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Selected pharmaceutical chemicals, steroids and xenoestrogens (PCSXs) consisting of 29 endocrine modulators, therapeutic drugs, pesticides, detergents, plastics, and active ingredients in household products were measured in water, riverbed sediments and fish collected in a tributary embayment of the Potomac River (Hunting Creek, Alexandria, VA, USA) in the vicinity of wastewater discharge. A total of 17 PCSXs were found in the Hunting Creek samples, with steroid hormones (e.g., progesterone and 17α-ethinylestradiol), triclosan, dextromethorphan and bisphenol A being the most prominent micropollutants detected.The geospatial distribution of the PCSXs in Hunting Creek indicated that the steroids correlated with wastewater treatment plant discharge in all matrices, but such an association is tentative in Hunting Creek given the complex nature of urban sources of PCSXs and hydrodynamics in an urban tidal river. The sediment PCSX concentrations correlated with sediment total organic carbon content at all sampling sites. For the most part, the PCSXs showed an enrichment in fish tissue relative to sediments when concentrations were normalized to lipids and sediment organic carbon contents, but the influence of endogenous steroids is also an important consideration for these chemicals.
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Monitoreo del Ambiente/métodos , Peces , Sedimentos Geológicos/química , Ríos/química , Contaminantes Químicos del Agua/análisis , Animales , Estrógenos/análisis , Hidrodinámica , Preparaciones Farmacéuticas/análisis , Esteroides/análisis , Urbanización , Virginia , Aguas Residuales/química , Xenobióticos/análisisRESUMEN
A new photoactivatable trifunctional cross-linker, cBED (cadaverine-2-[6-(biotinamido)-2-(p-azidobenzamido) hexanoamido]ethyl-1,3'-dithiopropionate), was synthesized by chemical conversion of sulfo-SBED (sulfosuccinimidyl-2-[6-(biotinamido)-2-(p-azidobenzamido) hexanoamido]ethyl-1,3'-dithiopropionate) with cadaverine. This cross-linker was purified by reversed-phase high-performance liquid chromatography (RP-HPLC) and characterized using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis. cBED is based on sulfo-SBED that has a photoactivatable azido group, a cleavable disulfide bond for label transfer methods, and a biotin moiety for highly sensitive biotin/avidin detection. By ultraviolet (UV) light, the azido group is converted to a reactive nitrene, transforming transient bindings of interacting structures to covalent bonds. In contrast to the sulfo-N-hydroxysuccinimide (sulfo-NHS) moiety of sulfo-SBED, which attaches quite unspecifically to amino groups, cBED includes a cadaverine moiety that can be attached by transglutaminase more specifically to certain glutamine residues. For instance, thymosin ß4 can be labeled with cBED using tissue transglutaminase. By high-resolution HPLC/ESI-MS (electrospray ionization-mass spectrometry) and tandem MS (MS/MS) of the trypsin digest, it was established that glutamine residues at positions 23 and 36 were labeled, whereas Q39 showed no reactivity. The covalent binding of cBED to thymosin ß4 did not influence its G-actin sequestering activity, and the complex could be used to identify new interaction partners. Therefore, cBED can be used to better understand the multifunctional role of thymosin ß4 as well as of other proteins and peptides.
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Azidas/química , Biotina/análogos & derivados , Biotina/metabolismo , Cadaverina/análogos & derivados , Cadaverina/química , Reactivos de Enlaces Cruzados/química , Procesos Fotoquímicos , Timosina/química , Timosina/metabolismo , Actinas/metabolismo , Aminas/metabolismo , Secuencia de Aminoácidos , Animales , Biotina/química , Bovinos , Datos de Secuencia Molecular , Unión Proteica , Ratas , Coloración y Etiquetado , Transglutaminasas/metabolismo , Rayos UltravioletaRESUMEN
The role of patient-specific instrumentation in total knee arthroplasty (TKA) is yet to be clearly defined. Current evidence evaluating peri-operative and cost differences against conventional TKA is unclear. We reviewed 356 TKAs between July 2008 and April 2013; 306 TKAs used patient-specific instrumentation while 50 had conventional instrumentation. The patient-specific instrumentation cohort averaged 20.4 min less surgical time (P < 0.01) and had a 42% decrease in operating room turnover time (P = 0.022). At our institution, the money saved through increased operating room efficiency offset the cost of the custom cutting blocks and pre-operative advanced imaging. Routine use of patient-specific TKA can be performed with less surgical time, no increase in peri-operative morbidity, and at no increased cost when compared to conventional TKA.
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Artroplastia de Reemplazo de Rodilla/instrumentación , Artropatías/cirugía , Articulación de la Rodilla/cirugía , Cirugía Asistida por Computador/economía , Anciano , Artroplastia de Reemplazo de Rodilla/economía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo OperativoRESUMEN
Popliteal artery injury is a relatively rare but potentially devastating complication of total knee arthroplasty (TKA). We analyzed the Nationwide Inpatient Sample from 1998 to 2009 to determine the actual incidence, risk factors and consequences of this complication. There were 1,120,508 hospitalizations coded for TKA; of these, 633 (0.057%) were identified as having a popliteal artery injury. The rate of injury remained relatively constant though the number of both TKAs and injuries have risen annually by 0.65% and 0.5%, respectively. Significant risk factors included revision surgery, peripheral vascular disease, weight loss, renal failure, coagulopathy, and metastatic cancer. Consequences were increased hospital charges, length of stay, and mortality rates. Because the rate of popliteal artery injury is not diminishing with time and morbidity and mortality are high, patients should be assessed for known risk factors for popliteal artery injury.
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Artroplastia de Reemplazo de Rodilla/efectos adversos , Arteria Poplítea/lesiones , Lesiones del Sistema Vascular/epidemiología , Bases de Datos Factuales , Precios de Hospital , Humanos , Incidencia , Factores de Riesgo , Lesiones del Sistema Vascular/economía , Lesiones del Sistema Vascular/etiologíaRESUMEN
Background: The impact of amphetamine abuse on total hip arthroplasty (THA) outcomes has yet to be studied. As the rates of methamphetamine abuse continue to rise, understanding the risk profile of this population is imperative. This study aims to determine the risk of major surgical and medical complications for those with amphetamine abuse undergoing THA, with the hypothesis that amphetamine abuse carries increased risk. Methods: A retrospective review was performed with all-claims data files of a large national database querying International Classification of Disease, tenth revision, procedure codes identifying 333,038 primary THA, and 1027 with active amphetamine abuse. Medical and surgical complications including infection, dislocation, implant failure, periprosthetic fracture, and revision, as well as length of hospital stay and 90-day readmission rate, were identified. Univariate analysis compared rates of dependent outcomes. To account for independent variables, logistic regression was performed using age, Charlson comorbidity index, sex, obesity, tobacco use, and alcohol use. The results were presented as odds ratios (OR) and P values with significance set at <0.05. Results: Patients with active amphetamine abuse carried an increased risk of dislocation (OR 1.82, P ≤ .001), infection (OR 2.37, P ≤ .001), mechanical complications (OR 1.64, P ≤ .001), periprosthetic fracture (OR 1.53, P ≤ .05), revision (OR 1.70, P ≤ .001), 90-day readmission (OR 1.79, P ≤ .001), as well as medical complications (1.43, P = .02) compared to those without documented amphetamine abuse. Conclusions: Patients with amphetamine abuse are at increased risk of postoperative surgical and medical complications following THA. We recommend consideration of these risks prior to primary THA in this patient population.
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Per- and polyfluoroalkyl substances (PFAS) are a class of toxic manufactured chemicals in commercial and consumer products. They are resistant to environmental degradation and mobile in soil, air, and water. This study used the introduced bivalve Corbicula fluminea as a passive biomonitor at sampling locations in a primary drinking water source in Virginia, USA. Many potential PFAS sources were identified in the region. Perfluorohexane sulfonate (PFHxS) and 6:2 fluorotelomer sulfonic acid (6:2 FTS) levels were highest downstream of an airport. The highest levels of short-chain carboxylic acids were in locations downstream of a wastewater treatment plant. Measured PFAS concentrations varied by location in C. fluminea, sediment, and surface water samples. Two compounds were detected across all three mediums. Calculated partitioning coefficients confirm bioaccumulation of PFAS in C. fluminea and sorption to sediment. C. fluminea bioaccumulated two PFAS not found in the other mediums. Perfluoroalkyl carboxylic acids and short-chain compounds dominated in clam tissue, which contrasts with findings of accumulation of longer-chain and perfluorosulfonic acids in fish. These findings suggest the potential for using bivalves to complement other organisms to better understand the bioaccumulation of PFAS and their fate and transport in a freshwater ecosystem.
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Corbicula , Fluorocarburos , Contaminantes Químicos del Agua , Animales , Contaminantes Químicos del Agua/análisis , Fluorocarburos/análisis , Corbicula/metabolismo , Corbicula/química , Monitoreo del Ambiente/métodos , Sedimentos Geológicos/química , Sedimentos Geológicos/análisis , Monitoreo Biológico , VirginiaRESUMEN
The impact on patient care of introducing a protocol of obtaining 5 or more intra-operative separate tissue biopsies that were cultured for 10 days was assessed for hip and knee arthroplasty revision. The charts of seventy-three patients undergoing 77 cases of revision arthroplasty were reviewed one year post-operatively. When compared to the prior standard of obtaining only one intra-operative culture, the protocol changed the microbiological diagnosis in 26/77 cases (34%, 95% Confidence Interval (CI): 23-45%) and antibiotic treatment in 23/77 cases (30%, 95% CI: 20-41%). In addition, the protocol had a predictive value of joint sterility in culture negative cases of 95% (95% CI: 85-99%). This data demonstrated the new protocol significantly changed patient care, and suggests that 1 or 2 cultures are insufficient. Adopting a similar protocol should be considered by surgeons and institutions as a new minimum standard for management of prosthetic joint infections.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Manejo de la Enfermedad , Prótesis de Cadera/microbiología , Prótesis de la Rodilla/microbiología , Técnicas Microbiológicas/métodos , Infecciones Relacionadas con Prótesis/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Artroplastia de Reemplazo de Cadera/instrumentación , Artroplastia de Reemplazo de Rodilla/instrumentación , Biopsia , Femenino , Estudios de Seguimiento , Articulación de la Cadera/microbiología , Articulación de la Cadera/patología , Articulación de la Cadera/cirugía , Humanos , Periodo Intraoperatorio , Articulación de la Rodilla/microbiología , Articulación de la Rodilla/patología , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Falla de Prótesis , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/microbiología , Reoperación , Estudios RetrospectivosRESUMEN
Wetland shorelines around the world are susceptible to wave erosion. Previous work has suggested that the lateral erosion rate of their cliff-like edges can be predicted as a function of intercepting waves, and yet numerous field studies have shown that other factors, for example, tidal currents or mass wasting of differing soil types, induce a wide range of variability. Our objective was to isolate the unique effects of wave heights, wavelengths, and water depths on lateral erosion rates and then synthesize a mechanistic understanding that can be applied globally. We found a potentially universal relationship, where the lateral erosion rates increase exponentially as waves increase in height but decrease exponentially as waves become longer in length. These findings suggest that wetlands and other sheltered coastlines likely experience outsized quantities of erosion, as compared to oceanic-facing coastlines.
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A broadly accepted paradigm is that vegetation reduces coastal dune erosion. However, we show that during an extreme storm event, vegetation surprisingly accelerates erosion. In 104-m-long beach-dune profile experiments conducted within a flume, we discovered that while vegetation initially creates a physical barrier to wave energy, it also (i) decreases wave run-up, which creates discontinuities in erosion and accretion patterns across the dune slope, (ii) increases water penetration into the sediment bed, which induces its fluidization and destabilization, and (iii) reflects wave energy, accelerating scarp formation. Once a discontinuous scarp forms, the erosion accelerates further. These findings fundamentally alter the current understanding of how natural and vegetated features may provide protection during extreme events.
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The tidal freshwater Potomac River (TFPR) in the metropolitan Washington, DC region receives wastewater discharge from eight major wastewater treatment plants with the potential to impact water quality. A total of 85 pharmaceutical chemicals and personal care products (PPCPs) were analyzed in surface water and sediments using solid-phase extraction and QuEChERS, respectively, in conjunction with liquid-chromatography tandem mass spectrometry-multiple reaction monitoring quantitation (LC-MS/MS-MRM). A total of 52 PPCPs were quantified in both surface water and sediment. The most frequently quantified PPCPs in water included caffeine, fexofenadine, nicotine, sulfamethoxazole, hydrochlorothiazide, MDA, desvenlafaxine, and metoprolol ranging from 10 to 360 ng/L, and in sediment included diphenhydramine, escitalopram, desvenlafaxine, fexofenadine, sertraline and triclocarban ranging from 20 to 120 ng/g (dry weight). Comparisons of PPCP constituents in WTP discharge and adjacent surface water showed altered compositions reflecting dispersal and transformation processes acted quickly following contact of effluent with surface water. Although the PPCPs were present at their greatest concentrations in surface water near the WTP discharge zones, PPCP concentrations rapidly attenuated yielding mainstem TFPR concentrations relatively consistent along the freshwater reach of the tidal range in the estuary. The PPCP concentrations in sediment maximized in the tributary shoals, but also decreased in the mainstem TFPR similarly to surface water. Compositional analysis showed sorption to geosolids was the most important factor in the loss of PPCPs following WTP discharge in the tributary embayments.
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The goal of this study was to develop a robust method of analyzing surface water samples for S-triazine herbicides, chloroacetanilide herbicides, and their transformation products (TPs) using solid-phase extraction (SPE) followed by liquid chromatograph-mass spectrometry (LC-MS) with electrospray ionization (ESI) by in-source collision-induced dissociation (ISCID) capability of an orthogonal electrospray ionization probe on a single quadrupole LC-MS system. The method developed here met the goals of the study and yielded estimated method detection limits (EMDLs) averaging 0.3 ± 0.1 ng L(-1) for S-triazines and their TPs and 0.7 ± 0.4 ng L(-1) for chloroacetanilides and TPs. Spiked filtered river water yielded SPE recoveries ranging from 94.2 % ± 4.8 % for S-triazines and TPs after eliminating three compounds with less that 65 % recovery from analysis and 95.9 % ± 19 % for chloroacetanilides and their TPs. The method was field-tested with filtered water samples collected from four sites over a four-month period. Detectible values of S-triazines and TPs ranged from 0.3 to 1540 ng L(-1) with a mean of 79.3 and a median of 19.4 ng L(-1). Detectible values for chloroacetanilides and TPs ranged from 0.31 to 3780 ng L(-1) with a mean of 252 and a median of 25.6 ng L(-1). An additional goal was to determine if the method was useful for microbial degradation studies using native bacterial communities. The bacteria transformed atrazine (2-chloro-4-ethylamino-6-isopropylamino-S-triazine) solely into 2-hydroxy atrazine (2-hydroxy-4-ethylamino-6-isopropylamino-S-triazine) with concentrations of 78.4, 63.3 and 32.5 ng L(-1) after 12 days of incubation compared with 6.3 and 7.1 ng L(-1) for control dark and control sunlight respectively.
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Cromatografía Liquida/métodos , Herbicidas/análisis , Espectrometría de Masas/métodos , Contaminantes Químicos del Agua/análisis , Agua Dulce/análisis , Sensibilidad y EspecificidadRESUMEN
The maned wolf (Chrysocyon brachyurus) is an induced ovulator. Though the mechanism of ovulation induction remains unknown, it is suspected to be urinary chemical signals excreted by males. This study assessed volatile organic compounds (VOCs) in weekly urine samples across 5 months from 13 maned wolves (6 intact males, 1 neutered male, 6 females) with the goal of identifying VOCs that are differentially expressed across sex, reproductive status, and pairing status. Solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) were used to extract and separate VOCs that were identified via spectral matching with authentic standards, with spectral libraries, or with new software that further matches molecular fragment structures with mass spectral peaks. Two VOCs were present across all 317 urine samples: 2,5-dimethyl pyrazine and 2-methyl-6-(1-propenyl)-pyrazine. Fifteen VOCs differed significantly (Adj. P < 0.001 and |log2 fold change| >2.0) between intact males and females. Using partial least squares-discriminant analysis, the compounds with the highest importance to the sex classification were delta-decalactone, delta-dodecalactone, and bis(prenyl) sulfide. Sixty-two VOCs differed between intact males and the neutered male. Important classifier compounds were 3-ethyl 2,5-dimethyl pyrazine, 2-methyl-6-(1-propenyl)-pyrazine, and tetrahydro-2-isopentyl-5-propyl furan. Several VOCs established as important here have been implicated in reproductive communication in other mammals. This study is the most robust examination of differential expression in the maned wolf thus far and provides the most comprehensive analysis of maned wolf urinary VOCs to date, increasing the sample size substantially over previous chemical communication studies in this species. New data analysis software allowed for the identification of compounds in the hormone-producing mevalonate pathway which were previously unreported in maned wolf urine. Several putative semiochemicals were identified as good candidates for behavioral bioassays to determine their role in maned wolf reproduction, and specifically in ovulation induction.
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Canidae , Animales , Reproducción , Compuestos Orgánicos VolátilesRESUMEN
BACKGROUND: Creating highly efficient operating room (OR) protocols for total joint arthroplasty (TJA) is a challenging and multifactorial process. We evaluated whether spinal anesthesia in a designated block bay (BBSA) would reduce time to incision, improve first case start time and decrease conversion to general anesthesia (GA). METHODS: Retrospective cohort study on the first 86 TJA cases with BBSA from April to December 2018, compared with 344 TJA cases with spinal anesthesia performed in the OR (ORSA) during the same period. All TJA cases were included if the anesthetic plan was for spinal anesthesia. Patients were excluded if circumstances delayed start time or time to incision (advanced vascular access, pacemaker interrogation, surgeon availability). Data were extracted and analyzed via a linear mixed effects model to compare time to incision, via a Wilcoxon rank-sum test to compare first case start time, and via a Fisher's exact test to compare conversion to GA between the groups. RESULTS: In the mixed effect model, the BBSA group time to incision was 5.37 min less than the ORSA group (p=0.018). The BBSA group had improved median first case start time (30.0 min) versus the ORSA group (40.5 min, p<0.0001). There was lower conversion to GA 2/86 (2.33%) in the BBSA group versus 36/344 (10.47%) in the ORSA group (p=0.018). No serious adverse events were noted in either group. CONCLUSIONS: BBSA had limited impact on time to incision for TJA, with a small decrease for single OR days and no improvement on OR days with two rooms. BBSA was associated with improved first case start time and decreased rate of conversion to GA. Further research is needed to identify how BBSA affects the efficiency of TJA.
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Anestesia Raquidea , Artroplastia de Reemplazo de Cadera , Anestesia General/efectos adversos , Bahías , Humanos , Quirófanos , Estudios RetrospectivosRESUMEN
Over the past decade, femoroacetabular impingement (FAI) has become an increasingly recognized pathomechanism that may explain why some hips that were previously considered to have normal morphology fail early in life. Subtle morphologic alterations in the acetabulum or femur, as well as the degree of hypermobility or impact on the hip, affect the potential for joint damage. The most frequent location of FAI is the anterosuperior acetabular rim, and the most critical motion is internal rotation of the hip in flexion. Because medication, activity restrictions, and physical therapy are rarely successful in treating symptoms caused by FAI, surgery has become a mainstay of treatment. Acetabular causes of FAI, called pincer FAI, can be treated by improving hip clearance. Independent of whether local or global overcoverage is present, rim reduction should be combined with labral preservation whenever possible.
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Articulación de la Cadera/cirugía , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/cirugía , Osteoartritis de la Cadera/diagnóstico , Osteoartritis de la Cadera/cirugía , Acetábulo , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/patología , Articulación de la Cadera/fisiopatología , Humanos , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/patología , Inestabilidad de la Articulación/fisiopatología , Osteoartritis de la Cadera/diagnóstico por imagen , Osteoartritis de la Cadera/patología , Osteoartritis de la Cadera/fisiopatología , Radiografía , Rango del Movimiento Articular , Factores de RiesgoRESUMEN
Osteotomies of the proximal femur for hip joint conditions are normally done at the intertrochanteric or subtrochanteric level. Intra-articular osteotomies would be more direct and therefore allow a more powerful correction with no or very little undesired side correction. However, concerns about the risk of vascular damage and osteonecrosis of the femoral head have so far basically excluded this technique from practical use. Based on detailed knowledge of the vascular anatomy of the proximal femur, an approach to safely dislocate the femoral head has been described and successfully performed. Experience as well as further studies of femoral head perfusion allowed a substantial extension of this approach, with subperiosteal exposure of the circumference of the femoral neck with constant intraoperative control of the blood supply to the head. Using the extended retinacular soft-tissue flap, four surgical techniques (relative neck lengthening, subcapital realignment in slipped capital femoral epiphysis, true femoral neck osteotomy, and femoral head reduction osteotomy) evolved or became safer with respect to perfusion of the femoral head. The extended retinacular soft-tissue flap offers the technical and biologic possibility for a new class of intra articular procedures. Although meticulous execution of the surgical steps is important, the procedures have a high level of safety for femoral head perfusion.
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Necrosis de la Cabeza Femoral/cirugía , Cabeza Femoral/cirugía , Cuello Femoral/cirugía , Articulación de la Cadera/cirugía , Osteotomía/métodos , Colgajos Quirúrgicos/irrigación sanguínea , Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/patología , Cuello Femoral/patología , Articulación de la Cadera/patología , Humanos , Luxaciones Articulares/patología , Luxaciones Articulares/cirugíaRESUMEN
INTRODUCTION: Beginning medical students' beliefs about the medical profession have been well studied internationally but have only been minimally studied in the United States (U.S.) recently. Up-to-date research on U.S. medical students' beliefs is warranted so educators can employ these predispositions as a baseline for curriculum and student professional development. METHODS: We conducted focus groups with a first-year class (n=189) of U.S. medical students at the beginning of their academic year. In an iterative theming process, investigators worked in dyads and subsequently as a group to develop a list of preliminary themes expressed in the focus groups. Investigators individually sorted preliminary themes into similar categories. All sorted preliminary themes and categories were placed in a matrix from which final themes were derived. FINDINGS: Investigators found eight themes for the question "Why pursue a career in medicine?" and six themes for "What makes a good doctor?". Students expected medicine to be intellectually and personally fulfilling, they expected to be respected by the community, indicated that early experiences with medicine impacted their career choices, and anticipated that a medical career would yield financial security. A good doctor was described as a committed, smart, decisive leader who enthusiastically partners with patients via effective interpersonal skills. DISCUSSION: Beginning U.S. medical students hold multi-faceted beliefs about medicine that are similar to international medical students' beliefs. Themes related to patient-centeredness, decisive leadership, and intellectual curiosity have particular utility in curriculum and professional development and should not be ignored. Administrators seeking to expand the physician workforce should consider early experiences, status, and monetary rewards.
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Actitud , Selección de Profesión , Médicos/normas , Estudiantes de Medicina/psicología , Femenino , Grupos Focales , Humanos , Masculino , Estados Unidos , Adulto JovenRESUMEN
Sinapic acid (SA) modulates the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in chondrocytes. In order to test the hypothesis that SA is protective against the development of osteoarthritis (OA), primary mouse chondrocytes were treated in vitro with SA and the promoter transactivation activity of heme oxygenase 1 (HO-1), nuclear translocation of Nrf2, and protein expression of HO-1 were assayed. To test the hypothesis in vivo, a destabilization of the medial meniscus (DMM) model was used to induce OA in the knees of mice and SA was delivered orally to the experimental group. The chondrocytes were harvested for further analysis. The expression of HO-1 was similarly upregulated in cartilage from both the experimental mice and human chondrocytes from osteoarthritic knees. SA was found to enhance the promoter transactivation activity of heme oxygenase 1 (HO-1) and increase the expression of Nrf2 and HO-1 in primary chondrocytes. Histopathologic scores showed that the damage induced by the DMM model was significantly lower in the SA treatment group. The addition of a HO-1 inhibitor with SA did not show additional benefit over SA alone in terms of cartilage degradation or histopathologic scores. The expression of TNF-α, IL-1ß, IL-6, MMP-1, MMP-3, MMP-13, ADAMTS4, and ADAMTS5 was significantly reduced both in vitro and in vivo by the presence of SA. Protein expressions of HO-1 and Nrf2 were substantially increased in knee cartilage of mice that received oral SA. Our results suggest that SA should be further explored as a preventative treatment for OA.
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Ácidos Cumáricos/administración & dosificación , Hemo-Oxigenasa 1/genética , Factor 2 Relacionado con NF-E2/genética , Osteoartritis de la Rodilla/tratamiento farmacológico , Administración Oral , Anciano , Animales , Cartílago/efectos de los fármacos , Cartílago/patología , Condrocitos/efectos de los fármacos , Condrocitos/patología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Meniscos Tibiales/efectos de los fármacos , Meniscos Tibiales/fisiopatología , Ratones , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/patología , Regiones Promotoras Genéticas/efectos de los fármacosRESUMEN
[This corrects the article DOI: 10.1016/j.artd.2016.11.002.].
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beta-thymosins constitute a family of highly conserved 5-kDa polypeptides. Thymosin beta(4), the most abundant member of this family, is expressed in most mammalian cell types and is regarded as the main intracellular G-actin sequestering peptide. In addition to this important intracellular function several other activities have been attributed to this peptide. Thymosin beta(4) is released from human platelets and cross-linked to fibrin after activation of platelets with thrombin. While in most mammalian tissues thymosin beta(4) is accompanied by a second member of this peptide family, in human platelets only thymosin beta(4) is present. To elucidate if it is common to mammalian platelets that only one beta-thymosin is present, we analyzed platelets from several mammals for their beta-thymosin content. In human platelets only thymosin beta(4) could be detected, whereas in bovine platelets thymosin beta(9), which is normally the minor beta-thymosin in bovine tissues, was identified as the main beta-thymosin. In rabbit platelets, thymosin beta(4) is not simply replaced by the most homologous thymosin beta(4)(Ala), as might be expected from sequence homology. Thymosin beta(4)(Ala) and thymosin beta(10) were found, but thymosin beta(10) is present in about 2.5-fold higher amounts. Because thymosin beta(4)(Ala) possesses about threefold higher affinity to G-actin, compared to thymosin beta(4), beta(10), and beta(9), we suggest that expression of beta-thymosins is triggered by functional requirements and not sequence homology.
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Plaquetas/química , Timosina/sangre , Animales , Bovinos , Humanos , Mamíferos , ConejosRESUMEN
Sixty male and female Long-Evans hooded rats were administered 1, 2, or 5mg/kg methylphenidate (MPH) suspended in apple juice on postnatal day (P)15 or P40 using a novel, non-invasive oral administration technique. Plasma was collected 15 min after ingestion and analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS) to confirm appropriate concentrations. HPLC-MS plasma analysis showed levels comparable to previous gavage studies using MPH. We have used this method successfully in subsequent behavioral studies as well. Since therapeutic MPH in humans is typically administered orally, oral dosing methods that have been verified in the rodent model are of value. We recommend employment of this alternative oral dosing technique as it is minimally invasive, can be used anytime during postnatal development, and does not depend upon voluntary consumption.