Day and night effects on the animal and plant kingdoms: The eve of chronobiology.

For a long time, cyclical changes in the body were assumed to be caused by the cyclicity of the environment (day-night, seasons). The concept of daily and seasonal changes was first documented in the 18th century by astronomer D'Ortous de Mairan, who demonstrated that plant leaf motions varied depending on the time of day, and by Linné's description of his floral clock in 1751. In 1832, De Candolle was the first to experimentally establish the endogeneity of rhythms in plants, underlining the notion of what we now term free-running rhythms. Julien-Joseph Virey made his own contribution in his thesis, published in 1814, against this backdrop, in which he examined the knowledge of his day on the daily and seasonal biological fluctuations of living matters. He emphasized the relevance of the environment's day-night cycle on plant life and created a list of plants based on their diurnality or nocturnality. He expanded on the issue of rhythmic changes in human health and sickness and provided his own data on the daily fluctuations in patient mortality he discovered at the Val-de-Grâce military hospital where he was chief pharmacist. What is crucial is his use of terms such as "living clock," "entrainment," and "innate rhythm" and the applicability of the advanced concepts Because Virey introduced the notion of temporal variations and the impact of the alternation of day and night on these variations, this thesis is a historic testimonial to understanding of biological rhythms in the first half of the 19th century. We may assume from his writings on rhythmic fluctuations that he offered the theory, followed by an experiment, however primitive, from which he drew conclusions and postulated a mechanism (the living clock) that would later prove accurate. All of these aspects indicate that this study represents an early exploration of the notion of temporal variations in humans.

[Light pollution]. / Pollution lumineuse.

LIGHT POLLUTION Artificial light can be a polluting agent deleterious for the retina, in relation to the toxicity of the blue band (380-500 nm) of the visible spectrum (380-700nm) specifically used in light-emitting diodes (LEDs). Photo-toxicity results from photochemical damage to the pigmented epithelium and retinal photoreceptors responsible for the visual function of the retina. Their photosensitive pigments, opsins for the cones and rhodopsin for the sticks, are consumed during the day and regenerated at night. Exposure to light at night seriously disrupts their metabolism. Photo-toxicity, along with heredity, is a major factor in degenerative diseases of the retina with, in addition to, the impact of age and tobacco for the most common of them, age-related macular degeneration: ARMD.Exposure to artificial light at night (LAN) has a deleterious effect on the internal clock. Intrinsically photosensitive ganglion cells (ipRGSs) are responsible for the non-visual functions of the retina, and perceive the light signal that is transmitted to the internal clock to reach the pineal gland. Light inhibits the secretion of melatonin and is able to advance or delay the clock depending on the time of exposure, causing desynchronization. Shift and night workers, like teenagers, are exposed to LAN. The incidence of breast cancer, higher in nurses exposed to LAN, is related to melatonin inhibition, sleep deprivation and desynchronization. The exposure of adolescents to screens is also questionable because the LEDs of the devices emit a blue light, the impact of which on the clock is considerable. The chronic desynchronizations of both shiftworkers and adolescents should be considered a major public health concern.

POLLUTION LUMINEUSE La lumière artificielle peut être un agent polluant délétère pour la rétine, en rapport avec la toxicité de la bande bleue (380-500 nm) du spectre visible (380-700 nm), notamment utilisée dans les diodes électroluminescentes (LED). La phototoxicité résulte de lésions photochimiques au niveau de l'épithélium pigmenté et des photorécepteurs rétiniens responsables de la fonction visuelle de la rétine. Leurs pigments photosensibles, opsines pour les cônes et rhodopsines pour les bâtonnets, sont consommés le jour et régénérés la nuit. L'exposition à la lumière la nuit perturbe gravement leur métabolisme. La phototoxicité constitue, avec l'hérédité, un facteur majeur pour les maladies dégénératives de la rétine avec, en plus, l'impact de l'âge et du tabac pour la plus fréquente d'entre elles, la dégénérescence maculaire liée à l'âge (DMLA). L'exposition à la lumière artificielle la nuit (LAN) dérègle l'horloge interne. Les cellules ganglionnaires intrinsèquement photosensibles (ipRPC), responsables des fonctions non visuelles de la rétine, perçoivent le signal lumineux qui est transmis à cette l'horloge interne pour aboutir à la glande pinéale. La lumière inhibe la sécrétion de mélatonine et est capable d'avancer ou de retarder l'horloge selon l'heure d'exposition, dans le cadre d'une désynchronisation. Les travailleurs postés et de nuit, comme les adolescents, sont exposés à la LAN. L'incidence de cancer du sein, plus élevée chez les infirmières exposées à la LAN, est attribuée à l'inhibition de la mélatonine, la privation de sommeil et la désynchronisation. L'exposition des adolescents aux écrans pose aussi question, car les diodes électroluminescentes (LED) des appareils émettent une lumière bleue dont l'impact sur l'horloge interne est considérable. Les désynchronisations chroniques des travailleurs postés, comme celles des adolescents, doivent être considérées comme des préoccupations importantes de santé publique.

Assessment of cortisol secretory pattern in workers chronically exposed to ELF-EMF generated by high voltage transmission lines and substations.

We investigated the effects of extremely-low frequency electromagnetic fields (ELF-EMFs; 50 Hz) on the secretion of cortisol in 14 men (mean age = 38.0 ± 0.9 years) working in extra-high voltage (EHV) substations. The workers dwelt in houses that were close to substations and high-voltage lines. Thus, they had long histories (1-20 years) of long-yerm exposure to ELF-EMFs. Magnetic field strength was recorded using Emdex dosimeters worn by the volunteers day and night for seven days; the one-week geometric mean ranged from 0.1 to 2.6 µT. Blood samples were taken hourly from 20:00 to 08:00 the next morning. Cortisol concentrations and patterns were compared to age-matched, unexposed control subjects whose exposure level was ten times lower. The comparison of the control group (n = 15) and the groups exposed to fields of 0.1-0.3 µT (n = 5) and > 0.3 µT (n = 9), respectively, revealed a significant effect of field intensity on the cortisol secretory pattern. This study strongly suggests that chronic exposure to ELF-EMFs alters the peak-time serum cortisol levels. Studies are required on the effect of this disruption in high-risk populations such as children, elderly people, and patients with cancer.

Influence of CYP3A polymorphisms on tacrolimus pharmacokinetics in kidney transplant recipients.

Tacrolimus is characterized by a highly variable pharmacokinetics (PK) and a small therapeutic window. It is metabolized specifically by the CYP3A isoenzymes. This study aimed to determine, in kidney transplant patients, the influence of different genotypic clusters involving these SNPs CYP3A4*1B, CYP3A4*22, and CYP3A5*3 on Tacrolimus bioavailability during the first (PTP1) and the second (PTP2) posttransplant phase (PT). We included kidney transplant patients who received Tacrolimus and underwent drug monitoring by C0 monitoring. CYP3A4 and CYP3A5 genotyping were performed using PCR-RFLP. We classified the patients into four groups: Slow, Intermediate, rapid, and ultra-rapid metabolizers. We included 80 patients. The Tacrolimus dose-normalized C0 (C0/D ratio) was significantly decreased in intermediate, rapid, and ultra-rapid comparing with slow metabolisers. During PTP1 only CYP3A5*3 and CYP3A4*22 polymorphisms correlate significantly with C0/D ratio. Regardless of the PT phase and during the late one, only the CYP3A4 polymorphisms correlate significantly with the C0/D ratio. We identified that these SNPs are all associated independently with Tacrolimus exposure in different PT phases. Moreover, we are the first to define a genotypic cluster including the three CYP3A SNPs.

Association Between Mobile Phone Radiation Exposure and the Secretion of Melatonin and Cortisol, Two Markers of the Circadian System: A Review.

The extremely important use of mobile phones in the world, at all ages of life, including children and adolescents, leads to significant exposure of these populations to electromagnetic waves of radiofrequency. The question, therefore, arises as to whether exposure to these radiofrequencies (RFs) could lead to deleterious effects on the body's biological systems and health. In the current article, we review the effects, in laboratory animals and humans, of exposure to RF on two hormones considered as endocrine markers: melatonin, a neurohormone produced by the pineal gland and cortisol, a glucocorticosteroid synthesized by the adrenal glands. These two hormones are also considered as markers of the circadian system. The literature search was performed using PubMed, Medline, Web of Sciences (ISI Web of Knowledge), Google Scholar, and EMF Portal. From this review on RF effects on cortisol and melatonin, it appears that scientific papers in the literature are conflicting, showing effects, no effects, or inconclusive data. This implies the need for additional research on higher numbers of subjects and with protocols perfectly controlled with follow-up studies to better determine whether the chronic effect of RF on the biological functioning and health of users exists (or not). Bioelectromagnetics. 2021;42:5-17. © 2020 Bioelectromagnetics Society.

Effects and mechanisms of action of light-emitting diodes on the human retina and internal clock.

White light-emitting diodes (LEDs) will likely become the most used lighting devices worldwide in the future because of their very low prices over the course of their long lifespans which can be up to several tens of thousands of hours. The expansion of LED use in both urban and domestic lighting has prompted questions regarding their possible health effects, because the light that they provide is potentially high in the harmful blue band (400-500 nm) of the visible light spectrum. Research on the potential effects of LEDs and their blue band on human health has followed three main directions: 1) examining their retinal phototoxicity; 2) examining disruption of the internal clock, i.e., an out-of-sync clock, in shift workers and night workers, including the accompanying health issues, most concerningly an increased relative risk of cancer; and 3) examining risky, inappropriate late-night use of smartphones and consoles among children and adolescents. Here, we document the recognized or potential health issues associated with LED lighting together with their underlying mechanisms of action. There is so far no evidence that LED lighting is deleterious to human retina under normal use. However, exposure to artificial light at night is a new source of pollution because it affects the circadian clock. Blue-rich light, including cold white LEDs, should be considered a new endocrine disruptor, because it affects estrogen secretion and has unhealthful consequences in women, as demonstrated to occur via a complex mechanism.

Effect of CYP3A4*22 and CYP3A4*1B but not CYP3A5*3 polymorphisms on tacrolimus pharmacokinetic model in Tunisian kidney transplant.

The pharmacokinetics of Tacrolimus is characterized by a high interindividual variability that is mainly explained by pharmacogenetics biomarkers. The aims were to develop a population pharmacokinetic model (Pk pop) taking into account post-transplant phases (PTP), CYP3A4*1B, CYP3A4*22 and CYP3A5*3 polymorphisms on Tac pharmacokinetics in adult kidney transplant patients. The Pk pop study was performed using a nonparametric approach (Pmetrics*). The influence of covariates (age, weight, sex, hematocrit and CYP3A4*1B, CYP3A4*22 and CYP3A5*3 polymorphisms) was tested on the model's Pk parameters. The performance of the final model was assessed using an external dataset. A one-compartment model (Vd: volume of distribution, CL: Tac Clearance) was found to correctly describe the evolution of the C0/D regardless of the PTP. The influence of the covariates has shown that only the CYP3A4*1B and CYP3A4*22 polymorphisms were significantly associated only with CL, regardless of PTP (p = .04 and 0.02, respectively). Only the CYP3A4*22 polymorphism influenced CL during early PTP (P1: the first three months, p = .02). During the late PTP (P2: >3 months), only CYP3A4 polymorphisms were found to affect CL (p = .03 for both). The external validation of the final model, including both CYP3A4 polymorphisms, showed an acceptable predictive performance during P1 and P2. We developed and validated a tac Pk pop model including both CYP3A4*22 and CYP3A4*1B polymorphisms, taking into account PTP. This model was very useful in the Tac dose proposal in this population on any PT day but could not be used in other organ transplants due to pharmacokinetic differences.

Evaluation in humans of ELF-EMF exposure on chromogranin A, a marker of neuroendocrine tumors and stress.

Chromogranin A (CgA), which is a major protein in adrenal chromaffin cells and adrenergic neurons, is a clinically relevant endocrine and neuroendocrine tumor marker including pheochromocytomas, neuroblastomas, and related neurogenic tumors. In this study, we looked at the effect in humans of chronic daily exposure to a 50-Hz magnetic field. We examined in 15 men (38.0 ± 0.9 years) the effects of chronic daily exposure to a 50-Hz magnetic field for 1-20 yrs both at home and at work. EMDEX II dosimeters were used to record magnetic field all day long every 30 s. for 1 week. The weekly geometric mean of the individual exposures ranged from 0.1 to 2.6 µT. Blood samples were taken hourly between 20:00 h and 08:00 h. CgA patterns of exposed subjects were compared to age-matched controls. The results of exposed subjects were compared with those for 15 unexposed men who served as controls and whose individual exposure was ten times lower ranging from 0.004 to 0.092 µT. This work shows that in the control group the serum CgA levels exhibited a nighttime peak with a progressive decline of the serum concentrations and a nadir in the morning. Both the profile and the serum concentrations of CgA, a marker of neuroendocrine tumors and stress, did not appear to be impaired in the subjects chronically exposed over a long period (up to 20 yrs) to magnetic fields though a trend toward lower levels were found at the highest exposure (>0.3 µT). This does not rule out, however, that the potential deleterious risk of ELF-EMF on frail populations such as children and the elderly may be greater at low exposure and should hence be documented, at least for their residential exposure.

Twenty-four-hour pattern of operations-related injury occurrence and severity of off-site/on-call volunteer French firefighters.

We assessed the 24-h pattern of operations-related injuries (ORI) experienced by scheduled off-site/on-call French volunteer firefighters (VFF) through analysis of an archival database. Occurrence and severity - evaluated by number of lost work days (LWD) and total medical costs (TMC) - of ORI were explored in terms of risk ratios, respectively, number of ORI/number of service operations (RRORI), number of LWD/number of ORI (RSLWD,) and TMC/number of ORI (RSTMC). Additionally, the collective work performance of all involved VFF was measured in terms of the lag time (LT) between emergency call-center firefighter-answered communication for service of observer-presumed out-of-hospital cardiac arrest (OHCA) and departure of vehicle from fire station to render aid, designated LTOHCA. Cosinor and cross-correlation statistical methods were applied. A total of 252 ORI occurred while performing 146,479 service operations. High-amplitude 24 h variation was detected in RRORI (p < .003), SRLWD (p < .001), SRTMC (p < .012), and LTOHCA (p < .001), all with nocturnal peak time. Coherence was found between the day/night variation of LTOHCA and RRORI (r = 0.7, p < .0002), SRLWD (r = 0.5, p < .02), and SRTMC (r = 0.4, p < .05). This investigation verifies the occurrence and severity of ORI of scheduled off-site/on-call VFF exhibit high-amplitude 24 h patterning with nocturnal excess that closely coincides with their day/night work performance measured by LTOHCA. These findings, which are essentially identical to ones of a previous study entailing on-site/on-call career firefighters, indicate the need for fatigue management and ORI prevention programs not yet available to VFF, who compose the majority of the field service workforce of French fire departments. Abbreviations:FF: firefighters; CFF: career firefighters; VFF: volunteer firefighters; FD: fire department; LTOHCA: lag time (LT) response in min:sec between fire department call-center-answered communication for service of presumed out-of-hospital cardiac arrest (OHCA) and departure from fire station of vehicle to render aid; LWD: lost work days; ORI: operations-related injuries; SRLWD: severity ratio of operations-related injuries in terms of number of lost work days, calculated as number of lost work days/number of operations-related injuries; RRORI: risk ratio of operations-related injuries calculated as number of operations-related injuries/number of operations; SRTMC: severity ratio of operations-related injuries in terms of total medical costs, calculated as total medical costs/number of operations-related injuries; TMC: total medical costs.

Daily, weekly and annual patterns in children's accidental sport injuries.

Details of serious injuries to children ≤16 yrs. of age that necessitated urgent surgical intervention by the Department of Pediatric Surgery of the University Hospital of Lausanne, Switzerland were recorded into a database registry. Some 15 110 entries listed the precise time of injury, and 3114 (20.6%) of these resulted from participating in sport-associated activities. Time-of-day, day-of-week and month-of-year differences in the total number of children's accidental sport injuries (CASI) were validated. Time-of-day patterns were substantiated for "All Sports", for both boys and girls 5-16 yrs. of age, with more boys than girls experiencing incidents at almost every clock hour. Moreover, they were substantiated for this age group for each of the six different considered individual and team CASI categories - Physical Exercises at School; Bicycle Riding; Roller Skating and Skateboarding; Snow Skiing, Sledding, and Tobogganing; Soccer; and Basketball - for which sample sizes were sufficiently large (n > 230) to perform statistical assessment by ANOVA, t-test and/or cosinor analyses. CASI happened primarily between 06:00 and 17:00 h and rarely evening or overnight. Features - specific clock-time and number of peaks and troughs - of the CASI daily curve pattern of the individual six sport categories differed somewhat; nonetheless, excess or greatest number of CASI typically happened between 12:00 and 14:00 h, even when summertime and other scheduled school and family vacation periods were taken into account. Time-of-day and day-of-week patterns in the boy/girl sex ratio were also validated, with midday and Friday/Saturday peaks, respectively. We hypothesize the prominent 24 h patterns of CASI of 5-16 yr. olds, in particular, are representative of a combination of several determinants. These include exogenous periodic and cyclic environmental and sociocultural phenomena, genetic sex-related traits, plus endogenous circadian cognitive and physiologic rhythms, with the common midday injury excess of many sport categories, at least in part, the consequence of the well-documented midday dip in attention and vigilance of children.

Do night and around-the-clock firefighters' shift schedules induce deviation in tau from 24 hours of systolic and diastolic blood pressure circadian rhythms?

Systolic (S) and diastolic (D) blood pressures (BP) [SBP and DBP] are circadian rhythmic with period (τ) in healthy persons assumed to be maintained at 24.0h. We tested this assumption in a sample of 30 healthy career (mean >12 yrs) 30-to-46 yr-old male Caucasian French firefighters (FFs) categorized into three groups according to work schedule and duties: Group A - 12 FFs working 12h day, 12h night, and occasionally 24h shifts and whose primary duties are firefighting plus paramedical and road rescue services; Group B - 9 FFs working mostly 12h day and 12h night shifts and whose duties are answering incoming emergency calls and coordinating service vehicle dispatch from fire stations with Group A personnel; Group C - 9 day shift (09:00-17:00h) FFs charged with administrative tasks. SBP and DBP, both in winter and in summer studies of the same FFs, were sampled by ambulatory BP monitoring every 1h between 06:00-23:00h and every 2h between 23:01-05:59h, respectively, their approximate off-duty wake and sleep spans, for 7 consecutive days. Activity (wrist actigraphy) was also sampled at 1-min intervals. Prominent τ of each variable was derived by a power spectrum program written for unequal-interval time series data, and between-group differences in incidence of τ≠24h of FFs were assessed by chi square test. Circadian rhythm disruption (τ≠24h) of either the SBP or DBP rhythm occurred almost exclusively in night and 24h shift FFs of Group A and B, but almost never in day shift FFs of Group C, and it was not associated with altered τ from 24.0h of the circadian activity rhythm. In summer, occurrence of τ≠24 for FFs of Group A and B differed from that for FFs of Group C in SBP (p=0.042) and DBP (p=0.015); no such differences were found in winter (p>0.10). Overall, manifestation of prominent τ≠24h of SBP or DBP time series was greater in summer than winter, 27.6% versus 16.7%, when workload of Group B FFs, i.e. number of incoming emergency telephone calls, and of Group A FFs, i.e. number of dispatches for provision of emergency services, was, respectively, two and fourfold greater and number of 12h night shifts worked by Group B FFs and number of 24h shifts worked by Group A FFs was, respectively, 92% and 25% greater. FFs of the three groups exhibited no winter-summer difference in τ≠24h of SBP or SDP; however, τ≠24h of DBP in Group B FFs was more frequent in summer than winter (p=0.046). Sleep/wake cycle disruption, sleep deprivation, emotional and physical stress, artificial light-at-night, and altered nutrient timings are hypothesized causes of τ≠24h for BP rhythms of affected Groups A and B FFs, but with unknown future health effects.

Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption.

Exposure to Artificial Light At Night (ALAN) results in a disruption of the circadian system, which is deleterious to health. In industrialized countries, 75% of the total workforce is estimated to have been involved in shift work and night work. Epidemiologic studies, mainly of nurses, have revealed an association between sustained night work and a 50-100% higher incidence of breast cancer. The potential and multifactorial mechanisms of the effects include the suppression of melatonin secretion by ALAN, sleep deprivation, and circadian disruption. Shift and/or night work generally decreases the time spent sleeping, and it disrupts the circadian time structure. In the long run, this desynchronization is detrimental to health, as underscored by a large number of epidemiological studies that have uncovered elevated rates of several diseases, including cancer, diabetes, cardiovascular risks, obesity, mood disorders and age-related macular degeneration. It amounts to a public health issue in the light of the very substantial number of individuals involved. The IARC has classified shift work in group 2A of "probable carcinogens to humans" since "they involve a circadian disorganization". Countermeasures to the effects of ALAN, such as melatonin, bright light, or psychotropic drugs, have been proposed as a means to combat circadian clock disruption and improve adaptation to shift and night work. We review the evidence for the ALAN impacts on health. Furthermore, we highlight the importance of an in-depth mechanistic understanding to combat the detrimental properties of exposure to ALAN and develop strategies of prevention.

Seven-day human biological rhythms: An expedition in search of their origin, synchronization, functional advantage, adaptive value and clinical relevance.

This fact-finding expedition explores the perspectives and knowledge of the origin and functional relevance of the 7 d domain of the biological time structure, with special reference to human beings. These biological rhythms are displayed at various levels of organization in diverse species - from the unicellular sea algae of Acetabularia and Goniaulax to plants, insects, fish, birds and mammals, including man - under natural as well as artificial, i.e. constant, environmental conditions. Nonetheless, very little is known about their derivation, functional advantage, adaptive value, synchronization and potential clinical relevance. About 7 d cosmic cycles are seemingly too weak, and the 6 d work/1 d rest week commanded from G-d through the Laws of Mosses to the Hebrews is too recent an event to be the origin in humans. Moreover, human and insect studies conducted under controlled constant conditions devoid of environmental, social and other time cues report the persistence of 7 d rhythms, but with a slightly different (free-running) period (τ), indicating their source is endogenous. Yet, a series of human and laboratory rodent studies reveal certain mainly non-cyclic exogenous events can trigger 7 d rhythm-like phenomena. However, it is unknown whether such triggers unmask, amplify and/or synchronize previous non-overtly expressed oscillations. Circadian (~24 h), circa-monthly (~30 d) and circannual (~1 y) rhythms are viewed as genetically based features of life forms that during evolution conferred significant functional advantage to individual organisms and survival value to species. No such advantages are apparent for endogenous 7 d rhythms, raising several questions: What is the significance of the 7 d activity/rest cycle, i.e. week, storied in the Book of Genesis and adopted by the Hebrews and thereafter the residents of nearby Mediterranean countries and ultimately the world? Why do humans require 1 d off per 7 d span? Do 7 d rhythms bestow functional advantage to organisms? Is the magic ascribed to the number 7 of relevance? We hypothesize the 7 d time structure of human beings is endogenous in origin - a hypothesis that is affirmed by a wide array of evidence - and synchronized by sociocultural factors linked to the Saturday (Hebrews) or Sunday (Christian) holy day of rest. We also hypothesize they are representative, at least in part, of the biological requirement for rest and repair 1 d each 7 d, just as the circadian time structure is representative, in part, of the biological need for rest and repair each 24 h.