Chronodisruption: Origin, Roots, and Developments of an 18-Year-Old Concept. Comment on Desmet et al. Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag. Nutrients 2021, 13, 3846.

We read with interest the article by Desmet and colleagues entitled "Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag" [...].

Health Risks and Interventions in Exertional Heat Stress.

BACKGROUND: With climate change, heat waves are expected to become more frequent in the near future. Already, on average more than 25 000 "heat deaths" are estimated to occur in Europe every year. However, heat stress and heat illnesses arise not just when ambient temperatures are high. Physical exertion increases heat production within the organism many times over; if not enough heat is lost, there is a risk of exertional heat stress. This review article discusses contributing factors, at-risk groups, and the diagnosis and treatment of heat illnesses. METHODS: A selective literature search was carried out on PubMed. Current guidelines and expert recommendations were also included. RESULTS: Apart from muscular heat production (>70% of converted energy), there are other factors that singly or in combination can give rise to heat stress: clothing, climate/acclimatization, and individual factors. Through its insulating properties, clothing reduces the evaporation of sweat (the most effective physiological cooling mechanism). A sudden heat wave, or changing the climate zone (as with air travel), increases the risk of a heat-related health event. Overweight, low fitness level, acute infections, illness, dehydration, and other factors also reduce heat tolerance. In addition to children, older people are particularly at risk because of their reduced physiological adaptability, (multi-)morbidity, and intake of prescription drugs. A heat illness can progress suddenly to life-threatening heat stroke. Successful treatment depends on rapid diagnosis and cooling the body down as quickly as possible. The aim is to reduce core body temperature to <40 °C within 30 minutes. CONCLUSION: Immediately effective cooling interventions are the only causal treatment for heat stroke. Time once lost cannot be made up. Prevention (acclimatization, reduced exposure, etc.) and terminating the heat stress in good time (e.g., stopping work) are better than any cure.

A new approach to assess movements and isometric postures of spine and trunk at the workplace.

Low back pain is regarded as the primary cause of occupational disability in many countries worldwide. However, there is a lack of valid assessment of kinematic spine and trunk parameters to provide further insight into occupational spine loads. A new 3-dimensional mobile measurement system (3D-SpineMoveGuard) was developed and evaluated by means of repeated dynamic and isometric trunk positions by 10 male and 10 female volunteers. The interclass correlation coefficient indicates high test-retest reliability (r = 0.975-0.999) of the 3D-SpineMoveGuard. Moreover, analysis of validity revealed almost identical results for the new measurement system. The evaluation study indicates a good scientific quality for the use in occupational task analyses. The objective assessment of indirectly measured spine and trunk kinematics will give further insight to predict and prevent job-related spine loads.

Physical performance in middle age and old age: good news for our sedentary and aging society.

BACKGROUND: Physical performance often declines in middle age, but it is unclear to what extent this is due to biological aging. It can be difficult to determine whether such physical changes are truly age-related, as they might alternatively be explained as the negative consequences of a sedentary lifestyle. METHODS: We assessed the endurance of a physically active subgroup of the population by performing an age- and sex-stratified analysis of over 900,000 running times of marathon and half-marathon participants aged 20 to 79. We also analyzed the responses of 13,171 marathon and half-marathon runners to a questionnaire about sports, lifestyle, and health. RESULTS: No significant age-related decline in performance appears before age 55. Moreover, only a moderate decline is seen thereafter; in fact, 25% of the 65- to 69-year-old runners were faster than 50% of the 20- to 54-year-old runners. Our survey also revealed that more than 25% of the 50- to 69-year-old runners had started their marathon training only in the past 5 years. CONCLUSION: Performance losses in middle age are mainly due to a sedentary lifestyle, rather than biological aging. The large contingent of older "newcomers" among marathon runners demonstrates that, even at an advanced age, non-athletes can achieve high levels of performance through regular training.

Shift work and cancer: the evidence and the challenge.

BACKGROUND: In 2007, the International Agency for Research on Cancer (IARC) classified shift work with circadian disruption or chronodisruption as a probable human carcinogen. Short-term disturbances of biological 24-hour-rhythms following exposures to light and darkness at unusual times are well-known as "jet-lag" and "shift-lag" symptoms. However, that chronic disturbances or disruptions of timely sequenced circadian rhythms (chronodisruption) should contribute to long-term developments of cancer is a relatively new concept. This review provides background and practical information with regard to the open question "does shift-work cause cancer?" METHODS: Overview on the basis of a selective literature search via Medline and ISI Web of Knowledge until 2009 from the viewpoints of occupational medicine, epidemiology, chronobiology, and occupational science. RESULTS: The postulated causal links between shift-work and cancer in humans are biologically plausible in the light of experimental findings, but to date we lack epidemiological studies which could describe or exonerate risks in humans. Monetary compensation has already been paid for such cases in at least one country (Denmark). In Germany, however, according to the applicable law, a new occupational disease can only be recognized when certain conditions for the recognition of "general scientific merit" have been met. We present the current state of knowledge regarding prevention. CONCLUSION: While causal links between shift-work and cancer developments are not established, future shift-work planning should pay more attention to insights from occupational medicine, chronobiology, and occupational science.

Shift work, chronodisruption and cancer?--The IARC 2007 challenge for research and prevention and 10 theses from the Cologne Colloquium 2008.

In October of 2007, an IARC panel of 24 scientists systematically evaluated epidemiologic, experimental, and mechanistic data and concluded that shift work that involves circadian or chronodisruption is probably carcinogenic in humans. In view of the possible scope of the problem--shift work is widespread and unavoidable on one hand and breast cancer and prostate cancer, which may be causally associated with chronodisruption, are epidemic worldwide on the other--German representatives of science and occupational medicine discussed the experimental and epidemiologic background and possible implications of the challenge identified by the International Agency for Research on Cancer (IARC) at a colloquium in Cologne in September 2008. This overview summarizes the key ideas presented at the Cologne Colloquium and offers 10 theses concerning the need for targeted studies and the necessity to develop possible means of prevention.

Is exposure to silica associated with lung cancer in the absence of silicosis? A meta-analytical approach to an important public health question.

OBJECTIVE: This report investigates epidemiologically whether exposure to silica is associated with lung cancer risks in individuals without silicosis. METHODS: We searched the PubMed reference data base from 1966 through 1/2007 for reports of lung cancer in silica-exposed persons without and with silicosis. To explore heterogeneity between studies, a multi-stage strategy was employed. First, fixed-effect summaries (FES) and corresponding 95% confidence intervals (CI) for various combinations of studies were calculated, weighting individual results by their precision. The homogeneity of the contributing results was examined using chi(2) statistics. Where there was evidence of substantial heterogeneity, the CI around the FES was increased to take account of the between-study variability. Random-effect summaries and their CI for identical combinations of studies were also computed. Meta regression was used to explore interactions with covariates. To draw comparisons, parallel analyses were performed for non-silicotics and for silicotics. RESULTS: The persistence of a significant link between silicosis and lung cancer since the characterisation in 1997 of silica as a human carcinogen [our estimates of lung cancer relative risks (RR) exceeded unity in each of 38 eligible studies of silicotics published until 1/2007, averaging 2.1 in analyses based on both fixed and random effect models (95% CI = (2.0-2.3) and (1.9-2.3), respectively)] does not resolve our study question, namely whether exposure to silica levels below those required to induce silicosis are carcinogenic. Importantly, our detailed examination of 11 studies of lung cancer in silica-exposed individuals without silicosis included only three with data allowing adjustment for smoking habits. They yielded a pooled RR estimate of 1.0 [95% CI = (0.8-1.3)]. The other eight studies, with no adjustment for smoking habits, suggested a marginally elevated risk of lung cancer [RR = 1.2; 95% CI (1.1-1.4)], but with significant heterogeneity between studies (P approximately 0.05). CONCLUSIONS: Necessary further research should concentrate on silica exposures both above and below those that induce silicosis, so that the shape of the exposure-response relationship may be identified, with adjustments for likely confounding factors including silicosis. Time-dependent information on silicosis and on silica dust is required as well as the application of methods like G-estimation to answer the important public health question: Is silicosis a necessary condition for the elevation of silica-associated lung cancer risks?

Chronodisruption and cancer.

Research into health effects of chronodisruption (CD), a relevant disturbance of the circadian organization of physiology, endocrinology, metabolism and behaviour, is evolving at a rapid pace. With regard to malignancies, our synthesis of key experiments indicates that CD can play a causal role for cancer growth and tumor progression in animals. Moreover, our meta-analyses of 30 epidemiological studies evince that flight personnel and shift workers exposed to chronodisruption may have increased breast and prostate cancer risks: summary relative risks (RRs) for investigations of flight personnel and of shift workers suggested a 70 and 40% increase in the risk of breast cancer, respectively, and excess relative risks of prostate cancer in nine studies in flight personnel (40%) and in two studies in male shift workers. There was a remarkable indication of homogeneity of results from the individual studies that contribute to the average statistics. However, in view of doubts about whether the differing assessments of CD can really be regarded as valid reflections of the same causative phenomenon and the lack of control of covariates in the majority of studies, it is premature to conclude that the risk observations reflect a real, rather than spurious, association with CD. The challenge for future epidemiological investigations of the biologically plausible links between chronodisruption and human cancers is to conduct studies which appreciate details of transmeridian travelling, of shift work and of covariates for the development of the diseases.

Sporting activity, prevalence of overweight, and risk factors: cross-sectional study of more than 12 500 participants aged 16 to 25 years.

BACKGROUND: Recent studies show that habits detrimental to health are becoming established ever earlier in life. Because most of these investigations focus on adolescents up to the age of 18 years, it is largely unknown whether and to what extent negative behavioral modifications are intensified in young adults. METHODS: Within the cross-sectional study "Fit fürs Leben" (Fit for Life) 12 835 volunteers aged 16 to 25 years were anthropometrically investigated and interviewed about their lifestyle and habits (sporting activity, nutrition and health-related behavior). RESULTS: Data on anthropometric (BMI, waist circumference, body fat) and health-relevant (lack of exercise, smoking) characteristics as well as the frequency of cardiovascular risk factors show a clear increase in unhealthy attributes, particularly among those aged 20 to 25 years. Fifty percent of 25-year-old men are overweight, 60% smoke, and around one third do not participate in sport. Although only one quarter of women aged 16 to 25 years are overweight, women engage in sport much less frequently. Only one quarter of all study participants display none of the investigated cardiovascular risk factors. DISCUSSION: The health-detrimental tendencies increase considerably after the age of 20. Efficient cross-institutional prevention campaigns are urgently necessary to promote and continually support a health-conscious life-style.

Light at night, chronodisruption, melatonin suppression, and cancer risk: a review.

Light exposure during the night is becoming progressively more common throughout the world, particularly in areas where electricity is commonly used. Also, the availability of artificial light has allowed humans to work or recreate throughout the 24-hour day. Based on photographs taken of the Earth from outer space, it is also apparent that true darkness is disappearing. For years it was assumed that polluting the daily dark period with light was inconsequential in terms of animal/human physiology. That assumption, however, has proven incorrect. Light at night has two major physiological actions, i.e., it disrupts circadian rhythms and suppresses the production of melatonin by the pineal gland. Moreover, both these changes are light intensity and wavelength dependent. Both human epidemiological and experimental studies on animals have documented that a potential negative consequence of chronodisruption and nocturnal melatonin inhibition is cancer initiation and growth. In epidemiological studies, the frequency of each of the following cancers has been reportedly increased in individuals who routinely work at night or whose circadian rhythms are disrupted for other reasons (e.g., due to jet lag): breast, prostate, endometrial, and colorectal. Likewise, in experimental animals, cancer growth is exaggerated when the animals are repeatedly phase advanced (as occurs during easterly flights) or exposed to light at night. A variety of mechanisms have been examined to explain how the suppression of melatonin exaggerates cancer risk. Mechanistically, how chronodisruption (without a consideration of melatonin suppression) would enhance cancer frequency is less clear. In addition to cancer, there may be other diseases that result from the chronic suppression of melatonin by light at night.

Lung cancer mortality and carbon black exposure: Cox regression analysis of a cohort from a German carbon black production plant.

OBJECTIVE: We undertook a lung cancer mortality analysis of 1528 German carbon black workers, followed between the years of 1976-1998, who produced furnace black, lamp black, and gas black. METHODS: We used Cox modeling across age with time-dependent covariates, ie, cumulative and mean carbon black exposure, duration of work in departments, adjusting for calendar time, a smoking indicator, and age at hire. Exposures were lagged up to 20 years. Analyses were performed with the full cohort and after restriction to an inception cohort. RESULTS: A total of 50 lung cancer deaths occurred. No positive association was found with carbon black exposure indices. Some models indicated an increasing risk across duration of work in the lamp black producing department. CONCLUSIONS: Our results do not suggest that carbon black exposure is a human lung carcinogen. The lamp black results, if no artifact, may point at historical exposures to gaseous polycyclic aromatic hydrocarbons.

Lung cancer mortality and carbon black exposure: uncertainties of SMR analyses in a cohort study at a German carbon black production plant.

OBJECTIVE: We undertook a sensitivity analysis of the lung cancer standardized mortality ratios (SMRs) in a study of 1522 German carbon black workers from 1976 to 1998. METHODS: We applied results from a case-control study to adjust the SMR for smoking habits and exposures experienced before the carbon black job. In addition, sensitivity to reference rates was explored. RESULTS: On the basis of 47 lung cancer deaths, the SMRs were 1.62, 1.72, and 2.08 (local, state, and national rates, respectively). Adjustment for previous exposures and smoking yielded additional correction factors of 0.64 or 0.74, varying with the chosen reference. CONCLUSIONS: Lung cancer SMRs (95% confidence intervals) for the full cohort ranged from 1.20 (0.88-1.59) to 2.08 (1.53-2.77) in this sensitivity analysis. Thus, overall SMRs are only weak measures of causal associations and should be complemented by internal modeling of exposure effects whenever possible.

Lung cancer mortality and carbon black exposure: a nested case-control study at a German carbon black production plant.

OBJECTIVE: The objective of this study was to conduct a case-control study of lung cancer nested within a cohort of 1528 German carbon black workers, 1976-1998. METHODS: The authors conducted risk-set sampling of two controls matched on year of birth and conditional logistic regression modeling of cumulative carbon black exposure, duration of work in different departments, feedstock contact, asbestos exposure, smoking, age at hire, exposures before the carbon black job, and serving as a soldier in World War II or being a prisoner of war. Analyses were performed with both the full cohort and members of an inception cohort subset. Exposures were lagged by 10 years. RESULTS: Analysis of 50 lung cancer deaths showed no association to carbon black exposure. CONCLUSIONS: Carbon black exposure was not linked to lung cancer risk. Suggestions of positive associations with asbestos exposure, feedstock contact, and work in specific departments are inconclusive due to small numbers.

The chronosense -- what light tells man about biological time.

In the past 10 years, experimental studies have provided further evidence for the suggestion that the eye serves man as a dual sense organ, viz as a sense organ for sight but also for time and the regulation of biological rhythms. A small group of scientists interested in the adjustment of biological rhythms to the key Zeitgeber light wanted to answer the question whether rods and/or cones and/or other uncharacterized retinal photoreceptors contribute to this function in mammals. Intriguingly, in the course of elegant research, a number of laboratories around the world have been zeroing in on a novel non-rod, non-cone ocular photopigment which serves a number of responses to non-image-forming (NIF) photoreception in mammals. This paper intends to draw attention to possible implications of photoreception and phototransduction research for other scientific disciplines which study health and diesase effects in man. We therefore review the pivotal role of the photoreceptors -- old and new -- for the light-related timing and coordination of the interplay of otherwise less efficient biological rhythms. To distinguish our focus on time- and timing-related effects from classic image-forming (IF) and other NIF responses to ambient light, we refer informatively to chronoreceptors which mediate the sense of time, or chronosense. We conclude that syndisciplinary research into the physiology and pathophysiological implications of the chronosense is warranted and summarize a series of research questions.

Light, timing of biological rhythms, and chronodisruption in man.

This paper reviews abundant evidence suggesting that causes and course of aging and cancers can be considered as being both light- and rhythm-related. We define chronodisruption as a relevant disturbance of orderly biological rhythms over days and seasons and years in man. Light is the primary external mediator and melatonin a primary internal intermediary of such disturbances, which can result in earlier deaths via premature aging and cancers. We conclude that experimental and epidemiological research can provide further insights into common denominators of these chronic processes and may offer novel and uniform targets for prevention.

Light and life--facts and research perspectives at the Cologne Light Symposium 2002.

The international meeting Light, Endocrine Systems and Cancer--Facts and Research Perspectives was convened because recent research suggests that ubiquitous light may have more serious cancer consequences than expected. Beyond the established causal link between (over) exposure to sunlight and skin cancer, many scientists consider a causal relationship between light, endocrine systems and internal cancers as biologically plausible. To identify options to turn biological plausibility of mechanisms into true understanding and to assess the possible public health relevance we chose to bring together leading specialists from clinical, experimental laboratory and epidemiological studies of these issues to stimulate a critical, multi-disciplinary discussion of published and new results. Presentations at the symposium covered the physics of light and evolutionary aspects and provided intriguing information about chronobiology, physiology and patho-physiology of endocrine systems and carcinogenesis. Experimental and epidemiological findings on light and skin cancer, and of very recent investigations of relationships between light and internal cancers such as breast cancer were presented. The meeting concluded with a lively discussion of future research options. The symposium's essence and constructive atmosphere are captured in these proceedings [Neuroendocrinol Lett 2002 Jul;23 Suppl 2:1-104] which contain: (i) original presentation papers [Vladimir Anisimov, David Blask, Roland Böni, George Brainard, Thomas Erren, Alexander Lerchl, Sidney Perkowitz, Chris Portier, Russel Reiter, Richard Stevens, Günter Vollmer]; (ii) abstracts of oral and poster presentations; (iii) four commentaries [Charles Poole, Chris Portier, Till Roenneberg and Rob Lucas, Vladimir Anisimov and Johnni Hansen] on the presentations at the meeting and possible implications for research and public health. In our view, the biological plausibility of mechanistic links between light and hormones and cancer can serve as a unique basis for syn-disciplinary research and we expect that investigations in this area will become a higher priority research focus.