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Background: Telemedicine use increased during the COVID-19 pandemic due to concerns for patient and provider safety. Given the lack of testing resources initially and the large geographical range served by Augusta University (AU), a telemedicine platform with up-to-date screening guidelines was implemented for COVID-19 testing in March 2020. Our objective was to understand the level of adherence to telemedicine screening guidelines for COVID-19. Methods: The study population included health care providers and population who participated in an encounter in the AU Health Express Care virtual care program from March 22 to May 21, 2020. All encounters were intended to be for COVID-19 screening, free, and available 24 h per day, 7 days per week. Screening guidelines were developed by AU based on information from the Centers for Disease Control and Prevention and the Georgia Department of Public Health. Results: Among 17,801 total encounters, 13,600 were included in the final analysis. Overall adherence to screening guidelines was 71% in the adult population and 57% in the pediatric population. When providers did not follow guidelines, 72% determined that the patient should have a positive screen. Guidelines themselves determined that only 52% of encounters should have a positive screen. Providers' specialty significantly correlated with guideline adherence (p = 0.002). Departments with the highest adherence were psychiatry, neurology, and ophthalmology. No significant correlation was found between guideline adherence and provider degree/position. Conclusions: This study provides proof of concept of a free telehealth screening platform during an ongoing pandemic. Our screening experience was effective and different specialties participated. Our patient population lived in lower than average income zip codes, suggesting that our free telemedicine screening program successfully reached populations with higher financial barriers to health care. Early training and a posteriori knowledge of telemedicine was likely key to screening guideline adherence.
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COVID-19 , Telemedicina , Adulto , COVID-19/epidemiología , Prueba de COVID-19 , Niño , Personal de Salud , Humanos , Pandemias/prevención & controlRESUMEN
The shift from volume-based to value-based reimbursement has created a need for quantifying clinical performance of infectious diseases (ID) physicians. Nationally recognized ID specialty-specific quality measures will allow stakeholders, such as patients and payers, to determine the value of care provided by ID physicians and will promote clinical quality improvement. Few ID-specific measures have been developed; herein, we provide an overview of the importance of quality measurement for ID, discuss issues in quality measurement specific to ID, and describe standards by which candidate quality measures can be evaluated. If ID specialists recognize the need for quality measurement, then ID specialists can direct ID-related quality improvement, quantify the impact of ID physicians on patient outcomes, compare their performance to that of peers, and convey to stakeholders the value of the specialty.
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Infectología/normas , Atención al Paciente/normas , Médicos/normas , Mejoramiento de la Calidad , Especialización , Humanos , Atención al Paciente/estadística & datos numéricosRESUMEN
The Center for Medicare and Medicaid Services adopted the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) performance measure to the Hospital Inpatient Quality Reporting Program in July 2015 to help address the high mortality and high cost associated with sepsis. The SEP-1 performance measure requires, among other critical interventions, timely administration of antibiotics to patients with sepsis or septic shock. The multistakeholder workgroup recognizes the need for SEP-1 but strongly believes that multiple antibiotics listed in the antibiotic tables for SEP-1 are not appropriate and the use of these antibiotics, as called for in the SEP-1 measure, is not in alignment with prudent antimicrobial stewardship. To promote the appropriate use of antimicrobials and combat antimicrobial resistance, the workgroup provides recommendations for appropriate antibiotics for the treatment of sepsis.
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Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos , Sepsis/tratamiento farmacológico , Humanos , Guías de Práctica Clínica como Asunto , Indicadores de Calidad de la Atención de SaludRESUMEN
A high-throughput small-molecule screen was conducted to identify inhibitors of epithelial-mesenchymal transition (EMT) that could be used as tool compounds to test the importance of EMT signaling in vivo during fibrogenesis. Transforming growth factor (TGF)-ß1-induced fibronectin expression and E-cadherin repression in A549 cells were used as 48-hour endpoints in a cell-based imaging screen. Compounds that directly blocked Smad2/3 phosphorylation were excluded. From 2,100 bioactive compounds, methacycline was identified as an inhibitor of A549 EMT with the half maximal inhibitory concentration (IC50) of roughly 5 µM. In vitro, methacycline inhibited TGF-ß1-induced α-smooth muscle actin, Snail1, and collagen I of primary alveolar epithelial cells . Methacycline inhibited TGF-ß1-induced non-Smad pathways, including c-Jun N-terminal kinase, p38, and Akt activation, but not Smad or ß-catenin transcriptional activity. Methacycline had no effect on baseline c-Jun N-terminal kinase, p38, or Akt activities or lung fibroblast responses to TGF-ß1. In vivo, 100 mg/kg intraperitoneal methacycline delivered daily beginning 10 days after intratracheal bleomycin improved survival at Day 17 (P < 0.01). Bleomycin-induced canonical EMT markers, Snail1, Twist1, collagen I, as well as fibronectin protein and mRNA, were attenuated by methacycline (Day 17). Methacycline did not attenuate inflammatory cell accumulation or alter TGF-ß1-responsive genes in alveolar macrophages. These studies identify a novel inhibitor of EMT as a potent suppressor of fibrogenesis, further supporting the concept that EMT signaling is important to lung fibrosis. The findings also provide support for testing the impact of methacycline or doxycycline, an active analog, on progression of human pulmonary fibrosis.
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Células Epiteliales/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Metaciclina/farmacología , Alveolos Pulmonares/efectos de los fármacos , Fibrosis Pulmonar/tratamiento farmacológico , Actinas/metabolismo , Animales , Cadherinas/metabolismo , Línea Celular , Colágeno Tipo I/metabolismo , Células Epiteliales/metabolismo , Femenino , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-akt/metabolismo , Alveolos Pulmonares/metabolismo , Fibrosis Pulmonar/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Smad/metabolismo , Factores de Transcripción de la Familia Snail , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: The purpose of this document is to provide initial recommendations to telemental health (TMH) professionals for the selection of assessment and outcome measures that best reflect the impacts of mental health treatments delivered via live interactive videoconferencing. MATERIALS AND METHODS: The guidance provided here was created through an expert consensus process and is in the form of a lexicon focused on identified key TMH outcomes. RESULTS: Each lexical item is elucidated by a definition, recommendations for assessment/measurement, and additional commentary on important considerations. The lexicon is not intended as a current literature review of the field, but rather as a resource to foster increased dialogue, critical analysis, and the development of the science of TMH assessment and evaluation. The intent of this lexicon is to better unify the TMH field by providing a resource to researchers, program managers, funders, regulators and others for assessing outcomes. CONCLUSIONS: This document provides overall context for the key aspects of the lexicon.
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Servicios de Salud Mental , Evaluación de Procesos y Resultados en Atención de Salud , Telemedicina , Terminología como Asunto , Consenso , Humanos , Trastornos Mentales/terapiaRESUMEN
OBJECTIVE: The Gulf Coast continues to struggle with service need far outpacing available resources. Since 2005, the Regional Coordinating Center for Hurricane Response (RCC) at Morehouse School of Medicine, Atlanta, GA, has supported telehealth solutions designed to meet high service needs (e.g., psychiatry) within primary care and other healthcare organizations. The overall RCC vision is to support autonomous, useful, and sustainable telehealth programs towards mitigating unmet disaster-related needs. SUBJECTS AND METHODS: To assess Gulf Coast telehealth experiences, we conducted semistructured interviews with both regional key informants and national organizations with Gulf Coast recovery interests. Using qualitative-descriptive analysis, interview transcripts were analyzed to identify shared development themes. RESULTS: Thirty-eight key informants were interviewed, representing a 77.6% participation rate among organizations engaged by the RCC. Seven elements critical to telehealth success were identified: Funding, Regulatory, Workflow, Attitudes, Personnel, Technology, and Evaluation. These key informant accounts reveal shared insights with telehealth regarding successes, challenges, and recommendations. CONCLUSIONS: The seven elements critical to telehealth success both confirm and organize development principles from a diverse collective of healthcare stakeholders. The structured nature of these insights suggests a generalizable framework upon which other organizations might develop telehealth strategies toward addressing high service needs with limited resources.
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Tormentas Ciclónicas , Planificación en Desastres/organización & administración , Telemedicina/organización & administración , Actitud del Personal de Salud , Personal de Salud/organización & administración , Humanos , Sistemas de Información/organización & administración , Flujo de TrabajoRESUMEN
BACKGROUND: The California Department of Public Health received serial spirometry data for flavoring manufacturing workers at 20 companies at risk of bronchiolitis obliterans. METHODS: We graded spirometry quality; identified individual workers with excessive decline in forced expiratory volume in 1 s (FEV(1)) using relative longitudinal limits of decline based on 4% average within-person variability; and analyzed declines by occupational risk factors. RESULTS: The quality of 1,696 spirometry tests from 724 workers varied by 17 providers, with poorer quality from commercial providers. Of 416 workers with at least two tests, 40 (9.6%) had abnormal FEV(1) decline. Of 289 workers with high quality spirometry, 21 (7.3%) had abnormal decline. Only one of the 21 had airways obstruction. Abnormal FEV(1) decline rates (per person-month) were greater among workers at companies using ≥800 lbs/year diacetyl than at companies using lesser amounts. Abnormal FEV(1) decline rates were greater at companies previously having four-person clusters of spirometric obstruction than at companies with no or only one worker with obstruction. CONCLUSIONS: Spirometric surveillance of flavoring workers can identify individual workers with an abnormal FEV(1) decline for preventive intervention, even when the FEV(1) itself remains within the normal range. Good quality spirometry and classification of abnormal with relative longitudinal limit of decline minimize misclassification of possible work-related health effects.
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Bronquiolitis Obliterante/prevención & control , Diacetil/efectos adversos , Aromatizantes/efectos adversos , Volumen Espiratorio Forzado , Industrias , Enfermedades Profesionales/prevención & control , Vigilancia de la Población , Adolescente , Adulto , Anciano , Bronquiolitis Obliterante/inducido químicamente , Bronquiolitis Obliterante/diagnóstico , Bronquiolitis Obliterante/fisiopatología , California , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/fisiopatología , Exposición Profesional/efectos adversos , Exposición Profesional/estadística & datos numéricos , Espirometría/normas , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: To report a birth of a healthy boy after long-term cryopreservation of oocytes by vitrification. DESIGN: Clinical application. SETTING: IVF Center. PATIENT: A 17 year-old female with secondary pulmonary hypertension caused by transposition of great vessels visited our center in 2002, and she wished oocytes cryopreservation to avoid possible sterility after the following category X medication treatment. INTERVENTION(S): Vitrified oocytes on Electron Microscope (EM) grids were warmed after 5 years of storage. Surviving MII oocytes were microinjected for fertilization and two embryos were transferred into a gestational carrier day 5 after microinjection. MAIN OUTCOME MEASURE(S): Survival, fertilization, cleavage, clinical pregnancy and delivery. RESULT(S): Eleven out of fourteen oocytes (78.6%) survived warming. Eight Metaphase II (MII) oocytes and 3 in vitro matured oocytes were microinjected; all 11 oocytes (100%) fertilized and 2 embryos were transferred on day 5. A healthy baby boy weighing 3,600 g was delivered at 38 weeks of gestation. Live-birth rates per warmed oocyte and per injected oocyte were 7.1% and 9.1% respectively. CONCLUSION(S): Cryopreservation after vitrification with EM grids maintained the developmental competence of oocytes after long-term storage and resulted in a successful live birth.
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Criopreservación , Nacimiento Vivo , Oocitos/crecimiento & desarrollo , Vitrificación , Adolescente , Transferencia de Embrión , Desarrollo Embrionario , Femenino , Fertilización In Vitro , Humanos , Lactante , Masculino , Metafase , Embarazo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Background: Although engagement of infectious disease physicians has been demonstrated to improve clinical outcomes in a variety of disease states, the extent of infectious disease (ID) physician engagement in quality improvement (QI) or their knowledge of QI has not been assessed. Methods: A 12-question, web-based survey was distributed to members of the Infectious Diseases Society of America (IDSA) between August and October 2019 to assess knowledge of and engagement in QI. The survey link was sent to IDSA members who self-identified patient care as their primary professional activity. Results: Responses were received from 200 individuals (5.4% response rate, which is just below the standard IDSA survey response rate of 6%), consisting of 175 adult infectious disease physicians (IDPs). Most respondents were employed in a hospital or clinic (41%), private or group practice (25%), or university/medical center (24%). Fifty-eight percent of respondents currently participate in QI projects, while 38% serve on QI oversight committees. Among respondents, 27% reported not being engaged in QI. Infection prevention/hospital epidemiology (77%), stewardship (72%), and antimicrobial resistance (56%) were the most commonly reported measure types. Respondents reported barriers that limited participation in QI, including cost (61%), lack of time (56%), lack of data collection resources (48%), and lack of an ID-specific registry (46%). IDPs report significant interest in additional training in QI and new quality measures. Conclusions: Although IDPs participate in QI, there are gaps in QI knowledge and measurement systems. The low response rate of our survey also suggests a lack of engagement in QI among IDPs. Closing these gaps will benefit ID in a value-driven health care economy.
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PURPOSE: Measurements of breast arterial calcifications (BAC) can offer a personalized, non-invasive approach to risk-stratify women for cardiovascular diseases such as heart attack and stroke. We aim to detect and segment breast arterial calcifications in mammograms accurately and suggest novel measurements to quantify detected BAC for future clinical applications. METHODS: To separate BAC in mammograms, we propose a lightweight fine vessel segmentation method Simple Context U-Net (SCU-Net). Due to the large image size of mammograms, we adopt a patch-based way to train SCU-Net and obtain the final whole-image-size results by stitching patchwise results together. To further quantify calcifications, we test five quantitative metrics to inspect the progression of BAC for subjects: sum of mask probability metric ( P M ), sum of mask area metric ( A M ), sum of mask intensity metric ( S I M ), sum of mask area with threshold intensity metric T A M X , and sum of mask intensity with threshold X metric T S I M X . Finally, we demonstrate the ability of the metrics to longitudinally measure calcifications in a group of 26 subjects and evaluate our quantification metrics compared with calcified voxels and calcium mass on breast CT for 10 subjects. RESULTS: Our segmentation results are compared with state-of-the-art network architectures based on recall, precision, accuracy, F1 score/Dice score, and Jaccard index evaluation metrics and achieve corresponding values of 0.789, 0.708, 0.997, 0.729, and 0.581 for whole-image-size results. The quantification results all show >95% correlation between quantification measures on predicted masks of SCU-Net as compared to the groundtruth and measurement of calcification on breast CT. For the calcification quantification measurement, our calcification volume (voxels) results yield R2 -correlation values of 0.834, 0.843, 0.832, 0.798, and 0.800 for the P M , A M , S I M , T A M 100 , T S I M 100 metrics, respectively; our calcium mass results yield comparable R2 -correlation values of 0.866, 0.873, 0.840, 0.774, and 0.798 for the same metrics. CONCLUSIONS: Simple Context U-Net is a simple method to accurately segment arterial calcification retrospectively on routine mammograms. Quantification of the calcifications based on this segmentation in the retrospective cohort study has sufficient sensitivity to detect the normal progression over time and should be useful for future research and clinical applications.
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Enfermedades de la Mama , Aprendizaje Profundo , Mama/diagnóstico por imagen , Enfermedades de la Mama/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Mamografía , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To determine the predictive value of an aneuploid diagnosis with a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy (PGT-A) assay in prognosticating the failure of a successful delivery. DESIGN: Prospective, blinded, multicenter, nonselection study. All usable blastocysts were biopsied, and the single best morphologic blastocyst was transferred before genetic analysis. Preimplantation genetic testing for aneuploidy was performed after clinical outcome was determined. Clinical outcomes were compared to PGT-A results to calculate the predictive value of a PGT-A aneuploid diagnosis. SETTING: Fertility centers. PATIENT(S): Couples undergoing their first in vitro fertilization cycle without recurrent pregnancy loss, antral follicle count < 8, or body mass index ≥ 35 kg/m2. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was the ability of the analytical result of aneuploid to predict failure to deliver (clinical result). A secondary outcome was the impact of the trophectoderm biopsy on sustained implantation. RESULT(S): Four hundred two patients underwent 484 single, frozen, blastocyst transfers. The PGT-A aneuploid diagnosis clinical error rate was 0%. There was no difference in sustained implantation between the study group and an age-matched control group, where biopsy was not performed (47.9% vs. 45.8). CONCLUSION(S): The PGT-A assay evaluated was highly prognostic of failure to deliver when an aneuploid result was obtained. Additionally, the trophectoderm biopsy had no detectable adverse impact on sustained implantation. CLINICAL TRIAL REGISTRATION NUMBERS: NCT02032264 and NCT03604107.
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Aneuploidia , Transferencia de Embrión/normas , Pruebas Genéticas/normas , Secuenciación de Nucleótidos de Alto Rendimiento/normas , Diagnóstico Preimplantación/normas , Análisis de Secuencia de ADN/normas , Adolescente , Adulto , Biopsia/métodos , Biopsia/normas , Blastocisto/fisiología , Transferencia de Embrión/métodos , Femenino , Estudios de Seguimiento , Pruebas Genéticas/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Recuperación del Oocito/métodos , Recuperación del Oocito/normas , Valor Predictivo de las Pruebas , Diagnóstico Preimplantación/métodos , Estudios Prospectivos , Análisis de Secuencia de ADN/métodos , Método Simple Ciego , Adulto JovenRESUMEN
BACKGROUND: Two cases of bronchiolitis obliterans in flavor manufacturing workers prompted California health and labor agencies to initiate industry-wide surveillance. METHODS: Companies' physicians submitted cross-sectional questionnaire and spirometry data for 467 workers in 16 workplaces. We compared prevalence ratios of respiratory symptoms, diagnoses, and abnormal spirometry to a general population sample. We calculated odds ratios for risk factors for spirometric obstructive abnormality. RESULTS: Flavoring workers were 2.7 times more likely than the general population to have severe airways obstruction. Risk factors identified for 18 cases with obstruction from six companies included younger age, Hispanic ethnicity, liquid and powder production work, greater company diacetyl usage, and having a coworker with obstruction. Severity of obstruction was related to tenure. At least 12 workers had probable occupational fixed airways obstruction. CONCLUSIONS: The flavoring industry risk of severe lung disease justifies lowering flavoring exposures and medical screening for secondary prevention until worker safety is demonstrated.
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Diacetil/uso terapéutico , Aromatizantes/efectos adversos , Industrias/estadística & datos numéricos , Enfermedades Pulmonares/epidemiología , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Salud Laboral/estadística & datos numéricos , Adulto , Bronquiolitis Obliterante/epidemiología , California/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Oportunidad Relativa , Vigilancia de la Población , Prevalencia , Factores de Riesgo , Espirometría , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: To determine the utility of treating facial palsy with mirror book therapy in conjunction with facial physical rehabilitation. METHODS: We randomly selected and reviewed the charts of 25 patients with idiopathic facial palsy. 10 of these patients received facial physical rehabilitation including manual therapy and postural exercises. 15 of these patients received mirror book therapy in conjunction with standard facial rehabilitation. Before and after treatment, patients in both groups were rated using the Facial Grading System (FGS) score, the Facial Disability Index--Physical (FDIP) score, and the Facial Disability Index--Social (FDIS) score. Differences in response to therapy were analyzed. RESULTS: Patients in the facial physical rehabilitation group without mirror book therapy group showed on average a 20.8% increase in the FGS score, a 19% increase in the FDIP score, and a 14.6% increase in the FDIS score. Patients in the mirror book therapy group showed an average of 24.9% increase in the Facial Grading System (FGS) score, a 21.6% increase in the Facial Disability Index--Physical (FDIP) score, and a 24.5% increase in the Facial Disability Index--Social (FDIS) score. CONCLUSION: The addition of mirror book therapy to standard facial rehabilitation treatments does significantly improve outcomes in the treatment of idiopathic facial palsy.
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Emergent operation after renal transplantation (RT) has traditionally been associated with substantial morbidity and mortality. We reviewed 2340 adult patients who underwent RT at our tertiary care center and identified 55 patients who required acute care surgical consultation within 1 year of transplantation. Of these, 43 were treated operatively and 12 nonoperatively. Primary diagnoses were intestinal problems in 29 patients (53%), including diverticulitis, ischemia, perforation, obstruction, and bleeding; cholecystitis in 10 (18%); fluid collections in six (11%), appendicitis and hernias in two each (4%); gastritis in one (2%); and no diagnosis in five (9%). Colonic pathology was treated with resection and diversion in 14 of 16 patients who underwent surgery. Acute allograft rejection preceded the surgical problem in five patients. Complications occurred in 13 per cent of patients, and mortality was 9 per cent. Colonic ischemia had a fulminating presentation and particular morbidity. We conclude that acute gastrointestinal emergencies after RT are rare and that early and aggressive intervention using an acute care surgical model yields excellent results.
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Procedimientos Quirúrgicos del Sistema Digestivo , Enfermedades Gastrointestinales/cirugía , Hernia Ventral/cirugía , Trasplante de Riñón/efectos adversos , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Urgencias Médicas , Femenino , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etiología , Hernia Ventral/diagnóstico , Hernia Ventral/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The one-dimensional deformation of shape memory alloy (SMA) wires and springs can be implemented into different types of functional structures with three-dimensional deformations. These structures can be classified based on the type of structure and how the SMA element has been implemented into the following categories: rigid mechanical joints, semi-rigid flexural hinges, SMA elements externally attached to a soft structure, and embedded into the soft structure. These structures have a wide range of properties and implementation requirements, and they have been used to produce a variety of robots with rigid and soft motions. The different research efforts to develop actuators and robots related to each type of structure are presented along with their respective strengths and weaknesses. A model is then developed to discuss the performance and applicability of SMA wires versus SMA springs for actuators with a polymeric matrix to see the effect of each type of SMA on the selection of design parameters. A comparison of the different types of structures and the applicability of different types of SMA elements for different types of structures is then presented.
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TGF-ß1 signaling is a critical driver of collagen accumulation and fibrotic disease but also a vital suppressor of inflammation and epithelial cell proliferation. The nature of this multifunctional cytokine has limited the development of global TGF-ß1 signaling inhibitors as therapeutic agents. We conducted phenotypic screens for small molecules that inhibit TGF-ß1-induced epithelial-mesenchymal transition without immediate TGF-ß1 receptor (TßR) kinase inhibition. We identified trihydroxyphenolic compounds as potent blockers of TGF-ß1 responses (IC50 ~50 nM), Snail1 expression, and collagen deposition in vivo in models of pulmonary fibrosis and collagen-dependent lung cancer metastasis. Remarkably, the functional effects of trihydroxyphenolics required the presence of active lysyl oxidase-like 2 (LOXL2), thereby limiting effects to fibroblasts or cancer cells, the major LOXL2 producers. Mechanistic studies revealed that trihydroxyphenolics induce auto-oxidation of a LOXL2/3-specific lysine (K731) in a time-dependent reaction that irreversibly inhibits LOXL2 and converts the trihydrophenolic to a previously undescribed metabolite that directly inhibits TßRI kinase. Combined inhibition of LOXL2 and TßRI activities by trihydrophenolics resulted in potent blockade of pathological collagen accumulation in vivo without the toxicities associated with global inhibitors. These findings elucidate a therapeutic approach to attenuate fibrosis and the disease-promoting effects of tissue stiffness by specifically targeting TßRI kinase in LOXL2-expressing cells.
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Inhibidores Enzimáticos , Transición Epitelial-Mesenquimal , Fibroblastos/metabolismo , Neoplasias Pulmonares , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Fibrosis Pulmonar , Receptores de Factores de Crecimiento Transformadores beta/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Células A549 , Aminoácido Oxidorreductasas/genética , Aminoácido Oxidorreductasas/metabolismo , Animales , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Fibroblastos/patología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Ratones , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Fenoles/química , Fenoles/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/genética , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
OBJECTIVE: To assess the usefulness of the vitrification method in clinical practice. DESIGN: Clinical study of vitrification of human oocytes. SETTING: A university-affiliated hospital. PATIENT(S): Thirty-four patients who agreed to undergo additional IVF-ET after the failed fresh cycle using the previously vitrified/thawed oocytes. INTERVENTION(S): Surplus oocytes from the IVF-ET patients were vitrified for the next cycle. MAIN OUTCOME MEASURES: Morphologic normality of post-thawed oocytes, fertilization, cleavage, pregnancy, and implantation rate. RESULT(S): Overall morphological survival and fertilization rates of vitrified/liquefied oocytes were 68.6% (325/474) and 71.7% (142/198), respectively. Pregnancy rate and implantation rate per embryo transfer were 21.4% (6/28) and 6.4% (8/125), respectively. All pregnancies resulted in the delivery of healthy babies (1 twin and 5 singletons/6 pregnancies). CONCLUSION(S): The feasibility of the vitrification method for human oocytes was confirmed by our clinical results. Subsequent studies on vitrification and thawing procedures should be undertaken for further optimizing the vitrification method.
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Criopreservación/métodos , Transferencia de Embrión , Fertilización In Vitro , Oocitos , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Inyecciones de Esperma IntracitoplasmáticasRESUMEN
Acute nausea and vomiting are often self-limited or easily treated. Persistent vomiting, however, poses diagnostic and therapeutic challenges for the primary care physician. In addition to gastrointestinal, neurologic, and endocrine disorders, the differential diagnosis includes psychiatric illnesses, such as eating and factitious disorders. We present the case of a 52-year-old woman referred to the Tulane University Internal Medicine/Psychiatry clinic with persistent daily vomiting for 8 years despite repeated medical evaluations. The vomiting was of sufficient severity to require intensive care unit admission for hematemesis. A dually trained internal medicine-psychiatry house officer obtained further history and identified that the woman experienced an intrusive thought that urged her to vomit after each meal. Resisting the urge resulted in intolerable anxiety that was relieved only by vomiting. Obsessive-compulsive disorder (OCD) was diagnosed according to DSM-IV criteria. Initiation of escitalopram with titration to clinical response resulted in full symptom resolution and meaningful quality of life improvement. Pertinent literature was reviewed using 2 methods: (1) an English-language MEDLINE search (1966-February 2004) using the search terms vomiting and (chronicor psychogenicor psychiatric), and obsessive-compulsive disorder and (primary care or treatment); and (2) a direct search of reference lists of pertinent journal articles. A review of psychiatric etiologies of vomiting and primary care aspects of OCD is presented. Primary care clinicians are strongly encouraged to consider psychiatric etiologies, including OCD, when common symptoms persist or present in atypical ways. Such disorders can be debilitating but also responsive to treatment.
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Blood transfusion after orthopaedic surgery accounts for 10% of all packed red blood-cell transfusions, but use varies substantially across hospitals and surgeons. Transfusions can cause systemic complications, including allergic reactions, transfusion-related acute lung injury, transfusion-associated circulatory overload, graft-versus-host disease, and infections. Tranexamic acid is a new cost-effective blood management tool to reduce blood loss and decrease the risk of transfusion after total joint arthroplasty. Current clinical evidence does not justify transfusions for a hemoglobin level of >8 g/dL in the absence of symptoms. Studies have also supported the use of this trigger in patients with a history or risk of cardiovascular disease.