5,943 research outputs found

    Are women residency supervisors obligated to nurture?

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73923/1/j.1365-2929.2006.02635.x.pd

    Number of Nanoparticles per Cell through a Spectrophotometric Method - A key parameter to Assess Nanoparticle-based Cellular Assays

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    Engineered nanoparticles (eNPs) for biological and biomedical applications are produced from functionalised nanoparticles (NPs) after undergoing multiple handling steps, giving rise to an inevitable loss of NPs. Herein we present a practical method to quantify nanoparticles (NPs) number per volume in an aqueous suspension using standard spectrophotometers and minute amounts of the suspensions (up to 1 μL). This method allows, for the first time, to analyse cellular uptake by reporting NPs number added per cell, as opposed to current methods which are related to solid content (w/V) of NPs. In analogy to the parameter used in viral infective assays (multiplicity of infection), we propose to name this novel parameter as multiplicity of nanofection.JJDM thanks Spanish Ministerio de Economía y Competitividad for a Ramon y Cajal Fellowship and for supporting this work partially by Grant CTQ2012-34778. This research was partially supported by Marie Curie Career Integration Grants within the 7th European Community Framework Programme (FP7-PEOPLE-2011-CIG-Project Number 294142 and FP7-PEOPLE-2012-CIG-Project Number 322276) to RMSM and JJDM, respectively. This research was partially supported by the Consejería de Economía, Innovación y Ciencia de la Junta de Andalucía (BIO-1778) to JJDM. RMSM and JDUB thank CEI Biotic Granada for funding P_BS_54 and mP_BS_37 projects. JDUB thanks Spanish Ministerio de Economía y Competitividad for a Torres Quevedo fellowship (PTQ-13-06046)

    Rural-to-urban migration and risk of hypertension: longitudinal results of the PERU MIGRANT study.

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    Urbanization can be detrimental to health in populations due to changes in dietary and physical activity patterns. The aim of this study was to determine the effect of migration on the incidence of hypertension. Participants of the PERU MIGRANT study, that is, rural, urban and rural-to-urban migrants, were re-evaluated after 5 years after baseline assessment. The outcome was incidence of hypertension; and the exposures were study group and other well-known risk factors. Incidence rates, relative risks (RRs) and population attributable fractions (PAFs) were calculated. At baseline, 201 (20.4%), 589 (59.5%) and 199 (20.1%) participants were rural, rural-to-urban migrant and urban subjects, respectively. Overall mean age was 47.9 (s.d.±12.0) years, and 522 (52.9%) were female. Hypertension prevalence at baseline was 16.0% (95% confidence interval (CI) 13.7-18.3), being more common in urban group; whereas pre-hypertension was more prevalent in rural participants (P<0.001). Follow-up rate at 5 years was 94%, 895 participants were re-assessed and 33 (3.3%) deaths were recorded. Overall incidence of hypertension was 1.73 (95%CI 1.36-2.20) per 100 person-years. In multivariable model and compared with the urban group, rural group had a greater risk of developing hypertension (RR 3.58; 95%CI 1.42-9.06). PAFs showed high waist circumference as the leading risk factor for the hypertension development in rural (19.1%), migrant (27.9%) and urban (45.8%) participants. Subjects from rural areas are at higher risk of developing hypertension relative to rural-urban migrant or urban groups. Central obesity was the leading risk factor for hypertension incidence in the three population groups

    Obesity risk in rural, urban and rural-to-urban migrants: prospective results of the PERU MIGRANT study.

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    BACKGROUND: Although migration and urbanization have been linked with higher obesity rates, especially in low-resource settings, prospective information about the magnitude of these effects is lacking. We estimated the risk of obesity and central obesity among rural subjects, rural-to-urban migrants and urban subjects. METHODS: Prospective data from the PERU MIGRANT Study were analyzed. Baseline data were collected in 2007-2008 and participants re-contacted in 2012-2013. At follow-up, outcomes were obesity and central obesity measured by body mass index and waist circumference. At baseline, the primary exposure was demographic group: rural, rural-to-urban migrant and urban. Other exposures included an assets index and educational attainment. Cumulative incidence, incidence ratio (IR) and 95% confidence intervals (95% CI) for obesity and central obesity were estimated with Poisson regression models. RESULTS: At baseline, mean age (±s.d.) was 47.9 (±12.0) years, and 53.0% were females. Rural subjects comprised 20.2% of the total sample, whereas 59.7% were rural-to-urban migrants and 20.1% were urban dwellers. A total of 3598 and 2174 person-years were analyzed for obesity and central obesity outcomes, respectively. At baseline, the prevalence of obesity and central obesity was 20.0 and 52.5%. In multivariable models, migrant and urban groups had an 8- to 9.5-fold higher IR of obesity compared with the rural group (IR migrants=8.19, 95% CI=2.72-24.67; IR urban=9.51, 95% CI=2.74-33.01). For central obesity, there was a higher IR only among the migrant group (IR=1.95; 95% CI=1.22-3.13). Assets index was associated with a higher IR of central obesity (IR top versus bottom tertile 1.45, 95% CI=1.03-2.06). CONCLUSIONS: Peruvian urban individuals and rural-to-urban migrants show a higher incidence of obesity compared with their rural counterparts. Given the ongoing urbanization occurring in middle-income countries, the rapid development of increased obesity risk by rural-to-urban migrants suggests that measures to reduce obesity should be a priority for this group

    The value of subtraction MRI in detection of amyloid-related imaging abnormalities with oedema or effusion in Alzheimer's patients: An interobserver study

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    BACKGROUND: Immunotherapeutic treatments targeting amyloid-β plaques in Alzheimer's disease (AD) are associated with the presence of amyloid-related imaging abnormalities with oedema or effusion (ARIA-E), whose detection and classification is crucial to evaluate subjects enrolled in clinical trials. PURPOSE: To investigate the applicability of subtraction MRI in the ARIA-E detection using an established ARIA-E-rating scale. METHODS: We included 75 AD patients receiving bapineuzumab treatment, including 29 ARIA-E cases. Five neuroradiologists rated their brain MRI-scans with and without subtraction images. The accuracy of evaluating the presence of ARIA-E, intraclass correlation coefficient (ICC) and specific agreement was calculated. RESULTS: Subtraction resulted in higher sensitivity (0.966) and lower specificity (0.970) than native images (0.959, 0.991, respectively). Individual rater detection was excellent. ICC scores ranged from excellent to good, except for gyral swelling (moderate). Excellent negative and good positive specific agreement among all ARIA-E imaging features was reported in both groups. Combining sulcal hyperintensity and gyral swelling significantly increased positive agreement for subtraction images. CONCLUSION: Subtraction MRI has potential as a visual aid increasing the sensitivity of ARIA-E assessment. However, in order to improve its usefulness isotropic acquisition and enhanced training are required. The ARIA-E rating scale may benefit from combining sulcal hyperintensity and swelling. KEY POINTS: • Subtraction technique can improve detection amyloid-related imaging-abnormalities with edema/effusion in Alzheimer's patients. • The value of ARIA-E detection, classification and monitoring using subtraction was assessed. • Validation of an established ARIA-E rating scale, recommendations for improvement are reported. • Complementary statistical methods were employed to measure accuracy, inter-rater-reliability and specific agreement

    Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

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    CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

    Improved xylose and arabinose utilization by an industrial recombinant Saccharomyces cerevisiae strain using evolutionary engineering

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    <p>Abstract</p> <p>Background</p> <p>Cost-effective fermentation of lignocellulosic hydrolysate to ethanol by <it>Saccharomyces cerevisiae </it>requires efficient mixed sugar utilization. Notably, the rate and yield of xylose and arabinose co-fermentation to ethanol must be enhanced.</p> <p>Results</p> <p>Evolutionary engineering was used to improve the simultaneous conversion of xylose and arabinose to ethanol in a recombinant industrial <it>Saccharomyces cerevisiae </it>strain carrying the heterologous genes for xylose and arabinose utilization pathways integrated in the genome. The evolved strain TMB3130 displayed an increased consumption rate of xylose and arabinose under aerobic and anaerobic conditions. Improved anaerobic ethanol production was achieved at the expense of xylitol and glycerol but arabinose was almost stoichiometrically converted to arabitol. Further characterization of the strain indicated that the selection pressure during prolonged continuous culture in xylose and arabinose medium resulted in the improved transport of xylose and arabinose as well as increased levels of the enzymes from the introduced fungal xylose pathway. No mutation was found in any of the genes from the pentose converting pathways.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first report that characterizes the molecular mechanisms for improved mixed-pentose utilization obtained by evolutionary engineering of a recombinant <it>S. cerevisiae </it>strain. Increased transport of pentoses and increased activities of xylose converting enzymes contributed to the improved phenotype.</p

    A Symbiotic Brain-Machine Interface through Value-Based Decision Making

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    BACKGROUND: In the development of Brain Machine Interfaces (BMIs), there is a great need to enable users to interact with changing environments during the activities of daily life. It is expected that the number and scope of the learning tasks encountered during interaction with the environment as well as the pattern of brain activity will vary over time. These conditions, in addition to neural reorganization, pose a challenge to decoding neural commands for BMIs. We have developed a new BMI framework in which a computational agent symbiotically decoded users' intended actions by utilizing both motor commands and goal information directly from the brain through a continuous Perception-Action-Reward Cycle (PARC). METHODOLOGY: The control architecture designed was based on Actor-Critic learning, which is a PARC-based reinforcement learning method. Our neurophysiology studies in rat models suggested that Nucleus Accumbens (NAcc) contained a rich representation of goal information in terms of predicting the probability of earning reward and it could be translated into an evaluative feedback for adaptation of the decoder with high precision. Simulated neural control experiments showed that the system was able to maintain high performance in decoding neural motor commands during novel tasks or in the presence of reorganization in the neural input. We then implanted a dual micro-wire array in the primary motor cortex (M1) and the NAcc of rat brain and implemented a full closed-loop system in which robot actions were decoded from the single unit activity in M1 based on an evaluative feedback that was estimated from NAcc. CONCLUSIONS: Our results suggest that adapting the BMI decoder with an evaluative feedback that is directly extracted from the brain is a possible solution to the problem of operating BMIs in changing environments with dynamic neural signals. During closed-loop control, the agent was able to solve a reaching task by capturing the action and reward interdependency in the brain

    Assistência pré-natal à adolescente e os atributos da Atenção Primária à Saúde

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    OBJECTIVE: evaluate prenatal care for adolescents in health units, in accordance with the attributes of Primary Health Care (PHC) guidelines. METHOD: quantitative study conducted with health professionals, using the Primary Care Assessment Tool-Brazil to assess the presence and extent of PHC attributes. RESULTS: for all the participating units, the attribute Access scored =6.6; the attributes Longitudinality, Coordination (integration of care), Coordination (information systems) and Integrality scored =6.6, and the Essential Score =6.6. Comparing basic units with family health units, the attribute scores were equally distributed; Accessibility scored =6.6, the others attributes scored =6.6; however, in the basic units, the Essential Score was =6.6 and, in the family health units, =6.6. CONCLUSION: expanding the coverage of family health units and the training of professionals can be considered strategies to qualify health care.OBJETIVO: evaluar la atención prenatal a las adolescentes en unidades de salud, según los atributos de la Atención Primaria a la Salud. MÉTODO: estudio de abordaje cuantitativo, realizado con profesionales de la salud, utilizando el instrumento Primary Care Assessment Tool-Brasil para analizar la presencia y extensión de los atributos vinculados a la APS en las unidades de salud. RESULTADOS: para todas las unidades participantes, el atributo Acceso obtuvo un puntaje =6,6; los atributos Longitudinalidad, Coordinación (integración de cuidados), Coordinación (sistemas de información) e Integralidad obtuvieron puntajes =6,6 y el Puntaje Esencial fue =6,6. Comparando las unidades básicas de salud y las unidades de salud de la familia, los puntajes están igualmente distribuidos: Accesibilidad =6,6 y los demás atributos con puntajes =6,6; sin embargo, el puntaje Esencial en las unidades básicas fue =6,6 y el de las unidades de salud de la familia fue =6,6. CONCLUSIÓN: la ampliación de la cobertura de las unidades de salud de la familia y la capacitación profesional pueden ser estrategias para calificar la atención a la salud.OBJETIVO: avaliar a atenção pré-natal às adolescentes em unidades de saúde, segundo os atributos da Atenção Primária à Saúde. MÉTODO: estudo de abordagem quantitativa, realizado com profissionais de saúde, utilizando-se o instrumento Primary Care Assessment Tool-Brasil, para analisar a presença e extensão dos atributos. RESULTADOS: para todas as unidades participantes, o atributo acesso obteve escore =6,6; os atributos longitudinalidade, coordenação (integração de cuidados), coordenação (sistemas de informação) e integralidade obtiveram escores =6,6 e escore essencial =6,6. Comparando-se as unidades básicas e as unidades de saúde da família, os escores estão igualmente distribuídos: acessibilidade: =6,6 e os demais atributos com escores =6,6, no entanto, o escore essencial nas unidades básicas foi =6,6 e nas unidades de saúde da família foi =6,6. CONCLUSÃO: a ampliação da cobertura das unidades de saúde da família e a capacitação profissional podem ser estratégias para qualificar a atenção à saúde
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