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1.
J Cardiothorac Surg ; 19(1): 320, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840211

RESUMO

BACKGROUND: Pre-operative coronary angiography and concomitant, planned coronary artery bypass are infrequently performed with type A aortic dissection repair. We present a case in which pre-operative coronary computed tomography angiography was appropriate, and subsequent dissection repair and concomitant coronary artery bypass were successfully performed. CASE PRESENTATION: The patient is a 58-year-old male with heart failure with preserved ejection fraction, renal insufficiency, hypertension, obesity, and smoking history, who presented with a three-to-four-day history of persistent back pain, worsening exertional dyspnea, and orthopnea, as well as a two-to-three month history of dyspnea, lower extremity edema, and intermittent angina. He was diagnosed with an acute type A aortic dissection and anti-impulse control was initiated. However, repair was delayed in order to allow apixaban to metabolize and decrease the risk of bleeding, as the patient was approximately six days post-dissection, without malperfusion, with a well-controlled blood pressure on anti-impulse therapy, and had received five days of anticoagulation. During this time, coronary computed tomography angiography was performed to assess the need for concomitant revascularization and showed coronary artery disease. Ascending aorta hemiarch replacement with aortic valve resuspension, two-vessel coronary artery bypass grafting, and left atrial appendage clipping were performed successfully. CONCLUSIONS: Pre-operative imaging can be considered in a select group of acute type A aortic dissections that present without malperfusion, and with well-controlled blood pressure on anti-impulse/negative inotropic therapy.


Assuntos
Dissecção Aórtica , Ponte de Artéria Coronária , Humanos , Masculino , Pessoa de Meia-Idade , Dissecção Aórtica/cirurgia , Dissecção Aórtica/complicações , Ponte de Artéria Coronária/métodos , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença Aguda , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/complicações
2.
Front Immunol ; 14: 1227751, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37520569

RESUMO

Acute respiratory distress syndrome (ARDS) is a leading cause of morbidity and mortality in polytrauma patients. Pharmacological treatments of ARDS are lacking, and ARDS patients rely on supportive care. Accurate diagnosis of ARDS is vital for early intervention and improved outcomes but is presently delayed up to days. The use of biomarkers for early identification of ARDS development is a potential solution. Inflammatory mediators high-mobility group box 1 (HMGB1), syndecan-1 (SDC-1), and C3a have been previously proposed as potential biomarkers. For this study, we analyzed these biomarkers in animals undergoing smoke inhalation and 40% total body surface area burns, followed by intensive care for 72 h post-injury (PI) to determine their association with ARDS and mortality. We found that the levels of inflammatory mediators in serum were affected, as well as the degree of HMGB1 and Toll-like receptor 4 (TLR4) signal activation in the lung. The results showed significantly increased HMGB1 expression levels in animals that developed ARDS compared with those that did not. Receiver operating characteristic (ROC) analysis showed that HMGB1 levels at 6 h PI were significantly associated with ARDS development (AUROC=0.77) and mortality (AUROC=0.82). Logistic regression analysis revealed that levels of HMGB1 ≥24.10 ng/ml are associated with a 13-fold higher incidence of ARDS [OR:13.57 (2.76-104.3)], whereas the levels of HMGB1 ≥31.39 ng/ml are associated with a 12-fold increase in mortality [OR: 12.00 (2.36-93.47)]. In addition, we found that mesenchymal stem cell (MSC) therapeutic treatment led to a significant decrease in systemic HMGB1 elevation but failed to block SDC-1 and C3a increases. Immunohistochemistry analyses showed that smoke inhalation and burn injury induced the expression of HMGB1 and TLR4 and stimulated co-localization of HMGB1 and TLR4 in the lung. Interestingly, MSC treatment reduced the presence of HMGB1, TLR4, and the HMGB1-TLR4 co-localization. These results show that serum HMGB1 is a prognostic biomarker for predicting the incidence of ARDS and mortality in swine with smoke inhalation and burn injury. Therapeutically blocking HMGB1 signal activation might be an effective approach for attenuating ARDS development in combat casualties or civilian patients.


Assuntos
Queimaduras , Proteína HMGB1 , Síndrome do Desconforto Respiratório , Lesão por Inalação de Fumaça , Suínos , Animais , Receptor 4 Toll-Like , Prognóstico , Proteína HMGB1/metabolismo , Síndrome do Desconforto Respiratório/terapia , Lesão por Inalação de Fumaça/complicações , Lesão por Inalação de Fumaça/terapia , Queimaduras/complicações , Biomarcadores , Fumaça
3.
Labour Econ ; 772022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37035254

RESUMO

This paper analyzes how computerization affected the labor market outcomes of older workers between 1984 and 2017. Using the computerization supplements of the Current Population Survey (CPS) we show that different occupations were computerized at different times, older workers tended to start using computers with a delay compared to younger workers, but computer use within occupations converged to the same levels across age groups eventually. That is, there was a temporary knowledge gap between younger and older workers in most occupations. We estimate how this knowledge gap affected older workers' labor market outcomes using data from the CPS and the Health and Retirement Study. Our models control for occupation and time fixed effects and in some models; we also control for full occupation-time interactions and use middle aged (age 40-49) workers as the control group. We find strong and robust negative effects of the knowledge gap on wages, and a large, temporary increase in transitions from work to non-participation, consistent with a model of creative destruction in which the computerization of jobs made older workers' skills obsolete in birth cohorts that experienced computerization relatively late in their careers. We find larger effects on females and on middle-skilled workers.

4.
Am Surg ; 88(8): 2011-2016, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34047203

RESUMO

BACKGROUND: Emergency medical personnel must expeditiously triage acutely injured patients to the appropriate medical facility. Efficient and objective variables to facilitate this process and provide information to the receiving trauma center are needed. Currently, multiple variables are used to prognosticate injury severity and risk of mortality including vital signs, mental status, lactate, and base excess. We investigated the prehospital use of end-tidal carbon dioxide (ETCO2) as a noninvasive physiologic measure that can be obtained in the acutely injured patient. METHODS: We performed a retrospective analysis of 557 acutely injured patients over 2 years at a Level 1 trauma center. All patients arriving as trauma activations with ETCO2 measurements were included in analysis. End-tidal carbon dioxide measurements were categorized as low, normal, and high based on reference levels. Mortality was the primary outcome. Secondary receiver operator curves (ROC) for base excess, venous lactate, blood pressure, and venous pH were compared. We hypothesized ETCO2 levels would be able to predict mortality. RESULTS: End-tidal carbon dioxide levels conferred a mortality rate of 38%, 17.3%, and 2.9% for low, normal, and high, respectively (P < .001). Receiver operator curve analysis produced an area under the curve predictive value for ETCO2 (.748) which was superior to lactate (.660), SBP (.578), pH (.560), and base excess (.497). DISCUSSION: End-tidal carbon dioxide is a more sensitive and specific predictor of mortality in the acutely injured patient compared to venous lactate, base deficit, blood pressure, or venous pH. Additional studies are needed to determine if ETCO2 can be used as an effective prehospital adjunct to prevent mortality in acutely injured patients.


Assuntos
Dióxido de Carbono , Triagem , Dióxido de Carbono/análise , Humanos , Lactatos , Estudos Retrospectivos , Centros de Traumatologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-38567026

RESUMO

We compare the optical properties of various geometric shapes with single atmospheric Asian dust and marine background air particles collected at Mauna Loa Observatory. Three-dimensional representations of the particles were acquired with focused ion-beam (FIB) tomography, which involves FIB milling of individual particles followed by imaging and elemental mapping with scanning electron microscopy. Particles were heterogeneous with mainly dolomite or calcite and a minor amount of iron; marine air particles contained gypsum but no iron. Extinction and backscatter fraction were calculated with the discrete dipole approximation method. Geometric shapes were grouped as ellipsoids (sphere, spheroid, ellipsoid), cuboids (cube, square prism, rectangular prism), and pyramids (tetrahedron, triangular pyramid). Each group represented a progression of shapes with 1, 2, or 3 non-identical axes. Most shapes underestimated particle extinction and overestimated the backscatter fraction. Not surprisingly, extinction and the backscatter fraction of the sphere and cube were furthest from those of the particles. While the 3-axis ellipsoid and rectangular prism were closer dimensionally to the particles, extinction and the backscatter fraction for the 2-axis spheroid and square prism, respectively, were often closer to the particles. The extinction and backscatter fraction for the tetrahedron and triangular pyramid were closer on average to the actual particles than were the other shapes. Tetrahedra have the advantage that parameterization of an aerosol model for remote sensing would not require an aspect ratio distribution. Particle surface roughness invariably decreased the backscatter fraction. While surface roughness typically contributes a minor part to overall scattering, in some cases the larger surface area of the tetrahedron and triangular pyramid sufficiently accounted for enhanced forward scattering of particles from surface roughness.

6.
J Am Pharm Assoc (2003) ; 61(4S): S39-S48, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33483273

RESUMO

OBJECTIVE(S): Tobacco use is a leading cause of preventable morbidity and mortality in the United States. Community pharmacists are in an advantageous position to increase patient accessibility to tobacco cessation medications and counseling. Pharmacists are permitted to prescribe or furnish tobacco cessation medications in 13 states with varying requirements and limitations. The primary objective of this study was to evaluate the perspectives and perceived barriers that pharmacy personnel have in providing pharmacist-prescribed tobacco cessation services in the community pharmacy setting. The secondary objectives were to evaluate current practices of the 5 A's model and to identify additional training needed to provide the service. METHODS: This study was a descriptive cross-sectional electronic survey of pharmacy personnel from a large grocery pharmacy chain. The respondents were asked about their demographics, current practices of the 5 A's model, perceived barriers and attitudes toward pharmacist-prescribed tobacco cessation services, and additional training needed to provide the service. RESULTS: The survey received 79 responses from pharmacists. The results showed that 92.4% (73/79) of the respondents agreed that community pharmacists should provide tobacco cessation services. The biggest barrier identified was "lack of time during normal workflow to deliver tobacco cessation services" at 54.4% (43/79). Regarding the 5 A's model, 74.7% (59/79) of the pharmacists responded "never" or "somewhat infrequently" to how often they practice the "Ask" step, with other steps in the 5 A's model reported at similar frequencies. The top 3 additional trainings that the pharmacists identified were "strategies developing a follow-up plan with patients," "incorporating service into workflow," and "strategies providing counseling on tobacco cessation." CONCLUSION: Efforts should be made to give community pharmacy personnel more time and guidance to provide patient care services beyond traditional dispensing roles to provide tobacco cessation services.


Assuntos
Serviços Comunitários de Farmácia , Farmácias , Abandono do Uso de Tabaco , Estudos Transversais , Humanos , Farmacêuticos , Estados Unidos
7.
Gerontologist ; 60(3): 460-471, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-31289823

RESUMO

BACKGROUND AND OBJECTIVES: Recent research suggests that working longer may be protective of cognitive functioning in later life, especially for workers in low complexity jobs. As postretirement work becomes increasingly popular, it is important to understand how various retirement pathways influence cognitive function. The present study examines cognitive changes as a function of job complexity in the context of different types of retirement transitions. RESEARCH DESIGN AND METHODS: We use data from the Health and Retirement Study (HRS) to examine change in cognitive function for workers who have held low, moderate, and high complexity jobs and move through distinct retirement pathways-retiring and returning to work, partial retirement-compared with those who fully retire or remain full-time workers. Inverse probability weighted regression adjustment (a propensity score method) is used to adjust for selection effects. RESULTS: There are systematic variations in the relationships between work and cognitive performance as a function of job complexity and retirement pathways. All retirement pathways were associated with accelerated cognitive decline for workers in low complexity jobs. In contrast, for high complexity workers retirement was not associated with accelerated cognitive decline and retiring and returning to work was associated with modest improvement in cognitive functioning. DISCUSSION AND IMPLICATIONS: Both policy makers and individuals are beginning to embrace longer working lives which offer variety of potential benefits. Our findings suggest that continued full-time work also may be protective for cognitive health in workers who hold low complexity jobs.


Assuntos
Cognição , Emprego/psicologia , Aposentadoria/psicologia , Idoso , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Neurobiol Aging ; 83: 140-144, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31732017

RESUMO

Many studies have shown that early-life experiences can contribute to later life cognitive reserve and resilience. However, there is evidence to suggest that later life experiences and lifestyle choices can also play a vital role in the brain's ability to respond to and compensate for neural insults associated with aging. Engaging in a diversity of behaviorally, socially, and cognitively rich activities may forge new neural pathways that can perhaps provide greater flexibility in confronting the challenges associated with accumulating brain pathology. Studies of cognitively normal individuals with pathology and of individuals who have aged exceptionally well may provide insights that are generalizable to the overall elderly population.


Assuntos
Doença de Alzheimer/fisiopatologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Reserva Cognitiva/fisiologia , Idoso , Envelhecimento/fisiologia , Doença de Alzheimer/patologia , Encéfalo/patologia , Humanos , Estilo de Vida
9.
J Geophys Res Atmos ; 124(5)2019.
Artigo em Inglês | MEDLINE | ID: mdl-32166055

RESUMO

We have determined optical properties of heterogeneous particles from aerosol samples collected at Hawaii's Mauna Loa Observatory. Back trajectories, satellite imagery, and composition differences among particles from scanning electron microscopy revealed a subset of particles with dolomite or calcite that likely came from Asia. Using focused ion-beam tomography and the discrete dipole approximation, we show how small amounts of an iron phase (oxide or carbonate), or in one case soot, affected extinction and scattering compared with particles of neat dolomite or calcite. We show how particles exhibit a range scattering values due to varying orientations of the inclusion phases. Extinction efficiencies for the heterogeneous particles with dolomite (3.47) and calcite (3.36) were 19% to 21% lower than extinction for marine background air particles (3.72). Extinction for the Asian dust was, however, generally higher than for the neat particles. Compared to iron carbonate, the presence of an absorbing iron oxide affected scattering in Asian dust particles even at the low oxide concentrations studied here (0.6% to 8.1%). Scattering efficiency decreased by <1% with a 1% increase in hematite but by 2% to 5% with magnetite. Asian dust scattered light strongly forward, but backscattering was 56% larger than for the marine background air particles. Backscattering in the Asian dust was also larger with magnetite than hematite. Single scattering albedo for Asian dust with hematite, magnetite, or soot averaged 0.96 ± 0.06 ( x ¯ ± s , n = 19 ) but was as low as 0.72 with a magnetite mass of 5.8%.

10.
Am J Pharm Educ ; 82(6): 6302, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30181670

RESUMO

Objective. To address the gap in evidence-based knowledge among pharmacy students and practicing pharmacists regarding complementary and integrative health approaches due to insufficient education and a lack of standardized training. Methods. The National Center for Integrative Primary Healthcare (NCIPH) developed 22 pharmacy competencies linked to a set of 10 interprofessional "metacompetencies" in integrative health care. Results. The NCIPH pharmacy competencies are well-aligned with the current educational standards and Center for the Advancement of Pharmacy Education (CAPE) outcomes for pharmacy programs. Therefore, the NCIPH competencies may provide a foundation for the incorporation of interprofessional integrative health care education into pharmacy curricula. Conclusion. The NCIPH pharmacy competencies in integrative health care, linked to the interprofessional "metacompetencies," are aligned with educational standards and outcomes, and may serve as a basis for pharmacy curriculum.


Assuntos
Competência Clínica/normas , Educação em Farmácia/normas , Medicina Integrativa/educação , Desenvolvimento de Programas/métodos , Currículo/normas , Humanos , Medicina Integrativa/normas , Relações Interprofissionais , Farmacêuticos/normas , Desenvolvimento de Programas/normas , Estudantes de Farmácia
11.
J Am Pharm Assoc (2003) ; 58(4S): S24-S29.e2, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30006184

RESUMO

OBJECTIVE: To evaluate patient satisfaction with pharmacist-administered long-acting injectable antipsychotics (LAIAs) in the community pharmacy. DESIGN: Prospective survey. SETTING: Albertsons Companies community pharmacies during December 2016 to February 2017. PARTICIPANTS: Patients receiving LAIAs at participating pharmacies. MAIN OUTCOME MEASURES: A survey assessed patients' satisfaction with pharmacist-administered LAIAs in the community pharmacy. RESULTS: LAIA recipients (N = 104) reported satisfaction with community pharmacist-administered LAIAs. Participants who had received the service at other types of health clinics (N = 57) also reported higher satisfaction with current service compared to a similar service received elsewhere. Participants indicated that they would recommend service to others and that service was more convenient than a similar service received in an alternative setting. There was not a statistically significant relationship between patient demographic characteristics and likelihood of recommending service to others. CONCLUSION: Patients were satisfied with a pharmacist-administered LAIA service in the community pharmacy, and they found it more convenient than similar services provided elsewhere.


Assuntos
Antipsicóticos/administração & dosagem , Satisfação do Paciente/estatística & dados numéricos , Farmacêuticos/estatística & dados numéricos , Adulto , Serviços Comunitários de Farmácia/estatística & dados numéricos , Feminino , Humanos , Masculino , Farmácias/estatística & dados numéricos , Papel Profissional , Estudos Prospectivos , Inquéritos e Questionários
12.
Curr Pharm Teach Learn ; 9(6): 1063-1070, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29233374

RESUMO

BACKGROUND AND PURPOSE: The University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences (SSPPS) used the opportunity of curriculum renewal to integrate knowledge and skills learned from didactic courses into the introductory pharmacy practice experiences (IPPEs) occurring simultaneously. This paper describes and evaluates the meaningful application of course content into IPPEs, and evaluates the success using qualitative feedback. EDUCATIONAL ACTIVITY AND SETTING: Students entering the renewed curriculum starting in fall 2012 were provided a list of pharmacy skills and activities from didactic course directors that reinforced course content for that semester. The skills and activities were to be completed during the students' IPPE visits in the community or health systems settings, depending on the program year and semester. FINDINGS: Students successfully completed course assignments during their IPPE course program. Not all activities could be completed as designed, and many required modification, including simulated experiences. Feedback from faculty and preceptor members of the school's experiential education committee demonstrated that these activities were valuable and improved learning of course material, but were challenging to implement. DISCUSSION AND SUMMARY: A renewed curriculum that mapped course assignments for completion in experiential settings was successfully established, after some modifications. The program was modified at regular intervals to improve the ability of preceptors to complete these activities in their individual practice environment. A balance between the school providing guidance on what activities students should perform and allowing unstructured independent learning with the preceptor is needed for an optimal experience.


Assuntos
Currículo/tendências , Educação em Farmácia/métodos , Aprendizagem Baseada em Problemas/métodos , Desenvolvimento de Programas/métodos , Colorado , Currículo/normas , Educação em Farmácia/tendências , Humanos , Aprendizagem Baseada em Problemas/normas , Avaliação de Programas e Projetos de Saúde/métodos , Estudantes de Farmácia
13.
Work Aging Retire ; 4(1): 37-51, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29270302

RESUMO

Population aging and attendant pressures on public budgets have spurred considerable interest in understanding factors that influence retirement timing. A range of sociodemographic and economic characteristics predict both earlier and later retirement. Less is known about the role of job characteristics on the work choices of older workers. Researchers are increasingly using the subjective ratings of job characteristics available in the Health and Retirement Study in conjunction with more objective measures of job characteristics from the Occupational Information Network (O*NET) database. Employing a theoretically-informed model of job demands-personal resources fit, we constructed mismatch measures between resources and job demands (both subjectively and objectively assessed) in physical, emotional, and cognitive domains. When we matched comparable measures across the two data sources in the domains of physical, emotional, and cognitive job demands, we found that both sources of information held predictive power in relation to retirement timing. Physical and emotional but not cognitive mismatch were associated with earlier retirement. We discuss theoretical and practical implications of these findings and directions for future research.

14.
Environ Pollut ; 218: 1180-1190, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27593352

RESUMO

The Cleveland airshed comprises a complex mixture of industrial source emissions that contribute to periods of non-attainment for fine particulate matter (PM2.5) and are associated with increased adverse health outcomes in the exposed population. Specific PM sources responsible for health effects however are not fully understood. Size-fractionated PM (coarse, fine, and ultrafine) samples were collected using a ChemVol sampler at an urban site (G.T. Craig (GTC)) and rural site (Chippewa Lake (CLM)) from July 2009 to June 2010, and then chemically analyzed. The resulting speciated PM data were apportioned by EPA positive matrix factorization to identify emission sources for each size fraction and location. For comparisons with the ChemVol results, PM samples were also collected with sequential dichotomous and passive samplers, and evaluated for source contributions to each sampling site. The ChemVol results showed that annual average concentrations of PM, elemental carbon, and inorganic elements in the coarse fraction at GTC were ∼2, ∼7, and ∼3 times higher than those at CLM, respectively, while the smaller size fractions at both sites showed similar annual average concentrations. Seasonal variations of secondary aerosols (e.g., high NO3- level in winter and high SO42- level in summer) were observed at both sites. Source apportionment results demonstrated that the PM samples at GTC and CLM were enriched with local industrial sources (e.g., steel plant and coal-fired power plant) but their contributions were influenced by meteorological conditions and the emission source's operation conditions. Taken together the year-long PM collection and data analysis provides valuable insights into the characteristics and sources of PM impacting the Cleveland airshed in both the urban center and the rural upwind background locations. These data will be used to classify the PM samples for toxicology studies to determine which PM sources, species, and size fractions are of greatest health concern.


Assuntos
Poluentes Atmosféricos/química , Monitoramento Ambiental , Material Particulado/química , Aerossóis/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Humanos , Indústrias , Ohio , Material Particulado/análise , Estações do Ano
15.
Environ Sci Technol ; 50(14): 7581-9, 2016 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-27300163

RESUMO

We report on the precision and accuracy of measuring PM10-2.5 and its components with particles collected by passive aerosol samplers and analyzed by computer-controlled scanning electron microscopy with energy dispersive X-ray spectroscopy. Passive samplers were deployed for week-long intervals in triplicate and colocated with a federal reference method sampler at three sites and for 5 weeks in summer 2009 and 5 weeks in winter 2010 in Cleveland, OH. The limit of detection of the passive method for PM10-2.5 determined from blank analysis was 2.8 µg m(-3). Overall precision expressed as root-mean-square coefficient of variation (CVRMS) improved with increasing concentrations (37% for all samples, n = 30; 19% for PM10-2.5 > 10 µg m(-3), n = 9; and 10% for PM10-2.5 > 15 µg m(-3), n = 4). The linear regression of PM10-2.5 measured passively on that measured with the reference sampler exhibited an intercept not statistically different than zero (p = 0.46) and a slope not statistically different from unity (p = 0.92). Triplicates with high CVs (CV > 40%, n = 5) were attributed to low particle counts (and mass concentrations), spurious counts attributed to salt particles, and Al-rich particles. This work provides important quantitative observations that can help guide future development and use of passive samplers for measuring atmospheric particulate matter.


Assuntos
Microscopia Eletrônica de Varredura , Tamanho da Partícula , Aerossóis , Poluentes Atmosféricos , Monitoramento Ambiental , Material Particulado
16.
J Med Chem ; 59(3): 1003-20, 2016 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-26751273

RESUMO

FTY720 is the first oral small molecule approved for the treatment of people suffering from relapsing-remitting multiple sclerosis. It is a potent agonist of the S1P1 receptor, but its lack of selectivity against the S1P3 receptor has been linked to most of the cardiovascular side effects observed in the clinic. These findings have triggered intensive efforts toward the identification of a second generation of S1P3-sparing S1P1 agonists. We have recently disclosed a series of orally active tetrahydroisoquinoline (THIQ) compounds matching these criteria. In this paper we describe how we defined and implemented a strategy aiming at the discovery of selective structurally distinct follow-up agonists. This effort culminated with the identification of a series of orally active tetrahydropyrazolopyridines.


Assuntos
Descoberta de Drogas , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Piridinas/administração & dosagem , Piridinas/farmacologia , Receptores de Lisoesfingolipídeo/agonistas , Administração Oral , Animais , Linhagem Celular , Cães , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química , Piridinas/síntese química , Piridinas/química , Ratos , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Receptores de Esfingosina-1-Fosfato , Relação Estrutura-Atividade
17.
Int J Hyg Environ Health ; 218(3): 345-57, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25747543

RESUMO

Due to their antifungal, antibacterial, antiviral, and antimicrobial properties, silver nanoparticles (AgNPs) are used in consumer products intended for use by children or in the home. Children may be especially affected by the normal use of consumer products because of their physiological functions, developmental stage, and activities and behaviors. Despite much research to date, children's potential exposures to AgNPs are not well characterized. Our objectives were to characterize selected consumer products containing AgNPs and to use the data to estimate a child's potential non-dietary ingestion exposure. We identified and cataloged 165 consumer products claiming to contain AgNPs that may be used by or near children or found in the home. Nineteen products (textile, liquid, plastic) were selected for further analysis. We developed a tiered analytical approach to determine silver content, form (particulate or ionic), size, morphology, agglomeration state, and composition. Silver was detected in all products except one sippy cup body. Among products in a given category, silver mass contributions were highly variable and not always uniformly distributed within products, highlighting the need to sample multiple areas of a product. Electron microscopy confirmed the presence of AgNPs. Using this data, a child's potential non-dietary ingestion exposure to AgNPs when drinking milk formula from a sippy cup is 1.53 µg Ag/kg. Additional research is needed to understand the number and types of consumer products containing silver and the concentrations of silver in these products in order to more accurately predict children's potential aggregate and cumulative exposures to AgNPs.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/análise , Manufaturas/análise , Nanopartículas/análise , Prata/análise , Anti-Infecciosos/química , Criança , Comércio , Humanos , Íons/análise , Microscopia Eletrônica , Tamanho da Partícula , Plásticos/análise , Têxteis/análise
18.
Int J Environ Res Public Health ; 12(2): 2090-104, 2015 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-25689348

RESUMO

Outdoor and indoor (subway) samples were collected by passive sampling in urban Seoul (Korea) and analyzed with computer-controlled scanning electron microscopy coupled with energy dispersive x-ray spectroscopy (CCSEM-EDX). Soil/road dust particles accounted for 42%-60% (by weight) of fine particulate matter larger than 1 µm (PM(2.5-1.0)) in outdoor samples and 18% of PM2.5-1.0 in subway samples. Iron-containing particles accounted for only 3%-6% in outdoor samples but 69% in subway samples. Qualitatively similar results were found for coarse particulate matter (PM(10-2.5)) with soil/road dust particles dominating outdoor samples (66%-83%) and iron-containing particles contributing most to subway PM(10-2.5) (44%). As expected, soil/road dust particles comprised a greater mass fraction of PM(10-2.5) than PM(2.5-1.0). Also as expected, the mass fraction of iron-containing particles was substantially less in PM(10-2.5) than in PM(2.5-1.0). Results of this study are consistent with known emission sources in the area and with previous studies, which showed high concentrations of iron-containing particles in the subway compared to outdoor sites. Thus, passive sampling with CCSEM-EDX offers an inexpensive means to assess PM(2.5-1.0) and PM(10-2.5) simultaneously and by composition at multiple locations.


Assuntos
Poluentes Atmosféricos/química , Poeira/análise , Monitoramento Ambiental/métodos , Microscopia Eletrônica de Varredura/métodos , Material Particulado/análise , Ferro/análise , Ferrovias , Seul , Espectrometria por Raios X
19.
J Econ Educ ; 46(1): 83-104, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27616783

RESUMO

This paper describes the job market experiences of new PhD economists, 2007-10. Using information from PhD programs' job candidate websites and original surveys, the authors present information about job candidates' characteristics, preferences and expectations; how job candidates fared at each stage of the market; and predictors of outcomes at each stage. Some information presented in this paper updates findings of prior studies. However, design features of the data used in this paper may result in more generalizable findings. This paper is unique in comparing pre-market expectations and preferences with post-market outcomes on the new PhD job market. It shows that outcomes tend to align with pre-market preferences, and candidates' expectations are somewhat predictive of their outcomes. Several analyses also shed light on sub-group differences.

20.
Toxicol Sci ; 142(2): 403-17, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25239632

RESUMO

Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe.


Assuntos
Cério/toxicidade , Gasolina/toxicidade , Lesão Pulmonar/induzido quimicamente , Pulmão/efeitos dos fármacos , Nanopartículas/química , Emissões de Veículos/toxicidade , Acetilglucosaminidase/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Líquido da Lavagem Broncoalveolar/química , Cério/química , Cério/farmacocinética , Relação Dose-Resposta a Droga , Gasolina/análise , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Pulmão/enzimologia , Pulmão/ultraestrutura , Lesão Pulmonar/enzimologia , Lesão Pulmonar/patologia , Masculino , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Ratos Sprague-Dawley , Fatores de Tempo , Vasoconstrição/efeitos dos fármacos
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