708 resultados para multifactorial
Resumo:
Obesity is a chronic metabolic disease characterized by adipose tissue formation excess leading to an increase in body fat mass, of multifactorial origin, produced mainly by poor eating habits combined with a sedentary lifestyle. Data consider obesity as a serious disease that affects the world's population, ranking fifth in death rates. Faced with this situation, individuals seek, increasingly, means to lose weight with less physical effort and food. In 2009 and 2010 the drug liraglutide was lauched in order to reduce weight in individuals with diabetes mellitus type 2, thus avoiding the emergence of other diseases. The aggravating factor is that obese nondiabetic individuals are making use of this substance, even if its use is not authorized by ANVISA (Brazilian Health Surveillance Agency). Thus the objective of this research is to evaluate the effect of liraglutide for muscle or fat tissues and biochemical parameters in Swiss mice submitted to cafeteria diet and physical activity. The study was approved by the Ethics Committee on Animal Use - CEUA (nº003 Protocol / 2014). For this study 74 animals (Swiss mice) were used, divided as follows: in the initial phase of this study, we carried out a pilot study (n = 10) divided into a control group (PCON) (n = 5) and cafeteria group (PCAF) (n = 5), in order to evaluate a cafeteria diet which was both attractive to the animals and that could provide an increase in adipose tissue. After the induction of the diet, animals were euthanized and as a result, the animals in the PCAF group showed an intra-abdominal adiposity 0.74 ± 0.05 g, taken as the parameter for increasing fat in animals. Subsequently the study base was conducted for this research where animals were used (n = 64) divided into 2 groups: the Cafeteria Study Base Group (EBCAF) divided as follows: cafeteria + exercise + liraglutide (CEL) (n = 8), cafeteria + exercise + saline (CES) (n = 8), cafeteria + liraglutide (CL) (n = 8) and cafeteria + saline (CS) (n = 8). The Chow Study Base group (EBR) was divided into: exercise + liraglutide (EL) (n = 8), exercise + saline + (ES) (n = 8), liraglutide (L) (n = 8) and saline solution (SS) (n = 8). All animals went through the submission process to the cafeteria diet, followed by exercise protocol through swimming and treatment with the test substance intraperitoneally (200 mg / mL / kg). After the treatments, the animals were euthanized and had the following parameters evaluated: the muscle tissue mass, adipose tissue mass and biochemical parameters. It was observed that the processing done with the exercise-associated liraglutide reduced adipose tissue mass significantly (0.32 ± 0.05 g) compared to the saline group (0.53 ± 0.07 g). There were no changes in the muscle tissue of the group which was treated and exercised (1.39 ± 0.03 g) compared to the saline group (1.33 ± 0.03 g). Regarding biochemical parameters it was evident that there were changes in these parameters. Interesting to note that, although blood glucose values have been changed, the animals did not become diabetic. Thus, it appears that physical activity together with liraglutide is eficcient to the loss of intraabdominal adipose tissue and the maintenance of lean body mass thereby generating a satisfactory result in the pursuit of quality of life and disease prevention.
Resumo:
Obesity is a chronic metabolic disease characterized by adipose tissue formation excess leading to an increase in body fat mass, of multifactorial origin, produced mainly by poor eating habits combined with a sedentary lifestyle. Data consider obesity as a serious disease that affects the world's population, ranking fifth in death rates. Faced with this situation, individuals seek, increasingly, means to lose weight with less physical effort and food. In 2009 and 2010 the drug liraglutide was lauched in order to reduce weight in individuals with diabetes mellitus type 2, thus avoiding the emergence of other diseases. The aggravating factor is that obese nondiabetic individuals are making use of this substance, even if its use is not authorized by ANVISA (Brazilian Health Surveillance Agency). Thus the objective of this research is to evaluate the effect of liraglutide for muscle or fat tissues and biochemical parameters in Swiss mice submitted to cafeteria diet and physical activity. The study was approved by the Ethics Committee on Animal Use - CEUA (nº003 Protocol / 2014). For this study 74 animals (Swiss mice) were used, divided as follows: in the initial phase of this study, we carried out a pilot study (n = 10) divided into a control group (PCON) (n = 5) and cafeteria group (PCAF) (n = 5), in order to evaluate a cafeteria diet which was both attractive to the animals and that could provide an increase in adipose tissue. After the induction of the diet, animals were euthanized and as a result, the animals in the PCAF group showed an intra-abdominal adiposity 0.74 ± 0.05 g, taken as the parameter for increasing fat in animals. Subsequently the study base was conducted for this research where animals were used (n = 64) divided into 2 groups: the Cafeteria Study Base Group (EBCAF) divided as follows: cafeteria + exercise + liraglutide (CEL) (n = 8), cafeteria + exercise + saline (CES) (n = 8), cafeteria + liraglutide (CL) (n = 8) and cafeteria + saline (CS) (n = 8). The Chow Study Base group (EBR) was divided into: exercise + liraglutide (EL) (n = 8), exercise + saline + (ES) (n = 8), liraglutide (L) (n = 8) and saline solution (SS) (n = 8). All animals went through the submission process to the cafeteria diet, followed by exercise protocol through swimming and treatment with the test substance intraperitoneally (200 mg / mL / kg). After the treatments, the animals were euthanized and had the following parameters evaluated: the muscle tissue mass, adipose tissue mass and biochemical parameters. It was observed that the processing done with the exercise-associated liraglutide reduced adipose tissue mass significantly (0.32 ± 0.05 g) compared to the saline group (0.53 ± 0.07 g). There were no changes in the muscle tissue of the group which was treated and exercised (1.39 ± 0.03 g) compared to the saline group (1.33 ± 0.03 g). Regarding biochemical parameters it was evident that there were changes in these parameters. Interesting to note that, although blood glucose values have been changed, the animals did not become diabetic. Thus, it appears that physical activity together with liraglutide is eficcient to the loss of intraabdominal adipose tissue and the maintenance of lean body mass thereby generating a satisfactory result in the pursuit of quality of life and disease prevention.
Resumo:
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease, rare, multisystem, with a very heterogeneous clinical and serological manifestations standard. The patient, in addition to suffering injuries on his physical and physiological functioning, may also face a number of psychosocial problems. Research indicates that SLE can cause significant damage to the psychological realm, especially with the presence of anxiety and depression. In 1999, the American College of Rheumatology (ACR), proposed the establishment of 19 neuropsychiatric clinical syndromes attributed to SLE. Depression lies between mood disorders and is one of the most common psychiatric manifestations in this group, being found more frequently in these patients than in the general population. Studies also suggest that social support plays an important role in the development of coping strategies, in SLE management and depression. This study has as main objective verify the association between depressive symptoms and perceived social support in patients with SLE. The specific objectives turned to: investigte the prevalence of depressive symptoms; investigate the perceived social support and verify if there is an association between depression, social support and sociodemographic variables. We used a sociodemographic questionnaire, the Beck Depression Scale, and the Perceived Social Support Scale. The analysis was performed through descriptive and inferential statistics. The final sample could count with 79 SLE women, with an average age of 35.7 years. 44 (55.7%) of the participants were married. Only 6 (7.59%) had completed higher education and 32 (40.51%) have not finished high school. Seventy-one (89.87%) had an income below three minimum salaries and 71 (89.87) practiced a religion, and the Catholic (67.71%) was the most mentioned by them. Of the total sample, 37 (46.74%) had been diagnosed SLE more than 7 years before, and 25 (31.65%) had the disease for more than 10 years. Only 19 (24.05%) had some work activity. Forty-two of them (53.17%) had depressive symptoms levels from mild to severe, and 51 (64.46%) reported pain levels of 5, or above. The study found a significant association between depressive symptoms and pain (p = 0.013) and depressive symptoms and work activity (p = 0.02). When we examined the perception of social support, the results showed high levels among participants. Using the Spearman correlation test we found a strong correlation between depressive symptoms and social support (p= 0,000037). It means that the higher the frequency of support, the lower the score of depression. These findings are relevant because depressive symptoms in patients with SLE have a multicausal and multifactorial character and may remain unnoticed, since many of them are confused with the manifestations of the disease. This fact requires a careful assessment from professionals, not only in the clinical setting, but also considering other psychosocial reasons, that may be influencing the emergence or worsening of symptoms. These results also corroborate other studies, which not only confirm the predictive role of social support in the physical wellbeing, but also in the psychological.
Resumo:
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease, rare, multisystem, with a very heterogeneous clinical and serological manifestations standard. The patient, in addition to suffering injuries on his physical and physiological functioning, may also face a number of psychosocial problems. Research indicates that SLE can cause significant damage to the psychological realm, especially with the presence of anxiety and depression. In 1999, the American College of Rheumatology (ACR), proposed the establishment of 19 neuropsychiatric clinical syndromes attributed to SLE. Depression lies between mood disorders and is one of the most common psychiatric manifestations in this group, being found more frequently in these patients than in the general population. Studies also suggest that social support plays an important role in the development of coping strategies, in SLE management and depression. This study has as main objective verify the association between depressive symptoms and perceived social support in patients with SLE. The specific objectives turned to: investigte the prevalence of depressive symptoms; investigate the perceived social support and verify if there is an association between depression, social support and sociodemographic variables. We used a sociodemographic questionnaire, the Beck Depression Scale, and the Perceived Social Support Scale. The analysis was performed through descriptive and inferential statistics. The final sample could count with 79 SLE women, with an average age of 35.7 years. 44 (55.7%) of the participants were married. Only 6 (7.59%) had completed higher education and 32 (40.51%) have not finished high school. Seventy-one (89.87%) had an income below three minimum salaries and 71 (89.87) practiced a religion, and the Catholic (67.71%) was the most mentioned by them. Of the total sample, 37 (46.74%) had been diagnosed SLE more than 7 years before, and 25 (31.65%) had the disease for more than 10 years. Only 19 (24.05%) had some work activity. Forty-two of them (53.17%) had depressive symptoms levels from mild to severe, and 51 (64.46%) reported pain levels of 5, or above. The study found a significant association between depressive symptoms and pain (p = 0.013) and depressive symptoms and work activity (p = 0.02). When we examined the perception of social support, the results showed high levels among participants. Using the Spearman correlation test we found a strong correlation between depressive symptoms and social support (p= 0,000037). It means that the higher the frequency of support, the lower the score of depression. These findings are relevant because depressive symptoms in patients with SLE have a multicausal and multifactorial character and may remain unnoticed, since many of them are confused with the manifestations of the disease. This fact requires a careful assessment from professionals, not only in the clinical setting, but also considering other psychosocial reasons, that may be influencing the emergence or worsening of symptoms. These results also corroborate other studies, which not only confirm the predictive role of social support in the physical wellbeing, but also in the psychological.
Resumo:
The inadequacy about eating habits have been established as a serious problem nowadays. It is a multifactorial and difficult to handle, given their different nuances and causes. A population particularly exposed to the bad eating habits arising harm are individuals with Down syndrome, both with regard to the aspects inherent to the individual's own condition, regarding eating misfits, making it the weight control a necessary measure for a proper development. Thus, this study aimed to develop and evaluate a proposal based nutrition education from the assumptions of mediated learning, with children three to four years with Down syndrome. The participants were five children, four girls and a boy. Also included his parents and / or guardians. The data collection procedure involved the use of eight playful workshops with children and nutritional evaluation of those five meetings with parents and three home visits with each participating family. We tried to build with these children and their families a nutritional education to contribute to their daily choices of eating. Using listening, observation and questionnaire, besides playful interventions, it was observed that the first meaning of the act of eating is built in the family and reinforced by their social life. Overall, our sample characteristics seem to agree with the literature. During the intervention, the children showed attention, but little understanding of the content. With mothers, the results were different, with reflections on the inadequate power both the type of food offered, and quantity and so this offer is performed, conducted along the interventions changes in your lifestyle, such as perception of influence they had on their children in the formation of their eating habits, as well as less frequent intake of soft drinks and sweets. Nutritional interventions and mediations conducted with the mothers is that they seem to be effective strategies to combat obesity. Face of what was discussed, we see the importance of implementing intervention measures in combating and preventing overweight or obese since childhood, particularly with children with Down syndrome. One should prevent childhood obesity with educational and informative measures from birth, with family and with each child, through the primary health care and schools.
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The current study includes theoretical and methodological reflections on the quality of life in the city of Uberlândia, Minas Gerais. It started from the thought that the quality of life is multifactorial and is permanently under construction and the main objective of analyzing it as one of the componets of Healthy Cities's moviment. The theoretical research focused on the concepts of healthy cities, quality of life, health, sustainability, well-being, happiness, indexes and indicators. From the use of multiple search strategies, documentary and on field of quantitative and qualitative character, this research of exploratory descriptive nature can offers a contribution to the studies on the quality of life in cities. It is proposed that the studies startes to work with some concept, like some notions os life quality adequated for some paticular reality, whose notions can approach concepts already established as health. This step is important on the exploratory researches. The studies may include aspects of objective analysis, subjective or both. The objective dimension, which is most common approach, are traditionally considered variables and indicators related to: the urban infrastructure (health, education, leisure, security, mobility), dwelling (quantitative and qualitative dwlling deficit), the urban structure (density and mix uses), socioeconomic characteristics (age, income, education), urban infrastructure (sanitation, communication), governance (social mobilization and participation). To focus on the subjective dimension, most recent and unusual, it is proposed to consider the (dis)satisfaction, the personal assessment in relation to the objective aspects. In conclusion, being intrinsically related to the health, the quality of life also has a number of determinants, and the ideal of the reach of quality of life depends on the action of all citizens based on the recognition of networks and territories, in a interescalar perspective and intersectoral. Therefore, emphasis in given on the potential of tools, such as the observatories, to monitor and intervent in reality, aiming in a building process of healthy cities.
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La obesidad es un problema de salud pública a nivel mundial. Su prevalencia se ha multiplicado por más de dos entre 1980 y 2014. La Organización Mundial de la salud (OMS) ha estimado que 170 millones de jóvenes menores de 18 años presentan exceso de peso y ha considerado la obesidad como una epidemia a nivel mundial. La obesidad es una enfermedad crónica de origen multifactorial que viene determinada por la interacción de factores genéticos, biológicos, socioeconómicos, conductuales y ambientales actuando a través de mediadores fisiológicos nutricionales en la ingesta y gasto de energía. El sobrepeso y la obesidad son factores de riesgo relacionados con el desarrollo de diabetes, alteraciones del metabolismo lipídico, síndrome metabólico, hipertensión arterial, esteatosis hepática, litiasis biliar, alteraciones respiratorios, ortopédicas, trastornos psicológicos y de la alimentación y también en ocasiones inadaptación social del adolescente. Estos desajustes se pueden perpetuar y agravarse en la edad adulta, por lo que tanto el sobrepeso como la obesidad suponen un grave problema sanitario, económico y social, frente al cual es prioritario luchar. Numerosos estudios e investigaciones evidencian la relación existente entre la obesidad y sus inicios en la vida intrauterina, es decir, la relación entre el comportamiento nutricional y ponderal de la madre antes y/o durante el embarazo y las consecuencias en la salud de sus descendientes en la edad adulta...
Resumo:
La hernia perineal es una patología que se presenta en el macho de la especie canina de forma casi exclusiva, apareciendo de forma muy esporádica en la hembra y el gato, pero no se presenta en las otras especies domésticas. Se ha descrito en la especie humana sobre todo asociada a cirugías agresivas del abdomen caudal y siempre en relación a trastornos del suelo pélvico. En el perro la hernia perineal se produce por un fallo del diafragma pélvico, en el que destaca la atrofia y a veces la total desaparición del M. elevador de ano de forma uni- o bilateral. La debilidad-ausencia-desaparición de este músculo conduce a un posicionamiento más caudal de todos los órganos contenidos en el canal pélvico, vejiga, próstata, uretra post prostática, grasa periprostática y recto. Aparece en un rango muy amplio de edades aunque su tendencia más frecuente es alrededor de los 7-8 años de edad. Las manifestaciones clínicas de la hernia varían en función de la gravedad y antigüedad del proceso; el síntoma más frecuente es el estreñimiento y la deformación (tumefacción) de la fosa isquiática, pero se han descrito también la diarrea paradójica, vómitos y hasta la anuria obstructiva. La etiología de la hernia perineal esta poco clara, aunque existen diferentes hipótesis relacionadas con fenómenos que producen estreñimiento como hipertrofia prostática, o la existencia de quistes prostáticos y/o paraprostáticos. También se ha relacionado con saculitis o con la existencia de hernias inguinales. Otras teorías han relacionado la hernia con trastornos hormonales, desequilibrios entre receptores de andrógenos/estrógenos. Recientemente se la ha relacionado con la producción de relaxina en los quistes prostáticos y por último se la ha relacionado con alteraciones neurológicas del plexo pudendo. Pero lo cierto es que los porcentajes de perros con enfermedad prostática son muy altos sobre todo a partir de los 7- 8 años de edad y la incidencia de la hernia es muy baja. Tampoco todos los animales que padecen la hernia tienen quistes prostáticos y existen muchos animales con grandes quistes que no la desarrollan. En resumen, esta afección parece ser multifactorial aunque la lesión es siempre la misma, la debilidad progresiva del diafragma y la falta de funcionalismo hace el resto. Respecto a la cirugía ofrece también dificultades, se han descrito varias técnicas y las que mejores resultados ofrecen son las basadas en la elevación del obturador interno. No obstante en ocasiones este músculo también se encuentra atrofiado y la restauración del plano anatómico no es todo lo sólida que se desearía por lo cual se añade a la elevación del obturador, la utilización de mallas de polipropileno, la sobreposición del m. glúteo caudal, del músculo semitendinoso o la fijación intrabdominal de la vejiga, colon y conductos deferentes. A pesar de todo las recidivas siguen presentándose, aunque cada vez en menor porcentaje según las técnicas desarrolladas con posterioridad.
Resumo:
La especialidad de fisioterapia y rehabilitación veterinaria ha adquirido una importancia creciente experimentando un constante desarrollo en las últimas décadas. Prueba de ello es la aparición de varios cursos de postgrado en diferentes universidades veterinarias o la creación del American College of Veterinary Sports Medicine and Rehabilitation en 2010. En términos generales, esta especialidad se ha nutrido de los protocolos de medicina humana sin existir una base científica sólida, por lo que las publicaciones científicas en el campo veterinario, aunque han ido incrementando recientemente, son aún escasas. Por lo tanto, son necesarios estudios que exploren tratamientos, protocolos y métodos de valoración funcional en veterinaria. En la clínica equina, la fisioterapia se ha centrado en gran medida en la rehabilitación de lesiones musculoesqueléticas, donde los problemas de dorso son una de las principales causas de disminución del rendimiento en caballos de deporte. Su etiología suele ser multifactorial y su presentación hace difícil un diagnóstico claro. Basándonos en el modelo de medicina humana, donde se ha demostrado el papel vital que juega la musculatura multífida en la estabilidad dinámica de la columna y en el desarrollo de patologías, se han comenzado a describir diferentes programas de ejercicios en caballos con el objetivo de mejorar la estabilidad y el control motor del raquis. Aunque algunos han demostrado ser efectivos, aún se necesitan muchos estudios que pongan de manifiesto la aplicación clínica de estos protocolos y su metodología exacta de aplicación en medicina equina...
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La sinostosis sagital precoz o escafocefalia es la forma más frecuente de craneosinostosis. Se produce por el cierre prematuro de la sutura sagital lo que da lugar a un cráneo alargado en su diámetro anteroposterior. El término escafocefalia fue acuñado por Baer en 1860, y significa cabeza en forma de quilla o bote (gr. σκαφοζ, barco), lo que describe a la perfección las deformidades presentes en estos pacientes: una cabeza alargada en su diámetro anteroposterior, con estrechamiento del diámetro biparietal y abombamientos compensadores frontales y occipitales. Su incidencia se calcula en torno a uno de cada 2000 a 3000 recién nacidos vivos con una proporción de 3,5 a 1 entre varones y mujeres. Aproximadamente el 72 % de los casos son de tipo esporádico aunque se ha observado agregación familiar en un 6% de los pacientes afectados. Se acepta que la causa de las craneosinostosis simples es multifactorial, con un origen heterogéneo desde el punto de vista etiológico y distintos procesos fisiopatológicos que pueden confluir en su desarrollo. Se postula que las craneosinostosis no sindrómicas tienen un componente genético, con interacciones entre genes y factores ambientales que aún no se conocen en su totalidad. Junto a factores mecánicos (como la restricción del movimiento fetal, compresiones por gestaciones múltiples, anomalías anatómicas uterinas...), se reconocen causas relacionadas con trastornos en la hidrodinámica del LCR (mielomeningocele, derivaciones ventriculoperitoneales en el tratamiento de la hidrocefalia), teratógenos o malformaciones del SNC que limitan la expansión de las vesículas telencefálicas (holoprosencefalia, microcefalia...)...
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El glaucoma es una neuropatía óptica crónica de etiología multifactorial, que provoca una pérdida progresiva e irreversible de la visión debida a la degeneración de los axones del nervio óptico y la muerte apoptótica de las células ganglionares de la retina (Downs et al., 2011; Quigley, 2011; Soto et al., 2014). Actualmente es la principal causa de ceguera irreversible en el mundo (Pascolini et al., 2012). Aunque su etiología aún no está clara, se sabe que el principal factor de riesgo para desarrollar la enfermedad es el aumento de la PIO debido a anomalías en la dinámica del humor acuoso (Casson et al., 2012). La presencia de receptores purinérgicos P2X y P2Y ha sido descrita en las principales estructuras oculares relacionadas con la producción y drenaje del humor acuoso, los procesos ciliares y la malla trabecular, que son bañadas por dicho fluido (Guzman-‐Aranguez et al., 2013). Al mismo tiempo, se ha referido la presencia del dinucleótido Ap4A, agonista de dichos receptores, en el humor acuoso, y cómo sus niveles se veían significativamente incrementados en pacientes glaucomatosos (Castany et al., 2011). El objetivo de esta tesis ha sido evaluar la implicación de los receptores purinérgicos P2Y2 de los procesos ciliares en la hipertensión ocular. Más concretamente determinar el papel del Ap4A a través de la activación de dichos receptores sobre la movilización del ion cloruro y del agua a través de las proteínas acuaporinas (AQPs), principales componentes del humor acuoso. Por otra parte, se ha investigado el origen de los niveles incrementados de Ap4A debidos al aumento de la PIO, caracterizando uno de los posibles sensores celulares implicados en dicho proceso. Al mismo tiempo se han evaluado y caracterizado los diferentes mecanismos implicados en dicha liberación...
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Introduction : Plusieurs études ont démontré que la pratique d’activité physique (AP) peut avoir un impact sur la vitalité cognitive des ainés. Le programme Musclez vos Méninges encourage les participants à être davantage actif et a été conçu pour promouvoir la vitalité cognitive. Ce mémoire vise à explorer : 1) les effets du programme sur l’AP; 2) l’effet modérateur et médiateur de l’AP sur les impacts du programme sur la cognition; 3) la corrélation entre l’AP et certaines dimensions cognitives des participants à l’entrée dans l’étude. Méthodologie: Au total, 294 personnes âgées de 60 ans et plus, intéressées à participer à un programme de vitalité cognitive ont été recrutées. Elles ont été évaluées avec des tests cognitifs (MoCA, MIA, CVLT, RBMT, MMQ, Attention, Stroop) et des instruments sur l’AP (une version adaptée du CHAMPS et le test de marche de 2 minutes du SFT). Des corrélations ont été faites à l’entrée dans l’étude et des régressions multivariées ont été réalisées pour mesurer l’impact du programme et celui de l’AP. Résultats : La participation au programme est associée à une hausse de l’AP (p< 0,05). Les analyses n’indiquent cependant pas d’effet significatif (p< 0,05) modérateur ou médiateur. À l'entrée dans l'étude, les sujets les plus actifs présentent de meilleurs résultats pour le recours aux stratégies mnésiques (p< 0,05). Conclusion: Un programme multifactoriel, incluant la promotion de l’AP, peut modifier significativement l’engagement à être physiquement actif. Des études futures devront toutefois démontrer si la pratique d’AP peut avoir un effet modérateur ou médiateur sur la vitalité cognitive.
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A large proportion of the variation in traits between individuals can be attributed to variation in the nucleotide sequence of the genome. The most commonly studied traits in human genetics are related to disease and disease susceptibility. Although scientists have identified genetic causes for over 4,000 monogenic diseases, the underlying mechanisms of many highly prevalent multifactorial inheritance disorders such as diabetes, obesity, and cardiovascular disease remain largely unknown. Identifying genetic mechanisms for complex traits has been challenging because most of the variants are located outside of protein-coding regions, and determining the effects of such non-coding variants remains difficult. In this dissertation, I evaluate the hypothesis that such non-coding variants contribute to human traits and diseases by altering the regulation of genes rather than the sequence of those genes. I will specifically focus on studies to determine the functional impacts of genetic variation associated with two related complex traits: gestational hyperglycemia and fetal adiposity. At the genomic locus associated with maternal hyperglycemia, we found that genetic variation in regulatory elements altered the expression of the HKDC1 gene. Furthermore, we demonstrated that HKDC1 phosphorylates glucose in vitro and in vivo, thus demonstrating that HKDC1 is a fifth human hexokinase gene. At the fetal-adiposity associated locus, we identified variants that likely alter VEPH1 expression in preadipocytes during differentiation. To make such studies of regulatory variation high-throughput and routine, we developed POP-STARR, a novel high throughput reporter assay that can empirically measure the effects of regulatory variants directly from patient DNA. By combining targeted genome capture technologies with STARR-seq, we assayed thousands of haplotypes from 760 individuals in a single experiment. We subsequently used POP-STARR to identify three key features of regulatory variants: that regulatory variants typically have weak effects on gene expression; that the effects of regulatory variants are often coordinated with respect to disease-risk, suggesting a general mechanism by which the weak effects can together have phenotypic impact; and that nucleotide transversions have larger impacts on enhancer activity than transitions. Together, the findings presented here demonstrate successful strategies for determining the regulatory mechanisms underlying genetic associations with human traits and diseases, and value of doing so for driving novel biological discovery.
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Hyperemesis gravidarum is a complex condition with a multifactorial etiology characterized by severe intractable nausea and vomiting. Despite a high prevalence, studies exploring underlying etiology and treatments are limited. We performed a literature review, focusing on articles published over the last 10 years, to examine current perspectives and recent developments in hyperemesis gravidarum.
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Aim: To investigate the characteristics, development and determinants of toothwear among Irish schoolchildren. Methods: A cross-sectional (examination at 16-years-old) and longitudinal (examinations at 5-,12-,14-years) study were conducted. Two indices were used to measure toothwear, children/parents completed a demographic profile and questionnaire on oral hygiene and dietary practices, health, and lifestyle in both studies. Saliva was collected from consenting 16-year-olds. The explanatory variables for the cross-sectional and longitudinal study were derived from children/parents responses. Differences in salivary profiles were determined for subsets; the protein concentration was determined with Bradford protein assay and protein carbonyl concentration (a protein oxidation marker) was determined spectrophotometrically. Gel-electrophoresis and mass spectrometry determined proteins and ion chromatography inorganic ions. Statistical significance was accepted at p<0.05. Results: At 16-years-old the prevalence of toothwear with dentine visible was 44%. No difference in salivary flow rates existed. In unstimulated saliva a higher mean, protein carbonyl (p<0.0001) and total calcium concentration (p<0.002) existed for the group with moderate toothwear. In stimulated saliva the moderate toothwear group had a lower mean protein concentration(p<0.0001). The 2-DE protein spots prepared for a sub-group differed between those with toothwear and without. Mass spectrometry, identified one of the different proteins as IgA. For 16-year-olds, the self-reported factors indicated that brushing after breakfast was associated with lower toothwear scores(p<0.03). Nail-biting, being asthmatic or reporting a dry mouth were associated with higher toothwear scores(all p<0.05). Eating an apple daily or less was associated with less toothwear(p<0.002). In the longitudinal study toothwear into dentine at age five or 12-years was associated with more toothwear at age 14(all p<0.05). Discussion: The results illustrate the multifactorial aetiology of toothwear. The biochemical and physical correlates of saliva with toothwear requires further research. Conclusion: The impact of previous toothwear, salivary, dietary and personal factors on toothwear in the early permanent dentition is demonstrated.