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1.
Trials ; 24(1): 115, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36803835

RESUMEN

BACKGROUND: Mindfulness-based interventions have been shown to improve psychological outcomes including stress, anxiety, and depression in general population studies. However, effectiveness has not been sufficiently examined in racially and ethnically diverse community-based settings. We will evaluate the effectiveness and implementation of a mindfulness-based intervention on depressive symptoms among predominantly Black women at a Federally Qualified Health Center in a metropolitan city. METHODS: In this 2-armed, stratified, individually randomized group-treated controlled trial, 274 English-speaking participants with depressive symptoms ages 18-65 years old will be randomly assigned to (1) eight weekly, 90-min group sessions of a mindfulness-based intervention (M-Body), or (2) enhanced usual care. Exclusion criteria include suicidal ideation in 30 days prior to enrollment and regular (>4x/week) meditation practice. Study metrics will be assessed at baseline and 2, 4, and 6 months after baseline, through clinical interviews, self-report surveys, and stress biomarker data including blood pressure, heart rate, and stress related biomarkers. The primary study outcome is depressive symptom score after 6 months. DISCUSSION: If M-Body is found to be an effective intervention for adults with depressive symptoms, this accessible, scalable treatment will widely increase access to mental health treatment in underserved, racial/ethnic minority communities. TRIAL REGISTRATION: ClinicalTrials.gov NCT03620721. Registered on 8 August 2018.


Asunto(s)
Depresión , Atención Plena , Adulto , Humanos , Femenino , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Depresión/diagnóstico , Depresión/terapia , Depresión/psicología , Atención Plena/métodos , Etnicidad , Grupos Minoritarios , Encuestas y Cuestionarios , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
Prostate ; 83(6): 516-523, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36591888

RESUMEN

BACKGROUND: Genetic evaluation of men with advanced prostate cancer is recognized as imperative both to guide treatment decisions and to trigger cascade genetic testing of family members. Here we investigate utilization patterns of genetic testing among a contemporary cohort of men with advanced prostate cancer at our institution. METHODS: We queried the Northwestern Electronic Data Warehouse from January 2021 to present for all men diagnosed with National Comprehensive Cancer Network high-risk/very high-risk, regional, or metastatic prostate cancer. Patients were excluded from analyses if treated at an outside institution and/or presented for a second opinion evaluation. Statistics were performed using t-test, Chi-squared test, and univariable and multivariable logistic regression with significance defined as p < 0.05. RESULTS: Atotal of 320 men (52.5%) had local/regional disease and 290 (47.5%) had metastatic disease, 53 (18.3%) of whom had castrate resistant prostate cancer. Rates of germline genetic testing rate were low in patients with localized disease (9.4%) and metastatic disease (34.1%). Only 19 (35.8%) men diagnosed with metastatic castrate resistant prostate cancer underwent germline genetic evaluation. Germline testing was most frequently discussed or ordered by medical oncologists (52%) followed by urologists (20%). Men who underwent germline testing were younger (p < 0.001), more likely to have Medicaid or private insurance (p = 0.002), and more likely to have metastatic disease (p < 0.001). There were no statistically significant differences in baseline PSA, ethnicity, race, or castration sensitivity status. Age (odds ratio [OR]: 0.94, 95% confidence interval [CI]: 0.91-0.97, p < 0.001) and metastatic disease (OR: 5.71, 95% CI: 3.63-9.22, p < 0.001) were significant independent predictors of genetic testing on multivariable logistic regression. CONCLUSIONS: Here we report that utilization of genetic testing is associated with metastatic disease and inversely associated with age. Overall, utilization rates of genetic testing remain low in all patient groups, including in the metastatic castrate resistant setting, where genetic testing can identify patients with homologous recombination repair deficiency who may benefit from use of targeted therapeutics such as PARP inhibitors. Genetic testing in men with aggressive prostate cancer is critical and barriers to routine implementation of testing require further study to develop strategies to improve utilization rates.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia , Pruebas Genéticas , Etnicidad
3.
Hernia ; 26(4): 1069-1075, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34743254

RESUMEN

PURPOSE: In 2003, randomized trials demonstrated potentially improved outcomes when local instead of general anesthesia is used for inguinal hernia repair. Our study aimed to evaluate how the use of local anesthesia for this procedure changed over time following the publication of the trials' level 1 evidence. METHODS: We used the 1998-2018 Veterans Affairs Surgical Quality Improvement Program database to identify adults who underwent open, unilateral inguinal hernia repair under local or general anesthesia. Our primary outcome was the percentage of cases performed under local anesthesia. We used a time-series design to examine the trend and rate of change of the use of local anesthesia. RESULTS: We included 97,437 veterans, of which 22,333 (22.9%) had hernia surgery under local anesthesia. The median age of veterans receiving local anesthesia remained stable at 64-67 years over time. The use of local anesthesia decreased steadily, from 38.2% at the beginning year to 15.1% in the final year (P < 0.0001). The publication of results from randomized trials (in 2003) did not appear to increase the overall use or change the rate of decline in the use of local anesthesia. Overall, we found that the use of local anesthesia decreased by about 1.5% per year. CONCLUSION: The utilization of local anesthesia for inguinal hernia repair in the VA has steadily declined over the last 20 + years, despite data showing equivalence or superiority to general anesthesia. Future studies should explore barriers to the use of local anesthesia for hernia repair.


Asunto(s)
Hernia Inguinal , Adulto , Anciano , Anestesia General , Anestesia Local/métodos , Hernia Inguinal/cirugía , Herniorrafia/efectos adversos , Herniorrafia/métodos , Humanos , Persona de Mediana Edad , Factores de Tiempo
4.
Int J Biometeorol ; 65(10): 1615-1628, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33877430

RESUMEN

Climate and weather directly impact plant phenology, affecting airborne pollen. The objective of this systematic review is to examine the impacts of meteorological variables on airborne pollen concentrations and pollen season timing. Using PRISMA methodology, we reviewed literature that assessed whether there was a relationship between local temperature and precipitation and measured airborne pollen. The search strategy included terms related to pollen, trends or measurements, and season timing. For inclusion, studies must have conducted a correlation analysis of at least 5 years of airborne pollen data to local meteorological data and report quantitative results. Data from peer-reviewed articles were extracted on the correlations between seven pollen indicators (main pollen season start date, end date, peak date, and length, annual pollen integral, average daily pollen concentration, and peak pollen concentration), and two meteorological variables (temperature and precipitation). Ninety-three articles were included in the analysis out of 9,679 articles screened. Overall, warmer temperatures correlated with earlier and longer pollen seasons and higher pollen concentrations. Precipitation had varying effects on pollen concentration and pollen season timing indicators. Increased precipitation may have a short-term effect causing low pollen concentrations potentially due to "wash out" effect. Long-term effects of precipitation varied for trees and weeds and had a positive correlation with grass pollen levels. With increases in temperature due to climate change, pollen seasons for some taxa in some regions may start earlier, last longer, and be more intense, which may be associated with adverse health impacts, as pollen exposure has well-known health effects in sensitized individuals.


Asunto(s)
Polen , Tiempo (Meteorología) , Alérgenos , Cambio Climático , Humanos , Estaciones del Año , Temperatura
5.
Osteoarthritis Cartilage ; 29(4): 507-517, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33434629

RESUMEN

OBJECTIVE: Explore patient and dietitian experiences with a multi-component dietary weight loss program for knee osteoarthritis to understand enablers and challenges to success at 6-months. DESIGN: Qualitative study embedded within a randomised controlled trial. Semi-structured individual interviews with 24 patients with knee osteoarthritis who undertook, and five dietitians who supervised, a weight management program (involving a ketogenic very low calorie diet (VLCD), video consultations, educational resources) over 6 months. Data were thematically analysed. RESULTS: Five themes were developed: (1) ease and convenience of program facilitated adherence (structure and simplicity of the meal replacements; not feeling hungry on diet; convenience of consulting via video) (2) social and professional support crucial for success (encouragement from partner, family, and friends; guidance from, and accountability to, dietitian; anxiety around going at it alone) (3) program was engaging and motivating (determination to stick to program; rapid weight loss helped motivation) (4) holistic nature of program was important (suite of high-quality educational resources; exercise important to compliment weight loss) (5) rewarding experience and lifelong impact (improved knee pain and function; positive lifestyle change). CONCLUSIONS: Patients and dietitians described positive experiences with the weight management program, valuing its simplicity, effectiveness, and convenience. Support from dietitians and a comprehensive suite of educational resources, incorporated with an exercise program, were considered crucial for success. Findings suggest this multi-component dietary program is an acceptable weight loss method in people with knee osteoarthritis that may benefit symptoms. Strategies for supporting long-term independent weight management should be a focus of future research.


Asunto(s)
Actitud del Personal de Salud , Actitud Frente a la Salud , Dieta Cetogénica , Dieta Reductora , Nutricionistas , Obesidad/dietoterapia , Osteoartritis de la Rodilla/rehabilitación , Programas de Reducción de Peso , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Osteoartritis de la Rodilla/complicaciones , Investigación Cualitativa
6.
Diabet Med ; 37(5): 805-813, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31872457

RESUMEN

AIM: To examine the value of peer support in the self-management of diabetes among veterans in an integrated health care system. METHODS: We conducted semi-structured in-depth interviews with veterans and clinicians 6 months after their participation in Empowering Patients in Chronic Care (EPIC), a group-based diabetes intervention with a peer-support component. Interviews elicited clinicians' narratives of how peer support unfolded in the groups and veterans' experiences of giving and receiving support from their peers. Data analysis was guided by principles of framework analysis using Heisler's peer-support model. RESULTS: Findings support Heisler's peer-support model and provide evidence supporting professional-led group visits with peer exchange. Clinicians and veterans endorsed informational and emotional support received in EPIC groups. Clinicians often referred to EPIC as an open forum or a support group where veterans could both give and receive help. Veterans noted the benefits of shared problem-solving and the support they received. Clinicians and veterans perceived the peer-support component of EPIC as facilitating increased empowerment in terms of self-efficacy, increased perceived social support and increased understanding of self-care. Ultimately, many veterans acknowledged that their participation in EPIC facilitated improved health-related quality of life, improved health behaviours and improved chronic disease control. CONCLUSIONS: Findings emphasize the value of peer support in managing chronic illness. Peer-support programmes may address veterans' unique challenges and have the potential to improve physical and mental health.


Asunto(s)
Diabetes Mellitus Tipo 2/terapia , Grupo Paritario , Autocuidado , Automanejo , Apoyo Social , Veteranos , Anciano , Humanos , Masculino , Participación del Paciente , Solución de Problemas , Investigación Cualitativa , Autoeficacia
7.
Int J Drug Policy ; 70: 61-69, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31082664

RESUMEN

South Africa is home to the largest number of people living with HIV/AIDS in the world. Alongside the HIV/AIDS epidemic, problematic alcohol and other drug (AOD) use is prevalent and associated with poor HIV treatment and secondary HIV prevention outcomes. International guidelines and local policy both support the integration of mental health care and AOD treatment into HIV care, yet barriers exist to implementation. This study aimed to explore patient and provider perspectives on the integration of HIV and AOD treatment services in Cape Town, South Africa. This included barriers and facilitators to task sharing AOD treatment in HIV care and preferences for a task shared approach to integrating AOD treatment in HIV care, including who should deliver the behavioural intervention. We conducted thirty semi-structured qualitative interviews with HIV and AOD treatment staff, providers, and people living with HIV/AIDS (PLWH) with moderate, problematic AOD use and difficulties (personal or structural) adhering to HIV treatment. Findings illustrated several key themes: (1) the separation between AOD and HIV services (a "siloed treatment experience"), even in the context of geographic co-location; (2) low AOD treatment literacy among HIV patients and providers, including a low awareness of existing AOD use services, even when co-located; (3) substance use stigma as a barrier to HIV and AOD treatment integration; (4) a strong patient preference for peer interventionists; and (5) the role of community health workers (CHWs) in detecting AOD use among some PLWH who had not followed up in HIV care. These findings will inform a future type 1 hybrid effectiveness-implementation trial, guided by the RE-AIM framework, to evaluate a task shared, evidence-based intervention to address problematic AOD use and improve HIV medication adherence in this setting.


Asunto(s)
Prestación Integrada de Atención de Salud/organización & administración , Infecciones por VIH/psicología , Accesibilidad a los Servicios de Salud , Grupo Paritario , Trastornos Relacionados con Sustancias/psicología , Adolescente , Adulto , Anciano , Actitud del Personal de Salud , Comorbilidad , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Investigación Cualitativa , Sudáfrica/epidemiología , Trastornos Relacionados con Sustancias/terapia , Adulto Joven
8.
Eur J Neurol ; 26(1): 142-154, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30133057

RESUMEN

BACKGROUND AND PURPOSE: We aimed to estimate the prevalence of perceived cognitive impairment (PCI) and explore its associations with lifestyle and disease characteristics in a large international cohort of people with multiple sclerosis (MS). METHODS: This study was a cross-sectional analysis. Participants rated their cognitive function over the preceding 4 weeks using four questions in a subscale within the Multiple Sclerosis Quality of Life questionnaire (MSQOL-54). These questions assessed perceived concentration, attention and memory by the patient and family/friends. Four definitions of PCI were derived, ranging from lowest to highest specificity. Associations with PCI were assessed by log-binomial regression. RESULTS: The prevalence of PCI in our sample ranged from 41.0% (95% confidence interval, 39.0-43.0) using the least-specific definition to 11.6% (95% confidence interval, 10.3-12.9) using the most specific definition. A number of factors were associated with PCI, increasing in magnitude as the definition specificity increased, including positive associations for smoking and body mass index, whereas physical activity, dietary quality and use of vitamin D/omega-3 supplements were inversely associated with PCI. CONCLUSIONS: Our study reports associations between healthy lifestyle behaviours and PCI in people with MS. Although reverse causality is a potential explanation for our findings, previous studies have shown comparable associations with healthy lifestyle and MS onset and progression. Subject to external validation, these results suggest benefits realized from a healthy lifestyle in people with MS.


Asunto(s)
Cognición , Estilo de Vida , Esclerosis Múltiple/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atención , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Estudios de Cohortes , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Memoria , Persona de Mediana Edad , Calidad de Vida , Autoinforme , Adulto Joven
9.
Eur J Pain ; 21(3): 562-572, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27807916

RESUMEN

BACKGROUND: Alpha power is believed to have an inverse relationship with the perception of pain. Increasing alpha power through an external stimulus may, therefore, induce an analgesic effect. Here, we attempt to modulate the perception of a moderately painful acute laser stimulus by separately entraining three frequencies across the alpha band: 8, 10 and 12 Hz. METHODS: Participants were exposed to either visual or auditory stimulation at three frequencies in the alpha-band range and a control frequency. We collected verbal pain ratings of laser stimuli from participants following 10 minutes of flashing LED goggle stimulation and 10 minutes of binaural beat stimulation across the alpha range. Alterations in sleepiness, anxiety and negative mood were recorded following each auditory or visual alpha-rhythm stimulation session. RESULTS: A significant reduction in pain ratings was found after both the visual and the auditory stimulation across all three frequencies compared with the control condition. In the visual group, a significantly larger reduction was recorded following the 10-Hz stimulation than succeeding the 8- and 12-Hz conditions. CONCLUSIONS: This study suggests that a short presentation of auditory and visual stimuli, oscillating in the alpha range, have an analgesic effect on acute laser pain, with the largest effect following the 10-Hz visual stimulation. Pain reductions following stimulation in the alpha range are independent of sleepiness, anxiety, and negative moods. SIGNIFICANCE: This study provides new behavioural evidence showing that visual and auditory entrainment of frequencies in the alpha-wave range can influence the perception of acute pain in humans.


Asunto(s)
Estimulación Acústica/métodos , Ritmo alfa , Percepción del Dolor , Estimulación Luminosa/métodos , Estimulación Acústica/efectos adversos , Estimulación Acústica/instrumentación , Adulto , Afecto , Ansiedad/psicología , Femenino , Voluntarios Sanos , Humanos , Rayos Láser , Masculino , Dimensión del Dolor , Estimulación Luminosa/efectos adversos , Estimulación Luminosa/instrumentación , Psicofísica , Fases del Sueño , Adulto Joven
10.
J Physiol ; 594(4): 1087-101, 2016 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-26613967

RESUMEN

KEY POINTS: Increased appetite and weight gain occurs during pregnancy, associated with development of leptin resistance, and satiety responses to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) are suppressed. This study investigated hypothalamic responses to α-MSH during pregnancy, using c-fos expression in specific hypothalamic nuclei as a marker of neuronal signalling, and in vivo electrophysiology in supraoptic nucleus (SON) oxytocin neurons, as a representative α-MSH-responsive neuronal population that shows a well-characterised α-MSH-induced inhibition of firing. While icv injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, supraoptic, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, this response was suppressed in pregnant rats. Similarly, SON oxytocin neurons in pregnant rats did not demonstrate characteristic α-MSH-induced inhibition of firing that was observed in non-pregnant animals. Given the known functions of α-MSH in the hypothalamus, the attenuated responses are likely to facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy. ABSTRACT: During pregnancy, a state of positive energy balance develops to support the growing fetus and to deposit fat in preparation for the subsequent metabolic demands of lactation. As part of this maternal adaptation, the satiety response to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) is suppressed. To investigate whether pregnancy is associated with changes in the response of hypothalamic α-MSH target neurons, non-pregnant and pregnant rats were treated with α-MSH or vehicle and c-fos expression in hypothalamic nuclei was then examined. Furthermore, the firing rate of supraoptic nucleus (SON) oxytocin neurons, a known α-MSH responsive neuronal population, was examined in non-pregnant and pregnant rats following α-MSH treatment. Intracerebroventricular injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, but no significant increase was observed in any of these regions in pregnant rats. In the SON, α-MSH did induce expression of c-fos during pregnancy, but this was significantly reduced compared to that observed in the non-pregnant group. Furthermore, during pregnancy, SON oxytocin neurons did not demonstrate the characteristic α-MSH-induced inhibition of firing rate that was observed in non-pregnant animals. Melanocortin receptor mRNA levels during pregnancy were similar to non-pregnant animals, suggesting that receptor down-regulation is unlikely to be a mechanism underlying the attenuated responses to α-MSH during pregnancy. Given the known functions of α-MSH in the hypothalamus, the attenuated responses will facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy.


Asunto(s)
Hipotálamo/metabolismo , Potenciales Postsinápticos Inhibidores , alfa-MSH/farmacología , Animales , Femenino , Hipotálamo/citología , Hipotálamo/efectos de los fármacos , Hipotálamo/fisiología , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/fisiología , Oxitocina/metabolismo , Embarazo , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Melanocortina/genética , Receptores de Melanocortina/metabolismo , alfa-MSH/metabolismo
11.
Free Radic Res ; 49(2): 175-85, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25426774

RESUMEN

Chronically haemodialysed end-stage renal disease patients are at high risk of morbidity arising from complications of dialysis, the underlying pathology that has led to renal disease and the complex pathology of chronic kidney disease. Anaemia is commonplace and its origins are multifactorial, involving reduced renal erythropoietin production, accumulation of uremic toxins and an increase in erythrocyte fragility. Oxidative damage is a common risk factor in renal disease and its co-morbidities and is known to cause erythrocyte fragility. Therefore, we have investigated the hypothesis that specific erythrocyte membrane proteins are more oxidised in end-stage renal disease patients and that vitamin C supplementation can ameliorate membrane protein oxidation. Eleven patients and 15 control subjects were recruited to the study. Patients were supplemented with 2 × 500 mg vitamin C per day for 4 weeks. Erythrocyte membrane proteins were prepared pre- and post-vitamin C supplementation for determination of protein oxidation. Total protein carbonyls were reduced by vitamin C supplementation but not by dialysis when investigated by enzyme linked immunosorbent assay. Using a western blot to detect oxidised proteins, one protein band, later identified as containing ankyrin, was found to be oxidised in patients but not controls and was reduced significantly by 60% in all patients after dialysis and by 20% after vitamin C treatment pre-dialysis. Ankyrin oxidation analysis may be useful in a stratified medicines approach as a possible marker to identify requirements for intervention in dialysis patients.


Asunto(s)
Ancirinas/química , Ácido Ascórbico/uso terapéutico , Membrana Eritrocítica/química , Fallo Renal Crónico/sangre , Diálisis Renal , Ancirinas/efectos de los fármacos , Membrana Eritrocítica/efectos de los fármacos , Humanos , Fallo Renal Crónico/tratamiento farmacológico , Fallo Renal Crónico/terapia , Oxidación-Reducción/efectos de los fármacos
12.
Arch Virol ; 159(12): 3427-33, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25287129

RESUMEN

Potato mop-top virus (PMTV; family Virgaviridae) was reported recently in the Pacific Northwestern USA. To better understand the genetic diversity of this virus, the complete genome of an isolate from Washington State (WA), USA, was characterized. Sequence comparisons of the WA isolate with other known sequences revealed that the RNA-Rep-encoded RdRp protein and the RNA-CP-encoded coat protein displayed >99 % amino acid sequence identity to those of two Nordic (RdRp) and several European and North American isolates (CP), respectively. The RNA-TGB-encoded TGB 1 and TGB 3 protein sequences had >99 % amino acid sequence identity to the corresponding proteins of Czech and Danish isolates, whereas the TGB 2 protein is identical to those of Colombian isolates. Phylogenetic analysis of the viral genes of the WA isolate reflected the close relationship between WA and European isolates. RFLP analysis of corresponding DNA of RNA TGB and RNA CP revealed that the WA isolate has the RNA TGB-II and RNA CP-B types, which are prevalent in Europe and other parts of world. This is the first report of the complete genome characterization of PMTV from the Americas.


Asunto(s)
Genoma Viral , Virus ARN/clasificación , Virus ARN/genética , ARN Viral/genética , Análisis de Secuencia de ADN , Solanum tuberosum/virología , Secuencia de Aminoácidos , Análisis por Conglomerados , Datos de Secuencia Molecular , Filogenia , Virus ARN/aislamiento & purificación , Homología de Secuencia de Aminoácido , Proteínas Virales/genética , Washingtón
13.
BMC Evol Biol ; 13: 172, 2013 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-23957559

RESUMEN

BACKGROUND: A dual olfactory system, represented by two anatomically distinct but spatially proximate chemosensory epithelia that project to separate areas of the forebrain, is known in several classes of tetrapods. Lungfish are the earliest evolving vertebrates known to have this dual system, comprising a main olfactory and a vomeronasal system (VNO). Lampreys, a group of jawless vertebrates, have a single nasal capsule containing two anatomically distinct epithelia, the main (MOE) and the accessory olfactory epithelia (AOE). We speculated that lamprey AOE projects to specific telencephalic regions as a precursor to the tetrapod vomeronasal system. RESULTS: To test this hypothesis, we characterized the neural circuits and molecular profiles of the accessory olfactory epithelium in the sea lamprey (Petromyzon marinus). Neural tract-tracing revealed direct and reciprocal connections with the dorsomedial telencephalic neuropil (DTN) which in turn projects directly to the dorsal pallium and the rostral hypothalamus. High-throughput sequencing demonstrated that the main and the accessory olfactory epithelia have virtually identical profiles of expressed genes. Real time quantitative PCR confirmed expression of representatives of all 3 chemoreceptor gene families identified in the sea lamprey genome. CONCLUSION: Anatomical and molecular evidence shows that the sea lamprey has a primordial accessory olfactory system that may serve a chemosensory function.


Asunto(s)
Lampreas/fisiología , Animales , Encéfalo/fisiología , Hipotálamo/fisiología , Lampreas/anatomía & histología , Lampreas/genética , Vías Olfatorias , Transcriptoma , Órgano Vomeronasal/metabolismo
14.
J Neuroendocrinol ; 25(8): 678-710, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23701531

RESUMEN

The hypothalamic supraoptic and paraventricular nuclei contain magnocellular neurosecretory cells (MNCs) that project to the posterior pituitary gland where they secrete either oxytocin or vasopressin (the antidiuretic hormone) into the circulation. Oxytocin is important for delivery at birth and is essential for milk ejection during suckling. Vasopressin primarily promotes water reabsorption in the kidney to maintain body fluid balance, but also increases vasoconstriction. The profile of oxytocin and vasopressin secretion is principally determined by the pattern of action potentials initiated at the cell bodies. Although it has long been known that the activity of MNCs depends upon afferent inputs that relay information on reproductive, osmotic and cardiovascular status, it has recently become clear that activity depends critically on local regulation by glial cells, as well as intrinsic regulation by the MNCs themselves. Here, we provide an overview of recent advances in our understanding of how intrinsic and local extrinsic mechanisms integrate with afferent inputs to generate appropriate physiological regulation of oxytocin and vasopressin MNC activity.


Asunto(s)
Vías Aferentes , Neuronas/fisiología , Animales , Hipotálamo/citología , Hipotálamo/metabolismo , Hipotálamo/fisiología , Neuronas/metabolismo , Oxitocina/metabolismo , Ratas
15.
Gene Ther ; 20(8): 853-60, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23303282

RESUMEN

Genetic modification of human T cells to express transgene-encoded polypeptides, such as tumor targeting chimeric antigen receptors, is an emerging therapeutic modality showing promise in clinical trials. The development of simple and efficient techniques for purifying transgene(+) T cells is needed to facilitate the derivation of cell products with uniform potency and purity. Unlike selection platforms that utilize physical methods (immunomagnetic or sorting) that are technically cumbersome and limited by the expense and availability of clinical-grade components, we focused on designing a selection system on the basis of the pharmaceutical drug methotrexate (MTX), a potent allosteric inhibitor of human dihydrofolate reductase (DHFR). Here, we describe the development of self inactivating (SIN) lentiviral vectors that direct the coordinated expression of a CD19-specific chimeric antigen receptor (CAR), the human EGFRt tracking/suicide construct, and a methotrexate-resistant human DHFR mutein (huDHFR(FS); L22F, F31S). Our results demonstrate that huDHFR(FS) expression renders lentivirally transduced primary human CD45RO(+)CD62L(+) central memory T cells resistant to lymphotoxic concentrations of MTX up to 0.1 µM. Our modular complementary DNA (cDNA) design insures that selected MTX-resistant T cells co-express functionally relevant levels of the CD19-specific CAR and EGFRt. This selection system on the basis of huDHFR(FS) and MTX has considerable potential utility in the manufacturing of clinical-grade T cell products.


Asunto(s)
Ingeniería Celular , Vectores Genéticos , Linfocitos T/citología , Tetrahidrofolato Deshidrogenasa/genética , Antígenos CD19/genética , Antagonistas del Ácido Fólico/farmacología , Técnicas de Transferencia de Gen , Humanos , Lentivirus/genética , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/genética , Metotrexato/farmacología , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo
16.
J Environ Monit ; 14(9): 2367-81, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22796730

RESUMEN

Total petroleum hydrocarbons (TPH) or petroleum hydrocarbons (PHC) are one of the most widespread soil contaminants in Canada, the United States and many other countries worldwide. Clean-up of PHC-contaminated soils costs the Canadian economy hundreds of millions of dollars annually. In Canada, most PHC-contaminated site evaluations are based on the methods developed by the Canadian Council of the Ministers of the Environment (CCME). However, the CCME method does not differentiate PHC from BOC (the naturally occurring biogenic organic compounds), which are co-extracted with petroleum hydrocarbons in soil samples. Consequently, this could lead to overestimation of PHC levels in soil samples. In some cases, biogenic interferences can even exceed regulatory levels (300 µg g(-1) for coarse soils and 1300 µg g(-1) for fine soils for Fraction 3, C(16)-C(34) range, in the CCME Soil Quality Level). Resulting false exceedances can trigger unnecessary and costly cleanup or remediation measures. Therefore, it is critically important to develop new protocols to characterize and quantitatively differentiate PHC and BOC in contaminated soils. The ultimate objective of this PERD (Program of Energy Research and Development) project is to correct the misconception that all detectable hydrocarbons should be regulated as toxic petroleum hydrocarbons. During 2009-2010, soil and plant samples were collected from over forty oil-contaminated and paired background sites in various provinces. The silica gel column cleanup procedure was applied to effectively remove all target BOC from the oil-contaminated sample extracts. Furthermore, a reliable GC-MS method in combination with the derivatization technique, developed in this laboratory, was used for identification and characterization of various biogenic sterols and other major biogenic compounds in these oil-contaminated samples. Both PHC and BOC in these samples were quantitatively determined. This paper reports the characterization results of this set of 21 samples. In general, the presence of petroleum-characteristic alkylated PAH homologues and biomarkers can be used as unambiguous indicators of the contamination of oil and petroleum product hydrocarbons; while the absence of petroleum-characteristic alkylated PAH homologues and biomarkers and the presence of abundant BOC can be used as unambiguous indicators of the predominance of natural organic compounds in soil samples.


Asunto(s)
Monitoreo del Ambiente/métodos , Hidrocarburos/química , Contaminación por Petróleo/análisis , Petróleo/análisis , Contaminantes del Suelo/química , Hidrocarburos/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Hidrocarburos Policíclicos Aromáticos/química , Suelo/química , Contaminantes del Suelo/análisis
17.
Neurosci Lett ; 520(2): 165-73, 2012 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-22487846

RESUMEN

The cognitive modulation of pain is influenced by a number of factors ranging from attention, beliefs, conditioning, expectations, mood, and the regulation of emotional responses to noxious sensory events. Recently, mindfulness meditation has been found attenuate pain through some of these mechanisms including enhanced cognitive and emotional control, as well as altering the contextual evaluation of sensory events. This review discusses the brain mechanisms involved in mindfulness meditation-related pain relief across different meditative techniques, expertise and training levels, experimental procedures, and neuroimaging methodologies. Converging lines of neuroimaging evidence reveal that mindfulness meditation-related pain relief is associated with unique appraisal cognitive processes depending on expertise level and meditation tradition. Moreover, it is postulated that mindfulness meditation-related pain relief may share a common final pathway with other cognitive techniques in the modulation of pain.


Asunto(s)
Encéfalo/fisiopatología , Meditación/métodos , Manejo del Dolor/métodos , Dolor/psicología , Atención , Terapia Cognitivo-Conductual , Humanos , Neuroimagen , Dolor/fisiopatología
18.
Artículo en Inglés | MEDLINE | ID: mdl-22454689

RESUMEN

Objective. To investigate the effects of an 8-week meditation program on perceived stress, sleep, mood, and related outcomes in adults with cognitive impairment and their caregivers. Methods. Community-dwelling adults with a diagnosis of mild cognitive impairment or early-stage Alzheimer's disease, together with their live-in caregivers, were enrolled in the study. After a brief training, participants were asked to meditate for 11 minutes, twice daily for 8 weeks. Major outcomes included measures of perceived stress (Perceived Stress Scale), sleep (General Sleep Disturbance Scale), mood (Profile of Mood States), memory functioning (Memory Functioning Questionnaire), and blood pressure. Participants were assessed pre- and post-intervention. Results. Ten participants (5 of 6 dyads) completed the study. Treatment effects did not vary by participant status; analyses were thus pooled across participants. Adherence was good (meditation sessions completed/week: X = 11.4 ± 1.1). Participants demonstrated improvement in all major outcomes, including perceived stress (P < 0.001), mood (overall, P = 0.07; depression, P = 0.01), sleep (P < 0.04), retrospective memory function (P = 0.04), and blood pressure (systolic, P = 0.004; diastolic, P = 0.065). Conclusions. Findings of this exploratory trial suggest that an 8-week meditation program may offer an acceptable and effective intervention for reducing perceived stress and improving certain domains of sleep, mood, and memory in adults with cognitive impairment and their caregivers.

19.
J Neuroendocrinol ; 24(7): 1012-29, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22420322

RESUMEN

Previous research suggests that the nonpeptide oxytocin receptor (OTR) agonist WAY 267,464 may only partly mimic the effects of oxytocin in rodents. The present study further explored these differences and related them to OTR and vasopressin 1a receptor (V(1a) R) pharmacology and regional patterns of c-Fos expression. Binding data for WAY 267,464 and oxytocin were obtained by displacement binding assays on cellular membranes, while functional receptor data were generated by luciferase reporter assays. For behavioural testing, adolescent rats were tested in a social preference paradigm, the elevated plus-maze (EPM) and for locomotor activity changes following WAY 267,464 (10 and 100 mg/kg, i.p.) or oxytocin (0.1 and 1 mg/kg, i.p.). The higher doses were also examined for their effects on regional c-Fos expression. Results showed that WAY 267,464 had higher affinity (K(i) ) at the V(1a) R than the OTR (113 versus 978 nm). However, it had no functional response at the V(1a) R and only a weak functional effect (EC(50) ) at the OTR (881 nm). This suggests WAY 267,464 is an OTR agonist with weak affinity and a possible V(1a) R antagonist. Oxytocin showed high binding at the OTR (1.0 nm) and V(1a) R (503 nm), with a functional EC(50) of 9.0 and 59.7 nm, respectively, indicating it is a potent OTR agonist and full V(1a) R agonist. WAY 267,464 (100 mg/kg), but not oxytocin, significantly increased the proportion of time spent with a live rat, over a dummy rat, in the social preference test. Neither compound affected EPM behaviour, whereas the higher doses of WAY 267,464 and oxytocin suppressed locomotor activity. WAY 267,464 and oxytocin produced similar c-Fos expression in the paraventricular hypothalamic nucleus, central amygdala, lateral parabrachial nucleus and nucleus of the solitary tract, suggesting a commonality of action at the OTR with the differential doses employed. However, WAY 267,464 caused greater c-Fos expression in the medial amygdala and the supraoptic nucleus than oxytocin, and lesser effects in the locus coeruleus. Overall, our results confirm the differential effects of WAY 267,464 and oxytocin and suggest that this may reflect contrasting actions of WAY 267,464 and oxytocin at the V(1a) R. Antagonism of the V(1a) R by WAY 267,464 could underlie some of the prosocial effects of this drug either through a direct action or through disinhibition of oxytocin circuitry that is subject to vasopressin inhibitory influences.


Asunto(s)
Conducta Animal/efectos de los fármacos , Benzodiazepinas/metabolismo , Benzodiazepinas/farmacología , Proteínas Proto-Oncogénicas c-fos/genética , Pirazoles/metabolismo , Pirazoles/farmacología , Receptores de Oxitocina/metabolismo , Factores de Edad , Animales , Células Cultivadas , Evaluación Preclínica de Medicamentos , Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Masculino , Unión Proteica , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Wistar , Receptores de Oxitocina/agonistas , Conducta Social , Distribución Tisular/efectos de los fármacos , Distribución Tisular/genética
20.
Clin Exp Dermatol ; 37(4): 346-9, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22369176

RESUMEN

BACKGROUND: Cosmetic products are not tested with the same rigour as medical treatments, but recent high-quality studies have shown significant reductions in changes of skin ageing with use of cosmetic antiageing products. AIM: To test whether a cosmetic 'anti-spot' two-step treatment containing a complex of seaweed-derived oligosaccharide and zinc would produce a significant improvement in mild acne. METHODS: A double-blind, vehicle-controlled trial of this treatment was performed for 8 weeks on 60 age-matched participants with mild acne. They were divided into two groups: 30 participants were treated with vehicle control and 30 with the active treatment containing a seaweed-derived oligosaccharide complexed with 0.1% zinc pyrrolidone. RESULTS: After 8 weeks, both groups had a reduction in comedones, papules and pustules, and this was significantly greater in the active than control group at 2, 4 and 8 weeks. CONCLUSIONS: Cosmetic products may offer some benefit for mild acne and still meet the requirements of the European Cosmetic Directive. In particular, the seaweed-derived oligosaccharide complexed with 0.1% zinc pyrrolidone used in this study produced a significant reduction in acne vs. a control treatment. Cosmetic companies should conduct blinded controlled trials of their product's efficacy and publish the results.


Asunto(s)
Acné Vulgar/tratamiento farmacológico , Cosméticos/uso terapéutico , Oligosacáridos/uso terapéutico , Extractos Vegetales/uso terapéutico , Algas Marinas/química , Compuestos de Zinc/uso terapéutico , Administración Tópica , Adolescente , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Adulto Joven
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