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Exercise-based cardiac rehabilitation (CR) is an evidence-based recommendation for patients with stable heart failure (HF). Less clear is how effective exercise-based CR is for women with HF. The aim of this review was to synthesize the evidence for the effects of exercise-based CR on mortality, hospitalizations, exercise capacity, and quality of life (QOL) among women with HF. We identified 18 studies comprising 4917 patients, of which 1714 were women. The interventions evaluated consisted of various combinations of supervised in-hospital and out-patient sessions as well as home-based programs that included aerobic (walking, treadmill, bicycle) and resistance training. The interventions ranged from 12 to 54 weeks, with a frequency of 2-7 sessions per week, lasting from 30 to 105 min per session. Because of a paucity of sex-specific analyses of the outcomes, it was not possible to draw conclusions for women. There was limited evidence for mortality benefit for men or women participating in exercise-based CR. There was more substantial evidence for reductions in hospitalizations for the participants. Generally, exercise training improved exercise capacity. The effects of exercise-based CR on QOL were mixed with most studies favoring CR at 3 months but not at 4, 5, and 12 months. Moreover, generally, the physical dimension of QOL but not the mental dimensions improved. Recommendations for future research to reduce the gap in knowledge about the effects of exercise-based CR for women are offered.
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Dual comb spectroscopy (DCS) of near-infrared H2O absorption has been demonstrated in the past for low-uncertainty flow measurements in ground test ramjets. However, H2O is scarce at actual ramjet flight altitudes, so oxygen is a preferable absorption target. Here, we demonstrate DCS of the O2 A-band (13000-13200â cm-1) and fit temperature and velocity across different flow conditions in a ground-test ramjet, demonstrating precisions of 3-5% and 7-11% respectively in five minutes and total uncertainty estimates of 7-9% and 8-12% respectively. The DCS measurements and uncertainty estimates are compared to predicted values for the test facility.
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BACKGROUND: Pediatric forearm fractures are common injuries and can sometimes require surgical treatment. Few studies have evaluated the long-term outcomes of pediatric forearm fracture plating. We evaluated long-term functional outcomes and satisfaction in children with forearm fractures treated with plate fixation. METHODS: We performed a single-institution case series at a pediatric level 1 trauma center. Inclusion criteria were: patients with radius and/or ulna diaphyseal fractures, index surgery at 18 years of age or younger, plate fixation, and a minimum of 2 years follow-up. We surveyed patients with the QuickDASH outcome measure and supplemented this with functional outcomes and satisfaction questions. Demographics and surgery characteristics were obtained from the electronic medical record. RESULTS: A total of 41 patients met the eligibility criteria, of whom 17 completed the survey with a mean follow-up of 7.2 ± 1.4 years. The mean age at index surgery was 13.1 ± 3.6 years (range, 4 to 17), with 65% males. All patients reported at least one symptom, with aching (41%) and pain (35%) occurring most frequently. There were 2 complications (12%), including one infection and one compartment syndrome treated with fasciotomy. Hardware removal occurred in 29% of patients. There were no refractures. The mean QuickDASH score was 7.7 ± 11.9, with an occupation module score of 1.6 ± 3.9 and a sports/performing arts module score of 12.0 ± 19.7. The mean surgery satisfaction was 92% and scar satisfaction was 75%. All patients returned to prior activities and 88% reported a return to their preoperative baseline level of function. CONCLUSIONS: Plate fixation for pediatric forearm fractures achieves osseous union but not without the potential for long-term sequelae. All patients reported residual symptoms 7 years later. Scar satisfaction and return to baseline function were imperfect. Patient education for long-term outcomes of surgery is essential, especially in the transition to adulthood. LEVEL OF EVIDENCE: Level IV, therapeutic study.
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Traumatismos del Antebrazo , Fracturas del Radio , Fracturas del Cúbito , Masculino , Humanos , Adolescente , Niño , Preescolar , Femenino , Fracturas del Radio/cirugía , Cicatriz , Antebrazo , Traumatismos del Antebrazo/cirugía , Fracturas del Cúbito/cirugía , Fijación Interna de Fracturas , Placas Óseas , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
INTRODUCTION: As implant technology has continued to improve over the past decade, there has been an increase in the utilization of highly porous metal substrate acetabular components for primary total hip arthroplasty (THA). These implants have several theoretical benefits including a lower modulus of elasticity, which may result in a reduction in stress shielding, a higher coefficient of friction, which may enable better initial implant fixation, as well as higher porosity that may facilitate improved biological fixation. Although these components are implanted frequently, there are some studies that have posed concerns regarding radiographic evidence of loosening. Therefore, the purpose of this study was to assess: 1) The quality of fixation of porous metal acetabular components based on radiographs; 2) clinical outcomes; and 3) revision rates. MATERIALS AND METHODS: A total of 159 patients (169 hips) who had undergone a primary THA utilizing a porous metal primary acetabular cup with minimum two-year follow up were assessed. The study cohort consisted of 51% women, had a mean age of 65 years (range, 30 to 92 years), a mean body mass index (BMI) of 29kg/m2 (range, 15 to 54), and a mean follow up of approximately four years (range, three to six years). Acetabular revision for component failure was documented. Radiographic assessments were independently performed by two fellowship-trained arthroplasty surgeons to determine implant stability and radiolucencies. Clinical evaluations were made by assessing the hip disability and osteoarthritis outcome score (HOOS-Jr) survey scores. Failure was defined as the need to revise the acetabular component, for either septic or aseptic pathology. RESULTS: At final follow up, one patient had definitive loosening, one had probable loosening, and three patients had possible loosening. Only 3.0% had radiolucencies or radiosclerotic lesions in at least one zone. Of these patients, three developed progressive radiolucencies. All patients achieved excellent postoperative HOOS-Jr scores, and no significant differences were noted between patients who did not have loosening compared to patients who had possible or probable loosening. Only two patients underwent revision for aseptic loosening of the cup (success rate for this implant was 98.8% [2/169]). DISCUSSION: There is a paucity of studies focused on the results of this porous metal substrate acetabular component, with some of the current literature reporting conflicting outcomes. Our study reported a low acetabular revision rate of only 1.2% at an approximate mean follow up of four years. The incidence of radiolucencies and progressive radiolucencies were lower (3.0%) than has been found in some studies. Overall, the results of this study support the utilization of this acetabular component in appropriately indicated patients. CONCLUSION: These data show a low rate of acetabular revision at mean four-year follow up.
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Islet transplantation is a potential therapy for type 1 diabetes, but it is expensive due to limited pancreas donor numbers and the variability in islet quality. The latter is often addressed by co-culture of harvested islets with stem cells to promote in vitro remodeling of their basement membrane and enable expression of angiogenic factors for enhancing vascularization. However, given the heterogeneity in islet size, shape and function, there is a need for metrics to assess the reorganization dynamics of single islets over the co-culture period. Based on shape-evolution of individual multi-cell aggregates formed during co-culture of human islets with adipose derived stem cells and the pressures required for their bypass through microfluidic constrictions, we present size-normalized biomechanical metrics for monitoring the reorganization. Aggregates below a threshold size exhibit faster reorganization, as evident from rise in their biomechanical opacity and tightening of their size distribution, but this size threshold increases over culture time to include a greater proportion of the aggregates. Such biomechanical metrics can quantify the subpopulation of reorganized aggregates by distinguishing them versus those with incomplete reorganization, over various timepoints during the co-culture.
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Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Tejido Adiposo , Técnicas de Cocultivo , Humanos , Insulina , Islotes Pancreáticos/metabolismo , Células Madre/metabolismoRESUMEN
A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of ginsenosides in three Panax ginseng reference materials (RMs). Extraction procedures were optimized to recover neutral and malonyl-ginsenosides using a methanol-water extraction under basic conditions. Optimized mass fragmentation transitions were obtained for the development of a multiple reaction monitoring (MRM) detection method with electrospray ionization in negative and positive ion mode. Mass fraction values were determined for ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 in the three ginseng materials (rhizomes, extract, and an oral dosage form). Quantitation of these seven compounds was accomplished with 4-methylestradiol and SRM 3389 Ginsenoside Calibration Solution serving as an internal standard (IS) and calibration standards, respectively. Mass fraction values for the seven ginsenosides ranged from 1.27 mg/g to 21.42 mg/g, 3.25 mg/g to 35.81 mg/g, and 0.56 mg/g to 2.51 mg/g for SRM 3384, SRM 3385, and RM 8664, respectively.
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Ginsenósidos , Panax , Panax/química , Ginsenósidos/análisis , Cromatografía Liquida , Espectrometría de Masas en Tándem/métodos , Rizoma/química , Cromatografía Líquida de Alta Presión/métodosRESUMEN
Intervertebral disc (IVD) degeneration is characterized by decreased cellularity and proteoglycan synthesis and increased inflammation, catabolism, and neural/vascular ingrowth. Regenerative methods for IVD degeneration are largely cell-therapy-based or involve viral vectors, which are associated with mutagenesis and undesired immune responses. The present study used bulk electroporation and engineered extracellular vesicles (EVs) to deliver forkhead-box F1 (FOXF1) mRNA to degenerate human nucleus pulposus (NP) cells as a minimally invasive therapeutic strategy for IVD regeneration. Bulk electroporation was used to investigate FOXF1 effects on human NP cells during a 4-week culture in 3D agarose constructs. Engineered EV delivery of FOXF1 into human IVD cells in monolayer was determined, with subsequent in vivo validation in a pilot mouse IVD puncture model. FOXF1 transfection significantly altered gene expression by upregulating healthy NP markers [FOXF1, keratin 19 (KRT19)], decreasing inflammatory cytokines [interleukin (IL)-1ß, -6], catabolic enzymes [metalloproteinase 13 (MMP13)] and nerve growth factor (NGF), with significant increases in glycosaminoglycan accumulation in human NP cells. Engineered EVs loaded with FOXF1 demonstrated successful encapsulation of FOXF1 cargo and effective uptake by human NP cells cultured in monolayer. Injection of FOXF1-loaded EVs into the mouse IVD in vivo resulted in a significant upregulation of FOXF1 and Brachyury, compared to controls at 7 d post-injection, with no evidence of cytotoxicity. This is the first study to demonstrate non-viral delivery of FOXF1 and reprogramming of human NP cells in vitro and mouse IVD cells in vivo. This strategy represents a non-addictive approach for treating IVD degeneration and associated back pain.
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Vesículas Extracelulares , Degeneración del Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Animales , Factores de Transcripción Forkhead/genética , Humanos , Degeneración del Disco Intervertebral/terapia , RatonesRESUMEN
BACKGROUND: Surgeons in resource-limited environments often provide care outside the expected scope of current general surgery training. Geographically isolated patients may be unwilling or unable to travel for specialty care. These same patients also present with life-threatening emergencies beyond the typical breadth of a general surgeon's practice, in hospitals with limited professional and material support. This review characterizes the unique role of isolated surgeons, so individual surgeons and health care organizations may focus professional development resources more efficiently, with the ultimate goal of improved patient care. METHODS: We performed a scoping review of the isolated surgeon, reviewing 25 years of literature regarding isolated US civilian and military surgeons. We examined emerging themes regarding the definition of an isolated surgeon, the scope of surgical practice beyond current training norms, and training gaps identified by surgeons in an isolated role. RESULTS: From 904 articles identified, we included 91 for final review. No prior definition exists for the isolated surgeon, although multiple definitions describe rural surgeons, patients, or hospitals; we propose an initial definition from consistent themes in the literature. Isolated surgeons across varied practice settings consistently performed relatively large volumes of cases of, and identified training gaps in, orthopedic, obstetric and gynecologic, urologic, and vascular surgery subspecialties. Life-threatening, "rare-but-real" cases in the above and neurosurgical disciplines are uncommon, but consistent across practice settings. CONCLUSIONS: This review represents the largest examination of the isolated surgeon in the current literature. Clarifying the identity, practice components, and training gaps of the isolated surgeon represent the first step in formalizing support for this small but critical group of surgeons and their patients.
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Competencia Clínica , Despliegue Militar , Rol Profesional , Servicios de Salud Rural , Cirujanos/educación , Cirugía General/educación , Ginecología/educación , Humanos , Obstetricia/educación , Ortopedia/educación , Cirujanos/organización & administración , Urología/educación , Procedimientos Quirúrgicos Vasculares/educaciónRESUMEN
Choline availability modulates neurogenesis and cerebral cortex development through the regulation of neural progenitor cell (NPC) proliferative and differentiation capacity. In this study, we demonstrated that cortical NPC self-renewal is controlled by choline via the expression of a microRNA (miR-129-5p), whose role in the developing brain has not been examined, and which, in turn, inhibits synthesis of the epidermal growth factor receptor (EGFR) protein. Specifically, we found that low choline (LC) availability led to the upregulation of miR-129-5p expression in cortical NPCs in vitro and in vivo, causing the downregulation of EGFR and thereby disrupting NPC self-renewal and cortical neurogenesis. Furthermore, in response to LC availability, methylation potential (the S-adenosylmethionine: S-adenosylhomocysteine ratio) in the developing brain was reduced. Restoring methylation potential in LC cortical NPCs led to the re-establishment of normal miR-129-5p expression. We concluded that inhibiting miR-129-5p function and restoring EGFR protein levels in vivo is sufficient to reverse LC-induced defects in cortical NPC self-renewal. For the first time, to our knowledge, we have identified the molecular links that explain how a change in the availability of the diet metabolite choline impacts the essential cellular processes underlying brain development.-Trujillo-Gonzalez, I., Wang, Y., Friday, W. B., Vickers, K. C., Toth, C. L., Molina-Torres, L., Surzenko, N., Zeisel, S. H. MicroRNA-129-5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex.
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Corteza Cerebral/fisiología , Colina/genética , Receptores ErbB/genética , MicroARNs/genética , Neurogénesis/genética , Animales , Diferenciación Celular/genética , Proliferación Celular/genética , Células Cultivadas , Regulación hacia Abajo/genética , Ratones , Ratones Endogámicos C57BL , Células Madre/fisiología , Regulación hacia Arriba/genéticaRESUMEN
Adequate supply of choline, an essential nutrient, is necessary to support proper brain development. Whether prenatal choline availability plays a role in development of the visual system is currently unknown. In this study, we addressed the role of in utero choline supply for the development and later function of the retina in a mouse model. We lowered choline availability in the maternal diet during pregnancy and assessed proliferative and differentiation properties of retinal progenitor cells (RPCs) in the developing prenatal retina, as well as visual function in adult offspring. We report that low choline availability during retinogenesis leads to persistent retinal cytoarchitectural defects, ranging from focal lesions with displacement of retinal neurons into subretinal space to severe hypocellularity and ultrastructural defects in photoreceptor organization. We further show that low choline availability impairs timely differentiation of retinal neuronal cells, such that the densities of early-born retinal ganglion cells, amacrine and horizontal cells, as well as cone photoreceptor precursors, are reduced in low choline embryonic d 17.5 retinas. Maintenance of higher proportions of RPCs that fail to exit the cell cycle underlies aberrant neuronal differentiation in low choline embryos. Increased RPC cell cycle length, and associated reduction in neurofibromin 2/Merlin protein, an upstream regulator of the Hippo signaling pathway, at least in part, explain aberrant neurogenesis in low choline retinas. Furthermore, we find that animals exposed to low choline diet in utero exhibit a significant degree of intraindividual variation in vision, characterized by marked functional discrepancy between the 2 eyes in individual animals. Together, our findings demonstrate, for the first time, that choline availability plays an essential role in the regulation of temporal progression of retinogenesis and provide evidence for the importance of adequate supply of choline for proper development of the visual system.-Trujillo-Gonzalez, I., Friday, W. B., Munson, C. A., Bachleda, A., Weiss, E. R., Alam, N. M., Sha, W., Zeisel, S. H., Surzenko, N. Low availability of choline in utero disrupts development and function of the retina.
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Deficiencia de Colina/embriología , Retina/anomalías , Animales , Ciclo Celular/fisiología , Diferenciación Celular/fisiología , Colina/administración & dosificación , Colina/metabolismo , Deficiencia de Colina/fisiopatología , Dieta , Regulación hacia Abajo , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neurofibromina 2/genética , Neurofibromina 2/metabolismo , Neurogénesis/fisiología , Embarazo , Retina/embriología , Retina/fisiopatología , Células Fotorreceptoras Retinianas Conos/ultraestructura , Células Ganglionares de la Retina/citología , Células Ganglionares de la Retina/fisiología , Células Madre/citología , Células Madre/fisiologíaRESUMEN
The intervertebral disc's ability to resist load and facilitate motion arises largely from osmotic swelling pressures that develop within the tissue. Changes in the disc's osmotic environment, diurnally and with disease, have been suggested to regulate cellular activity, yet knowledge of in vivo osmotic environments is limited. Therefore, the first objective of this study was to demonstrate proof-of-concept for a method to measure intra-tissue swelling pressure and osmolality, modeling micro-osmometer fluid flux using Darcy's law. The second objective was to compare flux-based measurements of the swelling pressure within nucleus pulposus (NP) tissue against ionic swelling pressures predicted by Gibbs-Donnan theory. Pressures (0.03- 0.57 MPa) were applied to NP tissue (n = 25) using equilibrium dialysis, and intra-tissue swelling pressures were measured using flux. Ionic swelling pressures were determined from inductively coupled plasma optical emission spectrometry measurements of intra-tissue sodium using Gibbs-Donnan calculations of fixed charge density and intra-tissue chloride. Concordance of 0.93 was observed between applied pressures and flux- based measurements of swelling pressure. Equilibrium bounds for effective tissue osmolalities engendered by a simulated diurnal loading cycle (0.2-0.6 MPa) were 376 and 522 mOsm/kg H2O. Significant differences between flux and Gibbs-Donnan measures of swelling pressure indicated that total tissue water normalization and non-ionic contributions to swelling pressure were significant, which suggested that standard constitutive models may underestimate intra-tissue swelling pressure. Overall, this micro-osmometer technique may facilitate future validations for constitutive models and measurements of variation in the diurnal osmotic cycle, which may inform studies to identify diurnal- and disease-associated changes in mechanotransduction.
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Disco Intervertebral/fisiología , Agujas , Ósmosis , Fisiología/métodos , Presión , Animales , Bovinos , Núcleo Pulposo/fisiología , Concentración Osmolar , PermeabilidadRESUMEN
Biomass burning is the largest combustion-related source of volatile organic compounds (VOCs) to the atmosphere. We describe the development of a state-of-the-science model to simulate the photochemical formation of secondary organic aerosol (SOA) from biomass-burning emissions observed in dry (RH <20%) environmental chamber experiments. The modeling is supported by (i) new oxidation chamber measurements, (ii) detailed concurrent measurements of SOA precursors in biomass-burning emissions, and (iii) development of SOA parameters for heterocyclic and oxygenated aromatic compounds based on historical chamber experiments. We find that oxygenated aromatic compounds, including phenols and methoxyphenols, account for slightly less than 60% of the SOA formed and help our model explain the variability in the organic aerosol mass (R2 = 0.68) and O/C (R2 = 0.69) enhancement ratios observed across 11 chamber experiments. Despite abundant emissions, heterocyclic compounds that included furans contribute to â¼20% of the total SOA. The use of pyrolysis-temperature-based or averaged emission profiles to represent SOA precursors, rather than those specific to each fire, provide similar results to within 20%. Our findings demonstrate the necessity of accounting for oxygenated aromatics from biomass-burning emissions and their SOA formation in chemical mechanisms.
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Contaminantes Atmosféricos , Compuestos Orgánicos Volátiles , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Atmósfera , Biomasa , Procesos Fotoquímicos , Compuestos Orgánicos Volátiles/análisisRESUMEN
Phenotypic quantification of cells based on their plasma membrane capacitance and cytoplasmic conductivity, as determined by their dielectrophoretic frequency dispersion, is often used as a marker for their biological function. However, due to the prevalence of phenotypic heterogeneity in many biological systems of interest, there is a need for methods capable of determining the dielectrophoretic dispersion of single cells at high throughput and without the need for sample dilution. We present a microfluidic device methodology wherein localized constrictions in the microchannel are used to enhance the field delivered by adjoining planar electrodes, so that the dielectrophoresis level and direction on flow-focused cells can be determined on each traversing cell in a high-throughput manner based on their deflected flow streamlines. Using a sample of human red blood cells diluted to 2.25 × 108 cells/mL, the dielectrophoretic translation of single cells traversing at a flow rate of 1.68 µL/min is measured at a throughput of 1.1 × 105 cells/min, to distinguish positive versus negative dielectrophoresis and determine their crossover frequency in media of differing conductivity for validation of the computed membrane capacitance to that from prior methods. We envision application of this dynamic dielectrophoresis (Dy-DEP) method towards high-throughput measurement of the dielectric dispersion of single cells to stratify phenotypic heterogeneity of a particular sample based on their DEP crossover frequency, without the need for significant sample dilution. Grapical abstract.
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Separación Celular/métodos , Electroforesis/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Análisis de la Célula Individual/métodos , Técnicas Analíticas Microfluídicas/instrumentaciónRESUMEN
The trapping and deflection of biological cells by dielectrophoresis (DEP) at field non-uniformities in a microfluidic device is often conducted in a contactless dielectrophoresis (cDEP) mode, wherein the electrode channel is in a different layer than the sample channel, so that field penetration through the interceding barrier causes DEP above critical cut-off frequencies. In this manner, through physical separation of the electrode and sample channels, it is possible to spatially modulate electric fields with no electrode-induced damage to biological cells in the sample channel. However, since this device requires interlayer alignment of the electrode to sample channel and needs to maintain a thin interceding barrier (~ 15 µm) over the entire length over which DEP is needed (~ 1 cm), variations in alignment and microstructure fidelity cause wide variations in cDEP trapping level and frequency response across devices. We present a strategy to eliminate interlayer alignment by fabricating self-aligned electrode and sample channels, simultaneously with the interceding barrier layer (14-µm width and 50-µm depth), using a single-layer imprint and bond process on cyclic olefin copolymer. Specifically, by designing support structures, we preserve fidelity of the high aspect ratio insulating posts in the sample channel and the interceding barrier between the sample and electrode channels over the entire device footprint (~ 1 cm). The device operation is validated based on impedance measurements to quantify field penetration through the interceding barrier and by DEP trapping measurements. The presented fabrication strategy can eventually improve cDEP device manufacturing protocols to enable more reproducible DEP performance. Graphical abstract.
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Alquenos/química , Electroforesis/instrumentación , Dispositivos Laboratorio en un Chip , Polímeros/química , Diseño de EquipoRESUMEN
PURPOSE: Physician burnout affects approximately half of US physicians, significantly higher than the general working population. The aims of this study were to determine the prevalence of burnout specifically among hand surgeons and to identify factors unique to the practice of hand surgery that may contribute to burnout. METHODS: A Web-based survey, developed in conjunction with the American Medical Association, was administered to all active and lifetime members of the American Society for Surgery of the Hand using the Mini Z Burnout assessment tool. Additional data were collected regarding physician demographics and practice characteristics. RESULTS: The final cohort included 595 US hand surgeons (American Society for Surgery of the Hand [ASSH] members) and demonstrated that 77% of respondents were satisfied with their job, although 49% regarded themselves as having burnout. Lower burnout rates were correlated with physicians aged older than 65, those who practice in an outpatient setting, practice hand surgery only, visit one facility per week, having a lower commute time, those who performed 10 or fewer surgeries per month, and being considered grandfathered for Maintenance of Certification. It was shown that sex, the use of physician extenders, compensation level, and travel club involvement had no impact on burnout rates. CONCLUSIONS: The survey demonstrated that nearly half of US hand surgeons experience burnout even though most are satisfied with their jobs. There is a need to increase awareness and promote targeted interventions to reduce burnout, such as creating a strong team culture, improving resiliency, and enhancing leadership. CLINICAL RELEVANCE: Burnout has been shown to affect physicians, their families, patient care, and the health care system as a whole negatively. The findings should promote awareness among hand surgeons and inform future quality improvement efforts targeted at reducing burnout for hand surgeons.
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Agotamiento Profesional , Cirujanos , Anciano , Agotamiento Profesional/epidemiología , Humanos , Satisfacción en el Trabajo , Prevalencia , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
Diagnostics based on exosomes and other extracellular vesicles (EVs) are emerging as strategies for informing cancer progression and therapies, since the lipid content and macromolecular cargo of EVs can provide key phenotypic and genotypic information on the parent tumor cell and its microenvironment. We show that EVs derived from more invasive pancreatic tumor cells that express high levels of tumor-specific surface proteins and are composed of highly unsaturated lipids that increase membrane fluidity, exhibit significantly higher conductance versus those derived from less invasive tumor cells, based on dielectrophoresis measurements. Furthermore, through specific binding of the EVs to gold nanoparticle-conjugated antibodies, we show that these conductance differences can be modulated in proportion to the type as well as level of expressed tumor-specific antigens, thereby presenting methods for selective microfluidic enrichment and cytometry-based quantification of EVs based on invasiveness of their parent cell.
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Antígenos de Neoplasias/análisis , Vesículas Extracelulares/química , Proteínas de Neoplasias/análisis , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/patología , Animales , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Comunicación Celular , Línea Celular Tumoral , Conductividad Eléctrica , Electroforesis , Oro/química , Xenoinjertos , Humanos , Masculino , Nanopartículas del Metal/química , Ratones , Ratones Desnudos , Técnicas Analíticas Microfluídicas , Invasividad Neoplásica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Páncreas/metabolismo , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Microambiente Tumoral/genéticaRESUMEN
We continue herein the exploration of detector orthogonality in size-based macromolecular separations. Previously [5], the sensitivity of viscometric detection was juxtaposed to that of differential refractometry (DRI) and light scattering (LS, both static and dynamic), and it was shown that viscometry is a truly orthogonal detection method to both DRI and LS. Here, via the size-exclusion chromatography (SEC) analysis of blends of polystyrene and poly(methyl methacrylate), we demonstrate the orthogonality of DRI to UV detection and, within the UV region of the electromagnetic spectrum, we also explore the phenomenon of "wavelength orthogonality:" Analytes observable by one detection method are shown to be spectroscopically invisible to another method, or even to the same detection method when operating at a different wavelength. While generally focusing on blends of analytes of different molar masses (different sizes in solution), we also investigate the less-explored case of blends of coeluting analytes (same sizes in solution) where detector orthogonality can inform one's knowledge of whether or not coelution has occurred. Finally, by incorporating a fluorescence (FL) detector into the experimental set-up, we demonstrate not only its orthogonality to DRI detection but also its sensitivity to the presence of even minor (≈ 1%) fluorescent components in a sample. We hope the present experiments assist in understanding the complementarity of different spectroscopic detection methods and also help highlight the potential role of FL detection, a method which has been largely overlooked in macromolecular separation science.
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Radial tunnel syndrome (RTS) has long been a difficult therapeutic and diagnostic entity for upper extremity surgeons. The presentation is vague and the diagnosis is typically one of exclusion. Multiple clinical entities are known to mimic RTS, but little attention has been paid to the distal biceps. Experience suggests that insertional biceps tendonitis is a potential confounding diagnosis in suspected RTS and that magnetic resonance imaging (MRI) may be of diagnostic benefit in chronic cases before surgical intervention is undertaken. This study is a 13-patient case series. The included patients presented with proximal forearm pain and positive provocative maneuvers for RTS. All included patients were found to have distal biceps pathology on MRI evaluation. At final follow-up (average 6.9 years), all patients had resolution of symptoms with therapy aimed specifically at addressing the distal biceps tendon. A diagnosis of insertional biceps tendonitis could explain both the typical success with conservative treatment and the poor results from surgical intervention for RTS. (Journal of Surgical Orthopaedic Advances 28(1):35-40, 2019).
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Errores Diagnósticos , Neuropatía Radial , Traumatismos de los Tendones , Diagnóstico Diferencial , Humanos , Neuropatía Radial/diagnóstico , Traumatismos de los Tendones/diagnósticoRESUMEN
Retention indices (I) for 45 polycyclic aromatic hydrocarbons (PAHs) and 63 methyl-substituted PAHs were determined by gas chromatography - mass spectrometry (GC-MS) using two different stationary phases: a Rxi-PAH phase (a "higher phenyl-content stationary phase") and a 50% (mole fraction) liquid crystalline dimethylpolysiloxane phase. Retention data were obtained for parent PAHs from molecular mass (MM) 128 g/mol (naphthalene) to 328 g/mol (benzo[c]picene) and for 12 sets of methyl-PAHs (methylfluorenes, methylanthracenes, methylphenanthrenes, methylfluoranthenes, methylpyrenes, methylbenz[a]anthracenes, methylbenzo[c]phenanthrenes, methylchrysenes, methyltriphenylenes, methylbenzo[a]pyrenes, methylperylenes, and methylpicenes). Molecular shape descriptors such as length-to-breath ratio (L/B) and thickness (T) were determined for all the PAHs studied. Correlation between I and L/B ratio was evaluated for both stationary phases with a better correlation observed for the 50% liquid crystalline phase (correlation coefficients ranging from 0.22 to 1.00). Graphical Abstract GC separation of six methylchrysene isomers (m/z 242) on two different stationary phases: 50 % phenyl-like methylpolysiloxane phase and 50 % liquid crystalline phase. Retention indices (I) are plotted as a function of L/B for both phases. The data marker numbers identify each isomer based on methyl-substitution position.
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The relationship of reversed-phase liquid chromatography (RPLC) retention on a polymeric C18 stationary phase and the shape of polycyclic aromatic hydrocarbons (PAHs) was investigated for three-ring to seven-ring cata-condensed isomers. We report the first RPLC separation for six-ring and seven-ring cata-condensed PAH isomers. Correlations of LC retention and shape parameters (length-to-breath ratio, L/B and thickness, T) were investigated for 2 three-ring isomers (molecular mass 178 Da), 5 four-ring isomers (molecular mass 228 Da), 11 five-ring isomers (molecular mass 278 Da), 17 six-ring isomers (molecular mass 328 Da), and 20 seven-ring isomers (molecular mass 378 Da). Significant linear correlations were found for all isomer groups (r = 0.71 to 0.94). Nonplanarity of the PAH isomers was found to influence retention (i.e., nonplanar isomers eluting earlier than expected based on L/B) and linear correlations of retention vs. T for isomer groups containing nonplanar isomers were significant (r = 0.71 to 0.86). Graphical abstract.