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1.
Prev Med ; : 108035, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38852889

RESUMEN

OBJECTIVE: Sexual minority (SM) women experience tobacco-related disparities and report a higher prevalence of cigarette use, as well as subgroup differences in use, but little is known about their quitting behavior. This study used data from a national sample of United States SM women to examine cigarette quit ratios overall and by age, race/ethnicity, and sexual orientation. METHODS: Using baseline survey data from the Generations Study (2016-2017, N = 812), we calculated quit ratios among SM women reporting lifetime smoking (100+ cigarettes) who reported currently smoking "not at all" relative to those reporting smoking "every day or some days." Quitting was compared across cohort, race/ethnicity, and sexual orientation, controlling for household income. RESULTS: SM women reporting lifetime smoking in the older cohort were significantly more likely to report quitting than those in the younger cohort. Bisexual women also reported a greater likelihood of quitting than gay/lesbian women. There was no association between race/ethnicity and the probability of quitting smoking. CONCLUSIONS: SM women remain a priority for tobacco prevention and cessation efforts. There is evidence that the probability of quitting cigarettes differs across sexual orientation and age cohorts, which has implications for tailoring of interventions and tobacco communications.

2.
Nicotine Tob Res ; 25(1): 73-76, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35439321

RESUMEN

INTRODUCTION: To eliminate tobacco-related disparities, tobacco control research would benefit from a paradigm shift. Intersectionality, a framework pioneered by Kimberlé Crenshaw in late 1980s, has the potential to improve our understanding of why and how certain social groups are disproportionately harmed by commercial tobacco use, and improve our ability to address persistent tobacco-related health disparities. AIMS AND METHODS: In this commentary, we outline the rationale and recommendations for incorporating intersectionality into equity-minded tobacco control research. These recommendations arose from intersectionality webinars organized by the Health Disparities (now Health Equity) Network of the Society for Research on Nicotine & Tobacco (SRNT) in 2019 and 2020. RESULTS: Specifically, we propose that eliminating tobacco-related disparities through intersectionality-informed research requires a multilevel, multipronged approach. We summarize priority actions for the tobacco control research field to achieve health equity through the intersectionality framework including acknowledging that structural factors, racism and power dynamics shape lived experiences, integrating critical theoretical frameworks and intersectionality scholarship into research questions, and embracing collaborative community-based approaches at every level of the research process. CONCLUSIONS: Through these actions, our field can take concrete steps to fundamentally improve our approach to conducting research to achieve health equity. IMPLICATIONS: Intersectionality is a valuable tool to align our field with our pursuit of health equity. The recommendations aim to improve methods of equity-focused tobacco control, prompt ongoing dialogue on the utility of this tool, and shift paradigms in how the research process is conducted at every level among stakeholders, including researchers, journal editors and reviewers, funders, practitioners, and policy makers.


Asunto(s)
Equidad en Salud , Nicotiana , Humanos , Marco Interseccional , Disparidades en el Estado de Salud
3.
BMC Health Serv Res ; 23(1): 117, 2023 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-36739389

RESUMEN

BACKGROUND: Inequities in health access and outcomes persist in low- and middle-income countries. While strengthening primary care is integral in improving patient outcomes, primary care networks remain undervalued, underfunded, and underdeveloped in many LMICs such as the Philippines. This paper underscores the value of strengthening primary care system interventions in LMICs by examining their impact on job satisfaction and intention to stay among healthcare workers in the Philippines. METHODS: This study was conducted in urban, rural, and remote settings in the Philippines. A total of 36 urban, 54 rural, and 117 remote healthcare workers participated in the study. Respondents comprised all family physicians, nurses, midwives, community health workers, and staff involved in the delivery of primary care services from the sites. A questionnaire examining job satisfaction (motivators) and dissatisfaction (hygiene) factors was distributed to healthcare workers before and after system interventions were introduced across sites. Interventions included the introduction of performance-based incentives, the adoption of electronic health records, and the enhancement of diagnostic and pharmaceutical capabilities over a 1-year period. A Wilcoxon signed-rank test and a McNemar's chi-square test were then conducted to compare pre- and post-intervention experiences for each setting. RESULTS: Among the factors examined, results revealed a significant improvement in perceived compensation fairness among urban (p = 0.001) and rural (p = 0.016) providers. The rural workforce also reported a significant improvement in medicine access (p = 0.012) post-intervention. Job motivation and turnover intention were sustained in urban and rural settings between periods. Despite the interventions introduced, a decline in perceptions towards supply accessibility, job security, and most items classified as job motivators was reported among remote providers. Paralleling this decline, remote primary care providers with the intent to stay dropped from 93% at baseline to 75% at endline (p < 0.001). CONCLUSION: The impact of strengthening primary care on health workforce satisfaction and turnover intention varied across urban, rural, and remote settings. While select interventions such as improving compensation were promising for better-supported settings, the immediate impact of these interventions was inadequate in offsetting the infrastructural and staffing gaps experienced in disadvantaged areas. Unless these problems are comprehensively addressed, satisfaction will remain low, workforce attrition will persist as a problem, and marginalized communities will be underserved.


Asunto(s)
Fuerza Laboral en Salud , Intención , Satisfacción en el Trabajo , Atención Primaria de Salud , Humanos , Agentes Comunitarios de Salud , Satisfacción Personal , Filipinas , Servicios de Salud Rural , Disparidades en Atención de Salud
4.
Soc Psychiatry Psychiatr Epidemiol ; 57(4): 749-760, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35059751

RESUMEN

INTRODUCTION: Research has demonstrated disparities in depressive symptoms among people who are marginalized. However, more work should examine depressive symptoms through an intersectional lens, recognizing that multiple systems of privilege and oppression interlock to create unique struggles where multiple marginalized identities meet. Recent methodological developments have advanced quantitative intersectionality research using multilevel modeling to partition variance in depressive symptoms to person-level sociodemographic variables and intersectional-level social strata. The purpose of this study is to leverage these methods to examine trajectories of depressive symptoms among young adults in Texas through an intersectional lens. METHODS: Multilevel modeling was used to examine the longitudinal trajectories of depressive symptoms among 3575 young adults from 24 colleges in Texas assessed seven times between Fall 2014 and Spring 2018. Intersectional identities included sex, race/ethnicity, and sexual and gender minority identities. The model examined time nested within individuals and individuals nested within intersectional social strata. RESULTS: Young adults in Texas experienced an increase in depressive symptoms from 2014-2018. Those with female, Hispanic, AAPI, other race/ethnicity, or LGBTQ + identities experienced more depressive symptoms. After controlling for the main effects of the sociodemographic variables, 0.08% of variance in depressive symptoms remained attributed to the effects of intersectional identities. CONCLUSION: Evaluating disparities in depressive symptoms through an intersectional lens offers a more complete description of the epidemiology of depressive symptoms. Communities and institutions that serve marginalized people should consider the elevated burden of depressive symptoms that marginalized people may carry, and integrate culturally competent psychoeducation, assessments, and therapies where possible.


Asunto(s)
Depresión , Minorías Sexuales y de Género , Depresión/diagnóstico , Depresión/epidemiología , Etnicidad , Femenino , Humanos , Masculino , Grupos Minoritarios , Texas/epidemiología , Adulto Joven
5.
Mol Genet Metab ; 133(2): 211-221, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33814269

RESUMEN

Previously we have shown that young mice with a dominant severe form of osteogenesis imperfecta (OI), caused by mutated collagen type I, exhibit an altered glucose/insulin metabolism and energy expenditure along with elevated levels of osteocalcin, a bone-derived hormone involved in the regulation of whole-body metabolism. This study aimed to examine the long-term effects of a western diet in these OI mice. Male and female OI mice and wild type littermates (WT) were fed a high-fat diet (HFD) or a matched low-fat diet (LFD) for 26 weeks. HFD-induced obesity was observed in male and female WT and female OI mice, but not in male OI mice. HFD-fed WT and OI mice of both sexes developed hyperglycemia and glucose intolerance, but the degree of glucose intolerance was significantly lower in male and female OI mice compared to sex- and diet-matched WT mice. Indirect calorimetry revealed increased movement of male OI mice on HFD compared to LFD and, while HFD lowered energy expenditure in WT mice, energy expenditure was not changed in OI mice. Further, HFD-fed male OI mice demonstrated a diet-induced increased expression of the thermogenesis genes, Ucp1 and Pgc1α, in brown adipose tissue. On LFD, total and Gla-13 osteocalcin levels were similar in 30-week-old WT and OI mice, but on HFD, both were significantly higher in OI mice than WT. Thus, male OI mice respond to HFD with increased movement, energy expenditure, brown adipose tissue thermogenesis, and higher levels of osteocalcin, resulting in partial protection against HFD-induced obesity.


Asunto(s)
Obesidad/metabolismo , Osteocalcina/genética , Osteogénesis Imperfecta/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Proteína Desacopladora 1/genética , Tejido Adiposo Pardo , Animales , Dieta Alta en Grasa/efectos adversos , Metabolismo Energético/genética , Femenino , Regulación de la Expresión Génica/genética , Intolerancia a la Glucosa/genética , Intolerancia a la Glucosa/metabolismo , Intolerancia a la Glucosa/patología , Humanos , Insulina/metabolismo , Resistencia a la Insulina/genética , Masculino , Ratones , Obesidad/complicaciones , Obesidad/genética , Obesidad/patología , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/patología , Caracteres Sexuales
6.
Acta Psychiatr Scand ; 143(1): 22-35, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33145770

RESUMEN

OBJECTIVE: To systematically review evidence on the efficacy and safety of sleep deprivation (SD) as a treatment option for patients with unipolar or bipolar depression. METHODS: A systematic review according to PRISMA guidelines was conducted. The certainty of evidence was assessed using the GRADE approach. Controlled trials were included in efficacy analysis, case series for evaluating complications and qualitative studies for patients' experiences. RESULTS: Eight controlled studies (368 patients), one qualitative study and seven case series (825 patients) were included. One week after treatment start, SD combined with standard treatment did not reduce depressive symptoms compared with standard treatment (standardized mean difference, SMD = -0.29, [95% confidence interval, CI: -0.84 to 0.25], p = 0.29). When excluding a study in elderly patients in a post hoc analysis, the difference was statistically significant (SMD = -0.54 ([95% CI: -0.86 to -0.22], p < 0.001)) but it diminished two weeks after treatment start. No superiority of SD was found compared with antidepressants, but SD may be superior to exercise in certain settings. It is uncertain whether SD affects quality of sleep, quality of life, everyday functioning or length of stay. Apart from switch to mania (ranging between 2.7% and 10.7%), no other serious complications were reported. CONCLUSION: Sleep deprivation has been studied in a wide range of settings resulting in divergent results for the short-term efficacy on depressive symptoms. Post hoc analyses indicated that there may be a significant but transient effect in certain populations. Further studies should focus on identifying subgroups of responders as well as examining feasibility in routine clinical care.


Asunto(s)
Depresión , Calidad de Vida , Anciano , Antidepresivos/uso terapéutico , Ejercicio Físico , Humanos , Privación de Sueño/tratamiento farmacológico
7.
J Musculoskelet Neuronal Interact ; 21(4): 517-527, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34854391

RESUMEN

OBJECTIVE: The objective of the current study is to assess the effect of a seven-week voluntary wheel running intervention on muscles and bones properties in a mouse model mimicking dominant severe osteogenesis imperfecta (OI). METHODS: Female wild-type (WT) and OI (Col1a1Jrt/+) mice either performed voluntarily wheel-running exercise for 7-weeks or remained sedentary. Running distance and speed, forelimb grip strength, isolated muscle force and fatigability as well as bone morphology and mechanical properties were assessed. RESULTS: We demonstrate that female WT and OI mice voluntarily performed exercise, although OI mice exercised less than WT littermates. The exercise regimen increased soleus muscle masses in WT and OI but increased relative grip strength in WT mice only. Specific muscle force and fatigability were similar between WT and OI mice and did not improve with exercise. Furthermore, the exercise regimen did not improve the femoral architectural and biomechanical properties in OI mice. CONCLUSION: Our study suggests that voluntary wheel running is not appropriate to assess the effects of exercise in a mouse model of OI. Findings from exercising OI mice model studies may not necessarily be transferable to humans.


Asunto(s)
Osteogénesis Imperfecta , Animales , Huesos , Modelos Animales de Enfermedad , Femenino , Ratones , Actividad Motora , Músculo Esquelético , Osteogénesis Imperfecta/genética
8.
Environ Sci Technol ; 54(9): 5391-5399, 2020 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-32227932

RESUMEN

Chemical sensitivity analysis (CSA) is a new probing tool for sampling sensitivities to chemistry parameters during a three-dimensional (3-D) simulation. CSA was applied to rank all of the parameters in the Carbon Bond 6 revision 4 (CB6r4) mechanism and to create an ensemble of six chemical mechanisms representing higher and lower O3 formations than CB6r4. This ensemble of mechanisms was used to estimate the uncertainty from the chemistry in a 3-D simulation and combined with uncertainties from other model inputs obtained from calculations of their sensitivities. The overall uncertainty (1σ) in O3 predictions for eastern Texas was 10-11 ppb in the Gulf of Mexico near Galveston and 7-8 ppb in much of the rest of the domain on the higher O3 days of June 2012. As a percent of the O3 concentration, the uncertainty was more uniform over the domain, 11-14%. Chemistry and emissions make the largest contributions to the O3 uncertainty. Uncertainty in the dry deposition velocities is less important in urban areas and the Gulf, but it is similar in importance to the uncertainty in chemistry and emissions at most other locations. Uncertainty in O3 boundary concentrations is the least important.


Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Ozono/análisis , Monitoreo del Ambiente , Golfo de México , Modelos Teóricos , Texas , Incertidumbre
9.
Nicotine Tob Res ; 22(12): 2276-2279, 2020 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-32335682

RESUMEN

INTRODUCTION: Sexual and gender minority (SGM) individuals have higher tobacco use prevalence and consequently higher burden of tobacco-caused diseases, including cancer and cardiovascular disease compared with their heterosexual or cisgender counterparts. Yet, there is a critical gap in research focused on measuring SGM tobacco-related health disparities and addressing unmet needs of SGM individuals in the context of nicotine and tobacco research. AIMS AND METHODS: In this commentary, we summarize recommendations discussed during a pre-conference workshop focused on challenges and opportunities in conducting SGM tobacco control research at the 2019 Society for Research on Nicotine and Tobacco Annual Meeting. RESULTS: Specifically, we recommend defining and measuring SGM identity in all nicotine and tobacco research routinely, using novel methods to engage a demographically diverse sample of the SGM population, and eliciting SGM community voices in tobacco control research. CONCLUSIONS: Addressing these critical research gaps will enable the scientific community to generate the data to fully understand and support SGM individuals in tobacco use prevention and cessation. IMPLICATIONS: Tobacco use and its consequences have become increasingly concentrated in disadvantaged groups, including sexual and gender minority (SGM) populations. Through concrete recommendations in this commentary, we aimed to promote health equity, diversity, and inclusion in tobacco research for SGM populations by urging the scientific community to consider expanding efforts to monitor and address tobacco-related health disparities of SGM populations within their respective research programs.


Asunto(s)
Investigación Biomédica/normas , Equidad en Salud , Promoción de la Salud/métodos , Disparidades en el Estado de Salud , Proyectos de Investigación , Minorías Sexuales y de Género/estadística & datos numéricos , Uso de Tabaco/prevención & control , Femenino , Conductas Relacionadas con la Salud , Humanos , Masculino , Uso de Tabaco/epidemiología , Uso de Tabaco/psicología
10.
BMC Pregnancy Childbirth ; 20(1): 199, 2020 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-32252679

RESUMEN

BACKGROUND: Women's experiences of labour and birth can have both short- and long-term effects on their physical and psychological health. The original Swedish version of the Childbirth Experience Questionnaire (CEQ) has shown to have good psychometric quality and ability to differentiate between groups known to differ in childbirth experience. Two subscales were revised in order to include new items with more relevant content about decision-making and aspects of midwifery support. The aim of the study was to develop new items in two subscales and to test construct validity and reliability of the revised version of CEQ, called CEQ2. METHOD: A total of 11 new items (Professional Support and Participation) and 14 original items from the first CEQ (Own capacity and Perceived safety), were answered by 682 women with spontaneous onset of labour. Confirmatory factor analysis was used to analyse model fit. RESULTS: The hypothesised four-factor model showed good fit (CMIN = 2.79; RMR = 0.33; GFI = 0.94; CFI = 0.94; TLI = 0.93; RMSEA = 0.054 and PCLOSE = 0.12) Cronbach's alpha was good for all subscales (0.82, 0.83, 0.76 and 0.73) and for the total scale (0.91). CONCLUSIONS: CEQ2, like the first CEQ, yields four important aspects of experience during labour and birth showing good psychometric performance, including decision-making and aspects of midwifery support, in both primiparous and multiparous women.


Asunto(s)
Toma de Decisiones , Partería , Parto/psicología , Satisfacción del Paciente , Adulto , Parto Obstétrico/psicología , Análisis Factorial , Femenino , Humanos , Trabajo de Parto/psicología , Embarazo , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Suecia , Traducciones
11.
Environ Sci Technol ; 53(8): 4003-4019, 2019 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-30830764

RESUMEN

Oxidative stress is a potential mechanism of action for particulate matter (PM) toxicity and can occur when the body's antioxidant capacity cannot counteract or detoxify harmful effects of reactive oxygen species (ROS) due to an excess presence of ROS. ROS are introduced to the body via inhalation of PM with these species present on and/or within the particles (particle-bound ROS) and/or through catalytic generation of ROS in vivo after inhaling redox-active PM species (oxidative potential, OP). The recent development of acellular OP measurement techniques has led to a surge in research across the globe. In this review, particle-bound ROS techniques are discussed briefly while OP measurements are the focus due to an increasing number of epidemiologic studies using OP measurements showing associations with adverse health effects in some studies. The most common OP measurement techniques, including the dithiothreitol assay, glutathione assay, and ascorbic acid assay, are discussed along with evidence for utility of OP measurements in epidemiologic studies and PM characteristics that drive different responses between assay types (such as species composition, emission source, and photochemistry). Overall, most OP assays respond to metals like copper than can be found in emission sources like vehicles. Some OP assays respond to organics, especially photochemically aged organics, from sources like biomass burning. Select OP measurements have significant associations with certain cardiorespiratory end points, such as asthma, congestive heart disease, and lung cancer. In fact, multiple studies have found that exposure to OP measured using the dithiothreitol and glutathione assays drives higher risk ratios for certain cardiorespiratory outcomes than PM mass, suggesting OP measurements may be integrating the health-relevant fraction of PM and will be useful tools for future health analyses. The compositional impacts, including species and emission sources, on OP could have serious implications for health-relevant PM exposure. Though more work is needed, OP assays show promise for health studies as they integrate the impacts of PM species and properties on catalytic redox reactions into one measurement, and current work highlights the importance of metals, organic carbon, vehicles, and biomass burning emissions to PM exposures that could impact health.


Asunto(s)
Contaminantes Atmosféricos , Material Particulado , Monitoreo del Ambiente , Oxidación-Reducción , Estrés Oxidativo
12.
Nucleic Acids Res ; 45(16): e149, 2017 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-28934485

RESUMEN

Advances in high throughput sequencing technologies have created a gap between data production and functional data analysis. Indeed, phenotypes result from interactions between numerous genes, but traditional methods treat loci independently, missing important knowledge brought by network-level emerging properties. Therefore, detecting selection acting on multiple genes affecting the evolution of complex traits remains challenging. In this context, gene network analysis provides a powerful framework to study the evolution of adaptive traits and facilitates the interpretation of genome-wide data. We developed a method to analyse gene networks that is suitable to evidence polygenic selection. The general idea is to search biological pathways for subnetworks of genes that directly interact with each other and that present unusual evolutionary features. Subnetwork search is a typical combinatorial optimization problem that we solve using a simulated annealing approach. We have applied our methodology to find signals of adaptation to high-altitude in human populations. We show that this adaptation has a clear polygenic basis and is influenced by many genetic components. Our approach, implemented in the R package signet, improves on gene-level classical tests for selection by identifying both new candidate genes and new biological processes involved in adaptation to altitude.


Asunto(s)
Redes Reguladoras de Genes , Selección Genética , Programas Informáticos , Adaptación Fisiológica/genética , Altitud , Biología Computacional/métodos , Humanos , Redes y Vías Metabólicas/genética , Transducción de Señal/genética
13.
Epidemiology ; 29(1): 22-30, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28926373

RESUMEN

BACKGROUND: Early-life exposure to traffic-related air pollution exacerbates childhood asthma, but it is unclear what role it plays in asthma development. METHODS: The association between exposure to primary mobile source pollutants during pregnancy and during infancy and asthma incidence by ages 2 through 6 was examined in the Kaiser Air Pollution and Pediatric Asthma Study, a racially diverse birth cohort of 24,608 children born between 2000 and 2010 and insured by Kaiser Permanente Georgia. We estimated concentrations of mobile source fine particulate matter (PM2.5, µg/m), nitrogen oxides (NOX, ppb), and carbon monoxide (CO, ppm) at the maternal and child residence using a Research LINE source dispersion model for near-surface releases. Asthma was defined using diagnoses and medication dispensings from medical records. We used binomial generalized linear regression to model the impact of exposure continuously and by quintiles on asthma risk. RESULTS: Controlling for covariates and modeling log-transformed exposure, a 2.7-fold increase in first year of life PM2.5 was associated with an absolute 4.1% (95% confidence interval, 1.6%, 6.6%) increase in risk of asthma by age 5. Quintile analysis showed an increase in risk from the first to second quintile, but similar risk across quintiles 2-5. Risk differences increased with follow-up age. Results were similar for NOX and CO and for exposure during pregnancy and the first year of life owing to high correlation. CONCLUSIONS: Results provide limited evidence for an association of early-life mobile source air pollution with childhood asthma incidence with a steeper concentration-response relationship observed at lower levels of exposure.


Asunto(s)
Contaminación del Aire/estadística & datos numéricos , Asma/epidemiología , Monóxido de Carbono , Exposición a Riesgos Ambientales/estadística & datos numéricos , Óxidos de Nitrógeno , Efectos Tardíos de la Exposición Prenatal/epidemiología , Emisiones de Vehículos , Contaminantes Atmosféricos , Niño , Preescolar , Estudios de Cohortes , Femenino , Georgia/epidemiología , Humanos , Incidencia , Lactante , Modelos Lineales , Masculino , Material Particulado , Embarazo , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
14.
Mol Pharm ; 15(12): 5781-5792, 2018 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-30392378

RESUMEN

Polyglutamine diseases are a set of progressive neurodegenerative disorders caused by misfolding and aggregation of mutant CAG RNA and polyglutamin protein. To date, there is a lack of effective therapeutics that can counteract the polyglutamine neurotoxicity. Two peptidylic inhibitors, QBP1 and P3, targeting the protein and RNA toxicities, respectively, have been previously demonstrated by us with combinational therapeutic effects on the Drosophila polyglutamine disease model. However, their therapeutic efficacy has never been investigated in vivo in mammals. The current study aims to (a) develop a brain-targeting delivery system for both QBP1 and L1P3V8 (a lipidated variant of P3 with improved stability) and (b) evaluate their therapeutic effects on the R6/2 transgenic mouse model of polyglutamine disease. Compared with intravenous administration, intranasal administration of QBP1 significantly increased its brain-to-plasma ratio. In addition, employment of a chitosan-containing in situ gel for the intranasal administration of QBP1 notably improved its brain concentration for up to 10-fold. Further study on intranasal cotreatment with the optimized formulation of QBP1 and L1P3V8 in mice found no interference on the brain uptake of each other. Subsequent efficacy evaluation of 4-week daily QBP1 (16 µmol/kg) and L1P3V8 (6 µmol/kg) intranasal cotreatment in the R6/2 mice demonstrated a significant improvement on the motor coordination and explorative behavior of the disease mice, together with a full suppression on the RNA- and protein-toxicity markers in their brains. In summary, the current study developed an efficient intranasal cotreatment of the two peptidylic inhibitors, QBP1 and L1P3V8, for their brain-targeting, and such a novel therapeutic strategy was found to be effective on a transgenic polyglutamine disease mouse model.


Asunto(s)
Proteínas Portadoras/administración & dosificación , Trastornos Heredodegenerativos del Sistema Nervioso/tratamiento farmacológico , Oligopéptidos/administración & dosificación , Péptidos/administración & dosificación , Péptidos/metabolismo , ARN Mensajero/antagonistas & inhibidores , Administración Intranasal , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/metabolismo , Proteínas Portadoras/farmacocinética , Modelos Animales de Enfermedad , Esquema de Medicación , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada/métodos , Trastornos Heredodegenerativos del Sistema Nervioso/genética , Trastornos Heredodegenerativos del Sistema Nervioso/patología , Humanos , Péptidos y Proteínas de Señalización Intercelular , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Oligopéptidos/farmacocinética , Péptidos/farmacocinética , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Expansión de Repetición de Trinucleótido/genética
15.
Pediatr Res ; 83(6): 1165-1171, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29538357

RESUMEN

BackgroundOsteogenesis imperfecta (OI) is most often caused by mutations in type I collagen genes. Respiratory complications have been largely attributed to spine and ribcage deformities. We hypothesized that direct involvement of the pulmonary parenchyma and/or diaphragm by the disease may occur.MethodsIn Col1a1Jrt/+ mice, a model of severe dominant OI, mean linear intercept length (Lm) was used to assess the distal airspace size. Cross-sectional area (CSA) and myosin heavy chain (MyHC) phenotype of the diaphragm muscle fibers, as well as contractile properties, were determined. OI mice were also treated with neutralizing antibodies against transforming growth factor-ß (TGF-ß).ResultsDistal airspace enlargement occurred in OI mice (Lm +27%). Diaphragmatic thickness and fiber number were reduced, with increases in fast-twitch type IIx/IIb MyHC fibers. Ex vivo force generation (normalized for CSA) of the diaphragm was also significantly reduced. The increased Lm values found in OI mice were not prevented by anti-TGF-ß antibody treatment.ConclusionsThe Col1a1Jrt/+ mouse model of OI demonstrates: (1) pulmonary airspace enlargement not driven by TGF-ß; and (2) reduced muscle mass and intrinsic contractile weakness of the diaphragm. These results suggest a complex and multifaceted basis for respiratory complications in OI that cannot be solely attributed to bone manifestations.


Asunto(s)
Colágeno Tipo I/genética , Diafragma/patología , Pulmón/patología , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/fisiopatología , Animales , Anticuerpos Neutralizantes/química , Huesos/patología , Cadena alfa 1 del Colágeno Tipo I , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Ratones Mutantes , Contracción Muscular , Cadenas Pesadas de Miosina/genética , Fenotipo , Alveolos Pulmonares/patología , Respiración , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Factor de Crecimiento Transformador beta1/genética
16.
Nicotine Tob Res ; 20(3): 383-387, 2018 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-28472411

RESUMEN

Introduction: Most research regarding sexual and gender minority (SGM) populations is limited to examination of cigarette or general tobacco use or does not examine heterogeneity across SGM groups other than lesbian or gay and bisexual individuals. This study examined differences in the odds of current use and age of initiation of five tobacco/nicotine products among three groups of SGM young adults who self-identified as (1) gay or lesbian, (2) bisexual, and (3) queer, transgender, or "other," compared to their heterosexual peers. Methods: Participants were 4252 college students aged 18-29 years from 24 colleges in Texas who completed an online tobacco use survey. Multilevel logistic regression models were used to examine the odds of SGM participants currently using each tobacco product. Multilevel linear regression models were used to examine the association of current product users' SGM status with self-reported age of each product's initiation. All models were adjusted for sociodemographic factors and accounted for students clustered within each college. Results: At least one SGM group had significantly greater odds of currently using every tobacco product type compared to heterosexual participants, except hookah. There were few differences across groups in age of initiation. However, queer, transgender, and "other-" identified participants initiated e-cigarettes 1.34 years younger than heterosexual participants, and bisexual participants initiated smokeless tobacco 3.66 years younger than heterosexual participants. Conclusions: Findings highlight some significant tobacco use disparities among SGM young adults compared to their heterosexual peers. Longitudinal studies with larger group sizes will identify prospective predictors of sustained SGM-related tobacco use disparities. Implications: This study extends the current literature by including the sexual and gender minority identity options of queer, transgender, and "other," highlighting disparities in tobacco use between young adults in these subgroups compared to their heterosexual peers, particularly in noncigarette tobacco product use. Findings underscore the need for the Food and Drug Association and other health agencies to tailor health communication efforts specific to sexual and gender minority populations pertaining to the risks and harms surrounding tobacco product use.


Asunto(s)
Minorías Sexuales y de Género/psicología , Estudiantes/psicología , Uso de Tabaco/epidemiología , Uso de Tabaco/psicología , Universidades , Adolescente , Adulto , Sistemas Electrónicos de Liberación de Nicotina , Femenino , Humanos , Masculino , Estudios Prospectivos , Autoinforme , Conducta Sexual/psicología , Encuestas y Cuestionarios , Texas/epidemiología , Productos de Tabaco , Uso de Tabaco/tendencias , Universidades/tendencias , Adulto Joven
17.
Nicotine Tob Res ; 20(3): 347-354, 2018 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-28199700

RESUMEN

Introduction: This study examined the association of sociodemographic characteristics, tobacco and substance use behaviors, and reasons to use cigars in young adults' flavored and non-flavored cigar use. Methods: Participants were 523, 18- to 29- year-old young adult college students (60.4% male; 40.9% non-Hispanic white) who reported current (past 30-day) cigar use. Results: Almost 75% of the sample regularly chose flavored cigar products. Multilevel logistic regression analyses indicated that younger, female, and racial/ethnic minority cigar users had significantly greater odds of using flavored cigars than their counterparts. Current marijuana smokers, ever-blunt smokers, and students who reported using cigars because they were affordable and/or available in flavors they liked had a greater odds of flavored cigar use compared to their counterparts. Moreover, among dual users of cigars and cigarettes, those who cited using cigars because they were cheaper than cigarettes and because cigars felt like smoking regular cigarettes had greater odds of using flavored cigars compared to their peers. Number of days cigars were smoked and current use of other tobacco products were not associated with flavored cigar use. Conclusions: Appealing attributes of flavored cigars have the potential to contribute to the tobacco use and subsequent nicotine addiction of younger, female, and racial/ethnic minority young adults. The wide variety of cigar flavors, their attractive price, and similarity to cigarette smoking underscore the need for additional research that links these unique traits to sustained tobacco use, and underscore the need for regulation of flavored products. Implications: This study extends the current literature by finding that younger, female, and racial/ethnic minorities have greater odds of flavored cigar use than their peers. Flavored cigars have characteristics that appeal to members of these populations, which can contribute to their long-term use and potential for addiction.


Asunto(s)
Fumar Puros/etnología , Fumar Puros/psicología , Aromatizantes , Estudiantes/psicología , Productos de Tabaco , Adolescente , Adulto , Fumar Puros/tendencias , Etnicidad/psicología , Femenino , Aromatizantes/administración & dosificación , Humanos , Masculino , Grupos Raciales/etnología , Grupos Raciales/psicología , Gusto , Adulto Joven
18.
J Intensive Care Med ; 33(12): 656-662, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30411670

RESUMEN

BACKGROUND:: The diagnosis of sepsis is challenging in the absence of a gold standard test. Recent studies have explored the role of neutrophil and monocyte volume, conductivity, and scatter (VCS), derived from automated hematology analyzers, in diagnosing sepsis. We assessed the diagnostic accuracy of VCS parameters in critically ill patients with sepsis. METHODOLOGY:: In this prospective study, VCS parameters, procalcitonin, and C-reactive protein (CRP) were assessed in patients with proven sepsis (cases) and 2 control groups (intensive care unit [ICU] patients without sepsis and healthy blood donors). The diagnostic property of each test was explored by calculating sensitivity, specificity, negative and positive predictive values, and area under the curve (AUC). RESULTS:: The study included 65 patients with sepsis, 58 nonseptic ICU controls, and 98 blood donors. Procalcitonin and CRP were not significantly different ( P > .06) between patients with sepsis and nonseptic patients. Mean (95% confidence interval [CI]) neutrophil volume (MNV) was significantly higher ( P < .001) in patients with sepsis (165.5; 95%CI 161.6-169.4) than in nonseptic (157.3; 95%CI 154.6-160.1) patients and donors (148.9; 95%CI 147.9-150). A similar pattern was seen with mean monocyte volume (MMoV). Neutrophil and monocyte conductivity and scatter parameters were variably associated. The AUC was highest for MMoV (0.74) and lowest for CRP (0.62). Among all parameters, MNV and MMoV had the highest specificity of 85% and 80%, respectively. CONCLUSION:: In critically ill patients with suspected sepsis, VCS parameters may help strengthen the diagnostic probability of sepsis. Future studies may explore the role of serial monitoring of VCS to track response to antimicrobial therapy.


Asunto(s)
Técnicas Citológicas , Monocitos/citología , Neutrófilos/citología , Sepsis/diagnóstico , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Polipéptido alfa Relacionado con Calcitonina/sangre , Estudios Prospectivos , Sensibilidad y Especificidad , Sepsis/sangre , Adulto Joven
19.
BMC Pregnancy Childbirth ; 18(1): 217, 2018 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-29879940

RESUMEN

BACKGROUND: Studies from around the world have shown that women living as undocumented migrants have limited and deficient access to perinatal care, increasing their risks of both physical and psychological complications during pregnancy and childbirth. Failures to provide equal access to healthcare have been criticized extensively by the United Nations. In 2013, undocumented migrants' rights to healthcare in Sweden were expanded to include full access to perinatal care. Research surrounding clinical encounters involving women living as undocumented migrants remains largely lacking. The present study aimed to provide a composite description of women's experiences of clinical encounters throughout pregnancy and childbirth, when living as undocumented migrants in Sweden. METHODS: Taking an inductive approach, qualitative content analysis was implemented. Thirteen women from ten different countries were interviewed. Meaning-units were extracted from the data collected in order to identify emergent overarching themes. RESULTS: In clinical encounters where healthcare professionals displayed empathic concern and listening behaviours, women felt empowered, acknowledged, and encouraged, leading them to trust clinicians, diminishing fears relating to seeking healthcare services. Conversely, when neglectful behaviour on part of healthcare professionals was perceived in encounters, anxiousness and fear intensified. Vulnerability and distress induced by the women's uncertain living circumstances were apparent across themes, and appeared exacerbated by traumatic memories, difficulties in coping with motherhood, and fears of deportation. CONCLUSION: The present study contributes unique and important knowledge surrounding women's experience of being pregnant and giving birth when living as undocumented migrants. The overarching findings indicated that the needs of undocumented migrant women were largely similar to those of all expectant mothers, but that due to vulnerabilities relating to their circumstances, flexible and informed care provision is essential. Being knowledgeable on undocumented migrants' rights to healthcare is vital, as clinical encounters appeared highly consequential to the women's well-being and help-seeking behaviours. Negative encounters inflicted emotional distress and fear. Contrastingly, positive encounters promoted trust in clinicians, personal empowerment, and relief. Positive clinical encounters could provide rare opportunities to assist an otherwise elusive population at increased risk for both physical and psychological complications, highlighting the crucial need for adherence to ethical principles in clinical practice.


Asunto(s)
Parto Obstétrico/psicología , Aceptación de la Atención de Salud/psicología , Atención Perinatal , Confianza/psicología , Inmigrantes Indocumentados/psicología , Adaptación Psicológica , Adolescente , Adulto , Miedo , Femenino , Humanos , Parto/psicología , Embarazo , Complicaciones del Embarazo/psicología , Investigación Cualitativa , Estrés Psicológico/psicología , Suecia , Adulto Joven
20.
Mol Biol Evol ; 33(5): 1205-18, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26764160

RESUMEN

Recent results from large-scale genomic projects suggest that allele frequencies, which are highly relevant for medical purposes, differ considerably across different populations. The need for a detailed catalog of local variability motivated the whole-exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population. Like in other studies, a considerable number of rare variants were found (almost one-third of the described variants). There were also relevant differences in allelic frequencies in polymorphic variants, including ∼10,000 polymorphisms private to the Spanish population. The allelic frequencies of variants conferring susceptibility to complex diseases (including cancer, schizophrenia, Alzheimer disease, type 2 diabetes, and other pathologies) were overall similar to those of other populations. However, the trend is the opposite for variants linked to Mendelian and rare diseases (including several retinal degenerative dystrophies and cardiomyopathies) that show marked frequency differences between populations. Interestingly, a correspondence between differences in allelic frequencies and disease prevalence was found, highlighting the relevance of frequency differences in disease risk. These differences are also observed in variants that disrupt known drug binding sites, suggesting an important role for local variability in population-specific drug resistances or adverse effects. We have made the Spanish population variant server web page that contains population frequency information for the complete list of 170,888 variant positions we found publicly available (http://spv.babelomics.org/), We show that it if fundamental to determine population-specific variant frequencies to distinguish real disease associations from population-specific polymorphisms.


Asunto(s)
Enfermedad/genética , Exoma , Bases de Datos de Ácidos Nucleicos , Resistencia a Medicamentos/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Variación Genética , Genética de Población/métodos , Humanos , Internet , Pruebas de Farmacogenómica , Polimorfismo Genético , España/epidemiología
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