O ciclo vigília/sono (CVS) muda durante a adolescência. Nos dias letivos, há maior sonolência diurna e menor duração de sono do que nos finais de semana. Além disso, os adolescentes apresentam atraso da fase de sono. Acredita-se que essas mudanças resultam da interação entre fatores biológicos e ambientais. Neste trabalho, observamos o CVS de 21 jovens Guarani da Aldeia Boa Vista - SP, que vivem numa floresta, sem energia elétrica. Pretendíamos verificar se eles apresentam um padrão semelhante ao descrito em adolescentes urbanos ou se tal característica é menos evidente, como tem sido relatado na população rural. Aplicamos o Questionário de Hábitos de Sono e o Questionário de Matutinidade e Vespertinidade. Os participantes preencheram diários de sono, usaram actímetros e coletaram temperatura a cada 3 horas, na vigília, por 10 ou mais dias consecutivos em 3 ocasiões com intervalos de 6 meses. Fizemos inspecção visual dos actogramas de diários e actímetros, comparando-os entre si por meio de teste t de Student; avaliamos a significância das oscilações da temperatura pelo Método Cosinor; utilizamos as correlações de Pearson e Spearman para identificar relações entre variáveis, adotando como nível de significância α=0,05. Comparamos as etapas e discutimos os resultados no cenário de outras pesquisas realizadas com adolescentes. Observamos atraso da fase do sono e da temperatura oral nos Guarani, conforme descrito entre adolescentes de regiões urbanas, e menor duração do sono nos finais de semana do que nos demais dias. Os resultados apontam para a importância de fatores biológicos no atraso da fase dos ciclos vigília/sono e de temperatura na adolescência. / The sleep/wake cycle (SWC) changes along adolescence. During weekdays there is higher diurnal sleepiness and shorter sleep duration than on weekends; moreover, they display sleep phase delay. Some authors believe these changes result from the interaction between biological and environmental factors. In this work, we observed the SWC in 21 adolescents from the ethnic group Guarani living in Boa Vista village (São Paulo) who live in a rural area, without electric light. We intended to verify whether they show a SWC pattern similar to that found in urban adolescents or if these characteristics are less evident under their condition as has been reported for rural area adolescents. We applied Sleep Habits and Morningness-Eveningness questionnaires. The participants kept Sleep Diaries and wore wrist actimeters for at least 10 consecutives days, and collected oral temperature every 3 hours when awake. This protocol was applied on 3 occasions with 6 months intervals between them. We examined the actograms from Diaries and Actimetries, comparing them with t Student test; we evaluated the temperature oscillations by Cosinor Method, we used Pearson’s and Spearman’s correlations in order to identify relationships between the measures, adopting the significance level at α=0.05. We compared the occasions and considered our results in the context of adolescent sleep researches. We observed sleep and temperature phase delays in Guarani adolescents similar to the delays found in other groups, as well as shorter sleep duration on weekends than on weekdays. Our results point to the importance of biological factors on sleep/wake and temperature phase delays along adolescence.

O objetivo do presente estudo foi avaliar possíveis relações entre o diabetes mellitus tipo 1 (DM1) e controle glicêmico, e o ciclo vigília/sono. Participaram 18 voluntários com DM1 (idade: 26,3±5,1), sem complicações, não obesos, sem alterações no sono; e 9 no grupo controle (idade: 28,8±5,3). Os dados foram coletados através de: diário de sono e de glicemia, actímetria (Tempatilumi), polissonografia, 6-sulfatoximelatonina, questionário de Epworth, e sensor de glicose durante a polissonografia nos DM1. A associação entre controle glicêmico e o ciclo vigília/sono foi evidenciada. A duração inadequada, a baixa qualidade, a fragmentação do sono e a secreção reduzida de melatonina, possivelmente, favoreceram um pior controle glicêmico em DM1. Por outro lado, indivíduos DM1, com melhor controle glicêmico, podem se beneficiar de maior secreção de melatonina noturna e menor fragmentação e latência do sono. O controle mais adequado, potencialmente, regulariza o ciclo vigília/sono e previne ou retarda o desenvolvimento de complicações crônicas. / The aim of the present study was to evaluate the association of type 1 diabetes mellitus (T1DM) and glycemic control with the sleep/wake cycle. Eighteen T1DM volunteers and 9 control subjects, non-obese, without chronic complications, and no sleep disorders participated. Data were collected with sleep and glycemia log, actigraphy (Tempatilumi), polysomnography, 6-sulphatoxymelatonin, Epworth questionnaire, and glucose sensor during the polysomnography night for T1DM. The association between glycemic control and sleep/wake cycle was observed. The inadequate duration, poor quality, and fragmented sleep besides the reduced melatonin secretion possibly favored a worse glycemic control in T1DM. On the other hand, we understand that T1DM individuals with better glycemic control may benefit from increased melatonin secretion and less sleep fragmentation and latency. Therefore, a better glycemic control potentially regulates the sleep/wake cycle and prevents or delays the development of chronic complications.

Le moment, la qualité et la quantité de sommeil dépendent de l'interaction fine entre l'horloge circadienne et la machinerie homéostatique (Borbely A. et al., 1982, Daan S. et al., 1984, Borbely et Achermann, 1999). Au cours des dernières années, l'utilisation de divers organismes modèles a fourni de nouvelles perspectives sur les mécanismes neuronaux et moléculaires de la régulation du sommeil (Miyazaki S. et al., 2017). Cependant, les bases moléculaires de l'homéostasie du sommeil et les circuits neuronaux sous-jacents à son interaction avec le réseau circadien n'ont pas été établis en détail.Dans ce travail de thèse, j'ai utilisé la mouche Drosophile melanogaster comme système modèle pour étudier la fonction d'un sous-ensemble de neurones d'horloge, les DN1ps, dans la mise en place du sommeil. Des études antérieures ont suggéré un rôle de ces neurones circadiens dans la régulation du sommeil (Kunst et al., 2014, Guo et al 2016, Lamaze et al., 2017, Guo et al., 2017). J’ai ainsi démontré que les cellules d'horloge DN1ps DH31 (+) CRY (+) sont impliquées dans la suppression du sommeil. Par ailleurs, j’ai mis en évidence un circuit en aval des DN1ps, qui comprend le groupe dopaminergique postérieur apparié latéral 1 (PPL1) et les neurones dorsaux en forme d’éventail (dFSB), un centre homéostatique récemment décrit pour la régulation du sommeil chez la drosophile (Donlea JM et al., 2011, Liu S. et al., 2012, Ueno et al., 2012, Donlea JM et al., 2014, Pimentel et al., 2016, Qian et al., 2017, Donlea JM. et al., 2018). Nos résultats indiquent que la suppression du sommeil nocturne nécessite la signalisation DH31-R2 dans une sous-population des neurones dopaminergiques PPL1, qui projette au dFSB. Fait intéressant, la perte de sommeil de jour et de nuit médiée par les DN1ps dépend de l'inhibition du dFSB. Néanmoins, nous suggérons que les neurones DN1ps CRY (-) favoriseraient le sommeil, en concordance avec d'autres travaux (Guo et al., 2016; Guo et al., 2017).Ces résultats fournissent de nouvelles données sur le lien entre l'horloge circadienne et l'homéostasie du sommeil, impliqué dans la régulation du comportement sommeil-éveil chez Drosophile melanogaster. / The timing, quality and quantity of sleep depend on the fine interaction between circadian clock and homeostatic machinery (Borbely A. et al., 1982; Daan S. et al., 1984; Borbely and Achermann, 1999). In the recent years, the employment of various model organisms has provided new insights into the neuronal and molecular mechanisms of sleep regulation (Miyazaki S. et al., 2017). However, the molecular basis of the sleep homeostat and the neuronal circuitry underlying its interaction with the circadian network haven’t been established in details.In this work, I use the fruit fly Drosophila melanogaster as a model system to investigate the sleep function of a subset of clock neurons, the DN1ps. Previous studies have already suggested a sleep-regulating role for these circadian neurons (Kunst et al. 2014, Guo et al. 2016; Lamaze et al., 2017; Guo et al. 2017). Here, we report the DH31-positive CRY-positive DN1ps as sleep suppressing clock cells. Furthermore, we identify a sleep-relevant circuit downstream of the DN1ps which includes the paired posterior lateral 1 (PPL1) dopaminergic cluster and the dorsal Fan-shaped body projecting (dFSB) neurons, a recently described homeostatic center for sleep regulation in Drosophila (Donlea JM. et al., 2011; Liu S. et al., 2012; Ueno et al., 2012; Donlea JM. et al., 2014; Pimentel et al., 2016; Qian et al., 2017; Donlea JM. et al., 2018). Our results indicate that the night-time sleep suppression requires DH31-R2 signaling in the PPL1-to-dFSB dopaminergic neurons. Interestingly, both day and night-time DN1ps-mediated sleep loss rely on the inhibition of the dFSB. Nevertheless, we suggest the CRY-negative DN1ps as sleep promoting clock neurons, in concordance with other works (Guo et al. 2016; Guo et al. 2017).These findings provide a novel link between circadian clock and sleep homeostat, in the regulation of sleep-wake behavior in Drosophila melanogaster.

Advances in wireless communication and microelectronics have led to the development of low-power compact sensor nodes (popularly called motes) that are capable of sensing, computing, and communication. A large number of these nodes can be deployed over some area of interest to form a multi-hop network, commonly referred to as a wireless sensor network (WSN). Typical applications of WSNs include, environment and process monitoring in industrial installations, forest fire detection, structural health monitoring, etc. In such applications where the variables to be measured are slowly varying, or the events to be monitored are rare, continuous sensing is unnecessary. Instead, the nodes, in order to conserve their battery power, can sleep-wake cycle whereby each node is allowed to independently alternate between an ON state and a low power OFF state. Sleep-wake cycling, while increasing the network lifetime, renders the network disconnected a large fraction of the time; however, connectivity can be established over time by transporting packets in a store-and-forward manner, whereby packets are held by a forwarding node until a suitable node wakes up in its neighborhood that can serve to forward the packet towards the destination. We are concerned with sleep-wake cycling multi-hop wireless networks whose main task is to carry sporadic alarms packets from sensing nodes to a sink node. Our objective is to design simple local-information based routing solutions for such networks. With this in mind, we propose a relay selection problem that arises at a forwarding node (which is currently holding the alarm packet) while choosing a next-hop relay node. The forwarder, as and when the relays wake-up, evaluating the goodness of a relay based on a “reward” metric (e.g., a function of the relay’s progress towards sink, and the power required to get the packet across), has to decide whether to forward to this relay or to wait for future ones (i.e., to stop or continue). The forwarder’s objective is to choose a relay so as to minimize a combination of the average delay incurred and the average reward achieved. A basic version of our relay selection problem is equivalent to the basic asset selling problem studied in the operations research literature. After reviewing the solution to the basic problem we will proceed to study a model with full information, referred to as the completely observable (CO) model, where the number of relays is exactly known to the forwarder. Formulating the problem as a Markov decision process (MDP) we will characterize the solution to the CO model in terms of recursively-computable threshold functions. Next, we consider the partially observable (PO) model where only a belief (probability mass function) on the number of relays is known. Hence, the PO model falls within the realm of partially observable MDPs. After incorporating our model into this framework we will characterize the solution in terms of stopping sets, which is the set of all belief states where it is optimal to stop. Our main contribution here is to obtain inner and outer bounds for the stopping sets. We next propose a variant where the relays, upon waking up, do not reveal their rewards immediately, but instead the forwarder can choose to probe the relay to know its reward, incurring a probing cost. Thus, to the existing set of stop and continue actions, we have added a new probe action. This model is motivated by the efforts required to learn the channel gains (by probing) in a wireless system. A key result we prove here is that the solution is characterized in terms of stage independent thresholds. Finally, we study a model comprising two forwarders which are competing against each other to choose a next-hop relay (one for each). Here, a relay is allowed to offer possibly different reward to each forwarder. We will first consider a complete information case where the reward pair of a relay is known to both the forwarders. Using stochastic game theory we will characterize the solution to this model in terms of Nash equilibrium policy pairs (NEPPs). We obtain results illustrating the structure of NEPPs. Next, we study a partial information model where each forwarder gets to observe only its reward value. Towards obtaining the solution for this model, we will first formulate a Bayesian game which is effectively played by both the forwarders at each stage. Next, for this Bayesian game we prove the existence of Nash equilibrium strategies within the class of threshold strategies. This result will enable us to construct NEPPs for the partial information model. Although our primary contribution from the thesis is the theoretical study of the above mentioned variants of the basic relay selection model, we have also conducted extensive simulations to study the end-to-end performance obtained by applying the solution to these models at each hop en-route to the sink in a sleep-wake cycling WSN.

Le sommeil est essentiel au bon fonctionnement de l’organisme. Ce dernier est régulé, entre autres, par le processus de régulation homéostatique qui dépend de la pression de sommeil accumulée suite à l’éveil. Des études ont suggéré que ce processus pourrait être lié à la plasticité synaptique, et que le changement de la pression de sommeil affecterait le degré de plasticité du cerveau. Les récepteurs N-méthyl-D-aspartate, des médiateurs importants de plasticité, semblent impliqués dans les conséquences délétères du manque de sommeil ainsi que dans la régulation de la synchronisation corticale caractéristique du sommeil lent profond. Leur activité est contrôlée par Neuroligine 1 (NLGN1), une molécule d’adhésion synaptique. Une mutation de Nlgn1 a des effets similaires à ceux de la privation de sommeil sur la mémoire et le comportement. Dans le manuscrit de mon mémoire, nous présentons l’hypothèse d’une implication de NLGN1 dans la régulation du sommeil et de l’éveil. Pour tester cette hypothèse, l’expression d’ARNm et de protéine NLGN1 a été mesurée suite à une privation de sommeil et le sommeil de souris n’exprimant pas NLGN1 a été caractérisé. Les résultats de mon projet de maîtrise montrent, en premier lieu, qu’une augmentation de la pression pour dormir altère l’expression de l’ARNm et de la protéine NLGN1 chez la souris. De plus, nos observations révèlent qu’une mutation de Nlgn1 diminue la quantité d’éveil et modifie l’activité spectrale en éveil et en sommeil. Ces observations dévoilent l’importance de NLGN1 dans le maintien de l’éveil et la régulation du sommeil, et supportent un rôle de NLGN1 dans la régulation de l’activité neuronale. / Sleep is essential for the well-functioning of the body. It has been suggested that sleep is regulated, in part, by the homeostatic process of sleep regulation which controls a pressure for sleep in function of the amount of time spent awake. Studies have suggested that the homeostatic process could be linked to synaptic plasticity, and that changes in sleep pressure can affect brain plasticity. N-methyl-D-aspartate receptors, which are important plasticity mediators, appear to be implicated in the deleterious effects related to sleep loss as well as in the regulation of cortical synchrony characteristic of slow wave sleep. Their activity is controlled by Neuroligin 1 (NLGN1), a synaptic adhesion molecule. Also, a Nlgn1 mutation has similar effects on memory and behavior as those observed following a sleep deprivation. In this master’s thesis, we hypothesized that NLGN1 is implicated in sleep and wake regulation. To test this hypothesis, Nlgn1 mRNA and protein expression has been measured after sleep deprivation, and the sleep of mice lacking NLGN1 has been studied. The results of my research project show that an increase in sleep pressure changes Nlgn1 mRNA and protein expression in mice. We also find that Nlgn1 mutation reduces wake duration and modifies the EEG spectral composition during wake and sleep. These results indicate that NLGN1 is important in the maintenance of wakefulness and the regulation of sleep, and provide further support to a role for NLGN1 in the regulation of neuronal activity.

Le traumatisme crânien léger (TCL) est l'un des troubles neurologiques les plus courants affectant la santé publique. Aussi, les troubles du sommeil sont fréquents chez les patients atteints de TCL. Les études chez les rongeurs montrent que certains marqueurs de plasticité synaptique diminuent après le TCL, ce qui pourrait nuire à la plasticité du cerveau. Nous suggérons que la perte de sommeil intensifie l'effet négatif de TCL, qui peut refléter les changements des marqueurs de plasticité synaptique ou des changements des voies physiologiques qui régulent le sommeil. En utilisant un modèle de traumatisme crânien sur crâne fermé (closed head injury), nous avons étudié la relation bidirectionnelle entre le TCL et le sommeil en évaluant les effets de TCL sur l’activité électrique du cerveau par électroencéphalographie (EEG), et ceux de la privation de sommeil (PS) sur l'expression génique post-TCL. Premièrement, l'activité EEG a été enregistrée pour voir si l'architecture du sommeil est altérée suite au TCL. Nous avons ensuite voulu tester si la PS suite TCL induit des changements dans l'expression des gènes : Arc, Homer1a, Hif1a, Bdnf, Fos et éphrines, qui ont été liés à la plasticité synaptique et à la régulation du sommeil. Nous avons également étudié l'effet de la PS post-TCL sur le génome complet dans les régions cibles (cortex et l'hippocampe). Les principaux résultats obtenus dans cette étude confirment que TCL modifie de manière significative l'activité spectrale pendant l'éveil, le sommeil Rapid Eye Movement (REM) et le sommeil non-REM dans le deuxième 24 heures post-TCL. Fait intéressant, la capacité de maintenir de longues périodes d'éveil a été altérée immédiatement après TCL (première 24h post-TCL). La dynamique de l'activité delta pendant l'éveil a été modifié par le TCL. Parallèlement à ces modifications, des changements dans l'expression des gènes ont été observés dans le cortex et l'hippocampe. Seulement Arc et EfnA3 ont montré une interaction TCL / PS et ce dans l’hippocampe, tandis que l'expression de tous les autres gènes semblait être affectée par la PS ou TCL indépendamment. Nos résultats montrent pour la première fois que le TCL induit l'expression de deux chimiokines (Ccl3 et Cxcl5) à la fois dans le cortex cérébral et l'hippocampe 2,5 jours post-TCL. Également, nous avons observé que le TCL induit une diminution de l'expression de Lgals3 et S100A8 dans le cortex, et une augmentation d’Olig2 dans l'hippocampe. Les résultats concernant les effets de la PS sur le génome complet du cortex et de l'hippocampe montrent des changements significatifs dans les gènes impliqués dans diverses fonctions physiologiques, telles que les rythmes circadiens, la réponse inflammatoire, ainsi que de l'activation des cellules gliales. En général, nos résultats précisent les changements dans la qualité de l’éveil ainsi que dans l'expression de divers gènes après TCL. / Mild traumatic brain injury (mTBI) is one of the most common neurological disorders affecting public health. Sleep disorders are common in patients with mTBI. Studies in rodents show that some synaptic plasticity markers decreased after mTBI which could impair brain plasticity. We suggest that sleep loss intensifies the negative effect of mTBI, which may reflect changes of synaptic plasticity markers or changes of different physiological pathway that regulates the sleep process. Using a "closed head injury" model, we have studied the bidirectional relationship between mTBI and sleep by investigating the effects of mTBI on sleep structure, and that of sleep deprivation (SD) on gene expression post-mTBI. First, EEG activity was monitored to investigate if sleep architecture is altered following mTBI. We then tested if SD, following mTBI, induces changes in gene expression of plasticity markers (Arc, Homer1a, Hif1a, Bdnf, Fos, and Ephrins), which have also been linked to sleep regulation. We also investigated the effect of SD post-mTBI on genome wide gene expression in target regions. The main results obtained in this study confirm that mTBI affects wakefulness, and significantly changes spectral activity during wakefulness, rapid eye movement (REM) sleep, and non-REM sleep on the second 24 hours post-TCL. Interestingly, the capacity to sustain long bouts of wakefulness was impaired immediately after mTBI. In addition, delta activity time course was altered by mTBI during wakefulness. In parallel to these alterations, changes in gene expression were observed. Only Arc and EfnA3 showed a mTBI/SD interaction in the hippocampus specifically, whereas expression of all other genes seemed to be affected by SD or mTBI independently. Our results indicate for the first time that the TCL induced the expression of two chemokines (Ccl3 and Cxcl5) in the cerebral cortex and hippocampus 2.5 days post-TCL. Also, we observed that the TCL induces a decrease in the expression of Lgals3 and S100A8 in the cortex, and an increase of Olig2 in the hippocampus.Results of SD effects on genome wide gene expression in the cortex and hippocampus show significant changes in genes involved in various physiological functions, such as circadian rhythms, inflammation, and also glial cell activation. In general, our results precise changes in wakefulness as well as in expression of various genes after mTBI.

Introdução: Uma das reconhecidas consequências do trabalho noturno nos trabalhadores é a perda da ordem temporal interna, a qual resulta em alterações fisiopatológicas. Objetivo: O presente estudo teve o objetivo de avaliar os efeitos do turno noturno de traballho na concentração e no ritmo circadiano de citocinas inflamatórias de trabalhadores de linha de produção e operadores de máquinas. Material e Métodos: Estudo transversal realizado em uma empresa do setor de bebidas. Na Etapa 1 foram avaliados em 123 trabalhadores (56 do turno fixo diurno e 67 do turno fixo noturno), dados sociodemográficos, condições de vida e lazer, condições e organização do trabalho, morbidades, sintomas osteomusculares, fadiga, sonolência excessiva e dados antropométricos. Quinze voluntários do turno diurno, 15 do turno noturno em período de trabalho e em momento de férias participaram da Etapa 2. Durante sete dias foram coletados dados do padrão de sono e vigília e em um Dia de Trabalho e um Dia de Folga foram realizadas coletas salivares em intervalos de três horas, durante a vigília, para estimar a concentração de melatonina, IL-1 e IL-6, além de coletados dados de sonolência, fadiga e dor. Também foi realizada coleta de urina para medir 6-sulfatoximelatonina após o episódio principal de sono. Foram verificadas diferenças de médias entre os dados dos grupos obtidos na Etapa 1, assim como análises de Odds Ratio. A ANOVA Nested foi utilizada na Etapa 2 para comparar os grupos (Diurno, Noturno e Noturno-Férias), seguida do teste de contraste de Dunnet. A Etapa 3 comparou a curva das citocinas IL-1, IL-6 e TNF- na saliva e no sangue em 7 indivíduos saudáveis em laboratório. O método do Cosinor individual e populacional foi aplicado para verificar ritmicidade circadiana. Resultados: Os resultados revelaram que os trabalhadores noturnos tinham menor amplitude do ritmo da melatonina salivar que os diurnos. Embora a concentração de 6-sulfatoximelatonina também tenha sido menor entre os trabalhadores noturnos comparados com os diurnos, sua concentração foi mais elevada durante as férias. Nas férias se observou um aumento da duração do sono, apesar de não ter sido verificada nenhuma diferença entre os parâmetros do sono principal e do cochilo entre os trabalhadores dos turnos diurnos e noturno no período de trabalho. No entanto, a acrofase da citocina IL-6 ocorreu em horário similar nos três grupos, ainda que os trabalhadores noturnos tenham apresentado maior concentração dessa citocina. A IL-1 apresentou ritmicidade apenas para o grupo diurno. Não houve diferença na prevalência de doenças entre os Grupos Diurno e Noturno. Os dados com os indivíduos em laboratório com ambiente controlado demonstraram ausência de ritmicidade da IL-1 e presença de ritmicidade da IL-6 tanto no sangue quanto na saliva. Conclusão: Trabalhadores noturnos estavam dessincronizados e apresentaram privação parcial de sono. O período de férias levou ao aumento da duração do sono; aumento da secreção de melatonina medida pela 6-sulfatoximelatonina, além da diminuição da sonolência, fadiga, dor e concentração de IL-1. Esses achados evidenciam as consequências negativas na saúde que o turno noturno de trabalho pode ocasionar e demonstram que há parcial reversão desses efeitos nas férias. / Introduction: A recognized consequence of night shift work on employees is the loss of internal temporal order, which results in pathophysiological alterations. Objective: This study aimed to evaluate the effects of night shift work on the level and circadian rhythm of inflammatory cytokines of line workers and machine operators. Methods: A cross-sectional study was conducted in a beverage company. On stage 1 of the study, demographic data, living and leisure conditions, work conditions and organization, morbidity, musculoskeletal symptoms, fatigue, excessive sleepiness and anthropometric data of 123 workers (56 fixed day workers and 67 fixed night shift workers) were evaluated. Fifteen volunteers from day shift, 15 from night shift, and 15 from the same night shift during vacation participated in stage 2. During seven consecutive days, data were collected regarding the pattern of sleep and wakefulness. Also, on one work day and one day off, within this 7 days, saliva samples were collected every three hours while subjects were awake to evaluate melatonin, IL-1 and IL-6, in addition to drowsiness, fatigue and pain data were also collected. Furthermore, urine samples were collected to measure 6-sulphatoxymelatonin after the main sleep episode. Mean differences between groups and analysis of Odds Ratio were used to evaluate the data collected on stage 1. For the analysis of data collected on stage 2, Nested ANOVA followed by Dunnet contrast test were used in order to compare the three groups (Day, Night and Night-vacation). On stage 3, salivary and blood IL-1, IL-6 and TNF- citokine curves from seven healthy subjects kept in a controled laboratory environment were compared. Individual and populational Cosinor was the method used to verify circadian rhythmicity in stage 2 and 3. Results: The results showed that night workers had lower amplitude of the rhythm of salivary melatonin then day workers. Although the concentration of 6-sulphatoxymelatonin was lower among night shift workers compared to day workers, its concentration was higher during vacation time. During vacation, an increase in sleep duration was observed, even though no differences between the main parameters of sleep and nap between day and night workers during work period were found. However, the IL-6 cytokine acrophase occurred in similar periods among the three groups, even though the night shift workers had a higher concentration of this cytokine. The IL-1 showed rhythmicity only for day workers. There was no difference in the prevalence of diseases among day and night workers. The data collected from healthy subjects in controlled environment showed absence of rhythmicity for IL-1, but presence of rhythmicity for IL-6 present in both blood and saliva. Conclusion: Night shift workers were desynchronized and showed signs of partial sleep deprivation. During vacation, sleep duration was increased; melatonin secretion measured by the 6-sulphatoxymelatonin was increased, in addition to decreased drowsiness, fatigue, pain and concentration of IL-1. These findings highlight the negative health consequences that night shift work can cause and show that there are partial reverse effects of these changes during vacation.

A hipóxia crônica intermitente (HCI) é um modelo experimental no qual o quimiorreflexo é ativado a cada episódio de hipóxia, assim como em alguns casos de apneia obstrutiva do sono. A HCI promove aumento da atividade simpática, hipertensão e alterações no acoplamento simpático-respiratório no tronco encefálico. No presente trabalho estudamos os parâmetros cardiorrespiratórios concomitantemente com o ciclo sono-vigília em uma janela temporal de 3 horas no período do dia em que esses registros são feitos no nosso laboratório. Foram também registradas ao longo deste período as respostas cardiovasculares associadas a inspirações profundas (IPs) que acontecem normalmente nos ratos. Ratos Wistar (~ 250 g) foram divididos nos grupos HCI (n = 12) e controle (CTL) (n = 12). Os animais foram submetidos à cirurgia de implantação de eletrodos no crânio e nos músculos cervicais para obtenção de registros eletrocorticográficos (ECoG) e eletromiográficos (EMG), respectivamente, para determinarmos as fases do ciclo sono-vigília (vigília, sono NREM (non-rapid eye movement) e sono REM (rapid eye movement)). Um grupo de animais CTL (n=5) e outro de animais HCI (n=6) tiveram também eletrodos implantados nos músculos diafragma (DIA) e abdominal oblíquo (ABD) para registros da atividade muscular respiratória. Após 48 horas, o grupo HCI foi exposto a um protocolo de hipóxia intermitente durante 10 dias (6% de O2 por 40 s, a cada 9 min, 8 h/d), enquanto o grupo CTL foi mantido em normoxia (20,8% de O2) pelo mesmo período. No último dia do protocolo, os ratos tiveram uma artéria femoral canulada para registros de pressão arterial (PA). No dia seguinte, ECoG, EMG e a PA foram registrados por 3 horas para análise da latência para o sono, o tempo total em cada uma das fases do ciclo sonovigília, o número e a duração dos episódios de sono REM e os parâmetros cardiovasculares pressão arterial sistólica (PAS), pressão arterial diastólica (PAD), pressão arterial média (PAM) e frequência cardíaca (FC) nas diferentes fases do ciclo. Os parâmetros respiratórios foram registrados por 2 horas para análise de frequência respiratória (fR), volume corrente (VT) e volume minuto (VE) nas diferentes fases do ciclo sono-vigília. Os animais dos grupos utilizados para avaliação da atividade respiratória muscular foram registrados por 2 horas. O protocolo de 10 dias de HCIpromoveu alterações significativas apenas na duração dos episódios de sono REM nos ratos HCI. Entretanto, os animais do grupo HCI apresentaram níveis médios mais elevados de PAS (145,0 ± 1,8 vs 129,3 ± 2,2 mmHg), PAD (104,1 ± 1,7 vs 91,4 ± 1,8 mmHg), PAM (121 ± 9 vs 107,7 ± 1,9 mmHg) e FC (387, ± 5,4 vs 363,5 ± 8,7 bpm) no período de 3 horas de registro, sendo estes aumentos igualmente observados em todas as fases do ciclo sono-vigília. A HCI também promoveu aumento significativo de VT durante os sonos NREM (6,6 ± 0,2 vs 5,8 ± 0,2 mL/kg) e REM (6,4 ± 0,2 vs 5,3 ± 0,2 mL/kg), porém este parâmetro não foi significativamente diferente durante a vigília nos animais HCI em relação aos animais CTL. Ambos os grupos apresentaram expirações ativas apenas durante a vigília, porém estas foram muito mais frequentes nos animais HCI. Além disso, nos animais HCI as respostas de queda da PAM (-18 ± 0,8 vs -14 ± 0,6 mmHg) e aumento da FC (28,4 ± 1,8 vs 21,8 ± 1,1 bpm) associadas às IPs apresentaram maiores magnitudes em relação aos animais CTL, embora o intervalo temporal entre as IPs não tenha se alterado. Esses achados indicam que a HCI aplicada durante 10 dias promove alterações significativas na duração dos episódios de sono REM, aumento da PA e FC em todas as fases do ciclo sono-vigília, aumento do VT durante o sono, aumento da ocorrência de expirações ativas durante a vigília e aumento das respostas hemodinâmicas associadas às IPs. Portanto, as alterações cardiovasculares observadas após a HCI são decorrentes dos episódios repetidos de hipóxia que acontecem ao longo desse protocolo, mas não parecem ser dependentes de alterações no ciclo sono-vigília, pois ainda que a duração dos episódios de sono REM tenha sido maior nos ratos HCI, os parâmetros cardiovasculares se apresentaram igualmente elevados em todas as fases do ciclo sono-vigília desses animais. / Chronic intermittent hypoxia (CIH) is an experimental model in which the chemoreflex is activated at each episode of hypoxia, as observed in some cases of obstructive sleep apnea. CIH induces increased sympathetic activity, hypertension, and changes in the sympathetic-respiratory coupling in the brainstem. In the present study, we recorded cardiorespiratory parameters concomitantly with the sleep-wake cycle during a 3-hour time window which corresponds to the period of the day in which these recordings are collected in our laboratory. During this period, we also studied the cardiovascular responses associated with the normally occurring deep breaths (DBs) in rats. Male Wistar rats (~ 250 g) were divided into CIH (n = 12) and control (CTL) groups (n = 12). Animals underwent implantation of electrodes in the skull and in the cervical muscles for electrocorticographic (ECoG) and electromyographic (EMG) recordings, respectively, to determine the phases of the sleep-wake cycle (wakefulness, NREM sleep and REM sleep). A group of CTL animals (n=5) and another of HCI animals (n=6) had electrodes implanted also in the diaphragm (DIA) and oblique abdominal muscle (ABD) for recordings of respiratory muscle activity. After 48 hours, the CIH group was exposed to an intermittent hypoxia protocol for 10 days (6% O2 for 40 s, every 9 min, 8 h/d), while the CTL group was maintained in normoxia (20.8 % of O2) for the same period. On the last day of the protocol, rats had a femoral artery cannulated for blood pressure (BP) recordings. On the following day, ECoG, EMG and BP were recorded for 3 hours for analysis of time for sleep onset, total time in each phase of the sleep-wake cycle, number and duration of REM sleep episodes, and the cardiovascular parameters systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) in the different phases of the cycle. The respiratory parameters were recorded for 2 hours for analysis of ventilatory frequency (fR), tidal volume (VT) and minute volume (VE) in the different phases of the sleep-wake cycle. The groups of animals used for analysis of respiratory muscle activity were recorded for only 2 hours. CIH promoted significant alterations only in the duration of REM episodes. However, animals from CIH group had higher average levels of SBP (145,0 ± 1,8 vs 129,3 ± 2,2 mmHg), DBP (104,1 ± 1,7 vs 91,4 ± 1,8mmHg), MAP (121 ± 9 vs 107,7 ± 1,9 mmHg) e HR (387, ± 5,4 vs 363,5 ± 8,7 bpm) in the 3-hour recording period. These increases were also observed in all phases of the sleep-wake cycle. CIH also promoted a significant increase in VT during NREM (6,6 ± 0,2 vs 5,8 ± 0,2 mL/kg) and REM (6,4 ± 0,2 vs 5,3 ± 0,2 mL/kg), although this parameter was not significantly different during wakefulness in CIH animals compared to CTL animals. Both groups presented active expiration only during wakefulness, however it was much more frequent in HCI rats. In addition, in CIH animals, the fall in MAP (-18 ± 0,8 vs -14 ± 0,6 mmHg) and the increase in HR (28,4 ± 1,8 vs 21,8 ± 1,1 bpm) associated with DBs presented higher magnitudes in relation to CTL animals, although the time interval between DBs did not change. These findings indicate that CIH for 10 days promotes longer REM episodes, increased BP and HR in all phases of the cycle, increased VT during sleep, increased active expiration occurrence and higher magnitudes of the hemodynamic responses associated with DBs. Therefore, the cardiovascular alterations observed after CIH are due to the intermittent hypoxia episodes that occur throughout this protocol, but do not seem to be related to changes in the sleep-wake cycle, for although the duration of REM episodes was longer, the cardiovascular parameters were equally increased in all phases of the sleep-wake cycle.

Die Atmung und das Herz-Kreislauf-System interagieren als zwei in Reihe angeordnete funktionelle Einheiten. Die gleichsinnige Kontrolle beider Systeme bildet die Grundlage homöostatischer Bedingungen im Organismus. Neurophysiologische Studien geben Hinweise auf die Existenz eines gemeinsamen neuronalen kardiorespiratorischen Netzwerkes, welches im ventrolateralen Teil der Medulla oblongata gelegen ist. Da zentrale Mechanismen der Regulation einer direkten Untersuchung nicht zugänglich sind, erweisen sich die linearen und nichtlinearen Verfahren der Zeitreihenanalyse als hilfreich, um Erkenntnisse von der Arbeitsweise des kardiorespiratorischen Kontrollsystems zu gewinnen. Grundlage der Studie bildet eine Datenbank polygraphischer Messungen (einschließlich EKG, thorakales und abdominales Respirogramm, Elektrookulogramm und Aktogramm), die an 42 gesunden Kindern, 11 Mädchen und 31 Knaben im Alter von 12 bis 15 Jahren erhoben wurde. Die Messungen erfolgten über 24 Stunden hinweg, während folgender Vigilanzstadien: ruhiger Wachzustand, REM- und nonREM-Schlaf. Die spektralen Charakteristika der Herzfrequenzvariabilität wurden berechnet, um die sympatho-vagale Einflußnahme auf den Nodus sinusoidalis kennzeichnen zu können. Die lineare Intensität der kardiorespiratorischen Beziehung wurde aus den Kohärenzspektren abgeleitet. Um nichtlineares Verhalten erfassen zu können, wurden der größte Lyapunov-Exponent und die Korrelationsdimension der Herzfrequenz, sowie die Korrelationsdimension des Atemsignals bestimmt. Die Analyse der Herzfrequenzvariabilität ergab für die Gesamtleistung die höchsten Werte innerhalb der REM-Phasen, im Wachzustand lagen diese deutlich niedriger und während des nonREM-Schlafes waren sie am kleinsten. Dieses Verhalten wurde im wesentlichen bestimmt von Änderungen der Spektralleistung im niederfrequenten Bereich. Die Komplexität der Herzfrequenz, die sich mit der Korrelationsdimension schätzen läßt, zeigte eine deutliche Abnahme im Schlaf. Dagegen erwies sich der Lyapunov-Exponent als weniger sensitiv bezüglich der Vigilanz. Die kardiorespiratorische Kohärenz ließ eine strenge Abhängigkeit vom Vigilanzstadium erkennen mit hohen Werten im nonREM-Schlaf und dem Minimum innerhalb der REM-Phasen. Im Gegensatz zur Komplexität der Herzfrequenz erreichte die Komplexität der Atmung die niedrigsten Werte in den REM-Phasen. Mit den Ergebnissen der Spektralanalyse lassen sich vigilanzstadienspezifische Einstellungen in der vegetativen Kontrolle der Herzfrequenz abgrenzen. Die nichtlinearen Verfahren offenbaren niederdimensionale deterministisch-chaotische Strukturen der Herzfrequenz. Die Zahl unabhängiger Mechanismen, die Anteil an der kardiorespiratorischen Regulation haben, ist im Wachzustand am größten. Diese Änderungen lassen das Gesamtsystem in Abhängigkeit von der Vigilanz verschiedene Arbeitspunkte einnehmen. / Breathing and blood flow interact as two, in series coupled units. To adapt heart beat and oxygen supply, a common coordination is required. Concluded from neurophysiological investigations, there is evidence for the existence of one cardiorespiratory network located in the ventrolateral part of the medulla. Since the physiological mechanisms inside the complex regulatory network are not readily accessible, linear and non-linear methods of time series analysis are a useful approach to investigate cardiorespiratory control. To study normal regulation, 42 healthy children, 11 girls and 31 boys (12-15 yr.), were investigated throughout 24 hours under different states of vigilance: wakefulness at rest, REM, and nonREM-sleep. All participants underwent polygraphic measurements, including ECG, thoracic and abdominal respirograms, electrooculogram, and actogram. To estimate the sympatho-vagal drive to the sinus node, the parameters of heart rate power spectra were calculated. The linear intensity of cardiorespiratory coupling was concluded from the coherence spectra. As to non-linear properties of heart rate, the largest Lyapunov exponents as well as the correlation dimension were determined. Similarly, the correlation dimension of the respiratory signals was evaluated. The total power of the heart rate spectrum was found to be greatest during REM, it decreased during wakefulness and was low in nonREM-sleep. These variations are mainly accounted for by low frequency power. The "complexity" of heart rate, as indicated by the correlation dimension, is diminished during sleep phases, whereas the Lyapunov exponents are less affected. The cardiorespiratory coherence is strongly modulated by vigilance with an increase during nonREM and lowest values during REM. The complexity of respiration was also affected by vigilance. A different behavior of heart rate complexity was found during REM-phases. Concluded from spectral analysis, a specific setting of autonomic heart rate regulation for each vigilance stage can be suggested. A low dimensional deterministic chaos is present in heart rate time series. More independent control loops were found to be active during wakefulness. Revealed by parameters of the non-linear dynamics, different stages of vigilance determine different operating points in the cardiorespiratory coordination.

Introdução: Uma das reconhecidas consequências do trabalho noturno nos trabalhadores é a perda da ordem temporal interna, a qual resulta em alterações fisiopatológicas. Objetivo: O presente estudo teve o objetivo de avaliar os efeitos do turno noturno de traballho na concentração e no ritmo circadiano de citocinas inflamatórias de trabalhadores de linha de produção e operadores de máquinas. Material e Métodos: Estudo transversal realizado em uma empresa do setor de bebidas. Na Etapa 1 foram avaliados em 123 trabalhadores (56 do turno fixo diurno e 67 do turno fixo noturno), dados sociodemográficos, condições de vida e lazer, condições e organização do trabalho, morbidades, sintomas osteomusculares, fadiga, sonolência excessiva e dados antropométricos. Quinze voluntários do turno diurno, 15 do turno noturno em período de trabalho e em momento de férias participaram da Etapa 2. Durante sete dias foram coletados dados do padrão de sono e vigília e em um Dia de Trabalho e um Dia de Folga foram realizadas coletas salivares em intervalos de três horas, durante a vigília, para estimar a concentração de melatonina, IL-1 e IL-6, além de coletados dados de sonolência, fadiga e dor. Também foi realizada coleta de urina para medir 6-sulfatoximelatonina após o episódio principal de sono. Foram verificadas diferenças de médias entre os dados dos grupos obtidos na Etapa 1, assim como análises de Odds Ratio. A ANOVA Nested foi utilizada na Etapa 2 para comparar os grupos (Diurno, Noturno e Noturno-Férias), seguida do teste de contraste de Dunnet. A Etapa 3 comparou a curva das citocinas IL-1, IL-6 e TNF- na saliva e no sangue em 7 indivíduos saudáveis em laboratório. O método do Cosinor individual e populacional foi aplicado para verificar ritmicidade circadiana. Resultados: Os resultados revelaram que os trabalhadores noturnos tinham menor amplitude do ritmo da melatonina salivar que os diurnos. Embora a concentração de 6-sulfatoximelatonina também tenha sido menor entre os trabalhadores noturnos comparados com os diurnos, sua concentração foi mais elevada durante as férias. Nas férias se observou um aumento da duração do sono, apesar de não ter sido verificada nenhuma diferença entre os parâmetros do sono principal e do cochilo entre os trabalhadores dos turnos diurnos e noturno no período de trabalho. No entanto, a acrofase da citocina IL-6 ocorreu em horário similar nos três grupos, ainda que os trabalhadores noturnos tenham apresentado maior concentração dessa citocina. A IL-1 apresentou ritmicidade apenas para o grupo diurno. Não houve diferença na prevalência de doenças entre os Grupos Diurno e Noturno. Os dados com os indivíduos em laboratório com ambiente controlado demonstraram ausência de ritmicidade da IL-1 e presença de ritmicidade da IL-6 tanto no sangue quanto na saliva. Conclusão: Trabalhadores noturnos estavam dessincronizados e apresentaram privação parcial de sono. O período de férias levou ao aumento da duração do sono; aumento da secreção de melatonina medida pela 6-sulfatoximelatonina, além da diminuição da sonolência, fadiga, dor e concentração de IL-1. Esses achados evidenciam as consequências negativas na saúde que o turno noturno de trabalho pode ocasionar e demonstram que há parcial reversão desses efeitos nas férias. / Introduction: A recognized consequence of night shift work on employees is the loss of internal temporal order, which results in pathophysiological alterations. Objective: This study aimed to evaluate the effects of night shift work on the level and circadian rhythm of inflammatory cytokines of line workers and machine operators. Methods: A cross-sectional study was conducted in a beverage company. On stage 1 of the study, demographic data, living and leisure conditions, work conditions and organization, morbidity, musculoskeletal symptoms, fatigue, excessive sleepiness and anthropometric data of 123 workers (56 fixed day workers and 67 fixed night shift workers) were evaluated. Fifteen volunteers from day shift, 15 from night shift, and 15 from the same night shift during vacation participated in stage 2. During seven consecutive days, data were collected regarding the pattern of sleep and wakefulness. Also, on one work day and one day off, within this 7 days, saliva samples were collected every three hours while subjects were awake to evaluate melatonin, IL-1 and IL-6, in addition to drowsiness, fatigue and pain data were also collected. Furthermore, urine samples were collected to measure 6-sulphatoxymelatonin after the main sleep episode. Mean differences between groups and analysis of Odds Ratio were used to evaluate the data collected on stage 1. For the analysis of data collected on stage 2, Nested ANOVA followed by Dunnet contrast test were used in order to compare the three groups (Day, Night and Night-vacation). On stage 3, salivary and blood IL-1, IL-6 and TNF- citokine curves from seven healthy subjects kept in a controled laboratory environment were compared. Individual and populational Cosinor was the method used to verify circadian rhythmicity in stage 2 and 3. Results: The results showed that night workers had lower amplitude of the rhythm of salivary melatonin then day workers. Although the concentration of 6-sulphatoxymelatonin was lower among night shift workers compared to day workers, its concentration was higher during vacation time. During vacation, an increase in sleep duration was observed, even though no differences between the main parameters of sleep and nap between day and night workers during work period were found. However, the IL-6 cytokine acrophase occurred in similar periods among the three groups, even though the night shift workers had a higher concentration of this cytokine. The IL-1 showed rhythmicity only for day workers. There was no difference in the prevalence of diseases among day and night workers. The data collected from healthy subjects in controlled environment showed absence of rhythmicity for IL-1, but presence of rhythmicity for IL-6 present in both blood and saliva. Conclusion: Night shift workers were desynchronized and showed signs of partial sleep deprivation. During vacation, sleep duration was increased; melatonin secretion measured by the 6-sulphatoxymelatonin was increased, in addition to decreased drowsiness, fatigue, pain and concentration of IL-1. These findings highlight the negative health consequences that night shift work can cause and show that there are partial reverse effects of these changes during vacation.