The Importance of Being a 'Lark' in Post-Menopausal Women with Obesity: A Ploy to Prevent Type 2 Diabetes Mellitus?

Chronotype is defined as the behavioral manifestation of circadian rhythms related to the external light-dark cycle. Evening chronotype has been associated with an increased risk of developing cardiometabolic diseases in obesity. Menopause is a lifestage associated with an increased risk of developing cardiometabolic diseases and a change in circadian rhythmicity compared to pre-menopause. However, the prevalence of chronotype categories in menopause and their role in determining menopause-related cardiometabolic risk, mostly in obesity, have not been investigated. Thus, we aimed to investigate the prevalence of chronotype categories in post-menopausal women with obesity and their role in menopause-related cardiometabolic risk. In this cross-sectional study we enrolled 49 pre-menopausal and 74 post-menopausal women with obesity. Anthropometric parameters, lifestyle habits, adherence to the Mediterranean Diet (MD), sleep quality, chronotype and the presence of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) were studied. No significance differences were detected in terms of lifestyle and adherence to the MD between pre- and post-menopausal women. Chronotype was classified as morning in 66 (53.6%), evening in 20 (16.3%) and intermediate in 37 (30.1%) women. In addition, pre-menopausal women with obesity showed a significantly higher chance to have an intermediate chronotype (OR = 2.21, 95% CI 1.28-3.83; p = 0.004), whereas post-menopausal women with obesity showed a trend to have a higher morning chronotype (OR = 1.42, 95% CI 0.98-2.06; p = 0.051), although this did not reach statistical significance. No significant differences were detected in terms of prevalence of evening chronotype between the two groups. However, the evening chronotype had a significantly higher risk to have T2DM compared to the morning (OR = 17.29, 95% CI 2.40-124.27; p = 0.005) and intermediate chronotypes (OR = 30.86, 95% CI 2.05-464.32; p = 0.013) in both pre- and post-menopausal women with obesity. In conclusion, the intermediate chronotype was significantly more prevalent in pre-menopausal women with obesity compared to post-menopausal women. Evening chronotype was associated to T2DM in both pre- and post-menopause. These results support the importance of including the assessment of chronotype in the management of women with obesity in post-menopause.

Cycles in epilepsy.

Epilepsy is among the most dynamic disorders in neurology. A canonical view holds that seizures, the characteristic sign of epilepsy, occur at random, but, for centuries, humans have looked for patterns of temporal organization in seizure occurrence. Observations that seizures are cyclical date back to antiquity, but recent technological advances have, for the first time, enabled cycles of seizure occurrence to be quantitatively characterized with direct brain recordings. Chronic recordings of brain activity in humans and in animals have yielded converging evidence for the existence of cycles of epileptic brain activity that operate over diverse timescales: daily (circadian), multi-day (multidien) and yearly (circannual). Here, we review this evidence, synthesizing data from historical observational studies, modern implanted devices, electronic seizure diaries and laboratory-based animal neurophysiology. We discuss advances in our understanding of the mechanistic underpinnings of these cycles and highlight the knowledge gaps that remain. The potential clinical applications of a knowledge of cycles in epilepsy, including seizure forecasting and chronotherapy, are discussed in the context of the emerging concept of seizure risk. In essence, this Review addresses the broad question of why seizures occur when they occur.

Sleep quality does not mediate the negative effects of chronodisruption on body composition and metabolic syndrome in healthcare workers in Ecuador.

BACKGROUND AND AIMS: The objective of the present work was to determine to what extent sleep quality may mediate the association between chronodisruption (CD) and metabolic syndrome (MS), and between CD and body composition (BC). METHODOLOGY: Cross-sectional study which included 300 adult health workers, 150 of whom were night shift workers and thereby exposed to CD. Diagnosis of MS was made based on Adult Treatment Panel III criteria. Sleep quality was measured using the Pittsburgh Sleep Quality Index. Body mass index (BMI), fat mass percentage, and visceral fat percentage were measured as indicators of body composition (BC). Data were analyzed using logistic, linear regression and structural equation models. RESULTS: The odds of health workers exposed to CD to suffer MS was 22.13 (IC95 8.68-66.07) when the model was adjusted for age, gender, physical activity and energy consumption. CD was also significantly associated with an increase in fat mass and visceral fat percentages, but not to BMI. Surprisingly, there was not enough evidence supporting the hypothesis that sleep quality contributes to the association between CD and MS or between CD and BC. CONCLUSIONS: Sleep quality does not mediate the negative effects of CD on MS nor on BC.

Sleep timing, chronotype and social jetlag: Impact on cognitive abilities and psychiatric disorders.

Sleep timing is controlled by the subtle interplay between circadian and homeostatic oscillators which, according to their endogenous properties, allow beings to feel spontaneously that it is time to go to bed or wake up in synchrony with the earth's light/dark cycle. In humans, however, social time and nocturnal artificial light modify sleep timing. Our modern lifestyle and artificial nocturnal light delay our bedtime, make us wake up, and lead to a greater intraindividual variability in sleep timing. Depending on the constraints that social time places on us, our sleep timing may be in or out of phase with the internal circadian timing determined by the circadian clock. When a person's social time is out of phase with their circadian time, they may be considered to suffer from circadian disruption or 'social jetlag'. There are interindividual differences in sleep timing that are known as morningness-eveningness preferences or chronotype, e.g. late chronotypes go to bed later. Chronotype may be assessed in terms of differences in kinetic homeostatic sleep pressure, intrinsic circadian period (ICP) and/or phase angle entrainment. In addition, chronotype depends on genetic and age-related factors, e.g. it gets earlier as people grow older. The social time of late chronotype individuals during week days is not adapted to their circadian time, unlike on free days. This results in social jetlag and circadian disruption, which in turn induces a chronic sleep debt due to a late bedtime and an early wake time, which is compensated on free days but only partially. Sleep and circadian clock disruption generally alter cognitive performance (alertness, attention, memory, higher-order executive functions such as response inhibition and decision-making) but their impact remains to be clarified. When subjects adopt their preferred sleep timing, a "synchrony effect" often appears with chronotypes performing better during daytime at optimal than at suboptimal timing (late chronotypes perform better in the evening, early chronotypes in the morning). Evening types appear to be cognitively more vulnerable to suboptimal times than morning types, probably because they have to deal with social jetlag and the "wake effort" period after awakening. Circadian disruption, but not chronotype, may impact attentional/inhibitory performance (more impulsivity and inattention). Strong associations have been found between mood disorders or attention deficit hyperactivity disorder (ADHD) and chronotype, with these psychiatric disorders typically being overrepresented in evening types. The association between social jetlag and these psychiatric disorders is less obvious. Social jetlag can be corrected by reducing exposure to evening light, although eveningness may be considered as a lifelong factor predisposing to depression or inattention.

Different Renal Chronotoxicity of Bromobenzene and Its Intermediate Metabolites in Mice.

Bromobenzene (BB) is known to pose a serious threat to human health. We previously demonstrated that BB showed chronotoxicity, that is, daily fluctuations in the severity of hepatotoxicity induced in mice. Although BB showed mild nephrotoxicity, a daily fluctuation was not observed in this toxicity. This might be attributed to the fact that BB-induced chronotoxicity is observed only in the liver and not in the kidneys and that the damage caused by BB is prominent in the liver, masking the daily fluctuation in nephrotoxicity. To confirm these two possibilities, we examined the daily fluctuations in nephrotoxicity due to BB intermediate metabolites that target the kidneys: 3-bromophenol, bromohydroquinone, and 4-bromocatechol. Mice were injected with 3-bromophenol, bromohydroquinone, or 4-bromocatechol intraperitoneally at six different time points in a day (zeitgeber time (ZT): ZT2, ZT6, ZT10, ZT14, ZT18, or ZT22). Mortality was monitored for 7 d post-injection. Mice were more sensitive to the acute toxicity of these metabolites around at ZT14 (dark-phase) exposure than around at ZT2 (light-phase) exposure. Furthermore, mice administered with a non-lethal dose of 4-bromocatechol showed significant increases in the levels of plasma blood urea nitrogen and renal malondialdehyde at ZT14 exposure. Moreover, glutathione peroxidase-4, a ferroptosis indicator, was attenuated at ZT14 exposure. These results indicate the toxicity of BB metabolites was higher during the dark-phase exposure, and demonstrate the reason why the diurnal variation of nephrotoxicity by BB was not observed in our previous report is that renal damage was masked due to severe hepatic damage.

Effects of dual task on gait velocity and cadence in cerebral palsied children with spastic hemiparesis or diparesis.

Gait is generally considered an automated process with little or no cognitive input. In most individuals with Cerebral Palsy (CP), walking restrictions may accompany during childhood and adolescence. The aim of this study was to determine the effects of dual task on Gait Velocity (GV) and Cadence (C) in Cerebral Palsied Children with Spastic Hemiparesis or Diparesis (CPCSHD). Fourteen boys, seven girls' spastic hemiparesis children (mean age: 13.33 ± 3.79 years) and twelve girls, nine boys' diparesis children (mean age: 14.44 ± 3.24 years) were included in the study. Forty-two CPCSHD having level 1 or 2 according to the Gross Motor Function Classification System (GMFCS) were included in this comparative study. GV was calculated using a chronometer for a 10-m walk on the ground with shoes. Cadence was calculated accounting the number of steps during 1-min walk. Both GV and C tests were performed by each participant with single task first. After the single task, all were asked to perform the dual task carrying a plastic water-filled bottle. There were no significant differences between the hemiparesis and diparesis in terms of demographics data. When children with hemiparesis and diparesis compare each other, no significant differences were found in terms of all the outcome parameters. The results obtained from this study indicate that walking speed and cadence decrease during a dual motor task in CPCSHD (p > 0.05). When hemiparesis and diparesis groups were compared, no difference was found between the groups.

Chronobiotic effect of melatonin in experimental optic neuritis.

Optic neuritis (ON) is an inflammatory condition of the optic nerve, which leads to retinal ganglion cell (RGC) loss. A subset of RGCs expressing the photopigment melanopsin regulates non-image-forming visual system (NIFVS) functions such as pupillary light reflex (PLR) and circadian rhythms. Melatonin is a chronobiotic agent able to regulate the circadian system. We analyzed the effect of ON on the NIFVS, and the effect of melatonin on the NIFVS alterations induced by ON. For this purpose, optic nerves from male Wistar rats received vehicle or bacterial lipopolysaccharide (LPS), and one group of animals received a subcutaneous pellet of melatonin or a sham procedure. The NIFVS was analyzed in terms of: i) blue light-evoked PLR, ii) the communication between the retina and the suprachiasmatic nuclei (by anterograde transport, and ex vivo magnetic resonance images), iii) locomotor activity rhythm, and iv) Brn3a(+) and melanopsin(+) RGC number (by immunohistochemistry). Experimental ON significantly decreased the blue light-evoked PLR, induced a misconnection between the retina and the suprachiasmatic nuclei, decreased Brn3a(+) RGCs, but not melanopsin(+) RGC number. A bilateral injection of LPS significantly increased the light (but not dark) phase locomotor activity, rhythm periodicity, and time of offset activity. Melatonin prevented the decrease in blue light-evoked PLR, and locomotor activity rhythm alterations induced by ON. These results support that ON provoked alterations of the circadian physiology, and that melatonin could restore the circadian system misalignment.

Women amateur street runners have a higher level of chronotype self- perception than men

Abstract Aim: The aims of the present study were to verify the self-perception level of the chronotype of amateur street runners and to test the association between the chronotype, gender, age, and preferred training time. Methods: A total of 166 amateur street runners were included (♀ = 89, age 38.9 ± 11.2 years; ♂ = 77, age 38.0 ± 9.7 years). The Brazilian version of the Horne & östberg questionnaire was used to assess chronotypes and the preferred training time was determined through a multiple choice question. Based on chronotype definitions that suggest that when free to choose, morning-types (MT) would prefer training in the morning, evening-types (ET) in the evening and neither-types (NT) would not have a predilection for any specific time. The corroboration of this hypothesis was assumed as self-perception level of the chronotypes. Results: Women showed higher self-perception levels of their chronotype compared to men (58.4% vs. 41.6%; χ2 = 4.699; p = 0.030). By chronotypes, MT, NT, and ET self-perception levels were 73.9%, 15.9%, 88.9%, respectively (χ2 = 57.489; p < 0.001). The most observed women circadian typology was MT, while in men it was NT (χ2 = 8.951; p = 0.011). However, there was no significant association between gender and preferred training time (χ2 = 2.654; p = 0.265). Age, female gender and preference to exercise during the day are associated with MT. Conclusion: Women runners showed a greater perception of their circadian traits than men, despite there was no association between gender and preferred training time.

Morning chronotype is a protective factor against chemotherapy-induced hot flashes in premenopausal women with breast cancer.

PURPOSE: Adjuvant chemotherapy in patients with breast cancer often causes hot flashes, impairing quality of life. However, the chronobiological or psychiatric factors associated with the development of chemotherapy-induced hot flashes (CIHFs) remain undetermined. The purpose of this study was to investigate whether chronotype was associated with the incidence of CIHFs. METHODS: A total of 119 premenopausal women with non-metastatic breast cancer awaiting adjuvant chemotherapy after surgery without hot flashes were included. The presence of CIHF was defined as having moderate to severe hot flashes, as measured by the subscale of hot flashes in the Menopause Rating Scale, at 4 weeks after the completion of chemotherapy. Chronotype (Morning/Intermediate/Evening) was assessed with the Composite Scale of Morningness before adjuvant chemotherapy. To examine the association between chronotype and CIHF, we built logistic regression models, adjusting for age, body mass index, sleep quality, and radiation therapy. RESULTS: CIHF occurred in 50.4% of participants. Morning type was inversely associated with CIHF (reference: Intermediate type, odds ratio [OR], 0.37; 95% confidence interval [CI], 0.16-0.94; p = 0.040) in the univariate model, and the association remained significant (OR, 0.37; CI, 0.13-0.96; p = 0.045) after adjusting for age, body mass index, sleep quality, and radiation therapy. CONCLUSIONS: Morning chronotype is a protective factor against the development of CIHF in patients with breast cancer. Chronotypes should be assessed and considered in the prediction and management of CIHF.

Lipolysis and Fat Oxidation Are Not Altered with Presleep Compared with Daytime Casein Protein Intake in Resistance-Trained Women.

BACKGROUND: To date, no studies have directly compared the differences between presleep and daytime protein (PRO) consumption on localized and systemic fat metabolism in active women. OBJECTIVE: The purpose of this study was to assess the effects of presleep compared with daytime PRO supplementation on subcutaneous abdominal adipose tissue (SCAAT) lipolysis and whole-body substrate utilization in women. METHODS: Thirteen young (mean ± SE age: 22 ± 1 y; BMI: 24.3 ± 0.8 kg/m2), resistance-trained [1 repetition maximum (1RM) squat percentage of body weight: 135% ± 6%; 1RM bench press percentage of body weight: 82% ± 4%] women volunteered. On overnight experimental visits, participants performed full-body resistance exercise (RE; 65% 1RM) and were randomly assigned to consume either daytime PRO (PRO, 30 g casein) 30 min post-RE and presleep (30 min before bed) noncaloric, sensory-matched placebo (PLA, 0 g casein) (PRO-PLA), or the opposite (PLA-PRO), switching the order of the supplements on the following visit. SCAAT lipolysis, resting metabolism (indirect calorimetry), and plasma biomarkers (glucose, insulin, nonesterified fatty acids, glycerol) were measured at baseline, overnight, and the next morning. RESULTS: There were no differences in overnight SCAAT lipolysis between conditions indicated by interstitial glycerol concentrations (PRO-PLA: baseline, 669 ± 137; next morning, 321 ± 77.1; PLA-PRO: baseline, 524 ± 109; next morning, 333 ± 68.0 µM), fat oxidation (PRO-PLA: baseline, 5.70 ± 0.35; next morning, 5.00 ± 0.28; PLA-PRO: baseline, 6.59 ± 0.32; next morning, 5.44 ± 0.27 g/min), or any other measure. CONCLUSIONS: There was no difference between the effects of daytime and presleep PRO supplementation on SCAAT lipolysis or whole-body substrate utilization in resistance-trained women. Presleep PRO is a viable option for increasing PRO consumption in resistance-trained women because it does not blunt overnight lipolysis, and will therefore likely not lead to increases in subcutaneous abdominal fat.This trial was registered at clinicaltrials.gov as NCT03573687.

The association between chronotype, food craving and weight gain in pregnant women.

BACKGROUND: This cross-sectional study investigated the association between chronotype, food craving and weight gain in pregnant women. METHODS: In total, 245 pregnant women attending the public health service in Brazil were included. Chronotype was derived from the time of mid-sleep time on free days, with a further correction for calculated sleep debt, and higher scores on this variable indicate a tendency to eveningness. A Food Craving Questionnaire Trait and State assessment was performed, and weight gain was calculated. Generalised linear models were used to determine the association between the variables under analysis. RESULTS: Evening types presented higher anticipation of relief from negative states and feelings as a result of eating as a usual behaviour compared to morning (P = 0.013) and non-evening types (P = 0.028); less intense desire to eat as a sporadic behaviour compared to morning (P = 0.012) and non-evening types (P = 0.009); and less anticipation of positive reinforcement that may result from eating as a sporadic behaviour than non-evening types (P = 0.022). We also found a significant association between chronotype score and anticipation of relief from negative states and feelings as a result of eating (P = 0.004); anticipation of positive reinforcement that may result from eating (P = 0.013) as a usual behaviour; weight gain during the early gestational period (P = 0.024); and intense desire to eat (P = 0.045) as a sporadic behaviour. CONCLUSIONS: We conclude that evening chronotype was associated with the food craving trait. Pregnant women who tend to eveningness are more likely to gain weight in the early gestational period.

Assessment of MTNR1B Type 2 Diabetes Genetic Risk Modification by Shift Work and Morningness-Eveningness Preference in the UK Biobank.

Night shift work, behavioral rhythms, and the common MTNR1B risk single nucleotide polymorphism (SNP), rs10830963, associate with type 2 diabetes; however, whether they exert joint effects to exacerbate type 2 diabetes risk is unknown. Among employed participants of European ancestry in the UK Biobank (N = 189,488), we aimed to test the cross-sectional independent associations and joint interaction effects of these risk factors on odds of type 2 diabetes (n = 5,042 cases) and HbA1c levels (n = 175,156). Current shift work, definite morning or evening preference, and MTNR1B rs10830963 risk allele associated with type 2 diabetes and HbA1c levels. The effect of rs10830963 was not modified by shift work schedules. While marginal evidence of interaction between self-reported morningness-eveningness preference and rs10830963 on risk of type 2 diabetes was seen, this interaction did not persist when analysis was expanded to include all participants regardless of employment status and when accelerometer-derived sleep midpoint was used as an objective measure of morningness-eveningness preference. Our findings suggest that MTNR1B risk allele carriers who carry out shift work or have more extreme morningness-eveningness preference may not have enhanced risk of type 2 diabetes.

Validity and reliability of the Slovene version of the Morningness-Eveningness Questionnaire.

Morningness-eveningness (ME) can be defined as individual differences in sleep-wake patterns, and the time of day people feel and perform best. Various self-report instruments that measure ME have been developed. The Horne and Östberg Morningness-Eveningness Questionnaire (MEQ) has most frequently been used for classifying ME types. The aim of this study was to investigate the validity and reliability of the Slovene version of the MEQ (Slovene MEQ). Two hundred and sixty-five participants (65.3% women, 34,7% men, mean age 38,1 years, range 19-67) took the Slovene MEQ twice, 2 weeks apart (MEQ test and retest). Internal consistency of the Slovene MEQ items was high, with Cronbach's Alpha coefficients of 0.86. The test-retest reliability was also high, with intraclass correlation coefficient (ICC) of 0.96. The classification of chronotypes on middle-aged population offered a more balanced representation of the five chronotypes than those proposed by the authors Horne and Östberg . Age changes in chronotype could be confirmed in this study in the supposed direction with older adults being more morning-oriented. The criterion validity of the Slovene MEQ through the relationship of morningness and basic personality traits showed that conscientiousness and agreeableness demonstrated positive and significant correlations with morningness. A low negative correlation was observed between openness and morningness, with higher eveningness among more open participants.

Discrimination between extreme chronotypes using the full and reduced version of the Morningness-Eveningness Questionnaire.

The aim of this study was to carry out a comparison of the ability to discriminate between extreme chronotypes, i.e., morning- and evening-types, among the Morningness-Eveningness Questionnaire (MEQ) and its reduced version (rMEQ). To this end a secondary analysis of cohort studies, using two different approaches, was carried out. The first, subjective, relied on the computing of overlap between extreme chronotypes according to their hourly ideal bedtime, get-up time and midpoint of sleep reported at the MEQ and rMEQ, while the second, objective, on the corresponding actual-actigraphic times. At the subjective approach, 2706 participants filled in the MEQ, while 940 the rMEQ (age range of both groups: 18-30 years). The overlap was significantly lower among those who filled the rMEQ than MEQ when considering ideal midpoint of sleep (13.70% and 46.28%, respectively) and get-up time (47.04% and 62.34%, respectively). At the objective approach, 51 participants filled in the MEQ while 52 the rMEQ (age range: 19-30 years in both groups) at the end of one week of actigraphic recording. No significantly different overlap across those who filled the MEQ or rMEQ was observed with reference to the examined actigraphic times. Results of subjective assessment showed as rMEQ more clearly discriminated between extreme chronotypes than MEQ. The attempt to find an objective confirmation did not provide the same results, probably as a consequence of a masking effect by social rhythms.

Is Santa Claus an evening owl?

Case studies have a long tradition in biomedical research. Here, I will analyze an important person from a chronobiological aspect, Santa Claus. Although it might be dangerous for researchers to publish analyses about Santa Claus, because, given the possibility that he may be unsatisfied with my analysis, this could lead to an embargo of parcels for my whole family. Nevertheless, some intrepid researches already diagnosed Santa Claus, ending up in some important research results. A search in Web of Science revealed only N = 224 publications about Santa Claus, which is really low. The question, I am addressing here is, whether Santa Claus is an "evening owl" or a night chronotype. In this report, I summarize the facts known about Santa Claus on the one side and about evening chronotypes on the other and sum up these results in a "vote counting" manner as pros and cons. The results are summarized in Table 1. In total, there is 12 times support for the hypothesis, 2 times against and 1 equivocal (Table 1). This result is significant (binomial test, p = 0.013). Therefore, the conclusion is "Santa Claus is an evening type".

Synchronization: The Key to Effective Communication in Animal Collectives.

From the rapidly expanding spiral waves exhibited by colonies of giant honeybees to the ripples of light that cross a turning school of fish, synchrony proves essential to the lives of group-living organisms. Here I consider what we know about the mechanisms and adaptive value of synchronization among animals, as well as outlining open questions that, if answered, could advance our understanding of the functional complexity of animal collectives.

Arterial pH and blood gas values in rats under three types of general anesthesia: a chronobiological study.

The aim of study was to review the status of arterial pH, pO(2) and pCO(2) under general anesthesias in dependence on the light-dark (LD) cycle in spontaneously breathing rats. The experiments were performed using three- to four-month-old pentobarbital(P)-, ketamine/xylazine(K/X)- and zoletil(Z)-anesthetized female Wistar rats after a four-week adaptation to an LD cycle (12 h light:12 h dark). The animals were divided into three experimental groups according to the anesthetic agent used: P (light n=11; dark n=8); K/X (light n=13; dark n=11); and Z (light n=18; dark n=26). pH and blood gases from arterial blood were analyzed. In P anesthesia, LD differences in pH, pO(2), and pCO(2) were eliminated. In K/X anesthesia, parameters showed significant LD differences. In Z anesthesia, LD differences were detected for pH and pO(2) only. Acidosis, hypoxia, and hypercapnia have been reported for all types of anesthesia during the light period. In the dark period, except for P anesthesia, the environment was more stable and values fluctuated within normal ranges. From a chronobiological perspective, P anesthesia was not the most appropriate type of anesthesia in these rat experiments. It eliminated LD differences, and also produced a more acidic environment and more pronounced hypercapnia than K/X and Z anesthesias.

Little evidence for a chronotolerance effect for impulse noise exposure in the C57BL/6J mouse.

Noise-induced hearing loss affects a large number of adults and children worldwide, and continues to be a major public health problem. The cochlea is an organ that maintains delicate metabolic homeostasis and precise mechanical architecture. Disruption of either can cause temporary or permanent injury. Impulse noises, which are short-duration, high-level bursts of sound caused by explosions, such as gunfire, can injure the cochlea through combinations of mechanical and metabolic injury. Susceptibility to the metabolic component of noise injury may vary with the circadian rhythm, a phenomenon known as chronotolerance. Chronotolerance to noise injury has been demonstrated for a one-hour noise exposure at a fixed level, but chronotolerance for impulse noise-induced hearing loss has never been studied. Forty-four mice were exposed to 500 short-duration clicks at 137 dB peSPL at one of four hours after light onset: 2, 8, 14, or 20. Auditory brainstem response threshold shifts were measured at 3, 7, and 21 days after the exposure to measure hearing loss, and post mortem outer hair cell counts were used to confirm cochlear injury. The testing revealed no significant differences between the four exposure times for hearing threshold shifts, but did detect a small, but statistically significant, difference in outer hair cell loss, in which the loss was greatest for the mice exposed two hours after light offset. Therefore, a weak chronotolerance effect for impulse noise was detected, though the functional significance of the effect is low. Further investigation is required to more fully understand the relationship between circadian rhythm and hearing loss from different types of noise exposure.

Clinical chronobiology: a timely consideration in critical care medicine.

A fundamental aspect of human physiology is its cyclical nature over a 24-h period, a feature conserved across most life on Earth. Organisms compartmentalise processes with respect to time in order to promote survival, in a manner that mirrors the rotation of the planet and accompanying diurnal cycles of light and darkness. The influence of circadian rhythms can no longer be overlooked in clinical settings; this review provides intensivists with an up-to-date understanding of the burgeoning field of chronobiology, and suggests ways to incorporate these concepts into daily practice to improve patient outcomes. We outline the function of molecular clocks in remote tissues, which adjust cellular and global physiological function according to the time of day, and the potential clinical advantages to keeping in time with them. We highlight the consequences of "chronopathology", when this harmony is lost, and the risk factors for this condition in critically ill patients. We introduce the concept of "chronofitness" as a new target in the treatment of critical illness: preserving the internal synchronisation of clocks in different tissues, as well as external synchronisation with the environment. We describe methods for monitoring circadian rhythms in a clinical setting, and how this technology may be used for identifying optimal time windows for interventions, or to alert the physician to a critical deterioration of circadian rhythmicity. We suggest a chronobiological approach to critical illness, involving multicomponent strategies to promote chronofitness (chronobundles), and further investment in the development of personalised, time-based treatment for critically ill patients.