A key feature of sleep is reduced responsiveness to the environment, which puts animals in a particularly vulnerable state; yet, sleep has been conserved throughout evolution, indicating that it fulfills a vital purpose. A core function of sleep across species has not been identified, but substantial advances in sleep research have been made in recent years using the genetically tractable model organism, Drosophila melanogaster. While a standard approach in sleep research is to study the effects of short-term sleep deprivation on an animal, tools are now available to genetically manipulate sleep amount in the fruit fly. In particular, a number of short-sleeping Drosophila mutants have been identified that model the long-term sleep restriction that is widespread in modern society. This thesis describes a body of work in which short-sleeping Drosophila mutants, as well as other genetic and pharmacological tools, were used to shed light on the function and regulation of sleep.

Orientador: Regina Maria Barretto Cicarelli / Banca: Marcia Graminha / Banca: Alberto José Cavalheiro / Resumo: Trypanosoma brucei é o agente etiológico da tripanossomíase africana ou doença do sono, transmitida por dípteros do gênero Glossina, conhecidos como moscas tsé-tsé. O diagnóstico e tratamento da doença não são satisfatórios, uma vez que para o tratamento está disponível um número de drogas altamente tóxicas e com um efeito limitado, pois dependem da fase da doença, das condições fisiológicas do hospedeiro, da suscetibilidade e variabilidade genética da cepa. Além do alto custo, o tratamento é potencialmente perigoso e está limitado ao surgimento de resistência generalizada aos fármacos utilizados. O diagnóstico é limitado à associação dos sintomas com a doença, muitas vezes é confundido com outras doenças pelo que o paciente não recebe o tratamento adequado. Por isso, tem-se a necessidade de buscar novos fármacos com melhor atividade tripanocida. Neste trabalho, avaliou-se a atividade tripanocida de 38 compostos diferentes e inéditos, como N1,N2-dibenziletano-1,2-diamina (cloridratos de benzil diaminas), N1-benzil,N2-metilferroceniletano-1,2-diamina (cloridratos de diaminas de ferroceno), 2-metoxi/hidroxi-3-(1-alquenil)-1,4-naftoquinonas e seus derivados 2-amina-1,4-naftoquinonas contra as cepas 427 e 29-13 de T. brucei. A eficácia dos compostos foi avaliada pelo método colorimétrico do MTT [brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazoliom]. Os resultados encontrados foram similares aos das atividades metabólicas das células (parasitas e/ou células HepG2 - linhagem de células de hepatoma, usada como modelo para simular funções hepáticas humanas in vitro), sendo o IC50 (metade da concentração inibitória máxima) calculado por regressão linear para cada composto. Da série anterior, o composto cloridrato de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Trypanosoma brucei is the etiologic agent of sleeping sickness (Human African Trypanosomiasis [HAT]), transmitted by flies of Glossina genus, known as tsetse flies. The diagnostic and treatment of this disease are not satisfactory, since the treatment uses many toxicity drugs with limited effects, because depend on the stage of the disease, morphological diversity, heterogeneous biological behaviour, different clinical courses and the virulence appears to be an intrinsic property of each strain and high genetic variability. Besides the high cost, the treatment is potentially dangerous and limited the emergence of widespread drug resistance. The diagnosis is limited to the association of symptoms with the disease, is often confused with other diseases so the patient does not receive adequate treatment. Thus, the development of new research is necessary in order to generate new drugs with trypanocidal activity. In this work, we evaluated the trypanocidal activity of 38 inedited compounds of N1,N2-dibenzylethane-1,2-diamine hydrochlorides, N1-benzyl,N2-methyferrocenylethane-1,2-diamine hydrochlorides, 2-metoxy/hydroxy-3-(1-alquenyl)-1,4-naphtoquinones and amine derivatives of this compounds (2-amine-1,4-naphtoquinones) against 427 and 29-13 T. brucei parasite strains. The efficacy of these compounds was also measured using the reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. The results were similar to the metabolic activity of cells (parasites and/or HepG2 - hepatoma cell line used as a model to simulate human hepatic functions in vitro), being the IC50 (half of the maximum inhibitory concentration) calculated by linear regression for each sample. The compounds N-(ferrocenylmetyl)-N'-(4-metoxybenzyl)ethane-1,2-diamine) hydrochlorides and 2-metoxy-3-(2-phenylethenyl)-1,4-naphtoquinone... (Complete abstract click electronic access below) / Mestre

Objetivo: Avaliar o impacto na qualidade de vida dos distÃrbios obstrutivos do sono (DOS) do sono em crianÃas atendidas pelo Sistema Ãnico de SaÃde (SUS), assim como a repercussÃo do tratamento com adenoidectomia ou adenotonsilectomia na qualidade de vida destas crianÃas. MÃtodos: Foi realizado um estudo de intervenÃÃo nÃo controlado do tipo antes e apÃs (before and after) com um componente avaliativo (avaliaÃÃo da qualidade de vida). Uma amostra consecutiva de crianÃas com indicaÃÃo de adenoidectomia ou adenotonsilectomia foi recrutada no ambulatÃrio de otorrinolaringologia do Hospital UniversitÃrio Walter CantÃdio da Faculdade de Medicina da Universidade Federal do CearÃ, e aplicados aos cuidadores um questionÃrio validado, especÃfico para a avaliaÃÃo da qualidade de vida de crianÃas com DOS, o OSA-18, antes da cirurgia e com pelo menos 30 dias apÃs a sua realizaÃÃo. AlÃm disso, foi realizado exame nasofibroscÃpico, otorrinolaringolÃgico, visando responder a questionÃrio semi-estruturado sobre o perfil clÃnico e social da crianÃa, em ambas as consultas. Resultados: A populaÃÃo do estudo foi de 48 crianÃas e a idade mÃdia de 5,93 anos (DP=2,43). A mÃdia de tempo de escolaridade do cuidador foi de 8,29 anos (DP=3,14). Os sintomas mais presentes foram de sono agitado, apnÃia e ronco. A mÃdia de tempo de queixa de DOS foi de 4,62 anos (DP=2,49), sendo a mÃdia de escore total do OSA-18 basal de 82,83 (grande impacto na qualidade de vida) e no pÃs-operatÃrio, de 34,15. As diferenÃas nos escores total e dos domÃnios entre o OSA-18 basal e pÃs operatÃrio foram todas significantes (p<0,00). ConclusÃes: A crianÃas com DOS apresentam impacto relevante na qualidade de vida e apresentam melhora considerÃvel apÃs o tratamento cirÃrgico. / Objective: To evaluate the impact of sleep-disordered breathing (SDB) in the quality of life of children under treatment by the âSistema Ãnico de SaÃde â SUSâ, and the outcomes of the treatment with adenoidectomy or adenotonsillectomy in these childrenâs quality of life. Methods: A non-controlled intervening study was made, of the kind âbefore and afterâ, with an assessment component (evaluation of the quality of life). A consecutive sample of children with indication of adenoidectomy or adenotonsillectomy was recruited from the Walter CantÃdio University Hospital otolaryngology clinic of the Federal University of Cearà Medical College, and the guardians answered a validated survey, specific for the evaluation of quality of life in children with SDB, the OSA-18, before the surgery and with, at least, 30 days after surgery, besides, a nasofibroscopic exam and an otolaryngology exam were done as well as the answering to a semi-structured survey about the childâs social and clinic profile, on both appointments. Results: The population under study was of 48 children with mean of 5,93 years of age (SD=2,43). The guardiansâ mean of years of study was 8,29 years (SD=3,14). The most frequent symptoms were agitated sleep, apnea and snoring. The SDB complaining time average was 4,62 years (SD=2,49). The total score mean of the initial OSA-18 was 82,83 (great impact in quality of life) and after surgery was 34,15. The differences in the total scores and in the domains between the initial OSA-18 and post-surgery were all significant (p<0,00). Conclusions: Children with SDB present a relevant impact in their quality of life, and they show a dramatic improvement after surgical treatment.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / O objetivo deste estudo foi verificar a presenÃa de parÃmetros morfolÃgicos maxilares na SÃndrome da ApnÃia Obstrutiva do Sono (SAOS) A amostra consistiu nos modelos de gesso da maxila de 23 indivÃduos (11 masculinos e 12 femininos) com diagnÃstico polissonogrÃfico de SÃndrome da ApnÃia Obstrutiva do Sono leve 34 indivÃduos (17 masculinos e 17 femininos) com sÃndrome moderada e 17 indivÃduos com sÃndrome grave (14 masculinos e 3 femininos) O grupo controle era composto por modelos de gesso da maxila de 50 jovens brasileiros de ambos os sexos com oclusÃo normal e sem indÃcios de SÃndrome da ApnÃia Obstrutiva do Sono Os resultados encontrados demonstraram que os parÃmetros morfolÃgicos da maxila avaliados nÃo apresentaram associaÃÃo com o Ãndice de apnÃia e hipopnÃia (IAH) mas ocorreram menores dimensÃes transversais da arcada dentÃria superior principalmente ao nÃvel de molares associado a um aumento da dessaturaÃÃo de oxi-hemoglobina (SaO2mÃn)IndivÃduos com SÃndrome da ApnÃia Obstrutiva do Sono tambÃm apresentaram dimensÃes transversais da maxila mais estreitas e maior profundidade do palato na regiÃo de prÃ-molares e molares quando comparados ao grupo controle / The objective of this study was to verify the presence of maxillary morphologic parameters on the Obstructive Sleep Apnea Syndrome (OSA) The sample was consisted on maxilla dental models of 23 individuals (11 males and 12 females) with the polyssonographic diagnosis of mild SAOS, 34 individuals (17 males and 17 females) with moderate SAOS and 17 individuals with severe SAOS (14 males and 3 females) Measures of maxilla dental models of 50 young Brazilians were used for the control group, both males and females and with normal occlusion and without any indication OSA The results found show that the maxillary morphologic parameters evaluated didnât show the association with the apnea/hypopnea index (AHI) but minor transversal dimensions of the maxilla mainly at the level of the molars associated to the increase of the dessaturation of oxyhemoglobin (minSaO2) The individuals with OSA also presented maxilla transversal dimensions narrower and more height on the palate at the region of pre-molars and molars when compared to the control group

The objective of this study was to determine the effects race, sex and sleep disturbance have on the severity of Parkinson’s disease as assessed by the Hoehn Yahr (HY) score in both the medicated (ON) and non-medicated (OFF) states. The potentially confounding variables of age, time in years from the onset of symptoms to database entry, and education were taken into account. Secondary analysis was also conducted to determine how the non-motor symptoms of dementia, hallucinations and autonomic dysfunction impacted Hoehn Yahr ON and OFF scores. This study used the statistical techniques of the Student’s t-test, ANOVA, Tukey-Kramer test, univariate linear regression, and multivariate regression. The t-tests and ANOVA test revealed that there was no significant differences in mean HY ON and OFF scores between the sexes, patients with and without sleep disturbance, and between the different races analyzed in this study. Patients with and without sleep disturbance did show significantly higher HY ON scores as compared to HY OFF scores, which is peculiar as this finding suggests that these patients are not responding to their medication. The univariate linear regression models did show, however, that time in years from the onset of symptoms to database entry did significantly impact both HY ON and OFF scores, whereas age is only shown to have a significant impact on HY OFF scores. Additionally, the univariate linear regression model analyzing the association between education and HY OFF scores showed that having some high school education, but not receiving a degree, was associated with an increase in HY OFF scores. Several multivariate linear regression models where built to assess the impact different predictor variables had on HY ON and HY OFF scores. The first two multivariate models used the predictor variables of age, race, and time in years from the onset of symptoms until database entry. These models showed that only time in years from the onset of symptoms until database entry impacted HY ON scores, whereas all three of these predictor variables impacted HY OFF scores. Two additional multivariate linear regression models were built to assess how age, race, time in years from the onset of symptoms until database entry, dementia, autonomic dysfunction and hallucinations all impacted HY ON and OFF scores. These models revealed that all of these predictors, when taken together, significantly impacted HY OFF scores, but not HY ON scores. Finally a scatter plot was made comparing HY ON and HY OFF scores. A LOWESS scatter plot smooth line was also superimposed on top of this plot to show the overall trend these scores had on one another. This scatter plot was interesting because it suggested that there were two spate groups of patients contained in this database, those that responded well to medication and those that did not. Overall, this study showed that age, time in years from the onset of symptoms until database entry, education and race impacted HY OFF scores. Furthermore, the analysis indicated that patients who were asked about sleep disturbance did not appear to be responding to medication. There are several limitations to this study, however, with the most important being missing data and the cross-sectional design. Missing data prevented sleep disturbance from being thoroughly analyzed and the cross-sectional design does not allow for any causal relationships to be determined.

abstract: College students are a niche of young adults, characterized by abnormal sleeping habits and inactive lifestyles. Many students entering college are as young as 18 years old and graduate by 22 years old, a window of time in which their bones are still accruing mineral. The purpose of this cross-sectional study was to determine whether sleep patterns and physical activity observed in college students (N= 52) 18-25 years old at Arizona State University influenced bone biomarkers, osteocalcin (OC) and N-terminal telopeptide of type 1 collagen (NTX-1) concentrations. Students completed various dietary and health history questionnaires including the International Physical Activity Questionnaire short form. Students wore an actigraphy watch for 7 consecutive nights to record sleep events including total sleep time, sleep onset latency and wake after sleep onset. Total sleep time had a significant, negative correlation with OC (r = -0.298, p-value =0.036) while sleep onset latency had a significant, positive correlation with NTX-1 serum concentration (r = 0.293, p-value = 0.037). Despite correlational findings, only sleep percent was found to be significant (beta coefficient = 0.271 p-value = 0.788) among all the sleep components assessed, after adjusting for gender, race, BMI and calcium intake in multivariate regression models. Physical activity alone was not associated with either bone biomarker. Physical activity*sleep onset latency interactions were significantly correlated with osteocalcin (r = 0.308, p-value =0.006) and NTX-1 (r = 0.286, p-value = 0.042) serum concentrations. Sleep percent*physical activity interactions were significantly correlated with osteocalcin (r = 0.280, p-value = 0.049) but not with NTX-1 serum concentrations. Interaction effects were no longer significant after adjusting for covariates in the regression models. While sleep percent was a significant component in the regression model for NTX-1, it was not clinically significant. Overall, sleep patterns and physical activity did not explain OC and NTX-1 serum concentrations in college students 18-25 years old. Future studies may need to consider objective physical activity devices including accelerometers to measure activity levels. At this time, college students should review sleep and physical activity recommendations to ensure optimal healthy habits are practiced. / Dissertation/Thesis / Masters Thesis Nutrition 2019

Research has shown that sleep disturbance (e.g., sleep latency, wakefulness after sleep onset [WASO]) negatively affects physical, emotional, and mental health. For many adults, the postpartum period is one that is particularly highlighted by sleep disturbance and fatigue. Postpartum mothers are also more vulnerable to psychiatric disorders such as depression. We sought to investigate whether the number of children and presence of an infant predicted clinically significant sleep disturbance, and subsequently, depressive symptoms, for both mothers and fathers. We found that having an infant was significantly associated with increased wife WASO, which in turn was associated with increased depressive symptoms for wives. Further, husband WASO was associated with decreased wife WASO which was similarly associated with decreased depressive symptoms for wives. Thus, by helping with nighttime care so that mothers can get more sleep fathers can greatly contribute to the physical and emotional health of mothers.

Effective memory representations must be specific to prevent interference between episodes that may overlap in terms of place, time, or items present. Pattern separation, a computational process performed by the hippocampus overcomes this interference by establishing non-overlapping memory representations. This project explores pattern separation and how it is impacted by age and sleep. Experiment 1. Structures of the medial temporal lobe (MTL) are known to be involved in declarative memory processes. However, little is known about how age-related changes in MTL structures, white matter integrity, and functional connectivity affect pattern separation processes in the MTL. In the present study, we used magnetic resonance imaging (MRI) to measure the volumes of MTL regions of interest, including hippocampal subfields (dentate gyrus, CA3, CA1, and subiculum) in healthy older and younger adults. Additionally, we used diffusion tensor imaging to measure white matter integrity for both groups. Finally, we used functional MRI to acquire resting functional connectivity measures for both groups. We show that, along with age, the volume of left CA3/dentate gyrus predicts memory performance. Differences in fractional anisotropy and the strength of resting functional connections between the hippocampus and other cortical structures implicated in memory processing were not significant predictors of performance. As previous studies have only hinted, it seems that the size of left CA3/dentate gyrus contributes more to successful discrimination between similar mnemonic representations than other hippocampal sub-fields, MTL structures, and other neuroimaging correlates. Accordingly, the implications of aging and atrophy on lure discrimination capacities are discussed. Experiment 2. Although it is widely accepted that declarative memories are consolidated during sleep, the effects of sleep on pattern separation have yet to be elucidated. We used whole-brain, high-resolution functional neuroimaging to investigate the effects of sleep on a task that places high demands on pattern separation. Sleep had a selective effect on memory specificity and not general recognition memory. Activity in brain regions related to attention, visual acuity, and visual recall demonstrated an interaction between sleep and delay. Surprisingly, there was no effect of sleep on hippocampal activity using a group-level analysis. To further understand the role of the hippocampus on our task, we performed a representational similarity analysis. We investigated whether hippocampal activity associated with looking at novel stimuli correlated more with similar-looking (lure) stimuli or repeated stimuli. Results indicate that while a single night's sleep does not significantly impact hippocampal responses, the hippocampus does treat lure stimuli similarly as it does novel stimuli.

Short sleep duration in childhood has been associated with an increased risk of overweight and obesity. Research suggests that physical activity might mediate this association; however, studies examining associations between physical activity and sleep in young children have reported equivocal findings. A possible explanation for these inconsistencies is that past studies have looked at total physical activity counts rather than examining physical activity regularity. We aim to explore the relationship of regular physical activity, sedentary behavior, and sleep in preschoolers and kindergartners. 131 children (ages 4-6) were included in this study. Each child wore a waist-worn accelerometer for three days and three nights. Waist-worn accelerometers reliably measure sleep and physical activity in children. Associations of regular physical activity, sedentary behavior, and sufficient sleep were determined using logistic regression models. There was no association between the number of days that children engaged in physical activity (≥ 60 minutes) and sufficient sleep. Further, there was no association between the number of days that children engaged in ≥ 20 minutes of vigorous activity and sufficient sleep. Children who engaged in minimal sedentary activity had greater odds of obtaining sufficient sleep as compared to children who engaged in more sedentary activity.

Breakfast intake is associated with numerous positive physical and mental health outcomes, yet breakfast skipping remains common in adults. Chronotype and sleep show potential as predictors of breakfast intake; however the existing literature has methodological limitations and fails to examine how psychological mechanisms might explain the relation between sleep and breakfast. The current investigation explored the association of means and variability of sleep behaviors (bedtime, midsleep, sleep duration) as predictors of breakfast intake frequency and high-protein breakfast intake frequency. Additionally, the role of positive and negative affect as mediators in the sleep—breakfast association was examined. Hierarchical regressions and PROCESS parallel mediation models were conducted to assess direct and indirect associations. Variability in bedtime was a significant predictor of breakfast intake frequency, with greater variability associated with less frequent intake. Future work is necessary to examine further the association of sleep and breakfast behaviors, and psychological mechanisms in this relation.