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BACKGROUND: Breast imaging clinics in the United States (U.S.) are increasingly implementing breast cancer risk assessment (BCRA) to align with evolving guideline recommendations but with limited uptake of risk-reduction care. Effectively communicating risk information to women is central to implementation efforts, but remains understudied in the U.S. This study aims to characterize, and identify factors associated with women's interest in and preferences for breast cancer risk communication. METHODS: This is a cross-sectional survey study of U.S. women presenting for a mammogram between January and March of 2021 at a large, tertiary breast imaging clinic. Survey items assessed women's interest in knowing their risk and preferences for risk communication if considered to be at high risk in hypothetical situations. Multivariable logistic regression modeling assessed factors associated with women's interest in knowing their personal risk and preferences for details around exact risk estimates. RESULTS: Among 1119 women, 72.7% were interested in knowing their breast cancer risk. If at high risk, 77% preferred to receive their exact risk estimate and preferred verbal (52.9% phone/47% in-person) vs. written (26.5% online/19.5% letter) communications. Adjusted regression analyses found that those with a primary family history of breast cancer were significantly more interested in knowing their risk (OR 1.5, 95% CI 1.0, 2.1, p = 0.04), while those categorized as "more than one race or other" were significantly less interested in knowing their risk (OR 0.4, 95% CI 0.2, 0.9, p = 0.02). Women 60 + years of age were significantly less likely to prefer exact estimates of their risk (OR 0.6, 95% CI 0.5, 0.98, p < 0.01), while women with greater than a high school education were significantly more likely to prefer exact risk estimates (OR 2.5, 95% CI 1.5, 4.2, p < 0.001). CONCLUSION: U.S. women in this study expressed strong interest in knowing their risk and preferred to receive exact risk estimates verbally if found to be at high risk. Sociodemographic and family history influenced women's interest and preferences for risk communication. Breast imaging centers implementing risk assessment should consider strategies tailored to women's preferences to increase interest in risk estimates and improve risk communication.
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Neoplasias de la Mama , Mamografía , Prioridad del Paciente , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/psicología , Neoplasias de la Mama/diagnóstico por imagen , Estudios Transversales , Persona de Mediana Edad , Prioridad del Paciente/estadística & datos numéricos , Prioridad del Paciente/psicología , Estados Unidos , Adulto , Mamografía/estadística & datos numéricos , Mamografía/psicología , Medición de Riesgo/métodos , Anciano , Comunicación , Encuestas y Cuestionarios , Centros de Atención Terciaria , Conocimientos, Actitudes y Práctica en SaludRESUMEN
IssueThere is a need for greater access to Spanish language services in United States healthcare. One approach to increasing language concordant care is the use of second language skills by healthcare staff. The desire to use second language skills may have unintended consequences when individuals step beyond their language abilities and can cause more harm than do good for limited-English proficiency patients. Medical students are in a unique position that places them at increased risk for inappropriately using second language skills. Evidence: The use of qualified healthcare interpreters has been shown to mitigate some of the disparities seen with limited-English proficiency patients including poorer healthcare outcomes, less access to care, and lower patient satisfaction. In spite of this knowledge, studies have demonstrated the phenomenon of residents and physicians "getting by" without the use of an interpreter, even when they recognized that their language competency was insufficient to provide high quality care. Regardless of language ability, medical students are asked to engage in conversations with Spanish speaking patients that are beyond their level of language competency. Students vary in their perceived language ability and level of comfort engaging in different clinical scenarios with limited-English proficiency patients. Implications: Students are in a unique position of vulnerability to pressures to use second language skills in situations that step beyond their abilities. We explore how hierarchy intensifies previously established factors, including a lack of adequate training or evaluation and other structural barriers, in contributing to medical students' inappropriate use of Spanish with limited-English proficiency patients. We propose an approach that includes student education, standardization of clinic rules regarding interpretation, and comprehensive faculty development to address this important patient care issue.
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Lenguaje , Estudiantes de Medicina , Humanos , Comunicación , Barreras de Comunicación , Relaciones Médico-Paciente , Estados UnidosRESUMEN
Spontaneous portosystemic shunts (SPSSs) have been associated with worse clinical outcomes in the pre-liver transplantation (LT) setting, but little is known about their post-LT impacts. Our aim was to compare LT candidates with and without SPSSs and assess the impact of SPSSs on patient mortality and graft survival in the post-LT setting. Patients 18 years or older with abdominal imaging done prior to LT were included. Exclusion criteria were the presence of pre-LT surgical shunts, LT indications other than cirrhosis, and combined solid organ transplantations. SPSSs were classified as absent, small, or large according to their maximum diameter (8 mm). Multiple variables that could influence the post-LT course were extracted for analysis. Patient and graft survival were estimated using the Kaplan-Meier method and were compared between groups using a log-rank test. The project received institutional review board approval. We extracted data from 326 patients. After comparing patients without SPSS or with small or large SPSSs, no statistical difference was found for overall patient survival: no SPSS (n = 8/63), reference; small SPSS (n = 18/150), hazard ratio (HR), 1.05 (95% confidence interval [CI], 0.45-2.46); and large SPSS (n = 6/113), HR, 0.60 (95% CI, 0.20-1.78); P = 0.20. Also, no difference was found for graft survival: no SPSS (n = 11/63), reference; small SPSS (n = 21/150), HR, 0.80 (95% CI, 0.38-1.70); large SPSS (n = 11/113), HR, 0.59 (95% CI, 0.25-1.40); P = 0.48. Similarly, no statistical significance was found for these variables when comparing if the graft used was procured from a donation after circulatory death donor versus a donation after brain death donor. In conclusion, the previously described association between SPSSs and worse clinical outcomes in pre-LT patients seems not to persist once patients undergo LT. This study suggests that no steps to correct SPSS intraoperatively are necessary.
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Trasplante de Hígado , Derivación Portosistémica Intrahepática Transyugular , Supervivencia de Injerto , Humanos , Cirrosis Hepática , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Donantes de Tejidos , Resultado del TratamientoAsunto(s)
Hemangioblastoma , Neoplasias Pancreáticas , Esclerosis Tuberosa , Humanos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/complicaciones , Hemangioblastoma/cirugía , Hemangioblastoma/complicaciones , Hemangioblastoma/patología , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/patología , Femenino , Adulto , Tomografía Computarizada por Rayos X , MasculinoRESUMEN
Organ-on-chip (OOC) models can be useful tools for cancer drug discovery. Advances in OOC technology have led to the development of more complex assays, yet analysis of these systems does not always account for these advancements, resulting in technical challenges. A challenging task in the analysis of these two-channel microfluidic models is to define the boundary between the channels so objects moving within and between channels can be quantified. We propose a novel imaging-based application of a thin plate spline method - a generalized cubic spline that can be used to model coordinate transformations - to model a tissue boundary and define compartments for quantification of invaded objects, representing the early steps in cancer metastasis. To evaluate its performance, we applied our analytical approach to an adapted OOC developed by Emulate, Inc., utilizing a two-channel system with endothelial cells in the bottom channel and colorectal cancer (CRC) patient-derived organoids (PDOs) in the top channel. Initial application and visualization of this method revealed boundary variations due to microscope stage tilt and ridge and valley-like contours in the endothelial tissue surface. The method was functionalized into a reproducible analytical process and web tool - the Chip Invasion and Contour Analysis (ChICA) - to model the endothelial surface and quantify invading tumor cells across multiple chips. To illustrate applicability of the analytical method, we applied the tool to CRC organoid-chips seeded with two different endothelial cell types and measured distinct variations in endothelial surfaces and tumor cell invasion dynamics. Since ChICA utilizes only positional data output from imaging software, the method is applicable to and agnostic of the imaging tool and image analysis system used. The novel thin plate spline method developed in ChICA can account for variation introduced in OOC manufacturing or during the experimental workflow, can quickly and accurately measure tumor cell invasion, and can be used to explore biological mechanisms in drug discovery.
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Dispositivos Laboratorio en un Chip , Invasividad Neoplásica , Humanos , Organoides/patología , Neoplasias Colorrectales/patología , Células Endoteliales/patología , Células Endoteliales/metabolismo , Microfluídica/métodosRESUMEN
Organ-on-chip (OOC) models can be useful tools for cancer drug discovery. Advances in OOC technology have led to the development of more complex assays, yet analysis of these systems does not always account for these advancements, resulting in technical challenges. A challenging task in the analysis of these two-channel microfluidic models is to define the boundary between the channels so objects moving within and between channels can be quantified. We propose a novel imaging-based application of a thin plate spline method - a generalized cubic spline that can be used to model coordinate transformations - to model a tissue boundary and define compartments for quantification of invaded objects, representing the early steps in cancer metastasis. To evaluate its performance, we applied our analytical approach to an adapted OOC developed by Emulate, Inc., utilizing a two-channel system with endothelial cells in the bottom channel and colorectal cancer (CRC) patient-derived organoids (PDOs) in the top channel. Initial application and visualization of this method revealed boundary variations due to microscope stage tilt and ridge and valley-like contours in the endothelial tissue surface. The method was functionalized into a reproducible analytical process and web tool - the Chip Invasion and Contour Analysis (ChICA) - to model the endothelial surface and quantify invading tumor cells across multiple chips. To illustrate applicability of the analytical method, we applied the tool to CRC organoid-chips seeded with two different endothelial cell types and measured distinct variations in endothelial surfaces and tumor cell invasion dynamics. Since ChICA utilizes only positional data output from imaging software, the method is applicable to and agnostic of the imaging tool and image analysis system used. The novel thin plate spline method developed in ChICA can account for variation introduced in OOC manufacturing or during the experimental workflow, can quickly and accurately measure tumor cell invasion, and can be used to explore biological mechanisms in drug discovery.
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Three-dimensional (3D) in vitro models are essential in cancer research, but they often neglect physical forces. In our study, we combined patient-derived tumor organoids with a microfluidic organ-on-chip system to investigate colorectal cancer (CRC) invasion in the tumor microenvironment (TME). This allowed us to create patient-specific tumor models and assess the impact of physical forces on cancer biology. Our findings showed that the organoid-on-chip models more closely resembled patient tumors at the transcriptional level, surpassing organoids alone. Using 'omics' methods and live-cell imaging, we observed heightened responsiveness of KRAS mutant tumors to TME mechanical forces. These tumors also utilized the γ-aminobutyric acid (GABA) neurotransmitter as an energy source, increasing their invasiveness. This bioengineered model holds promise for advancing our understanding of cancer progression and improving CRC treatments.
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OBJECTIVE: Published research on agitation is limited by the difficulty in generalizing findings from trials using moderately agitated, carefully selected patients treated with single agents. More specifically, there are few comparative studies examining common intramuscular (IM) regimens (ie, haloperidol with or without benzodiazepines) with IM atypical antipsychotics. Therefore, we conducted a retrospective chart review to compare IM olanzapine and haloperidol in a "real-world" population with agitation. METHOD: We performed a retrospective evaluation of charts from 146 consecutive emergency department patients who received either IM haloperidol or IM olanzapine for agitation. We used a clinically oriented proxy marker of efficacy--the necessity for additional medication intervention for agitation (AMI)--as our primary outcome measure. RESULTS: Additional medication intervention for agitation was required by 43% (13/30) patients when haloperidol was given alone and by 18% (13/72) when haloperidol was given with a benzodiazepine. In the case of olanzapine, AMI was required by 29% (6/21) of patients receiving olanzapine alone and by 18% (2/11) of patients given olanzapine plus a benzodiazepine. A significant percentage of patients had clinical characteristics (nonpsychiatric triage complaint, drug/alcohol use, severe agitation) that differ from more selective samples. CONCLUSIONS: Overall, these finding suggest that in a naturalistic emergency department setting, haloperidol monotherapy is less effective--at least in requiring AMI--than olanzapine with or without a benzodiazepine or haloperidol plus a benzodiazepine. Moreover, these later 3 regimens seemed comparable. Prospective studies examining the treatment of real-world agitation, including head-to-head comparisons of the haloperidol-benzodiazepine combination with newer IM antipsychotics, are needed.
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Antipsicóticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Haloperidol/uso terapéutico , Agitación Psicomotora/tratamiento farmacológico , Enfermedad Aguda , Adulto , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Benzodiazepinas/administración & dosificación , Benzodiazepinas/efectos adversos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada/efectos adversos , Servicio de Urgencia en Hospital , Femenino , Haloperidol/administración & dosificación , Haloperidol/efectos adversos , Humanos , Inyecciones Intramusculares , Masculino , Registros Médicos , Persona de Mediana Edad , Olanzapina , Agitación Psicomotora/complicaciones , Estudios Retrospectivos , Trastornos Relacionados con Sustancias/complicacionesRESUMEN
Hypothermic (cold) preservation is a limiting factor for successful cell and tissue transplantation where cell swelling (edema) usually develops, impairing cell function. University of Wisconsin (UW) solution, a standard cold preservation solution, contains effective components to suppress hypothermia-induced cell swelling. Antifreeze proteins (AFPs) found in many cold-adapted organisms can prevent cold injury of the organisms. Here, the effects of a beetle AFP from Dendroides canadensis (DAFP-1) on pancreatic ß-cells preservation were first investigated. As low as 500 µg/mL, DAFP-1 significantly minimized INS-1 cell swelling and subsequent cell death during 4 °C preservation in UW solution for up to three days. However, such significant cytoprotection was not observed by an AFP from Tenebrio molitor (TmAFP), a structural homologue to DAFP-1 but lacking arginine, at the same levels. The cytoprotective effect of DAFP-1 was further validated with the primary ß-cells in the isolated rat pancreatic islets in UW solution. The submilligram level supplement of DAFP-1 to UW solution significantly increased the islet mass recovery after three days of cold preservation followed by rewarming. The protective effects of DAFP-1 in UW solution were discussed at a molecular level. The results indicate the potential of DAFP-1 to enhance cell survival during extended cold preservation.
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Escarabajos , Animales , Ratas , Escarabajos/química , Escarabajos/metabolismo , Supervivencia Celular , alfa-Fetoproteínas/farmacología , Proteínas Anticongelantes/química , Glutatión/farmacología , Insulina/farmacología , EdemaRESUMEN
As in any field, radiologists may face a number of challenges as they navigate their early careers. Because with experience comes wisdom, early-career radiologists may find helpful the advice and perspectives of mid- and late-career radiologists. The Society of Abdominal Radiology recognizes the value of this pool of knowledge and experience, prompting the establishment of the Early Career Committee. This group is designed to support early-career radiologists by sharing the experiences and insights of leaders in the field. In this series, the authors interview trailblazers Matthew S. Davenport, MD; Jonathan B. Kruskal, MD, PhD; Katherine E. Maturen, MD, MS; David B. Larson, MD, MBA; and Desiree E. Morgan, MD. This perspective explores a wide range of subjects, including personal values in medicine, the role of teleradiology, diversity of backgrounds in radiology, how to navigate workplace conflict, and lifelong learning in medicine. Beyond conveying these pearls of wisdom, the aim of this perspective is to highlight for early-career radiologists the value that mid- and late-career mentors can provide in navigating careers in medicine.
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Mentores , Radiología , Humanos , Radiografía , RadiólogosRESUMEN
We developed an optimized Dipheylthiocarbazone or Dithizone (DTZ) with improved physical and chemical properties to characterize human islets and insulin-producing cells differentiated from embryonic stem cells. Application of the newly formulated iDTZ (i stands for islet) over a range of temperatures, time intervals and cell and tissue types found it to be robust for identifying these cells. Through high transition zinc binding, the iDTZ compound concentrated in insulin-producing cells and proved effective at delineating zinc levels in vitro.
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Separación Celular/instrumentación , Ditizona/química , Células Madre Embrionarias/citología , Insulina/biosíntesis , Islotes Pancreáticos/citología , Zinc/química , Técnicas de Cultivo de Célula , Diferenciación Celular , Humanos , Secreción de Insulina , Microscopía Fluorescente , Reproducibilidad de los Resultados , TemperaturaRESUMEN
BACKGROUND: Human pancreata contain many types of cells, such as endocrine islets, acinar, ductal, fat, and mesenchymal stromal cells (MSCs). MSCs are important and shown to have a promising therapeutic potential to treat various disease conditions. METHODS: We investigated intra-pancreatic tissue-derived (IPTD) MSCs isolated from tissue fractions that are routinely discarded during pancreatic islet isolation of human cadaveric donors. Furthermore, whether pro-angiogenic and anti-inflammatory properties of these cells could be enhanced was investigated. RESULTS: IPTD-MSCs were expanded in GMP-compatible CMRL-1066 medium supplemented with 5% human platelet lysate (hPL). IPTD-MSCs were found to be highly pure, with > 95% positive for CD90, CD105, and CD73, and negative for CD45, CD34, CD14, and HLA-DR. Immunofluorescence staining of pancreas tissue demonstrated the presence of CD105+ cells in the vicinity of islets. IPTD-MSCs were capable of differentiation into adipocytes, chondrocytes, and osteoblasts in vitro, underscoring their multipotent features. When these cells were cultured in the presence of a low dose of TNF-α, gene expression of tumor necrosis factor alpha-stimulated gene-6 (TSG-6) was significantly increased, compared to control. In contrast, treating cells with dimethyloxallyl glycine (DMOG) (a prolyl 4-hydroxylase inhibitor) enhanced mRNA levels of nuclear factor erythroid 2-related factor 2 (NRF2) and vascular endothelial growth factor (VEGF). Interestingly, a combination of TNF-α and DMOG stimulated the optimal expression of all three genes in IPTD-MSCs. Conditioned medium of IPTD-MSCs treated with a combination of DMOG and TNF-α contained higher levels of pro-angiogenic (VEGF, IL-6, and IL-8) compared to controls, promoting angiogenesis of human endothelial cells in vitro. In contrast, levels of MCP-1, a pro-inflammatory cytokine, were reduced in the conditioned medium of IPTD-MSCs treated with a combination of DMOG and TNF-α. CONCLUSIONS: The results demonstrate that IPTD-MSCs reside within the pancreas and can be separated as part of a standard islet-isolation protocol. These IPTD-MSCs can be expanded and potentiated ex vivo to enhance their anti-inflammatory and pro-angiogenic profiles. The fact that IPTD-MSCs are generated in a GMP-compatible procedure implicates a direct clinical application.
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Antiinflamatorios/metabolismo , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Neovascularización Fisiológica , Páncreas/citología , Adolescente , Adulto , Biomarcadores/metabolismo , Plaquetas/metabolismo , Diferenciación Celular/efectos de los fármacos , Linaje de la Célula/efectos de los fármacos , Membrana Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Endoglina/metabolismo , Glicina/análogos & derivados , Glicina/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Insulina/metabolismo , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Persona de Mediana Edad , Neovascularización Fisiológica/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Selection of enzymes for optimal pancreas digestion is essential for successful human islet isolations. The aim of this study was to evaluate the efficacy and outcome of using Collagenase Gold plus BP protease (VitaCyte) (n = 8) by comparing it to two commercially available enzymes, Liberase MTF C/T (Roche) (n = 48) and Collagenase NB1/NP (Serva) (n = 15). The isolation outcomes were assessed by islet counting, viability, glucose-stimulated oxygen consumption rate (OCR), and successful graft-rate following transplantation in diabetic NOD scid mice. The pancreas donor characteristics were not significantly different between the tested enzyme groups regarding their BMI, pancreas weight, cold ischemia time (CIT) and HbA1c. The results show that digested tissue volume was not statistically significant between the VitaCyte enzyme (34.25 ± 5.4 mL) and the Roche enzyme (55.25 ± 3.42 mL, p = 0.073), however, this was significant with Serva enzyme (64.07 ± 7.95 mL, p = 0.020). Interestingly, the islet yields were not statistically different between all enzyme groups. Moreover, when islets were transplanted into NOD scid mice, the reversal rate of diabetes for the VitaCyte enzyme group was similar to all enzyme groups. In conclusion, the effectiveness of Collagenase Gold plus BP protease is comparable to the MTF C/T and the Collagenase NB1/NP enzymes; the low cost could facilitate the use of more pancreata for islet isolations.
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Separación Celular/métodos , Colagenasas , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos/citología , Péptido Hidrolasas , Adulto , Animales , Supervivencia Celular , Supervivencia de Injerto , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Persona de Mediana Edad , Consumo de Oxígeno , Estudios Retrospectivos , Termolisina , Adulto JovenRESUMEN
Infectious diseases rarely end in extinction. Yet the mechanisms that explain how epidemics subside are difficult to pinpoint. We investigated host-pathogen interactions after the emergence of a lethal fungal pathogen in a tropical amphibian assemblage. Some amphibian host species are recovering, but the pathogen is still present and is as pathogenic today as it was almost a decade ago. In addition, some species have defenses that are more effective now than they were before the epidemic. These results suggest that host recoveries are not caused by pathogen attenuation and may be due to shifts in host responses. Our findings provide insights into the mechanisms underlying disease transitions, which are increasingly important to understand in an era of emerging infectious diseases and unprecedented global pandemics.
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Enfermedades de los Animales/microbiología , Anuros/microbiología , Quitridiomicetos/patogenicidad , Enfermedades Transmisibles/epidemiología , Brotes de Enfermedades , Interacciones Huésped-Patógeno , Modelos Biológicos , Animales , PanamáRESUMEN
Objective. To examine the efficacy of interdisciplinary rehabilitation for improving function in people with chronic pain. Design. Retrospective Chart Review. Setting. The Pain Rehabilitation Center (PRC) at a medical center. Participants. Individuals admitted to the PRC. Interventions. The PRC operates a 3-week outpatient program that utilizes an interdisciplinary approach to treat people with chronic pain. The main treatment elements include physical therapy, occupational therapy, cognitive behavioral therapy (CBT), and medication management. Physical therapy groups focus on moderate exercise despite symptoms. Occupational therapists teach moderation, time management, and activity modification. CBT groups, led by a pain psychologist, address the psychosocial comorbidities of chronic pain. Medical staff oversee the tapering of opiate analgesics and other symptom targeted treatments. This integrated approach is indicated when conventional treatments have been ineffective. Outcome Measures. The objective outcome was the 6-minute walk test (6 mWT) distance. The subjective outcomes were performance (COPM-PER) and satisfaction (COPM-SAT) as measured by the Canadian Occupational Performance Measure (COPM). Results. Average 6 mWT distances improved by 39% from 375 m to 523 m. Average COPM-PER scores increased from 3.4 to 7.5. Average COPM-SAT scores increased from 2.4 to 7.5. Conclusions. Comprehensive interdisciplinary outpatient rehabilitation can significantly improve function in people with chronic pain.
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Urbanization is a major driver of ecological change and comes with a suite of habitat modifications, including alterations to the local temperature, precipitation, light and noise regimes. Although many recent studies have investigated the behavioural and ecological ramifications of urbanization, physiological work in this area has lagged. We tested the hypothesis that anthropogenic noise is a stressor for amphibians and that chronic exposure to such noise leads to reproductive suppression. In the laboratory, we exposed male White's treefrogs, Litoria caerulea, to conspecific chorus noise either alone or coupled with pre-recorded traffic noise nightly for 1â week. Frogs presented with anthropogenic noise had significantly higher circulating concentrations of corticosterone and significantly decreased sperm count and sperm viability than did control frogs. These results suggest that in addition to having behavioural and ecological effects, anthropogenic change might alter physiology and Darwinian fitness. Future work should integrate disparate fields such as behaviour, ecology and physiology to elucidate fully organisms' responses to habitat change.
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Amphibian populations are declining globally. The potential contribution of glucocorticoid hormones to these declines has received little attention, but chronic elevation of glucocorticoids has been linked to a suite of negative outcomes across vertebrate taxa. Recently, chronic environmental stress has been associated with precipitous declines in sperm count and sperm viability in White's treefrogs (Litoria caerulea), but the mechanism remains unknown. In order to determine whether corticosterone is responsible for suppressing reproductive and immune function in this species, we elevated circulating concentrations of corticosterone in 10 male captive-bred frogs via transdermal application for 7 days. We compared sperm count, sperm viability, splenic cell count and circulating leucocyte counts in corticosterone-treated frogs with those in untreated control frogs. Chronic application of exogenous corticosterone led to supraphysiological circulating concentrations of corticosterone, but had no effect on sperm count or viability. However, corticosterone-treated frogs demonstrated a significant decrease in circulating eosinophils, which are immune cells implicated in fighting a variety of pathogens, including extracellular parasites. These findings suggest that although chronic elevation of circulating corticosterone is not necessarily associated with reproductive suppression in this species, it may cause immunosuppression. Thus, chronic glucocorticoid elevations in amphibians might enhance susceptibility to infection with pathogens and parasites, and their potential contributions to global population declines warrant further study.
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OBJECTIVE: The treatment of agitation in drug- and alcohol-using emergency patients is understudied. METHOD: We performed a retrospective chart review of 105 agitated emergency department patients who received either intramuscular (IM) haloperidol or IM olanzapine, comparing prescribing patterns, level of agitation, response to treatment and side effects in patients positive for drugs or alcohol [D/A(+)] and patients negative for drugs or alcohol [(D/A(-)]. RESULTS: The haloperidol-benzodiazepine combination was the most frequently prescribed treatment in both groups, although alcohol(+) status biased clinicians toward using haloperidol alone. Overall, D/A(+) and D/A(-) patients responded to the initial intervention at similar rates, although D/A(+) patients were rated as more agitated and had more posttreatment sedation than D/A(-) patients. In D/A(+) patients, haloperidol+benzodiazepine and IM olanzapine performed better than haloperidol alone. There were no serious adverse events with any treatment. CONCLUSION: Findings support the generalization of efficacy data from more rarified agitated samples to populations with high rates of substance use and highlight the need for prospective, inclusive, randomized trials comparing the commonly used haloperidol-benzodiazepine combination with newer injectable antipsychotics.
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Trastornos Relacionados con Alcohol/complicaciones , Antidiscinéticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Haloperidol/uso terapéutico , Agitación Psicomotora/tratamiento farmacológico , Trastornos Relacionados con Sustancias/complicaciones , Antidiscinéticos/administración & dosificación , Antipsicóticos/administración & dosificación , Antipsicóticos/uso terapéutico , Benzodiazepinas/administración & dosificación , Quimioterapia Combinada , Servicio de Urgencia en Hospital , Haloperidol/administración & dosificación , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/uso terapéutico , Inyecciones Intramusculares , Olanzapina , Agitación Psicomotora/etiología , Estudios RetrospectivosRESUMEN
Aldose reductase (AR) is implicated to play a critical role in diabetes and cardiovascular complications because of the reaction it catalyzes. Our data reveal that peroxisome proliferator WY 14,643, follows a pure non-competitive inhibition pattern in the aldehyde reduction activity as well as in the alcohol oxidation activity of AR. This finding communicates for the first time a novel feature of WY 14,643 in regulating AR activity. In addition, this observation indicates that AR, AR-like proteins and aldo-keto reductase (AKR) members may be involved in the WY 14,643 mechanism of action when it is administered as PPAR agonist.