitians, who used motivational interviewing to provide telephone counseling weekly for 8 weeks. Seven patients were assigned to a customized study-specific application and nine patients to a commercially available, free application (MyFitnessPal). Participant satisfaction was assessed via survey, and participants were invited to complete a semistructured interview. Outcomes assessed included sodium intake, Healthy Eating Index 2015 score, weight, and 24-hour blood pressure (BP). RESULTS: Mean age was 64.7 years, 31% were female, 100% were white, 13% had income <$25,000. Adherence was excellent with 14 (88%) entering dietary data at least 75% of total days. Patients reported high satisfaction with the intervention and dietitian telecounseling. Use of dietary apps was viewed positively for allowing tracking of sodium and energy intake although some participants experienced functionality issues with the customized application that were not generally experienced by those using the commercially available free application. Sodium intake (-604 mg/day, 95% confidence interval [CI]: -1,104 to -104), Healthy Eating Index 2015 score (3.97, 95% CI: 0.03-7.91), weight (-3.4, 95% CI: -6.6 to -0.1), daytime systolic BP (-5.8, 95% CI: -12.1 to 0.6), and daytime diastolic BP (-4.1, 95% CI: -7.9 to -0.2) improved after the intervention. CONCLUSIONS: An application-supported telecounseling program with a registered dietitian appears to be a feasible and well-accepted strategy to improve dietary quality and improve cardiovascular risk factors in patients with early kidney disease.


Asunto(s)
Consejo/métodos , Aplicaciones Móviles , Insuficiencia Renal Crónica/dietoterapia , Telemedicina/métodos , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Teléfono Inteligente
5.
J Allergy Clin Immunol ; 133(2): 461-7, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24144575

RESUMEN

BACKGROUND: Although anaphylaxis is recognized as an important life-threatening condition, data are limited regarding its prevalence and characteristics in the general population. OBJECTIVE: We sought to estimate the lifetime prevalence and overall characteristics of anaphylaxis. METHODS: Two nationwide, cross-sectional random-digit-dial surveys were conducted. The public survey included unselected adults, whereas the patient survey captured information from household members reporting a prior reaction to medications, foods, insect stings, or latex and idiopathic reactions in the previous 10 years. In both surveys standardized questionnaires queried anaphylaxis symptoms, treatments, knowledge, and behaviors. RESULTS: The public survey included 1,000 adults, of whom 7.7% (95% CI, 5.7% to 9.7%) reported a prior anaphylactic reaction. Using increasingly stringent criteria, we estimate that 5.1% (95% CI, 3.4% to 6.8%) and 1.6% (95% CI, 0.8% to 2.4%) had probable and very likely anaphylaxis, respectively. The patient survey included 1,059 respondents, of whom 344 reported a history of anaphylaxis. The most common triggers reported were medications (34%), foods (31%), and insect stings (20%). Forty-two percent sought treatment within 15 minutes of onset, 34% went to the hospital, 27% self-treated with antihistamines, 10% called 911, 11% self-administered epinephrine, and 6.4% received no treatment. Although most respondents with anaphylaxis reported 2 or more prior episodes (19% reporting ≥5 episodes), 52% had never received a self-injectable epinephrine prescription, and 60% did not currently have epinephrine available. CONCLUSIONS: The prevalence of anaphylaxis in the general population is at least 1.6% and probably higher. Patients do not appear adequately equipped to deal with future episodes, indicating the need for public health initiatives to improve anaphylaxis recognition and treatment.


Asunto(s)
Anafilaxia/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anafilaxia/etiología , Niño , Preescolar , Hipersensibilidad a las Drogas/epidemiología , Femenino , Hipersensibilidad a los Alimentos/epidemiología , Encuestas Epidemiológicas , Humanos , Lactante , Mordeduras y Picaduras de Insectos/epidemiología , Mordeduras y Picaduras de Insectos/inmunología , Masculino , Persona de Mediana Edad , Prevalencia , Estados Unidos/epidemiología , Adulto Joven
6.
Development ; 138(23): 5189-99, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22031549

RESUMEN

Hair follicle formation depends on reciprocal epidermal-dermal interactions and occurs during skin development, but not in adult life. This suggests that the properties of dermal fibroblasts change during postnatal development. To examine this, we used a PdgfraEGFP mouse line to isolate GFP-positive fibroblasts from neonatal skin, adult telogen and anagen skin and adult skin in which ectopic hair follicles had been induced by transgenic epidermal activation of ß-catenin (EF skin). We also isolated epidermal cells from each mouse. The gene expression profile of EF epidermis was most similar to that of anagen epidermis, consistent with activation of ß-catenin signalling. By contrast, adult dermis with ectopic hair follicles more closely resembled neonatal dermis than adult telogen or anagen dermis. In particular, genes associated with mitosis were upregulated and extracellular matrix-associated genes were downregulated in neonatal and EF fibroblasts. We confirmed that sustained epidermal ß-catenin activation stimulated fibroblasts to proliferate to reach the high cell density of neonatal skin. In addition, the extracellular matrix was comprehensively remodelled, with mature collagen being replaced by collagen subtypes normally present only in developing skin. The changes in proliferation and extracellular matrix composition originated from a specific subpopulation of fibroblasts located beneath the sebaceous gland. Our results show that adult dermis is an unexpectedly plastic tissue that can be reprogrammed to acquire the molecular, cellular and structural characteristics of neonatal dermis in response to cues from the overlying epidermis.


Asunto(s)
Fibroblastos/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Transducción de Señal/fisiología , Piel/citología , Factores de Edad , Animales , Proliferación Celular , Matriz Extracelular/metabolismo , Citometría de Flujo , Perfilación de la Expresión Génica , Proteínas Fluorescentes Verdes/metabolismo , Técnicas Histológicas , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Ratones , Microscopía Confocal , Reacción en Cadena en Tiempo Real de la Polimerasa , beta Catenina/metabolismo
7.
Dev Biol ; 366(2): 290-7, 2012 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-22537489

RESUMEN

Hair follicle development and growth are regulated by Wnt signalling and depend on interactions between epidermal cells and a population of fibroblasts at the base of the follicle, known as the dermal papilla (DP). DP cells have a distinct gene expression signature from non-DP dermal fibroblasts. However, their origins are largely unknown. By generating chimeric mice and performing skin reconstitution assays we show that, irrespective of whether DP form during development, are induced by epidermal Wnt activation in adult skin or assemble from disaggregated cells, they are polyclonal in origin. While fibroblast proliferation is necessary for hair follicle formation in skin reconstitution assays, mitotically inhibited cells readily contribute to DP. Although new hair follicles do not usually develop in adult skin, adult dermal fibroblasts are competent to contribute to DP during hair follicle neogenesis, irrespective of whether they originate from skin in the resting or growth phase of the hair cycle or skin with ß-catenin-induced ectopic follicles. We propose that during skin reconstitution fibroblasts may be induced to become DP cells by interactions with hair follicle epidermal cells, rather than being derived from a distinct subpopulation of cells.


Asunto(s)
Comunicación Celular , Diferenciación Celular , Dermis/citología , Folículo Piloso/citología , Cabello/crecimiento & desarrollo , Animales , Células Epidérmicas , Fibroblastos/citología , Cabello/citología , Ratones , Vía de Señalización Wnt
8.
Clin Pract Cases Emerg Med ; 7(3): 136-139, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37595303

RESUMEN

INTRODUCTION: The use of paralytics during rapid sequence intubation (RSI) in patients with myasthenia gravis (MG) remains a controversial topic in emergency medicine. Due to fewer functional acetylcholine receptors, these patients can be both sensitive and resistant to different types of neuromuscular blocking agents (NMBA). Their atypical sensitivity to non-depolarizing NMBAs such as rocuronium can increase both the duration and depth of paralysis after its use at typical RSI doses. However, the extent of rocuronium's prolonged duration of effect in patients with MG has yet to be quantified in an emergency department setting. CASE REPORT: We describe a case wherein a full RSI dose of 1.2 milligrams per kilogram of rocuronium led to a prolonged 232-minute duration of paralysis in a patient with MG. This sustained paralysis was suspected but only confirmed after the patient received the reversal agent sugammadex. Once administered, an acute change in neurologic function was seen, and the patient was emergently taken to the operating room for neurosurgical intervention. CONCLUSION: When intubating patients with MG, many emergency physicians are aware that using paralytics during RSI provides several challenges. If not properly dose-reduced, rocuronium may exert its paralytic effects for up to four hours in patients with MG. This unique case highlights the importance of personalizing care for this patient population before, during, and after RSI.

10.
J Am Heart Assoc ; 11(19): e027213, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-36172955

RESUMEN

Background Limited data exist on the benefits of lifestyle behavior change delivered using telehealth and web-based applications with varied support on blood pressure (BP). Methods and Results We conducted a 2-site randomized controlled trial at Geisinger (January 2019-March 2021) to compare the efficacy of 2 remotely delivered strategies using web-based applications in participants with 24-hour systolic BP 120-160 mm Hg and body mass index ≥25 kg/m2. Both arms received access to web-based applications and the same lifestyle guidance per American Heart Association guidelines. One arm received minimal nonclinical staff support, and the other arm received dietitian support with motivational interviewing during weekly calls. The primary outcome was 12-week change in 24-hour systolic BP. A total of 187 participants were randomly assigned, with 156 (83.4%) completing the trial. In both arms, 24-hour systolic BP was reduced at follow-up, but the difference in BP change was not significant (dietitian-led arm, -6.73 mm Hg [95% CI, -8.64 to -4.82]; minimal-support arm, -4.92 [95% CI, -7.01 to -2.77]; P comparing groups=0.2). The dietitian-support arm had greater 12-week improvements in the secondary outcomes sleep systolic BP (mean, -6.92 versus -1.45; P=0.004), sleep diastolic BP (-3.31 versus 0.73; P=0.001), and self-reported physical activity (866 versus -243 metabolic equivalent task minutes per week; P=0.01) and tended to have improvements in weight loss (-5.11 versus -3.89 kg; P=0.1) and Healthy Eating Index-2015 score (9.23 versus 6.43 units; P=0.09). Conclusions Both the dietitian- and minimal-support interventions reduced 24-hour systolic BP similarly, although the dietitian-led intervention led to greater improvements in several secondary cardiometabolic outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03700710.


Asunto(s)
Nutricionistas , Telemedicina , Presión Sanguínea , Humanos , Estilo de Vida , Pérdida de Peso
11.
Ann Am Thorac Soc ; 19(2): 303-314, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34384042

RESUMEN

Smoking burdens are greatest among underserved patients. Lung cancer screening (LCS) reduces mortality among individuals at risk for smoking-associated lung cancer. Although LCS programs must offer smoking cessation support, the interventions that best promote cessation among underserved patients in this setting are unknown. This stakeholder-engaged, pragmatic randomized clinical trial will compare the effectiveness of four interventions promoting smoking cessation among underserved patients referred for LCS. By using an additive study design, all four arms provide standard "ask-advise-refer" care. Arm 2 adds free or subsidized pharmacologic cessation aids, arm 3 adds financial incentives up to $600 for cessation, and arm 4 adds a mobile device-delivered episodic future thinking tool to promote attention to long-term health goals. We hypothesize that smoking abstinence rates will be higher with the addition of each intervention when compared with arm 1. We will enroll 3,200 adults with LCS orders at four U.S. health systems. Eligible patients include those who smoke at least one cigarette daily and self-identify as a member of an underserved group (i.e., is Black or Latinx, is a rural resident, completed a high school education or less, and/or has a household income <200% of the federal poverty line). The primary outcome is biochemically confirmed smoking abstinence sustained through 6 months. Secondary outcomes include abstinence sustained through 12 months, other smoking-related clinical outcomes, and patient-reported outcomes. This pragmatic randomized clinical trial will identify the most effective smoking cessation strategies that LCS programs can implement to reduce smoking burdens affecting underserved populations. Clinical trial registered with clinicaltrials.gov (NCT04798664). Date of registration: March 12, 2021. Date of trial launch: May 17, 2021.


Asunto(s)
Neoplasias Pulmonares , Cese del Hábito de Fumar , Adulto , Detección Precoz del Cáncer/métodos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Fumar , Cese del Hábito de Fumar/métodos , Poblaciones Vulnerables
13.
J Biomed Semantics ; 12(1): 12, 2021 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-34266499

RESUMEN

BACKGROUND: Recent advances in representation learning have enabled large strides in natural language understanding; However, verbal reasoning remains a challenge for state-of-the-art systems. External sources of structured, expert-curated verb-related knowledge have been shown to boost model performance in different Natural Language Processing (NLP) tasks where accurate handling of verb meaning and behaviour is critical. The costliness and time required for manual lexicon construction has been a major obstacle to porting the benefits of such resources to NLP in specialised domains, such as biomedicine. To address this issue, we combine a neural classification method with expert annotation to create BioVerbNet. This new resource comprises 693 verbs assigned to 22 top-level and 117 fine-grained semantic-syntactic verb classes. We make this resource available complete with semantic roles and VerbNet-style syntactic frames. RESULTS: We demonstrate the utility of the new resource in boosting model performance in document- and sentence-level classification in biomedicine. We apply an established retrofitting method to harness the verb class membership knowledge from BioVerbNet and transform a pretrained word embedding space by pulling together verbs belonging to the same semantic-syntactic class. The BioVerbNet knowledge-aware embeddings surpass the non-specialised baseline by a significant margin on both tasks. CONCLUSION: This work introduces the first large, annotated semantic-syntactic classification of biomedical verbs, providing a detailed account of the annotation process, the key differences in verb behaviour between the general and biomedical domain, and the design choices made to accurately capture the meaning and properties of verbs used in biomedical texts. The demonstrated benefits of leveraging BioVerbNet in text classification suggest the resource could help systems better tackle challenging NLP tasks in biomedicine.


Asunto(s)
Procesamiento de Lenguaje Natural , Semántica , Lenguaje
14.
BMJ Open ; 11(3): e044292, 2021 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-33658261

RESUMEN

INTRODUCTION: Weight loss, consumption of a Dietary Approaches to Stop Hypertension dietary pattern, reduced sodium intake and increased physical activity have been shown to lower blood pressure (BP). Use of web-based tools and telehealth to deliver lifestyle counselling could be potentially scalable solutions to improve BP through behavioural modification though limited data exists to support these approaches in clinical practice. METHODS AND ANALYSIS: This randomised controlled trial will compare the efficacy of a telehealth versus self-directed lifestyle intervention in lowering 24-hour SBP in patients with overweight/obesity (body mass index ≥25 kg/m2) and 24-hour SBP 120-160 mm Hg. All participants receive personalised recommendations to improve dietary quality based on a web-based Food Frequency Questionnaire, access to an online comprehensive weight management programme and a smartphone dietary app. The telehealth arm additionally includes weekly calls with registered dietitian nutritionists who use motivational interviewing. The primary outcome is change from baseline to 12 weeks in 24-hour SBP. Secondary outcomes include changes from baseline in 24-hour diastolic BP, daytime SBP, nighttime SP, daytime diastolic BP, nighttime diastolic BP, total Healthy Eating Index-2015 score, weight, waist circumference and physical activity. Other prespecified outcomes will include change in individual components of the Healthy Eating Index-2015 score, and satisfaction with the Healthy BP research study measured on a 5-point Likert scale. ETHICS AND DISSEMINATION: The study has been approved by the Geisinger Institutional Review Board. Results will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03700710.


Asunto(s)
Estilo de Vida , Telemedicina , Presión Sanguínea , Humanos , Obesidad/terapia , Sobrepeso/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto
15.
Jt Comm J Qual Patient Saf ; 47(2): 120-126, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32980255

RESUMEN

PROBLEM: Reducing diagnostic errors requires improving both systems and individual clinical reasoning. One strategy to achieve diagnostic excellence is learning from feedback. However, clinicians remain uncomfortable receiving feedback on their diagnostic performance. Thus, a team of researchers and clinical leaders aimed to develop and implement a diagnostic performance feedback program for learning that mitigates potential clinician discomfort. APPROACH: The program was developed as part of a larger project to create a learning health system around diagnostic safety at Geisinger, a large, integrated health care system in rural Pennsylvania. Steps included identifying potential missed opportunities in diagnosis (MODs) from various sources (for example, risk management, clinician reports, patient complaints); confirming MODs through chart review; and having trained facilitators provide feedback to clinicians about MODs as learning opportunities. The team developed a guide for facilitators to conduct effective diagnostic feedback sessions and surveyed facilitators and recipients about their experiences and perceptions of the feedback sessions. OUTCOMES: 28 feedback sessions occurred from January 2019 to June 2020, involving MODs from emergency medicine, primary care, and hospital medicine. Most facilitators (90.6% [29/32]) reported that recipients were receptive to learning and discussing MODs. Most recipients reported that conversations were constructive and nonpunitive (83.3% [25/30]) and allowed them to take concrete steps toward improving diagnosis (76.7% [23/30]). Both groups believed discussions would improve future diagnostic safety (93.8% [30/32] and 70.0% [21/30], respectively). KEY INSIGHTS AND NEXT STEPS: An institutional program was developed and implemented to deliver diagnostic performance feedback. Such a program may facilitate learning and improvement to reduce MODs. Future efforts should assess long-term effects on diagnostic performance and patient outcomes.


Asunto(s)
Aprendizaje del Sistema de Salud , Comunicación , Retroalimentación , Humanos , Pennsylvania
16.
Dev Biol ; 324(1): 55-67, 2008 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-18805411

RESUMEN

Retinoic acid (RA) signalling is essential for epidermal differentiation; however, the mechanisms by which it acts are largely unexplored. Partitioning of RA between different nuclear receptors is regulated by RA-binding proteins. We show that cellular RA-binding proteins CRABP1 and CRABP2 and the fatty acid-binding protein FABP5 are dynamically expressed during skin development and in adult tissue. CRABP1 is expressed in embryonic dermis and in the stroma of skin tumours, but confined to the hair follicle dermal papilla in normal postnatal skin. CRABP2 and FABP5 are expressed in the differentiating cells of sebaceous gland, interfollicular epidermis and hair follicles, with FABP5 being a prominent marker of sebaceous glands and anagen follicle bulbs. All three proteins are upregulated in response to RA treatment or Notch activation and are negatively regulated by Wnt/beta-catenin signalling. Ectopic follicles induced by beta-catenin arise from areas of the sebaceous gland that have lost CRABP2 and FABP5; conversely, inhibition of hair follicle formation by N-terminally truncated Lef1 results in upregulation of CRABP2 and FABP5. Our findings demonstrate that there is dynamic regulation of RA signalling in different regions of the skin and provide evidence for interactions between the RA, beta-catenin and Notch pathways.


Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Papiloma/metabolismo , Receptor Notch1/genética , Receptores de Ácido Retinoico/metabolismo , Neoplasias Cutáneas/metabolismo , Piel/metabolismo , beta Catenina/fisiología , Animales , Carcinoma de Células Escamosas/patología , Diferenciación Celular , Epidermis/embriología , Epidermis/metabolismo , Epidermis/patología , Proteínas de Unión a Ácidos Grasos/metabolismo , Folículo Piloso/embriología , Folículo Piloso/metabolismo , Folículo Piloso/patología , Factor de Unión 1 al Potenciador Linfoide/metabolismo , Ratones , Ratones Transgénicos , Proteínas de Neoplasias/metabolismo , Papiloma/patología , Transducción de Señal , Piel/embriología , Piel/patología , Neoplasias Cutáneas/patología , Células del Estroma/metabolismo , Células del Estroma/patología , Tretinoina/farmacología , Tretinoina/fisiología , Regulación hacia Arriba
17.
Methods Mol Biol ; 482: 319-30, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19089365

RESUMEN

Satellite cells are mononucleate muscle precursor cells resident beneath the basal lamina, which surrounds each skeletal muscle fibre. Normally quiescent in adult muscle, in response to muscle damage satellite cells are activated and proliferate to generate a pool of muscle precursor cells, which subsequently differentiate and fuse together to repair and replace terminally differentiated muscle fibre syncytia. Cells prepared by enzymatic digestion of whole muscle tissue are likely to contain myogenic cells derived both from the satellite cell niche and from other populations in the muscle interstitium and vasculature. Single muscle fibre preparations, in which satellite cells retain their normal anatomical position beneath the basal lamina, are free of interstitial and vascular tissue and can therefore be used to investigate satellite cell behaviour in the absence of other myogenic cell types. Here, we describe methods for the isolation of viable muscle fibres and for grafting of muscle fibres and their associated satellite cells into mouse muscles to assess the contribution of satellite cells to muscle regeneration.


Asunto(s)
Separación Celular/métodos , Fibras Musculares Esqueléticas/citología , Fibras Musculares Esqueléticas/trasplante , Animales , Disección , Enzimas , Miembro Posterior/citología , Ratones , Fibras Musculares Esqueléticas/fisiología , Regeneración , Células Satélite del Músculo Esquelético/citología
18.
J Clin Psychol ; 65(3): 268-80, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19137578

RESUMEN

Numerous studies have now demonstrated that integrating behavioral health and medical care can reduce medical costs, improve patient and provider satisfaction, and enhance clinical outcomes. Given this, one might expect that behavioral health programs would be fully integrated into primary care clinics across the country, but in fact integrated primary care programs remain quite rare. One reason for this discrepancy is that implementing such programs has proven to be extraordinarily challenging. Most of the integrated programs that are currently operating successfully are in settings where professionals are all members of the same health care system (e.g., HMOs, the Veterans Administration, Departments of Family Practice, etc.). Many providers, however, are in communities where various services are provided in different locations from different organizations that have very different clinical, administrative, and financial structures. In these situations, the challenges are even greater. The authors describe a set of strategies and techniques providers can use to move their health care system toward a higher level of integration and illustrate how they applied these steps to develop and assess the impact of an integrated primary care program in the state of Rhode Island.


Asunto(s)
Prestación Integrada de Atención de Salud/organización & administración , Atención Primaria de Salud , Desarrollo de Programa/métodos , Comorbilidad , Humanos , Servicios de Salud Mental , Estudios de Casos Organizacionales
19.
Am Psychol ; 74(4): 459-473, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30024215

RESUMEN

The gap between treatment development and efficacy testing to scaled up implementations of evidence-based treatment (EBT) is an estimated 20 years, and hybrid research designs aim to reduce the gap. One was used for a multisite study in cancer control, testing coprimary aims: (a) determine the feasibility and utility of a flexible EBT implementation strategy and (b) determine the clinical effectiveness of an EBT as implemented by newly trained providers. Therapists from 15 diverse sites implemented the biobehavioral intervention (BBI) for cancer patients (N = 158) as part of standard care. For implementation, therapists determined treatment format, number of sessions, and so forth and reported session-by-session fidelity. Patients completed fidelity and outcome assessments. Results showed therapists BBI implementation was done with fidelity, for example, session "dose" (59%), core content coverage (60-70%), and others. Patient reported fidelity was favorable and comparable to the BBI efficacy trial. Effectiveness data show the primary outcome, patients' scores on the Profile of Mood States total mood disturbance, significantly improved (R² = 0.06, ß = -0.24, p < .01) as did a secondary outcome, physical activity (R² = 0.02, ß = 0.13, p < .05). This first use of a hybrid design in health psychology provided support for a novel strategy that allowed providers implementation flexibility. Still, the EBT was delivered with fidelity and in addition, therapists generated novel procedures to enhance setting-specific usage of BBI and its ultimate effectiveness with patients. This research is an example of translational research spanning theory and efficacy tests to dissemination and implementation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Asunto(s)
Neoplasias/psicología , Psicoterapia/métodos , Estrés Psicológico/terapia , Adulto , Práctica Clínica Basada en la Evidencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Psicológicos , Apoyo Social , Estrés Psicológico/psicología , Resultado del Tratamiento
20.
Curr Opin Pharmacol ; 6(3): 301-6, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16563862

RESUMEN

Regeneration of adult skeletal muscle involves the activation, proliferation and differentiation of satellite cells - quiescent tissue-specific stem cells occupying a specialised niche beneath the basal laminae of myofibres. Recent studies show that transplanted satellite cells both generate new muscle and undergo self-renewal. Data from cell culture experiments suggest that self-renewal occurs through the return to quiescence of cycling progeny. Several molecules have been implicated in the regulation of satellite cell quiescence, activation and renewal, including the transcription factors Pax7, MyoD and Myf5, the cell-surface glycoprotein CD34, and the membrane lipid sphingomyelin. Evidence suggests that non-satellite cell types from muscle interstitium and bone marrow also give rise to myonuclei, although their contributions relative to the satellite cell remain to be established.


Asunto(s)
Proliferación Celular , Músculo Esquelético/citología , Células Satélite del Músculo Esquelético/citología , Animales , Células de la Médula Ósea/citología , Diferenciación Celular , Linaje de la Célula , Células Cultivadas , Humanos , Células Madre Mesenquimatosas/citología , Músculo Esquelético/fisiología , Regeneración
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