378 research outputs found
Review of the phenotype of early-onset generalised progressive dystonia due to mutations in KMT2B
In 2016, two research groups independently identified microdeletions and pathogenic variants in the lysine-specific histone methyltransferase 2B gene, KMT2B in patients with early-onset progressive dystonia. KMT2B-dystonia (DYT28) is emerging as an important and frequent cause of childhood-onset progressive generalised dystonia and is estimated to potentially account for up to 10% of early-onset generalised dystonia. Herein, we review variants in KMT2B associated with dystonia, as well as the clinical phenotype, treatment and underlying disease mechanisms. Furthermore, in context of this newly identified condition, we summarise our approach to the genetic investigation of paediatric dystonia
Healthcare Reform and the Next Generation: United States Medical Student Attitudes toward the Patient Protection and Affordable Care Act
CONTEXT: Over one year after passage of the Patient Protection and Affordable Care Act (PPACA), legislators, healthcare experts, physicians, and the general public continue to debate the implications of the law and its repeal. The PPACA will have a significant impact on future physicians, yet medical student perspectives on the legislation have not been well documented. OBJECTIVE: To evaluate medical students' understanding of and attitudes toward healthcare reform and the PPACA including issues of quality, access and cost. DESIGN, SETTING, AND PARTICIPANTS: An anonymous electronic survey was sent to medical students at 10 medical schools (total of 6982 students) between October-December 2010, with 1232 students responding and a response rate of 18%. MAIN OUTCOME MEASURES: Medical students' views and attitudes regarding the PPACA and related topics, measured with Likert scale and open response items. RESULTS: Of medical students surveyed, 94.8% agreed that the existing United States healthcare system needs to be reformed, 31.4% believed the PPACA will improve healthcare quality, while 20.9% disagreed and almost half (47.7%) were unsure if quality will be improved. Two thirds (67.6%) believed that the PPACA will increase access, 6.5% disagreed and the remaining 25.9% were unsure. With regard to containing healthcare costs, 45.4% of participants indicated that they are unsure if the provisions of the PPACA will do so. Overall, 80.1% of respondents indicated that they support the PPACA, and 78.3% also indicated that they did not feel that reform efforts had gone far enough. A majority of respondents (58.8%) opposed repeal of the PPACA, while 15.0% supported repeal, and 26.1% were undecided. CONCLUSION: The overwhelming majority of medical students recognized healthcare reform is needed and expressed support for the PPACA but echoed concerns about whether it will address issues of quality or cost containment
The role of melatonin in the pathogenesis of adolescent idiopathic scoliosis (AIS)
The cause of adolescent idiopathic scoliosis (AIS) in humans remains obscure and probably multifactorial. At present, there is no proven method or test available to identify children or adolescent at risk of developing AIS or identify which of the affected individuals are at risk of progression. Reported associations are linked in pathogenesis rather than etiologic factors. Melatonin may play a role in the pathogenesis of scoliosis (neuroendocrine hypothesis), but at present, the data available cannot clearly show the role of melatonin in producing scoliosis in humans. The data regarding human melatonin levels are mixed at best, and the melatonin deficiency as a causative factor in the etiology of scoliosis cannot be supported. It will be an important issue of future research to investigate the role of melatonin in human biology, the clinical efficacy, and safety of melatonin under different pathological situations. Research is needed to better define the role of all factors in AIS development
4-Aminopyridine is a promising treatment option for patients with gain-of-function KCNA2-encephalopathy
Developmental and epileptic encephalopathies are devastating disorders characterized by epilepsy, intellectual disability, and other neuropsychiatric symptoms, for which available treatments are largely ineffective. Following a precision medicine approach, we show for KCNA2-encephalopathy that the K+ channel blocker 4-aminopyridine can antagonize gain-of-function defects caused by variants in the KV1.2 subunit in vitro, by reducing current amplitudes and negative shifts of steady-state activation and increasing the firing rate of transfected neurons. In n-of-1 trials carried out in nine different centers, 9 of 11 patients carrying such variants benefitted from treatment with 4-aminopyridine. All six patients experiencing daily absence, myoclonic, or atonic seizures became seizure-free (except some remaining provoked seizures). Two of six patients experiencing generalized tonic-clonic seizures showed marked improvement, three showed no effect, and one worsening. Nine patients showed improved gait, ataxia, alertness, cognition, or speech. 4-Aminopyridine was well tolerated up to 2.6 mg/kg per day. We suggest 4-aminopyridine as a promising tailored treatment in KCNA2-(gain-of-function)–encephalopathy and provide an online tool assisting physicians to select patients with gain-of-function mutations suited to this treatment
Social Intelligence and Academic Achievement as Predictors of Adolescent Popularity
This study compared the effects of social intelligence and cognitive intelligence, as measured by academic achievement, on adolescent popularity in two school contexts. A distinction was made between sociometric popularity, a measure of acceptance, and perceived popularity, a measure of social dominance. Participants were 512, 14–15 year-old adolescents (56% girls, 44% boys) in vocational and college preparatory schools in Northwestern Europe. Perceived popularity was significantly related to social intelligence, but not to academic achievement, in both contexts. Sociometric popularity was predicted by an interaction between academic achievement and social intelligence, further qualified by school context. Whereas college bound students gained sociometric popularity by excelling both socially and academically, vocational students benefited from doing well either socially or academically, but not in combination. The implications of these findings were discussed
Common data elements for clinical research in mitochondrial disease: a National Institute for Neurological Disorders and Stroke project
Objectives The common data elements (CDE) project was
developed by the National Institute of Neurological
Disorders and Stroke (NINDS) to provide clinical researchers
with tools to improve data quality and allow for harmonization
of data collected in different research studies. CDEs have been
created for several neurological diseases; the aim of this project
was to develop CDEs specifically curated for mitochondrial
disease (Mito) to enhance clinical research.
Methods Nine working groups (WGs), composed of international
mitochondrial disease experts, provided recommendations
for Mito clinical research. They initially reviewed
existing NINDS CDEs and instruments, and developed new
data elements or instruments when needed. Recommendations
were organized, internally reviewed by the Mito WGs, and
posted online for external public comment for a period of eight
weeks. The final version was again reviewed by all WGs and
the NINDS CDE team prior to posting for public use
Improvement of the Trivalent Inactivated Flu Vaccine Using PapMV Nanoparticles
Commercial seasonal flu vaccines induce production of antibodies directed mostly towards hemaglutinin (HA). Because HA changes rapidly in the circulating virus, the protection remains partial. Several conserved viral proteins, e.g., nucleocapsid (NP) and matrix proteins (M1), are present in the vaccine, but are not immunogenic. To improve the protection provided by these vaccines, we used nanoparticles made of the coat protein of a plant virus (papaya mosaic virus; PapMV) as an adjuvant. Immunization of mice and ferrets with the adjuvanted formulation increased the magnitude and breadth of the humoral response to NP and to highly conserved regions of HA. They also triggered a cellular mediated immune response to NP and M1, and long-lasting protection in animals challenged with a heterosubtypic influenza strain (WSN/33). Thus, seasonal flu vaccine adjuvanted with PapMV nanoparticles can induce universal protection to influenza, which is a major advancement when facing a pandemic
A revised evolutionary history of the CYP1A subfamily : gene duplication, gene conversion, and positive selection
Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Molecular Evolution 62 (2006): 708-717, doi:10.1007/s00239-005-0134-z.Members of cytochrome P450 subfamily 1A (CYP1As) are involved in detoxification and bioactivation of common environmental pollutants. Understanding the functional evolution of these genes is essential to predicting and interpreting species differences in sensitivity to toxicity by such chemicals. The CYP1A gene subfamily comprises a single ancestral representative in most fish species and two paralogs in higher vertebrates, including birds and mammals. Phylogenetic analysis of complete coding sequences suggests that mammalian and bird paralog pairs (CYP1A1/2 and CYP1A4/5, respectively) are the result of independent gene duplication events. However, comparison of vertebrate genome sequences revealed that CYP1A genes lie within an extended region of conserved fine-scale synteny, suggesting that avian and mammalian CYP1A paralogs share a common genomic history. Algorithms designed to detect recombination between nucleotide sequences indicate that gene conversion has homogenized most of the length of the chicken CYP1A genes, as well as the 5’ end of mammalian CYP1As. Together, these data indicate that avian and mammalian CYP1A paralog pairs resulted from a single gene duplication event and that extensive gene conversion is responsible for the exceptionally high degree of sequence similarity between CYP1A4 and CYP1A5. Elevated non-synonymous/synonymous substitution ratios within a putatively unconverted stretch of ~250 bp suggests that positive selection may have reduced the effective rate of gene conversion in this region, which contains two substrate recognition sites. This work significantly alters our understanding of functional evolution in the CYP1A subfamily, suggesting that gene conversion and positive selection have been the dominant processes of sequence evolution.Funding for this work was provided by the NIH Superfund Basic Research Program at Boston University (5-P42-ES-07381) and by the Woods Hole Oceanographic Institution
Entrepreneurial intentions and entrepreneurship education to University students in Portugal
[EN] This article analyzes entrepreneurial intentions and motivations that encourage university students of Tourism to create their own company. Methodology is based on an empirical study, using a questionnaire adapted from a model of Veciana and Urbano (Actitudes de los estudiantes universitarios hacia la creación de empresas: un estudio empírico comparativo entre Catalunya y Puerto Rico. El emprendedor innovador y la creación de empresas de I + D + I, University of Valencia, pp 35 58, 2004), including the desirability and viability concepts. One hundred and sixty students answered the questionnaire from a total study population of 243 official Tourism degree students of the Superior Institute of Accounting and Management of Porto. This research finds out that the university students have a very positive perception about the desire to create their own company; a 90 % of students express their desire to do it, and 83.5 % express their intention. Moreover, a 57.5 % think that within actual crisis it is more difficult to do than before it. This research lets us get an in-depth study of a student of Tourism degree, finding out his entrepreneurial attitudes. It can be the first step to wake up and encourage students interest for starting up their own business.Del Rio-Rama, MDLC.; Peris-Ortiz, M.; Álvarez García, J.; Rueda Armengot, C. (2016). Entrepreneurial intentions and entrepreneurship education to University students in Portugal. Technology, Innovation and Education. 2(7):1-11. doi:10.1186/s40660-016-0013-5S11127Ajzen I (1991) The theory of plannes behavior. Organ Behav Hum Decis Process 50:179–211Aponte M (2002) Factores condicionantes de la creación de empresas en Puerto Rico: un enfoque institucional. Doctoral dissertation, Autonomous University of BarcelonaAponte M, Urbano D, Veciana JM (2006) Actitudes hacia la creación de empresas: un estudio comparativo entre Catalunya y Puerto Rico. Centro de Investigaciones Comerciales e Iniciativas Académicas de la Facultad de Administración de Empresas. Forum Empresarial 11(2):52–75Bae TJ, Qian S, Miao C, Fiet JO (2014) The relationship between entrepreneurship education and entrepreneurial intentions: a meta-analytic review. Entrep Theory Pract 38(2):217–254Brice J (2004) The role of personality dimensions on the formation of entrepreneurial intentions. USASBE Small Business Advancement National Center. University of Central Arkansas, USACabana-Villca R, Cortes-Castillo I, Plaza-Pasten D, Castillo-Vergara M, Alvarez-Marin A (2013) Análisis de las capacidades emprendedoras potenciales y efectivas en alumnos de centros de educación superior. J Technol Manag Innov 8(1):65–75Davidsson P (1989) Continued entrepreneurship and small firm business. Stockholm School of Economics, StockholmDavidsson P (1995) Culture, structure and regional levels of entrepreneurship. Entrep Reg Dev 7(1):41–62De Jorge-Moreno J, Castillo LL, Triguero MS (2012) The effect of business and economics education programs on students’ entrepreneurial intention. Eur J Train Dev 36(4):409–425Díaz JC, Hernández RM, Barata ML (2007) Estudiantes universitarios y creación de empresas. Un análisis comparativo entre España y Portugal. In Ayala, J.C. (coord.) Conocimiento, innovación y emprendedores: camino al futuro. Grupo FEDRA, MadridDo Paço AMF, Ferreira JM, Raposo M, Rodrigues RG, Dinis A (2011) Behaviours and entrepreneurial intention: empirical findings about secondary students. J Int Entrep 9(1):20–38Dohse D, Walter SG (2010) The role of entrepreneurship education and regional context in forming entrepreneurial intentions (No. 2010, 18). Document de treball de l’IEBEuropean Commission (2006). Entrepreneurship education in Europe: Fostering entrepreneurial mindsets through education and learning, Final Proceedings of the Conference on Entrepreneurship Education in OsloEurostat (2014) Informes sobre el empleo en la Unión Europea. Available in: http://europa.eu/publications/statistics/index_es.htmFuentes F, Saco F, Rodríguez P (2013) Estudio sobre el perfil emprendedor en el alumnado universitario de Córdoba. UCO Consejo Social de la Universidad de Córdoba, III Edición, Córdoba, pp 1–180Fuentes García FJ (2007) Análisis del Perfil Emprendedor del alumnado universitario y preuniversitario de Córdoba. Consejo Social Universidad de Córdoba, pp 1–105Genesca Garrigosa E, Veciana Verges JM (1984) Actitudes hacia la creación de empresas. Información Comercial Española 611:147–155Gerba DT (2012) Impact of entrepreneurship education on entrepreneurial intentions of business and engineering students in Ethiopia. Afr J Econ Manag Stud 3(2):258–277Gorman G, Hanlon D, King W (1997) Some research perspectives on entrepreneurship education and education for small business management: a ten-year literature review. Int Small Bus J 15(3):56–77Guerrero M, Rialp J, Urbano D (2008) The impact of desirability and feasibility on entrepreneurial intentions: a structural equation model. Int Entrep Manag J 4(1):35–50Haynie JM, Shepherd DA, McMullen JS (2009) An opportunity for me? The role of resources in opportunity evaluation decisions. J Manage Stud 46(3):337–361Hernangomez J, Martín N, Rodriguez AI, Saboia F (2005) El emprendedor nace o se hace? Un análisis de los determinantes del espíritu emprendedor. XVI Spanish-Portuguese Meeting of Scientic Management. Sevilla:33–44Hmieleski KM, Corbett AC (2006) Proclivity for improvisation as a predictor of entrepreneurial intentions. J Small Bus Manage 44(1):45–63Honjo Y (2004) Growth of new start-up firms: evidence from the Japanese manufacturing industry. Appl Econ Lett 11(1):21–32Hyde GC (1989) The relationship between policy and research. In Rosa, P.; Birley, S. Cannon, T. and O´Neill, K. The Role and Contribution of Small Business Research, Chap. 3:55–77, Institute ReportKolvereid L (1996) Prediction of employment status choice intentions. Entrep Theory Pract 21(1):47–57Kourilsky ML, Walstad WB (1998) Entrepreneurship and female youth: knowledge, attitude, gender differences, and educational practices. J Bus Ventur 13(1):77–88Krueger N, Brazeal D (1994) Entrepreneurial Potencial and Potencial Entrepreneurs. Entrep Theory Pract 18(3):91–104Krueger NF, Carsrud AL (1993) Entrepreneurial intentions: applying the theory of planned behaviour. Entrep Reg Dev 5(4):315–330Lanero A, Vázquez JL, Gutiérrez P, García MP (2011) The impact of entrepreneurship education in European universities: an intention-based approach analyzed in the Spanish area. Int Rev Public Nonprofit Marketin 8(2):111–130Miller BK, Bell JD, Palmer M, González A (2009) Predictors of entrepreneurial intentions: a quasi-experiment comparing students enrolled in introductory management and entrepreneurship classes. J Bus Entrep 21(2):39–62Neck HM, Zacharakis AL, Bygrave WD, Reynolds PD (2003) Global entrepreneurship monitor: 2002 executive report. Babson College, Babson, MANorth DC (1990) Institutions, Institutional Change and Economic Performance. Cambridge University Press, Cambridge (UK)North D (1993) Instituciones, cambio institucional y desempeño económico. Fondo de Cultura Económica, MéxicoNorth DC (2005) Understanding the Process of Economic Change. Academic Foundation. University Press, PrincentonGEM Portugal (2012) Estudo sobre o Empreendedorismo. Global Entrepreneruship Monitor (GEM). Instituto Universitário de Lisboa (ISCTEIUL) http://web.spi.pt/GEMportugal2012/files/GEM_PORTUGAL_2012.pdfRaposo M, do Paço A, Ferreira J (2008a) Entrepreneur’s profile: a taxonomy of attribu tes and motivations of university students. J Small Bus Enterp Dev 15(2):405–420Raposo MLB, Ferreira JJM, do Paço AMF, Rodrigues RJG (2008b) Propensity to firm creation: empirical research using structural equations. Int Entrep Manag J 4(4):485–504Robinson PB, Stimpson DV, Huefner JC, Hunt HK (1991) An attitude approach to the prediction of entrepreneurship. Entrep Theory Pract 15(4):13–31Samad Aghayi J (2008) Entrepreneurship organization. Public Administration Training Center Publications, TehranScherer RF, Adams JS, Carley S, Wiebe FA (1989) Role model performance effects on development of entrepreneurial career preference. Entrep Theory and Pract, spring:53–71Scherer RF, Brodzinski JD, Wiebe F (1991) Examining the relationship between personality and entrepreneurial career preference. Entrep Reg Dev 3(2):195–206Shane S (2003) A General Theory of Enttrepreneurship- The Individual Oportunity Nexus. Edward Elgar EditoresShapero A (1982) Social dimensions of entrepreneurship. In: Kent CA et al (eds) The encyclopedia of entrepreneurship. Prentice-Hall, Englewood Cliffs, pp 72–89Shapero A, Sokol L (1982) The social dimensions of entrepreneurship.Encyclopedia of Entrepreneurship:72–90Storey DJ (1994) Employment. In Storey, D.J. Understanding the small business sector. Capítulo 6, pp. 160–203. London: RoutledgeToledano N, Urbano D (2008) Promoting entrepreneurial mindsets at universities: a case study in the South of Spain. Eur J Int Manag 2(4):382–399Trequattrini R, Lombardi R, Lardo A, Cuozzo B (2015). The Impact of Entrepreneurial Universities on Regional Growth: a Local Intellectual Capital Perspective. Journal of the Knowledge Economy, 1–13Urbano D (2006) La creación de empresas en Catalunya. Organismos de apoyo y actitudes hacia la actividad emprendedora, Ed. Generalitat de Catalunya-CIDEM, BarcelonaUrbano D, Toledano N (2008) The systems of university education and their influence on the students’ attitudes in the business world: a multiple case study. Oikos 25:87–103Veciana JM (1989) Características del empresario en España. Papeles de Economía Española 39:19–36Veciana JM, Urbano D (2004) Actitudes de los estudiantes universitarios hacia la creación de empresas: un estudio empírico comparativo entre Catalunya y Puerto Rico. El emprendedor innovador y la creación de empresas de I + D + I, University of Valencia, pp 35–58Veciana JM, Aponte M, Urbano D (2005) University student’s attitudes towards entrepreneurship: a two countries comparison. Int Entrep Manag J 1:165–182Wang CK, Wong PK (2004) Entrepreneurial interest of university students in Singapore. Technovation 24(2):163–172White SB, Reynolds PD (1996) Government programs and high growth new firms. Frontiers of Entrepreneurship Research. Center for Entrepreneurial Studies Babson College. Wellesley, MA.: 621–635Yari A, Toulabi Z, Pourashraf Y (2013) Designing propensity to entrepreneurship paradigm in Ilam universities (structural equation model approach). J Novel Appl Sci 2:872–88
Atividade física, qualidade de vida e depressão durante a gravidez
This study examines physical activity patterns among women, from pre-pregnancy to the second trimester of pregnancy, and the relationship between physical activity status based on physical activity guidelines and health-related quality of life (HRQoL) and depression over pregnancy. 56 healthy pregnant women self reported physical activity, HRQoL and depression at 10-15 and 19-24 weeks of pregnancy and physical activity before pregnancy. Whereas vigorous leisure physical activity decreased after conception, moderate leisure physical activity and work related physical activity remained stable over time. The prevalence of recommended physical activity was 39.3% and 12.5% in the 1st and 2nd trimesters of pregnancy respectively, and 14.3% pre-pregnancy. From the 1st to the 2nd pregnancy trimester, most
physical HRQoL dimensions scores decreased and only mental component increased, independently
of physical activity status. No changes in mean depression scores were observed. These data suggest
that physical activity patterns change with pregnancy and that physical and mental components
are differentially affected by pregnancy course, independently of physical activity status.Este estudo examina os padrões de atividade física antes
da concepção até o segundo trimestre de gravidez
e a relação entre o nível de atividade física, com base
nas recomendações de atividade física, a qualidade de
vida relacionada à saúde (QVRS) e depressão ao longo
da gravidez. Cinquenta e seis grávidas saudáveis reportaram
nível de atividade física, QVRS e depressão
às 10-15 e 19-24 semanas de gravidez, além de atividade
física antes da concepção. Enquanto a atividade
física vigorosa no lazer diminuiu depois da concepção,
as atividades físicas moderadas no lazer e no trabalho
mantiveram-se estáveis. A prevalência de atividade fí-
sica recomendada foi de 39,3%, 12,5% e 14,3% antes,
no primeiro e no segundo trimestres de gravidez, respectivamente.
Independentemente do estatuto de atividade
física, a maior parte dos escores nas dimensões
físicas da QVRS diminui do primeiro para o segundo
trimestre de gestação, e apenas o componente mental
aumenta. Não se verificaram alterações nos escores
médios de depressão. Estes dados sugerem que, com a
gravidez, há alteração nos padrões de atividade física;
além disso, os componentes físico e mental são diferentemente
afetados pelo curso da gestação, independentemente
do nível de atividade física
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