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1.
J Intellect Disabil Res ; 68(2): 113-127, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37740553

RESUMEN

BACKGROUND: 3q29 deletion syndrome (3q29del) is associated with a significantly increased risk for neurodevelopmental and neuropsychiatric phenotypes. Mild to moderate intellectual disability (ID) is common in this population, and previous work by our team identified substantial deficits in adaptive behaviour. However, the full profile of adaptive function in 3q29del has not been described nor has it been compared with other genomic syndromes associated with elevated risk for neurodevelopmental and neuropsychiatric phenotypes. METHODS: Individuals with 3q29del (n = 32, 62.5% male) were evaluated using the Vineland Adaptive Behaviour Scales, Third Edition, Comprehensive Parent/Caregiver Form (Vineland-3). We explored the relationship between adaptive behaviour and cognitive function, executive function, and neurodevelopmental and neuropsychiatric comorbidities in our 3q29del study sample, and we compared subjects with 3q29del with published data on fragile X syndrome, 22q11.2 deletion syndrome and 16p11.2 deletion and duplication syndromes. RESULTS: Individuals with 3q29del had global deficits in adaptive behaviour that were not driven by specific weaknesses in any given domain. Individual neurodevelopmental and neuropsychiatric diagnoses had a small effect on adaptive behaviour, and the cumulative number of comorbid diagnoses was significantly negatively associated with Vineland-3 performance. Both cognitive ability and executive function were significantly associated with adaptive behaviour, and executive function was a better predictor of Vineland-3 performance than cognitive ability. Finally, the severity of adaptive behaviour deficits in 3q29del was distinct from previously published data on comparable genomic disorders. CONCLUSIONS: Individuals with 3q29del have significant deficits in adaptive behaviour, affecting all domains assessed by the Vineland-3. Executive function is a better predictor of adaptive behaviour than cognitive ability in this population and suggests that interventions targeting executive function may be an effective therapeutic strategy.


Asunto(s)
Síndrome del Cromosoma X Frágil , Discapacidad Intelectual , Humanos , Masculino , Femenino , Discapacidad Intelectual/psicología , Función Ejecutiva , Cognición , Síndrome del Cromosoma X Frágil/complicaciones , Adaptación Psicológica
2.
Diabet Med ; 37(11): 1816-1824, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-31365159

RESUMEN

AIM: In a high proportion of people with recently diagnosed Type 2 diabetes, a short (2-3-month) low-calorie diet is able to restore normal glucose and insulin metabolism. The aim of this study was to determine the feasibility of this approach in Barbados. METHODS: Twenty-five individuals with Type 2 diabetes diagnosed within past 6 years, not on insulin, BMI ≥ 27 kg/m2 were recruited. Hypoglycaemic medication was stopped on commencement of the 8-week liquid (760 calorie) diet. Insulin response was assessed in meal tests at baseline, 8 weeks and 8 months. Semi-structured interviews, analysed thematically, explored participants' experiences. 'Responders' were those with fasting plasma glucose (FPG) < 7 mmol/l at 8 weeks. RESULTS: Ten men and 15 women (mean age 48, range 26-68 years) participated. Mean (sd) BMI was 34.2 kg/m2 (6.0); FPG 9.2 mmol/l (2.2). Mean weight loss at 8 weeks and 8 months was 10.1 kg [95% confidence interval (CI) 8.1, 12.0] and 8.2 kg (95% CI 5.8, 10.6); FPG was lower by 2.2 mmol/l (95% CI 1.2, 3.2) and 1.7 mmol/l (95% CI 0.8, 2.7) respectively. Nine of 11 (82%) of those who lost ≥ 10 kg were 'responders' compared with 6 of 14 (43%) who lost < 10 kg (P = 0.048). The 30-min insulin increment was higher in responders at baseline and follow-up (P ≤ 0.01). A food culture based on starchy foods and pressures to eat large amounts at social events were among the challenges identified by participants. CONCLUSIONS: The feasibility of this approach to weight loss and diabetes remission in a predominantly black population in Barbados was demonstrated.


Asunto(s)
Restricción Calórica/métodos , Diabetes Mellitus Tipo 2/dietoterapia , Alimentos Formulados , Obesidad/dietoterapia , Adulto , Barbados , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Ayuno , Estudios de Factibilidad , Conducta Alimentaria , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Influencia de los Compañeros , Inducción de Remisión
3.
Anaesthesia ; 75(6): 809-815, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32026466

RESUMEN

The applicability of the results of any clinical trial will depend to a large extent on whether the study population is representative of the population seen in clinical practice. The growing older surgical population presents challenges for peri-operative researchers to ensure there is adequate representation of patients in terms of their age, sex, race and ethnicity in clinical trials. A review of purposively sampled published randomised controlled trials was performed to establish the age, sex, race and ethnicity of study participants. These data were compared with national registry data for the relevant surgical populations. We included 224 peri-operative trials that were cited in 469 retrieved meta-analyses. Of these, 50 (22.3%) had an upper age limit to recruitment. The median (range [IQR]) difference in study population age from the registry population age was: -2.4 (-6.2 to 1.0 [-34.7 to 14.5]) years for all randomised controlled trials; -6.2 (-9.4 to -2.8 [-18.6 to 4.6]) years for randomised controlled trials of patients undergoing hip arthroplasty; and -3.4 (-9.6 to -1.1 [-34.7 to 2.9]) years for randomised controlled trials of patients undergoing hip fracture surgery. In 92 (41.1%) randomised controlled trials, the proportion of each sex in the study population was more than 25% different from the proportion in the registry population. Only 5 (2.2%) trials published data on the race or ethnicity of participants. We conclude that peri-operative randomised controlled trials are unlikely to be representative of the age and sex of clinically treated surgical populations. Researchers must endeavour to ensure representative study populations are recruited to future clinical trials.


Asunto(s)
Etnicidad/estadística & datos numéricos , Fracturas de Cadera/cirugía , Medicina Perioperatoria/métodos , Grupos Raciales/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Factores de Edad , Humanos , Sistema de Registros , Factores Sexuales
4.
Clin Radiol ; 72(3): 236-241, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28040200

RESUMEN

AIM: To investigate the natural history of untreated small (<3 mm) and microscopic pulmonary arteriovenous malformations (PAVMs) in hereditary haemorrhagic telangiectasia (HHT) in order to discern the optimal frequency of follow-up thoracic computed tomography (CT). MATERIALS AND METHODS: A retrospective analysis was performed on the follow-up data for definite and suspected HHT patients with untreated PAVMs. RESULTS: For small PAVMs in definite HHT (n=13), PAVM enlargement was identified in one patient (1/13, 7.7%) after 10.7 years follow-up and was successfully treated using transcatheter embolisation (TCE). For microscopic PAVMs in definite HHT (n=28), two patients (2/28, 7%) developed small asymptomatic PAVMs, which did not meet the size criteria for TCE after 6.8 years of follow-up. For small PAVMs in suspected HHT (n=5), feeding artery enlargement was seen in one patient (1/5, 20%) after 7.9 years, but again, this did not meet the size criteria for embolisation. No macroscopic PAVM development was identified after a median follow-up of 5.4 years in suspected HHT with microscopic PAVMs (n=20). CONCLUSION: For small and microscopic PAVMs in HHT, PAVM enlargement was found to be more infrequent than would be expected based on current guidelines; therefore, potentially challenging the current surveillance imaging recommendation of a repeat thoracic CT every 5 years.


Asunto(s)
Malformaciones Arteriovenosas/diagnóstico por imagen , Arteria Pulmonar/anomalías , Venas Pulmonares/anomalías , Telangiectasia Hemorrágica Hereditaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Espera Vigilante/métodos , Adolescente , Adulto , Anciano , Malformaciones Arteriovenosas/etiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Arteria Pulmonar/diagnóstico por imagen , Venas Pulmonares/diagnóstico por imagen , Radiografía Torácica/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Telangiectasia Hemorrágica Hereditaria/complicaciones , Factores de Tiempo , Adulto Joven
5.
Diabet Med ; 33(6): 827-34, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26642039

RESUMEN

AIMS: To create a summative document containing aims, objectives and methods that can be used for the training of healthcare professionals in inpatient diabetes care. METHODS: A four-stage approach was introduced for the ward-based teaching of inpatient diabetes care at the University of the West Indies, Cave Hill over the 2014-2015 academic year. Within this approach, 55 students (100%) submitted aims, objectives and methods to support two 2-h, ward-based sessions. This was guided by brief instructions and access to a copy of the Endocrine Society Clinical Practice Guideline on the management of non-critical, non-perioperative inpatient diabetes. Conceptual content analysis was used to convert submissions into a unifying document. RESULTS: Six themes emerged from students' submissions: diagnosis; assessment and investigation of diabetes and its complications; planning individualized care and pharmacological management; hypoglycaemia management, including severe hypoglycaemia; patient education; discharge planning; and multidisciplinary teamwork. Students were primarily interested in patient management and treatment using higher-level objectives and active learning methods. CONCLUSIONS: This study produced comprehensive, student-generated, and hence student-centred, aims, objectives and methods for inpatient diabetes care with objectives appropriately set for higher cognitive levels of learning. This material can be used to guide teaching or for further development into a curriculum. This is the first known publication of content that could be used in a ward-based inpatient diabetes curriculum.


Asunto(s)
Curriculum , Diabetes Mellitus Tipo 2/terapia , Personal de Salud/educación , Hospitalización , Prácticas Clínicas/métodos , Humanos , Estudiantes de Medicina , Enseñanza , Indias Occidentales
6.
Rock Mech Rock Eng ; 49(2): 661-671, 2016 02.
Artículo en Inglés | MEDLINE | ID: mdl-26549926

RESUMEN

Ground control research in underground coal mines has been ongoing for over 50 years. One of the most problematic issues in underground coal mines is roof failures associated with weak shale. This paper will present a historical narrative on the research the National Institute for Occupational Safety and Health has conducted in relation to rock mechanics and shale. This paper begins by first discussing how shale is classified in relation to coal mining. Characterizing and planning for weak roof sequences is an important step in developing an engineering solution to prevent roof failures. Next, the failure mechanics associated with the weak characteristics of shale will be discussed. Understanding these failure mechanics also aids in applying the correct engineering solutions. The various solutions that have been implemented in the underground coal mining industry to control the different modes of failure will be summarized. Finally, a discussion on current and future research relating to rock mechanics and shale is presented. The overall goal of the paper is to share the collective ground control experience of controlling roof structures dominated by shale rock in underground coal mining.

7.
Climacteric ; 16(5): 550-4, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23374139

RESUMEN

OBJECTIVE: The aim of this study was qualitatively to describe and examine the expectations and experiences of the midlife transition in Arab women living in Qatar. METHOD: Six focus groups were conducted with Arab women living in Qatar: three groups of local Qatari women, and three groups of non-Qatari Arab women originating from neighboring countries. A purposive sample of 41 pre-, peri-, and postmenopausal women aged 40-60 years participated. The semi-structured group format encouraged discussion around knowledge about menopause; physical, emotional and social experiences related to menopause; and cultural differences that may exist related to menopause. RESULTS: The majority of women considered menopause as a maturing experience, although the term 'menopause' was considered to have negative connotations. Postmenopausal women described menopausal symptoms consistent with general knowledge, but many premenopausal women were unaware of symptoms, even if they knew someone who had experienced menopause. Postmenopausal women were more socially active than before and were able to participate in religious activities that they previously could not attend during menses. How a woman experienced menopause depended on the husband's level of support, and some women believed that Western women did not have the appropriate support from husbands and families that Arab women have; they felt this lack of support could lead to negative outcomes such as being at an increased risk for suicide caused by depression during menopause. CONCLUSION: Qatari and non-Qatari women had many similarities in how they perceived and experienced menopause, although they collectively believed that the experiences of Western women are different.


Asunto(s)
Árabes , Menopausia , Adulto , Árabes/psicología , Cultura , Emociones , Ejercicio Físico , Femenino , Grupos Focales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Menopausia/etnología , Menopausia/fisiología , Menopausia/psicología , Persona de Mediana Edad , Posmenopausia/etnología , Posmenopausia/psicología , Qatar , Religión , Conducta Social , Esposos
8.
Nutr Bull ; 48(2): 267-277, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36807740

RESUMEN

Suboptimal status of folate and/or interrelated B vitamins (B12 , B6 and riboflavin) can perturb one-carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate-related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence-based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition-epigenome-brain relationship, particularly focussing on folate-related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio-banked samples from existing well-characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition-epigenome-brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state-of-the-art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle.


Asunto(s)
Ácido Fólico , Complejo Vitamínico B , Niño , Femenino , Embarazo , Humanos , Anciano , Ácido Fólico/uso terapéutico , Complejo Vitamínico B/farmacología , Encéfalo/diagnóstico por imagen , Dieta , Vitamina A/farmacología , Vitamina K/farmacología , Epigénesis Genética
9.
J Community Health ; 37(4): 763-72, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22109386

RESUMEN

Employment status is related to treatment recovery and quality of life in breast cancer survivors, yet little is known about return to work in immigrant and minority survivors. We conducted an exploratory qualitative study using ethnically cohesive focus groups of urban breast cancer survivors who were African-American, African-Caribbean, Chinese, Filipina, Latina, or non-Latina white. We audio- and video-recorded, transcribed, and thematically coded the focus group discussions and we analyzed the coded transcripts within and across ethnic groups. Seven major themes emerged related to the participants' work experiences after diagnosis: normalcy, acceptance, identity, appearance, privacy, lack of flexibility at work, and employer support. Maintaining a sense of normalcy was cited as a benefit of working by survivors in each group. Acceptance of the cancer diagnosis was most common in the Chinese group and in participants who had a family history of breast cancer; those who described this attitude were likely to continue working throughout the treatment period. Appearance was important among all but the Chinese group and was related to privacy, which many thought was necessary to derive the benefit of normalcy at work. Employer support included schedule flexibility, medical confidentiality, and help maintaining a normal work environment, which was particularly important to our study sample. Overall, we found few differences between the different ethnic groups in our study. These results have important implications for the provision of support services to and clinical management of employed women with breast cancer, as well as for further large-scale research in disparities and employment outcomes.


Asunto(s)
Neoplasias de la Mama/etnología , Emigrantes e Inmigrantes/psicología , Empleo/psicología , Grupos Minoritarios/psicología , Sobrevivientes/psicología , Población Urbana , Adaptación Psicológica , Adulto , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/psicología , Emigrantes e Inmigrantes/estadística & datos numéricos , Empleo/estadística & datos numéricos , Etnicidad/psicología , Etnicidad/estadística & datos numéricos , Femenino , Grupos Focales , Humanos , Relaciones Interprofesionales , Persona de Mediana Edad , Grupos Minoritarios/estadística & datos numéricos , Investigación Cualitativa , Sobrevivientes/estadística & datos numéricos , Población Urbana/estadística & datos numéricos
10.
J Cell Biol ; 58(2): 340-5, 1973 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-4738104

RESUMEN

Mitochondrial DNA (mit-DNA) synthesis was compared in suspension cultures of Chinese hamster cells (line CHO) whose cell cycle events had been synchronized by isoleucine deprivation or mitotic selection. At hourly intervals during cell cycle progression, synchronized cells were exposed to tritiated thymidine ([(3)H]TdR), homogenized, and nuclei and mitochondria isolated by differential centrifugation. Mit-DNA and nuclear DNA were isolated and incorporation of radioisotope measured as counts per minute ([(3)H]TdR) per microgram DNA. Mit-DNA synthesis in cells synchronized by mitotic selection began after 4 h and continued for approximately 9 h. This time-course pattern resembled that of nuclear DNA synthesis. In contrast, mit-DNA synthesis in cells synchronized by isoleucine deprivation did not begin until 9-12 h after addition of isoleucine and virtually all [(3)H]TdR was incorporated during a 3-h interval. We have concluded from these results that mit-DNA synthesis is inhibited in CHO cells which are arrested in G(1) because of isoleucine deprivation and that addition of isoleucine stimulates synchronous synthesis of mit-DNA. We believe this method of synchronizing mit-DNA synthesis may be of value in studies of factors which regulate synthesis of mit-DNA.


Asunto(s)
División Celular , ADN/biosíntesis , Isoleucina , Mitocondrias/metabolismo , Animales , Fraccionamiento Celular , Línea Celular , Núcleo Celular/metabolismo , Centrifugación , Cricetinae , ADN Mitocondrial/metabolismo , Timidina/metabolismo , Factores de Tiempo , Tritio
11.
Trans Soc Min Metall Explor Inc ; 344(1): 31-37, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31057319

RESUMEN

An underground limestone mine in eastern Ohio was experiencing significant floor heave and roof falls, attributed to high horizontal stresses. Areas of the mine showing floor heave were monitored with roof-to-floor extensometers and photogrammetry surveys to determine the rate and magnitude of heave. Extensometer data were recorded hourly at four locations across adjacent entries while photogrammetry surveys of the floor were performed at the same locations every two to five weeks. A final survey was performed using an I-Site 8200 laser scanner. Following instrumentation, floor heave up to 10.1 cm (4 in.) was measured by the extensometers, photogrammetric reconstructions and laser scanner over a six-month period. The extensometers were biased by the location where they were placed, failing to consistently capture the location and extent of floor heave and cracking. The photogrammetry surveys were not precise enough to capture small magnitude movements. Mining in the area was halted and within several months the floor movement and incidence of roof falls were significantly lessened.

12.
J Clin Invest ; 77(1): 7-12, 1986 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-3753709

RESUMEN

Changes in the oral intake of phosphorus could induce the reported changes in the serum concentration of 1,25-dihydroxyvitamin D (1,25-(OH)2D) by inducing changes in its production rate (PR) or metabolic clearance rate (MCR), or both. To investigate these possibilities, we employed the constant infusion equilibrium technique to measure the PR and MCR of 1,25-(OH)2D in six healthy men in whom the oral intake of phosphorus was initially maintained at 1,500 mg/70 kg body weight per d for 9 d, then restricted to 500 mg/d (coupled with oral administration of aluminum hydroxide) for 10 d, and then supplemented to 3,000 mg/d for 10 d. With phosphorus restriction, the serum concentration of 1,25-(OH)2D increased by 80% from a mean of 38 +/- 3 to 68 +/- 6 pg/ml, P less than 0.001; the PR increased from 1.8 +/- 0.2 to 3.8 +/- 0.6 micrograms/d, P less than 0.005; the MCR did not change significantly. The fasting serum concentration of phosphorus decreased from 3.5 +/- 0.2 to 2.6 +/- 0.2 mg/dl, P less than 0.01. With phosphorus supplementation, the serum concentration of 1,25-(OH)2D decreased abruptly, reaching a nadir within 2 to 4 d; after 10 d of supplementation, the mean concentration of 27 +/- 4 pg/ml was lower by 29%, P less than 0.01, than the value measured when phosphorus intake was normal. The PR decreased to 1.3 +/- 0.2 micrograms/d, P less than 0.05; the MCR did not change significantly. The fasting serum concentration of phosphorus increased significantly, but only initially. These data demonstrate that in healthy men, reductions and increases in the oral intake of phosphorus can induce rapidly occurring, large, inverse, and persisting changes in the serum concentration of 1,25-(OH)2D. Changes in the PR of 1,25-(OH)2D account entirely for the phosphorus-induced changes in serum concentration of this hormone.


Asunto(s)
Calcitriol/sangre , Fósforo/administración & dosificación , Administración Oral , Adulto , Calcitriol/biosíntesis , Calcio/sangre , Calcio/orina , Dieta , Humanos , Magnesio/sangre , Magnesio/orina , Masculino , Tasa de Depuración Metabólica , Hormona Paratiroidea/sangre , Fósforo/sangre , Fósforo/orina
13.
Int J Vitam Nutr Res ; 77(1): 34-40, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17685093

RESUMEN

This cross-sectional study evaluated the association between daily calcium intake and body mass index (BMI) in 647 subjects from Reus, Spain. 261 men and 313 women, aged 18 to 70 years, were randomly selected from the population census. Food intake was quantified by the 24-hour recall method, for three non-consecutive days including one holiday. Weight and height were measured. The study sample was divided into quartiles of calcium intake adjusted for age, energy, and total fat and fiber intake in both men and women. Average calcium intake was low (557.6 +/- 234.0 mg/day). Calcium intake was significantly (p < 0.0001) and positively associated with energy intake (r = 0.50 for men; r = 0.49 for women; p < 0.0001) and dietary fiber consumption (r = 0.27 for men; r = 0.25 for women; p < 0.0001). After adjusting for age, energy intake, fat intake, and dietary fiber, the odds ratio of being in the highest quartile of BMI was significantly reduced in the highest quartile of calcium intake [men: 0.63 (0.30-1.29); women: 0.36 (0.17-0.79)] compared to the lowest quartile in both sexes. We conclude that our study showed a negative relationship between calcium intake and BMI in a Mediterranean community.


Asunto(s)
Índice de Masa Corporal , Calcio de la Dieta/administración & dosificación , Adolescente , Adulto , Anciano , Registros de Dieta , Grasas de la Dieta/administración & dosificación , Fibras de la Dieta/administración & dosificación , Ingestión de Energía , Femenino , Humanos , Masculino , Persona de Mediana Edad , España
14.
J Microbiol Biol Educ ; 17(3): 370-379, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28101263

RESUMEN

As part of an undergraduate pipeline program at our institution for students from underrepresented minorities in medicine backgrounds, we created an intensive four-week medical microbiology course. Team-based learning (TBL) was implemented in this course to enhance student learning of course content. Three different student cohorts participated in the study, and there were no significant differences in their prior academic achievement based on their undergraduate grade point average (GPA) and pre-course examination scores. Teaching techniques included engaged lectures using an audience response system, TBL, and guided self-directed learning. We hypothesized that more active learning exercises, irrespective of the amount of lecture time, would help students master course content. In year 2 as compared with year 1, TBL exercises were decreased from six to three with a concomitant increase in lecture time, while in year 3, TBL exercises were increased from three to six while maintaining the same amount of lecture time as in year 2. As we hypothesized, there was significant (p < 0.01) improvement in performance on the post-course examination in years 1 and 3 compared with year 2, when only three TBL exercises were used. In contrast to the students' perceptions that more lecture time enhances learning of course content, our findings suggest that active learning strategies, such as TBL, are more effective than engaged lectures in improving student understanding of course content, as measured by post-course examination performance. Introduction of TBL in pipeline program courses may help achieve better student learning outcomes.

16.
Cancer Epidemiol Biomarkers Prev ; 7(11): 1051-4, 1998 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9829716

RESUMEN

Lung cancer is the leading cause of cancer-related deaths. The development of sensitive screening methods to identify at-risk individuals before emergence of clinical disease would permit early intervention that could decrease this mortality. Our previous studies have shown that cells with trisomy 7 can be detected in bronchial epithelium from cancer-free smokers and former uranium miners. However, the use of more than one molecular marker could increase the chance of identifying at-risk individuals. Trisomy 20, which is found in 43-57% of non-small cell lung cancers, is a candidate marker. The purpose of the current investigation was to determine the percentage of cells with trisomy 20 in persons with a high risk for lung cancer. Bronchial epithelial cells that had been assayed for trisomy 7 were assayed for trisomy 20 by fluorescence in situ hybridization. Trisomy 20 was detected in bronchial epithelial cells from lung cancer patients and from smokers and ex-uranium miners without lung cancer. In some cases, patients who were negative for trisomy 7 exhibited trisomy 20. Consequently, more people with field cancerization were identified using both markers. However, the two markers combined did not appear to stratify the risk for lung cancer.


Asunto(s)
Bronquios/citología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/prevención & control , Cromosomas Humanos Par 20/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/prevención & control , Minería , Exposición Profesional/efectos adversos , Fumar/efectos adversos , Trisomía , Uranio/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Células Cultivadas , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas
17.
J Med Chem ; 39(8): 1601-8, 1996 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-8648599

RESUMEN

Encoded combinatorial organic synthesis has recently emerged as a powerful tool for the discovery of biologically active compounds from complex chemical libraries. This report describes a new encoding methodology that uses chemically robust secondary amines as tags. These amines are incorporated into an N-[(dialkylcarbamoyl)methyl]glycine-coding oligomer through simple chemistry that is compatible with a wide range of polymer-supported transformations useful in combinatorial synthesis. In the decoding process acidic hydrolysis of the tagging polymer regenerates the secondary amines, which after dansylation are resolved and detected at sub-picomole levels by reversed-phase HPLC. The versatility of this strategy is demonstrated here by encoded syntheses of members of several representative heterocyclic compound classes, including beta-lactams, 4-thiazolidinones, and pyrrolidines.


Asunto(s)
Antibacterianos/síntesis química , Pirrolidinas/síntesis química , Tiazoles/síntesis química , Lactamas
18.
J Med Chem ; 39(26): 5215-27, 1996 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-8978850

RESUMEN

A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta I, beta II, gamma, delta, epsilon and eta PKC isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b, was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.


Asunto(s)
Azepinas/química , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Inhibidores Enzimáticos/farmacología , Hidroxibenzoatos/química , Proteína Quinasa C/antagonistas & inhibidores , Animales , Azepinas/farmacología , Inhibidores Enzimáticos/química , Humanos , Hidroxibenzoatos/farmacología , Espectroscopía de Resonancia Magnética , Ratas , Proteínas Recombinantes/antagonistas & inhibidores , Especificidad por Sustrato
19.
Ann Thorac Surg ; 60(2 Suppl): S205-10, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7646160

RESUMEN

Intermediate-phase clinical results of 51 low-pressure (LP) and 234 standard-pressure (SP) fixation porcine Carpentier-Edwards (CE) valves implanted between 1977 and 1991 were compared for valve-related events. Group similarities included New York Heart Association functional class, ejection fraction, and sex. Patients with SP valves were younger (mean age, 58 versus 68 years; p = 0.0001). There were 20 in-hospital deaths (8.6%) in the SP valve group and 5 (9.8%) in the LP valve group (p = 0.79). Follow-up was 99%, with a mean of 104 months in the SP valve group versus 55 months in the SP valve group (p = 0.0001). The actuarial survival rate was 48.2% and 22.3% at 10 and 15 years, respectively, in the SP valve group and 34.1% at 10 years in the LP valve group (p = 0.42). Freedom from events at 5, 10, and 15 years in the SP valve group and at 5 years in the LP valve group was as follows: for late valve-related events, 86.3%, 51.4% and 20.2%, respectively, in the SP valve group versus 85% in the LP valve group (p = 0.44); for valve-related death, 96.4%, 93.6%, and 87.3% in the SP valve group versus 100% in the LP valve group (p = 0.20); for structural valve failure, 96%, 68%, and 35% in the SP valve group versus 100% in the LP valve group (p = 0.09); and for reoperation, 95%, 61%, and 30% in the SP valve group versus 92% in the LP valve group (p = 0.82). In conclusion, this study revealed no significant statistical difference between LP and SP valves. In the LP valve group, structural valve failure/valve-related death was not observed, perhaps indicating a more favorable result. Absolute verification of this trend awaits long-term follow-up.


Asunto(s)
Bioprótesis , Prótesis Valvulares Cardíacas , Válvula Mitral/cirugía , Análisis Actuarial , Anciano , Femenino , Prótesis Valvulares Cardíacas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Presión , Reoperación , Tasa de Supervivencia
20.
AJNR Am J Neuroradiol ; 20(9): 1682-7, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10543641

RESUMEN

BACKGROUND AND PURPOSE: Advances in thrombolytic therapy, brain imaging, and neurointerventional techniques provide new therapeutic options for acute stroke. Intra-arterial thrombolysis has proved to be a potent therapeutic tool. To show that this procedure can be performed in community hospitals, we describe our experience with a group of 11 patients treated for middle cerebral artery occlusions. METHODS: Twenty-two patients seen during a period of 1 year with clinical findings of acute major-vessel stroke met screening criteria and were evaluated under an institutional review board-approved protocol. After CT scanning, 17 of those patients met strict criteria, gave informed consent, and underwent angiography. Eleven patients had M1 and M2 middle cerebral artery occlusions and received local thrombolytic therapy with urokinase. Recanalization efficacy, complications, and outcome data were compiled. RESULTS: The average score on the National Institutes of Health Stroke Scale was 22.2 at the onset of treatment and 12.5 after therapy, with 91% of patients showing neurologic improvement. Complete (TIMI 3) recanalization occurred in 73% of cases and partial recanalization (TIMI 2) in 18%. At the 90-day follow-up evaluation, 56% of patients had good outcomes (modified Rankin score, 0 to 1). One intracranial hemorrhage occurred. CONCLUSION: Intra-arterial thrombolysis can be performed in a community hospital by radiologists with interventional and neuroradiologic skills given appropriate institutional preparation.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Embolia Intracraneal/tratamiento farmacológico , Trombosis Intracraneal/tratamiento farmacológico , Terapia Trombolítica , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico por imagen , Angiografía Cerebral , Femenino , Humanos , Infusiones Intraarteriales , Embolia Intracraneal/diagnóstico por imagen , Trombosis Intracraneal/diagnóstico por imagen , Masculino , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/efectos de los fármacos , Examen Neurológico/efectos de los fármacos , Resultado del Tratamiento , Activador de Plasminógeno de Tipo Uroquinasa/efectos adversos
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