Effects of an alternating work shift on air traffic controllers and the relationship with excessive daytime sleepiness and stress / Efeitos do turno de trabalho alternado em controladores de tráfego aéreo e relação com sonolência diurna excessiva e estresse

ABSTRACT Objective: To evaluate symptoms of stress and excessive daytime sleepiness (EDS) in air traffic control (ATC) officers in Brazil. Methods: Fifty-two ATC officers participated, based at three air traffic control units, identified as A, B and C. Stress symptoms were assessed using the Lipp Inventory of Stress Symptoms for Adults, and EDS by the Epworth Sleepiness Scale. Results: The sample mean age was 37 years, 76.9% of whom were male. Excessive daytime sleepiness was identified in 25% of the ATC officers, with 84.6% of these based at air traffic control unit A, which has greater air traffic flow, operating a 24-hour alternating work shift schedule. A total of 16% of the ATC officers had stress symptoms, and of these, 62% showed a predominance of physical symptoms. Conclusion: The high percentage of ATC officers with EDS identified in group A may be related to chronodisruption due to night work and alternating shifts.

RESUMO Objetivo: Avaliar sintomas de estresse e sonolência diurna excessiva (SDE) em controladores de tráfego aéreo (CTA) do Brasil. Métodos: Participaram 52 controladores pertencentes a 3 órgãos de controle de tráfego aéreo, denominados de A, B e C. Os sintomas de estresse, foram avaliados pelo Inventário de Sintomas de Estresse para Adultos, a SDE pela Escala de Sonolência Epworth. Resultados: 76,9% da amostra são do sexo masculino, com média de idade de 37 anos. SDE foi identificada em 25% dos controladores, desses 84,6%, pertencem aos órgãos de controle de tráfego aéreo A, caracterizado por maior movimento de aeronaves, funcionamento 24 horas e escala de serviço em turnos alternantes. Um total de 16% dos controladores apresentam sintomas de estresse, desses, 62% mostraram o predomínio de sintomas físicos. Conclusão: A porcentagem elevada de CTA com SDE identificada no grupo A pode estar relacionada a cronodisrupção devido ao trabalho noturno e alternado.

Chronopharmacology: Tailoring Therapy to Endogenous Rhythms.

Chronopharmacology aims at the use of biological rhythms in the clinical treatment so as to enhance both effectiveness and tolerance and minimize the side effects of a drug by determining the best biological time for its administration. Chronopharmacology is useful to solve problems of drug optimization. In the human organs, the metabolic fate of a pharmacologic agent as well is not constant as a function of time. Thus, the chronobiological approach of drug administration involves a lesser risk of errors than the conventional homeostatic approach. Chronopharmacology is now used as a routine to treat various disorders like hypertension, angina, cancer and various psychotic disorders. The newer drug delivery systems that are designed with the chronopharmacological approach hold great scope for delivering better patient care in terms of efficacy, tolerance and safety parameters of the drug. This review aims at introducing chronopharmacology, the role of the regulatory system of biological clock in pharmacotherapy and the benefits it has conferred in various clinical conditions.

The biological clock keeps ticking, but exercise may turn it back / O relógio biológico não para, mas o exercício físico pode atrasar o tempo

Aging is an inevitable process that is associated to loss of functional capacities in several body systems, like the cardiovascular, the skeletal muscle mass, the osteoarticular and the neuro-immune-endocrine systems. Changes appear due to interactions between genetic factors and way of life, such as diet and sedentary life style. This review shows evidence from the past twenty years concerning the importance of physical exercise to reduce the deleterious effects of aging, regarding the improvement in functional performance, the prevention of diseases and increased longevity. Moreover, physical exercise improves the cognitive function and the mood. Aerobic and strength training collaborate with the prevention and treatment of mental diseases, which are mostly prevalent in older adults, like major depression, dementia and Parkinson’s disease. Several mechanisms of neurobiological action are proposed to explain how exercise can actually reduce the effects of aging.

O envelhecimento é um processo inevitável. Está associado à perda progressiva da função de diversos sistemas, entre eles o sistema cardiovascular, musculoesquelético, osteoarticular e neuroimunoendócrino. Estas alterações acontecem devido à interação entre fatores genéticos e estilo de vida, como por exemplo, a alimentação e o sedentarismo. Esta revisão mostra as evidências da literatura dos últimos vinte anos quanto ao efeito do exercício físico na redução dos efeitos deletérios do envelhecimento, desde a melhora do desempenho à prevenção de doenças, aumento da longevidade, melhora da cognição e do humor. Tanto o treinamento aeróbio quanto o treinamento de força muscular contribuem na prevenção e no tratamento das doenças mentais mais prevalentes em idosos, como a depressão, as demências e a doença de Parkinson. Diversos mecanismos de ação neurobiológicos são propostos para explicar o efeito do exercício na redução do processo de envelhecimento.

Interrelação entre síndrome metabólica, estresse crônico e ritmos circadianos de marcadores adipogênicos: uma revisão / Interrelation between metabolic syndrome, chronic stress and circadian rhythms of adipogenic markers: a review

Alterações de ritmos circadianos são relacionadas ao desenvolvimento de transtornos metabólicos como obesidade e síndrome metabólica. Além disto, a disponibilidade e o consumo de alimentos altamente palatáveis ricos em gordura e a exposição a situações estressantes podem contribuir na incidência e na severidade destas doenças crônicas, provocando modificações no balanço energético, alterações no metabolismo de lipídeos e adipogênese. Nesta revisão, abordaremos os aspectos cronobiológicos que podem ser influenciados pela exposição a estresse crônico e a obesidade, além dos mecanismos que contribuem para o crescimento de doenças metabólicas (AU)

Alterations in circadian rhythms are associated with the development of metabolic disorders, such as obesity and metabolic syndrome. Moreover, the availability and consumption of highly palatable foods rich in fat and the exposure to stressful situations may contribute to the incidence and severity of these chronic diseases, leading to changes in energy balance, alterations in lipid metabolism and adipogenesis. This review aimed to discuss the chronobiological aspects that can be influenced by the response to chronic stress and obesity, as well as the mechanisms that contribute to the development of metabolic diseases (AU)

Correlation of shift work and waist circumference, body mass index, chronotype and depressive symptoms / Correlação entre trabalho de turno e circunferência abdominal, índice de massa corporal, cronotipo e sintomas depressivos

OBJECTIVE: Correlate shift work with body mass index (BMI), waist circumference, chronotype and depressive symptoms. SUBJECTS AND METHODS: This study comprising 14 shift workers and 13 day workers. Subjects were workers from the health area aged 25 to 60 years. Minor psychiatric disorders were accessed by Self Report Questionnaire (SRQ-20) and depressive symptoms by Beck Depression Inventory (BDI). Chronotype was accessed using Morningness-Eveningness Questionnaire (MEQ). Anthropometric measures were taken. RESULTS: Shift workers presented higher BMI (P = 0.03) and waist circumference (P = 0.004) than day workers. Years on shift work were significantly correlated to waist circumference (r = 0.43; P = 0.03) and age (r = 0.47; P = 0.02). Shift work was not correlated with depressive symptoms and chronotype. CONCLUSION: These results may suggest a role played by shift work on the development and/or the early clinic manifestations of metabolic disturbances, becoming a risk factor to metabolic syndrome.

OBJETIVO: Correlacionar o trabalho de turno com índice de massa corporal (IMC), circunferência abdominal, cronotipo e sintomas depressivos. SUJEITOS E MÉTODOS: Amostra de 14 trabalhadores de turno e 13 diurnos, com idade entre 25 e 60 anos. Transtornos psiquiátricos menores foram aferidos pelo Self Report Questionnaire (SRQ-20), sintomas depressivos pelo inventário de Depressão de Beck (BDI) e o cronotipo pelo Morningness-Eveningness Questionnaire (MEQ). As medidas antropométricas foram mensuradas. RESULTADOS: Trabalhadores de turno apresentaram maior IMC (P = 0,03) e circunferência abdominal (P = 0,004) quando comparados aos diurnos. O tempo de trabalho de turno foi correlacionado à circunferência abdominal (r = 0,43; P = 0,03). Não houve correlação entre trabalho e sintomas depressivos e cronotipo. CONCLUSÃO: Os resultados podem sugerir que o trabalho de turno desempenhe um papel no desenvolvimento e/ou nas precoces manifestações clínicas de distúrbios metabólicos, tornando-se um fator de risco para a síndrome metabólica.

Energy-responsive timekeeping.

An essential component of energy homeostasis lies in an organism's ability to coordinate daily patterns in activity, feeding, energy utilization and energy storage across the daily 24-h cycle. Most tissues of the body contain the molecular clock machinery required for circadian oscillation and rhythmic gene expression. Under normal circumstances, behavioural and physiological rhythms are orchestrated and synchronized by the suprachiasmatic nucleus (SCN) of the hypothalamus, considered to be the master circadian clock. However, metabolic processes are easily decoupled from the primarily light-driven SCN when food intake is desynchronized from normal diurnal patterns of activity. This dissociation from SCN based timing demonstrates that the circadian system is responsive to changes in energy supply and metabolic status. There has long been evidence for the existence of an anatomically distinct and autonomous food-entrainable oscillator (FEO) that can govern behavioural rhythms, when feeding becomes the dominant entraining stimulus. But now rapidly growing evidence suggests that core circadian clock genes are involved in reciprocal transcriptional feedback with genetic regulators of metabolism, and are directly responsive to cellular energy supply. This close interaction is likely to be critical for normal circadian regulation of metabolism, and may also underlie the disruption of proper metabolic rhythms observed in metabolic disorders, such as obesity and type-II diabetes.

The Drosophila melanogaster circadian pacemaker circuit.

As an experimental model system, the fruit fly Drosophila melanogaster has been seminal in shaping our understanding of the circadian clockwork. The wealth of genetic tools at our disposal over the past four decades has enabled discovery of the genetic and molecular bases of circadian rhythmicity. More recently, detailed investigation leading to the anatomical, neurochemical and electrophysiological characterization of the various neuronal subgroups that comprise the circadian machinery has revealed pathways through which these neurons come together to act as a neuronal circuit. Thus the D. melanogaster circadian pacemaker circuit presents a relatively simple and attractive model for the study of neuronal circuits and their functions.

Influence of chronotype and social zeitgebers on sleep/wake patterns

Inter-individual differences in the phase of the endogenous circadian rhythms have been established. Individuals with early circadian phase are called morning types; those with late circadian phase are evening types. The Horne and Östberg Morningness-Eveningness Questionnaire (MEQ) is the most frequently used to assess individual chronotype. The distribution of MEQ scores is likely to be biased by several fact, ors, such as gender, age, genetic background, latitude, and social habits. The objective of the present study was to determine the effect of different social synchronizers on the sleep/wake cycle of persons with different chronotypes. Volunteers were selected from a total of 1232 UFPR undergraduate students who completed the MEQ. Thirty-two subjects completed the study, including 8 morning types, 8 evening types and 16 intermediate types. Sleep schedules were recorded by actigraphy for 1 week on two occasions: during the school term and during vacation. Sleep onset and offset times, sleep duration, and mid-sleep time for each chronotype group were compared by the Mann-Whitney U-test separately for school term and vacation. School term and vacation data were compared by the Wilcoxon matched-pair test. Morning types showed earlier sleep times and longer sleep duration compared with evening types (23:00 ± 44 and 508.9 ± 50.27 vs 01:08 ± 61.95 and 456.44 ± 59.08, for the weekdays during vacation). During vacation, the subjects showed later sleep times, except for the morning types, who did not exhibit differences for sleep onset times. The results support the idea that social schedules have an impact on the expression of circadian rhythmicity but this impact depends on the individual chronotype.

The search for circadian clock components in humans: new perspectives for association studies

Individual circadian clocks entrain differently to environmental cycles (zeitgebers, e.g., light and darkness), earlier or later within the day, leading to different chronotypes. In human populations, the distribution of chronotypes forms a bell-shaped curve, with the extreme early and late types _ larks and owls, respectively _ at its ends. Human chronotype, which can be assessed by the timing of an individual's sleep-wake cycle, is partly influenced by genetic factors - known from animal experimentation. Here, we review population genetic studies which have used a questionnaire probing individual daily timing preference for associations with polymorphisms in clock genes. We discuss their inherent limitations and suggest an alternative approach combining a short questionnaire (Munich ChronoType Questionnaire, MCTQ), which assesses chronotype in a quantitative manner, with a genome-wide analysis (GWA). The advantages of these methods in comparison to assessing time-of-day preferences and single nucleotide polymorphism genotyping are discussed. In the future, global studies of chronotype using the MCTQ and GWA may also contribute to understanding the influence of seasons, latitude (e.g., different photoperiods), and climate on allele frequencies and chronotype distribution in different populations.

The male biological clock is ticking: a review of the literature / O relógio biológico masculino está batendo: revisão da literatura

The term biological clock is usually used by physicians and psychologists to refer to the declining fertility, increasing risk of fetal birth defects and alterations to hormone levels experienced by women as they age. Female fecundity declines slowly after the age of 30 years and more rapidly after 40 and is considered the main limiting factor in treating infertility. However, there are several scientific reports, chapters in books and review articles suggesting that men may also have a biological clock. The aim of our study was to conduct a review of the literature, based on the Medical Literature Analysis and Retrieval System Online (Medline), to evaluate the male biological clock. After adjustments for other factors, the data demonstrate that the likelihood that a fertile couple will take more than 12 months to conceive nearly doubles from 8 percent when the man is < 25 years old to 15 percent when he is > 35 years old. Thus, paternal age is a further factor to be taken into account when deciding on the prognosis for infertile couples. Also, increasing male age is associated with a significant decline in fertility (five times longer to achieve pregnancy at the age of 45 years). Patients and their physicians therefore need to understand the effects of the male biological clock on sexual and reproductive health, in that it leads to erectile dysfunction and male infertility, as well as its potential implications for important medical conditions such as diabetes and cardiovascular diseases.

O termo relógio biológico é geralmente usado por médicos e psicólogos para se referir ao declínio da fertilidade, aumento no risco de defeitos congênitos, e níveis hormonais alterados que a mulher com o passar dos anos apresenta. A fecundidade feminina declina paulatinamente após os 30 anos e mais rapidamente após os 40 anos e é considerada como o principal fator limitante nos tratamentos da infertilidade. Entretanto, existem vários artigos científicos capítulos de livros e artigos de revisão sugerindo que o homem também apresente um relógio biológico. O objetivo do nosso estudo foi realizar uma revisão no Medline (Medical Literature Analysis and Retrieval System Online) para avaliar o relógio biológico masculino. Após ajustar para outros fatores, foi demonstrado que a probabilidade de um casal apresentar uma demora superior a 12 meses para engravidar praticamente duplica de 8 por cento quando o homem possui idade inferior a 25 para 15 por cento quando possui idade superior a 35 anos; desta forma, a idade paterna é um fator a ser levado em consideração quando se decidir sobre o prognóstico de um casal infértil. Além disso, a idade avançada está associada com um declínio significante na fertilidade (tempo para engravidar superior a cinco vezes aos 45 anos de idade), sendo independente de idade da parceira, freqüência de relação sexual e estilo de vida, assim como os efeitos de outros fatores de risco para subfertilidade. Os pacientes e seus médicos devem entender os efeitos do relógio biológico na saúde sexual e reprodutiva, levado à disfunção erétil e infertilidade, assim como às potenciais contribuições para condições médicas como diabetes e doenças cardiovasculares.

The p53-MDM2 network: from oscillations to apoptosis.

The p53 protein is well-known for its tumour suppressor function. The p53-MDM2 negative feedback loop constitutes the core module of a network of regulatory interactions activated under cellular stress. In normal cells, the level of p53 proteins is kept low by MDM2, i.e. MDM2 negatively regulates the activity of p53. In the case of DNA damage, the p53-mediated pathways are activated leading to cell cycle arrest and repair of the DNA. If repair is not possible due to excessive damage, the p53-mediated apoptotic pathway is activated bringing about cell death. In this paper, we give an overview of our studies on the p53-MDM2 module and the associated pathways from a systems biology perspective.We discuss a number of key predictions, related to some specific aspects of cell cycle arrest and cell death, which could be tested in experiments.

A study of sleeping disorders in blind patients.

An internal 24-hour biological clock working in tandem with external environmental cues like bright light regulates our daily rhythms specially sleep-wake cycle. In a blind individual, due to absence of external cue endogenous rhythm may take upper hand and free running of sleep-wake cycle starts without any synchronicity with day-night cycle, creating ground for sleep disorders. To evaluate the frequency of sleep disorders, 65 blind individuals without any comorbid medical or surgical problem were interviewed according to the criteria of Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV). Simultaneously 70 persons with no visual impairment were assessed in the same manner as used for blind persons. Blind patients showed far higher presence (44.6%) of sleep problems compared to controls (15.7%), and this difference was highly significant statistically [odd's ratio (OR) = 4.32, CI 95 =1.8-10.54]. Blind patients showed far higher presence (43.1%) of DSM-IV based diagnosis compared to controls (8.6%), and this difference was highly significant statistically [OR = 8.072, CI 95 = 3.059-21.298]. Circadian sleep disorders, insomnia and hypersomnia were relatively higher in blind patients. High incidence of sleep disorders calls for development of short reliable screener for sleep disorders among blind persons and better liaison among ophthalmologists and psychiatrists for early detection of this problem.

Biological Rhythm in Livestock

The animal time structure is a basic fact of life, no matter if one wants to study it or not. The time- dependent, mostly rhythmic, and thus to a certain degree predictable, variations of biochemical and physiological functions and of sensitivity and resistance to many environmental agents are often quite large and offer not only new insight into animal physiology and pathology but also diagnostic possibilities and therapeutic advantages. Chronobiology, chronophysiology and its subspecialities, like chronopharmacology and chronotherapy, will certainly play an important role in the clinical medicine of the future. Successful application of chronobiology to veterinary clinical medicine, however, depends critically on a thorough knowledge of its basic principles.

El alimento como sincronizador de los ritmos biológicos: su relevancia para la identificación de un oscilador circadiano / Feeding as a biorhytm synchronizer

Aparte de las variaciones cíclicas tales como día-noche, estaciones y cambios de temperatura y humedad, los organismos vivos han desarrollado adaptaciones para ajustar su fisiología y su conducta a otros cambios exteriores y para ello aparecieron en la evolución los relojes biológicos, cuyo prototipo -y hasta ahora el único bien caracterizado-, es el ubicado en el núcleo supra-quiasmático del hipotálamo, que percibe señales aferentes de la retina e informa al resto del sistema nervioso central.Hay otros marcapasos locales identificados in vitro en el pulmón y el hígado, que muestran oscilaciones circadianas y se acepta que actúan como sincronizadores de otros ritmos biológicos del organismo.Los autores demuestran, en experimentos en ratas, que la llegada del alimento actúa como sincronizador, al restringir el mismo o cambiar la alternancia de su administración. Esto afecta los procesos de balance energético, los estados de anabolismo o catabolismo, reflejados en los niveles de ácidos grasos y cuerpos cetónicos en sangre, la glucosa, la insulina y la leptina. Es más, parece que el hígado contiene un sistema de estimación del tiempo que lo convierte en un oscilador circadiano.

Alteración de mecanismos moleculares y activación abortiva en oocitos humanos durante las fallas de fecundación: aspectos biológicos / Alteration of molecular mechanisms and abortive activation in human oocytes during the failures of fertilization

Introducción: Los primeros estudios relacionados con falla de fecundación en humanos se concentraron en la citogenética del oocito. Más recientemente, los avances en imágenes digitales y microscopía de fluorescencia han permitidos investigar eventos menos conocidos como la movilidad citoplásmica de los pronúcleos masculino y femenino y los mecanismos físicos que dirigen su unión. Objetivo: Analizar cualitativa y cuantitativamente oocitos no fecundados luego de FIV e ICSI, haciendo hincapié en la organización del citoesqueleto, estado de la cromatina, organización del áster y presencia de activaciones abortivas. Materiales y Métodos: Se estudiaron 248 oocitos clasificados como "no fecundados" luego de fertilización in vitro (FIV) e inyección intracitoplásmica de espermatozoides (ICSI) 20-40 hs post inseminación o inyección. El material se procesó para inmunofluorescencia mediante la utilización de anticuerpos monoclonales para la detección de Ó y ß tubulinas y Ó tubulinas acetiladas. El material genético se estudió por tinción con Hoechst 33258 y se analizó por microscopía óptica (UV). El análisis citogenético se realizó en 69 oocitos activados luego de ICSI de acuerdo a la técnica de Tarkowski (1966). Los resultados se analizaron estadísticamente mediante el test de Chi cuadrado. Resultados y Discusión: Inmunofluorescencia: 1) FIV: La principal causa de falla de fecundación luego de FIV fue la ausencia de penetración espermática (54,9 por ciento). De los restantes oocitos estudiados, el 11,4 por ciento mostraron una falla de activación oocitaria y el 23,9 por ciento presentaron fallas en los procesos de nucleación o migración de pronúcleos. 2) ICSI: La principal causa de falla de fecundación luego de ICSI resultó ser la falla de activación oocitaria (36,5 por ciento). Un 14,6 por ciento de los oocitos remanentes detuvieron su desarrollo en la primera placa metafásica. En general, las fallas detectadas luego de FIV ó ICSI resultaron cuantitativamente diferentes. Análisis cromosómico en oocitos activados post ICSI: El estudio cromosómico permitió identificar la presencia de activaciones abortivas, incluyendo metafases III (MIII), núcleos reticulares (NR) y núcleos telofásicos (NT)