The Green Surgical Block 4.0: Automation of the operating theatre's climate conditions through a real-time patient-flow solution.

The energy consumed by surgery units constitutes a staggering part of the overall healthcare carbon footprint. Partly due to the demanding climate conditions necessitated by operating theatres (OTs), energy is also wasted because of poorly managed heating, ventilation and air-conditioning systems (HVACs) that consume up to 57% of the total energy used in a hospital. With their goal of optimising OTs' performance and reducing patient waiting lists, heads of surgery units worldwide do not dare to risk cancelling scheduled surgery because of problems with the OT environment conditions (ie temperature, humidity, pressure). Current solutions are monolithic, complex and completely disconnected from healthcare logic, failing to take into account the idiosyncrasy of hospitals. This article presents an innovation that uses real-time patient flow data to automate and optimise the OT's climate conditions.

Chronodisruption and Ambulatory Circadian Monitoring in Cancer Patients: Beyond the Body Clock.

PURPOSE OF REVIEW: Circadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms' disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease. RECENT FINDINGS: In recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications. This review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the state-of-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer research.

Octodon degus, a new model to study the agonist and plexus-induced response in the urinary bladder.

Urinary bladder function consists in the storage and controlled voiding of urine. Translational studies require animal models that match human characteristics, such as Octodon degus, a diurnal rodent. This study aims to characterize the contractility of the detrusor muscle and the morphology and code of the vesical plexus from O. degus. Body temperature was measured by an intra-abdominal sensor, the contractility of detrusor strips was evaluated by isometric tension recording, and the vesical plexus was studied by electrical field stimulation (EFS) and immunofluorescence. The animals showed a diurnal chronotype as judged from core temperature. The myogenic contractile response of the detrusor muscle to increasing doses of KCl reached its maximum (31.04 mN/mm2) at 60 mM. In the case of cumulative dose-response of bethanecol, the maximum response (37.42 mN/mm2) was reached at 3.2 × 10-4 M. The response to ATP was clearly smaller (3.8 mN/mm2). The pharmacological dissection of the EFS-induced contraction identified ACh and sensory fibers as the main contributors to this response. The neurons of the vesical plexus were located mainly in the trigone area, grouped in big and small ganglia. Out of them, 48.1 % of the neurons were nitrergic and 62.7 % cholinergic. Our results show functional and morphological similarities between the urinary bladder of O. degus and that of humans.

Relevance of internal time and circadian robustness for cancer patients.

BACKGROUND: Adequate circadian timing of cancer treatment schedules (chronotherapy) can enhance tolerance and efficacy several-fold in experimental and clinical situations. However, the optimal timing varies according to sex, genetic background and lifestyle. Here, we compute the individual phase of the Circadian Timing System to decipher the internal timing of each patient and find the optimal treatment timing. METHODS: Twenty-four patients (11 male; 13 female), aged 36 to 77 years, with advanced or metastatic gastro-intestinal cancer were recruited. Inner wrist surface Temperature, arm Activity and Position (TAP) were recorded every 10 min for 12 days, divided into three 4-day spans before, during and after a course of a set chronotherapy schedule. Pertinent indexes, I < O and a new biomarker, DI (degree of temporal internal order maintenance), were computed for each patient and period. RESULTS: Three circadian rhythms and the TAP rhythm grew less stable and more fragmented in response to treatment. Furthermore, large inter- and intra-individual changes were found for T, A, P and TAP patterns, with phase differences of up to 12 hours among patients. A moderate perturbation of temporal internal order was observed, but the administration of fixed chronomodulated chemotherapy partially resynchronized temperature and activity rhythms by the end of the study. CONCLUSIONS: The integrated variable TAP, together with the asynchrony among rhythms revealed by the new biomarker DI, would help in the personalization of cancer chronotherapy, taking into account individual circadian phase markers.

Oral leukoplakia treatment with the carbon dioxide laser: A systematic review of the literature.

We conducted a systematic review of the literature to evaluate treatment of oral leukoplakia with the carbon dioxide (CO2) laser. A comprehensive search of studies published between 1981 and 2015 and listed in the PubMed (National Library of Medicine, NCBI) database yielded 378 articles which were screened in detail. Relevant studies were selected according to predetermined inclusion and exclusion criteria. A total of 33 articles met the final inclusion criteria and were analysed in detail in accordance with the PRISMA-P statement. These full-text papers were classified as synopses (n = 7), recurrence and malignant transformation studies (n = 17), comparative studies between CO2 laser and cold knife surgery (n = 3) and studies evaluating the efficacy of CO2, Nd:YAG and KTP lasers. According to the literature the CO2 laser is the workhorse of oral leukoplakia treatment due to its effectiveness and low associated morbidity. However, randomized clinical trials are needed to compare CO2 laser with other lasers. The results of our systematic review showed that there is no consensus regarding the factors involved in higher recurrence and malignization rates, so further studies are needed.

The treatment of oral leukoplakia with the CO2 laser: A retrospective study of 65 patients.

The use of CO2 laser has become a routine procedure for the treatment of oral leukoplakia. In this retrospective study, we evaluated 65 patients with oral leukoplakia treated with CO2 laser vaporization. The main location was the tongue (n = 21/65, 32.3%). The initial biopsy showed mild/moderate dysplasia in almost half the patients (n = 29, 44.6%) and hyperplasia without dysplasia in around a third of the patients (n = 21, 32.3%). The recurrence and malignant transformation rates were 33.8% (n = 22) and 15.4% (n = 10), respectively. The follow-up mean (standard deviation) was 15.0 (10.6) months. The procedure-related complications rate was 7.7% (n = 5). The Kaplan-Meier curves for time to recurrence showed differences only for gingiva lesions compared to tongue lesions (log rank, p = 0.032). Malignant leukoplakia transformation is independent of treatment, although it seems advisable to treat leukoplakia with or without dysplasia.

Methods for monitoring the functional status of the circadian system in dietary surveys studies: application criteria and interpretation of results.

To evaluate the circadian system status of the subject may be of special interest in nutrition. Particularly for those studies related to the assessment of diseases related to malnutrition, as it is the case of most of the degenerative diseases such as obesity, cancer, or cardiovascular diseases. For this purpose, one of the approaches consists to measure a) the external synchronizers of the internal clock, such as light intensity, and changes from fasting to eating and from resting to activity. Indeed, "chronodisruptors" have been defined as "exogenous and endogenous exposures or effectors which are chronobiologically active and can thus disrupt the timing and order. Another approach to assess the circadian system health is to measure the b) outputs of the internal clock (circadian marker rhythms). Among such outputs, the rhythm of body temperature, motor activity, melatonin, cortisol and clock gene expression are the most commonly used. From the genetic perspective, we are now able to measure failures in the internal clock, in order to assess c) the genetics of the molecular clock. Indeed, new nutrigenetics techniques are giving us the opportunity to measure the association between different genetic variants of our clock genes and several illnesses such as obesity, cardiovascular diseases, diabetes or cancer. In addition to these techniques, self-reported questionnaires based in the morning-evening preferences have been developed as complementary procedures to assess human chronotypes.

Evaluar el estado del sistema circadiano del sujeto puede ser de especial interés en la nutrición. En particular, para los estudios relativos a la evaluación de las enfermedades relacionadas con la malnutrición como es el caso de la mayoría de las enfermedades degenerativas tales como la obesidad, cáncer, o enfermedades cardiovasculares. Para este propósito, uno de los enfoques consiste en medir a) los sincronizadores externos del reloj interno, tales como intensidad de la luz, y los cambios de ayuno/ingesta y de reposo/actividad. De hecho, se ha definido el término de "cronodisruptor" que se refiere a "exposiciones o efectores exógenos y endógenos que son cronobiológicamente activos y que por lo tanto pueden interrumpir el tiempo". Otro enfoque para evaluar la salud del sistema circadiano es medir b) las salidas del reloj interno (ritmos circadianos). Entre ellos las más utilizadas son la medición del ritmo de la temperatura corporal, la actividad motora, la melatonina, el cortisol y la expresión de genes reloj. Desde el punto de vista genético, ahora somos capaces de medir c) las alteraciones del reloj interno, con el fin de evaluar la genética del reloj molecular. De hecho, las nuevas técnicas de nutrigenética nos están dando la oportunidad de medir la asociación entre las diferentes variantes genéticas de nuestros genes reloj y varias enfermedades como la obesidad, las enfermedades cardiovasculares, la diabetes o el cáncer. Además de estas técnicas, se han desarrollado cuestionarios basados en las preferencias de mañana-tarde como procedimientos complementarios para evaluar cronotipos humanos.

Effect of intra-alveolar placement of 0.2% chlorhexidine bioadhesive gel on the incidence of alveolar osteitis following the extraction of mandibular third molars. A double-blind randomized clinical trial.

UNLABELLED: Alveolar osteitis (AO) is a common complication after third molar surgery. One of the most studied agents in its prevention is chlorhexidine (CHX), which has proved to be effective. OBJECTIVES: The aim of this randomized double-blind clinical trial was to evaluate the efficacy of 0.2% bioadhesive chlorhexidine gel placed intra-alveolar in the prevention of AO after the extraction of mandibular third molars and to analyze the impact of risk factors such as smoking and oral contraceptives in the development of AO. STUDY DESIGN: The study was a randomized, double-blind, clinical trial performed in the Ambulatory Surgery Unit of Hospital Vall d'Hebron and was approved by the Ethics Committee. A total of 160 patients randomly received 0.2% bioadhesive gel (80 patients) or bioadhesive placebo (80 patients). RESULTS: 0.2% bioadhesive chlorhexidine gel applied in the alveolus after third molar extraction reduced the incidence of dry socket by 22% compared to placebo with differences that were not statistically significant. Smoking and the use of oral contraceptives were not related to higher incidence of dry socket. Female patients and the difficulty of the surgery were associated with a higher incidence of AO with statistically significant differences. 0.2% bioadhesive chlorhexidine gel did not produce any of the side effects related to chlorhexidine rinses. CONCLUSIONS: A 22% reduction of the incidence of alveolar osteitis with the application of 0.2% bioadhesive chlorhexidine gel compared to placebo with differences that were not statistically significant was found in this clinical trial. The lack of adverse reactions and complications related to chlorhexidine gel supports its clinical use specially in simple extractions and adds some advantages compared to the rinses in terms of duration of the treatment and reduction of staining and taste disturbance.

Protecting the melatonin rhythm through circadian healthy light exposure.

Currently, in developed countries, nights are excessively illuminated (light at night), whereas daytime is mainly spent indoors, and thus people are exposed to much lower light intensities than under natural conditions. In spite of the positive impact of artificial light, we pay a price for the easy access to light during the night: disorganization of our circadian system or chronodisruption (CD), including perturbations in melatonin rhythm. Epidemiological studies show that CD is associated with an increased incidence of diabetes, obesity, heart disease, cognitive and affective impairment, premature aging and some types of cancer. Knowledge of retinal photoreceptors and the discovery of melanopsin in some ganglion cells demonstrate that light intensity, timing and spectrum must be considered to keep the biological clock properly entrained. Importantly, not all wavelengths of light are equally chronodisrupting. Blue light, which is particularly beneficial during the daytime, seems to be more disruptive at night, and induces the strongest melatonin inhibition. Nocturnal blue light exposure is currently increasing, due to the proliferation of energy-efficient lighting (LEDs) and electronic devices. Thus, the development of lighting systems that preserve the melatonin rhythm could reduce the health risks induced by chronodisruption. This review addresses the state of the art regarding the crosstalk between light and the circadian system.

Chronobiology of the neuroimmunoendocrine system and aging.

The health maintenance depends on the preservation of the homeostatic systems, such as nervous, endocrine and immune system, and a proper communication between them. In this regard, the circadian system, which promotes a better physiological system functions and thus well being, could be considered part of that homeostatic complex, since the neuroimmunoendocrine system possesses circadian patterns in most variables, as well as circannual or seasonal variations. With aging, an impairment of the homeostatic systems occurs and an alteration of circadian system regulation has been demonstrated. In the immune system, several function parameters, which are good markers of health and of the rate of aging, change not only with age (immunosenescence) but also throughout the day and year. Indeed, with advancing age there is a modification of immune cell circadian function especially in lymphocytes. Moreover, immune functions at early afternoon correspond to more aged values than at morning, especially in mature subjects (60-79 years of age). In addition, these mature men and women showed a significant impaired immune cell function, which is especially remarkable in the winter. It is noteworthy the role of immunomodulatory hormones, such as melatonin, in the regulation of biological rhythms and their involvement in the aging process. Furthermore, the evidence of a neuroimmune regulation of the circadian system and its disturbance with aging, highlights the importance of proinflammatory cytokines in this complex cross-talk. The biological rhythms disruption with age and some diseases (jet lag, cancer and seasonal affective disorder), could contribute increasing the immune system impairment and consequently the loss of health.

The circadian rest-activity rhythm, a potential safety pharmacology endpoint of cancer chemotherapy.

The robustness of the circadian timing system (CTS) was correlated to quality of life and predicted for improved survival in cancer patients. However, chemotherapy disrupted the CTS according to dose and circadian timing in mice. A continuous and repeated measures longitudinal design was implemented here to characterize CTS dynamics in patients receiving a fixed circadian-based chemotherapy protocol. The rest-activity rhythm of 49 patients with advanced cancer was monitored using a wrist actigraph for 13 days split into four consecutive spans of 3-4 days each, i.e., before, during, right after and late after a fixed chronotherapy course. The relative amount of activity in bed vs. out of bed (I

Day-night contrast as source of health for the human circadian system.

Modern societies are characterized by a 24/7 lifestyle (LS) with no environmental differences between day and night, resulting in weak zeitgebers (weak day light, absence of darkness during night, constant environmental temperature, sedentary LS and frequent snacking), and as a consequence, in an impaired circadian system (CS) through a process known as chronodisruption. Both weak zeitgebers and CS impairment are related to human pathologies (certain cancers, metabolic syndrome and affective and cognitive disorders), but little is known about how to chronoenhance the CS. The aim of this work is to propose practical strategies for chronoenhancement, based on accentuating the day/night contrast. For this, 131 young subjects were recruited, and their wrist temperature (WT), activity, body position, light exposure, environmental temperature and sleep were recorded under free-living conditions for 1 week. Subjects with high contrast (HC) and low contrast (LC) for each variable were selected to analyze the HC effect in activity, body position, environmental temperature, light exposure and sleep would have on WT. We found that HC showed better rhythms than LC for every variable except sleep. Subjects with HC and LC for WT also demonstrated differences in LS, where HC subjects had a slightly advanced night phase onset and a general increase in day/night contrast. In addition, theoretical high day/night contrast calculated using mathematical models suggests an improvement by means of LS contrast. Finally, some individuals classified as belonging to the HC group in terms of WT when they are exposed to the LS characteristic of the LC group, while others exhibit WT arrhythmicity despite their good LS habits, revealing two different WT components: an exogenous component modified by LS and another endogenous component that is refractory to it. Therefore, intensifying day/night contrast in subject's LS has proven to be a feasible measure to chronoenhance the CS.

Ghost cell odontogenic carcinoma: A rare case report and review of literature.

OBJECTIVES: Ghost cell odontogenic carcinoma is a rare condition characterized by ameloblastic-like islands of epithelial cells with aberrant keratinitation in the form of Ghost cell with varying amounts of dysplastic dentina. MATERIAL AND METHODS: We report a case of a 70 year-old woman with a rapid onset of painful swelling right maxillary tumor. Magnetic resonance showed a huge tumor dependent on the right half of the right hard palate with invasion of the pterygoid process and focally to the second branch of the trigeminal. Radiological stage was T4N0. The patient underwent a right subtotal maxillectomy with clear margins. Adjuvant radiotherapy was given. The patient was free of residual or recurrent disease 12 months after surgery. RESULTS: The tumor was 3,9cm in diameter. It was spongy and whitish gray. Microscopically the tumor was arranged in nets and trabeculae, occasionally forming palisade. Tumoral cells had clear cytoplasm with vesicular nuclei. There was atipia and mitosi with vascular and perineural invasion. The excised tumor was diagnosed as a GCOC. CONCLUSIONS: Ghost cell carcinoma is a rare odontogenic carcinoma. Its course is unpredictable, ranging from locally invasive tumors of slow growth to highly aggressive and infiltrative ones. Wide surgical excision with clean margins is the treatment of choice although its combination with postoperative radiation therapy, with or without chemotherapy, remains controversial. Key words:Ameloblastic carcinoma, calcifying odontogenic cyst, Ghost cell carcinoma, keratinizing epithelial odontogenic cyst, maxillary tumor, odontogenic carcinoma.

Long-term social isolation in the adulthood results in CA1 shrinkage and cognitive impairment.

Social isolation in adulthood is a psychosocial stressor that can result in endocrinological and behavioral alterations in different species. In rodents, controversial results have been obtained in fear conditioning after social isolation at adulthood, while neural substrates underlying these differences are largely unknown. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) are prominent modulators of synaptic plasticity underlying memory processes in many tasks, including fear conditioning. In this study, we used adult female Octodon degus to investigate the effects of long-term social isolation on contextual and cued fear conditioning, and the possible modulation of the synaptic levels of NCAM and PSA-NCAM in the hippocampus. After 6½ months of social isolation, adult female degus showed a normal auditory-cued fear memory, but a deficit in contextual fear memory, a hippocampal dependent task. Subsequently, we observed reduced hippocampal synaptic levels of PSA-NCAM in isolated compared to grouped-housed female degus. No significant differences were found between experimental groups in hippocampal levels of the three main isoforms of NCAM (NCAM180, NCAM140 and NCAM120). Interestingly, social isolation reduced the volume of the hippocampal CA1 subfield, without affecting the volume of the CA3 subregion or the total hippocampus. Moreover, attenuated body weight gain and reduced number of granulocytes were detected in isolated animals. Our findings indicate for the first time, that long-term social isolation of adult female animals induces a specific shrinkage of CA1 and a decrease in synaptic levels of PSA-NCAM in the hippocampus. These effects may be related to the deficit in contextual fear memory observed in isolated female degus.

Effects of resveratrol on changes induced by high-fat feeding on clock genes in rats.

In mammals, the main component of the circadian system is the suprachiasmatic nucleus in the hypothalamus. However, circadian clocks are also present in most peripheral tissues, such as adipose tissue. The aim of the present study was to analyse the potential effects of resveratrol on changes induced by high-fat feeding in the expression of clock genes and clock-controlled genes in the white adipose tissue from rats. For this purpose, rats were divided into three groups: a control group, fed a standard diet, and two other groups, either fed a high-fat diet supplemented with resveratrol (RSV) or no resveratrol (HF). The expression of clock genes and clock-controlled genes was analysed by RT-PCR. Protein expression and fatty acid synthase (FAS) activity were also analysed. When comparing the controls, the RSV group showed similar patterns of response to the HF group, except for reverse erythroblastosis virus α (Rev-Erbα), which was down-regulated. The expression of this gene reached the same levels as in control rats. The response pattern of protein expression for Rev-Erbα was similar to that found for gene expression. High-fat feeding up-regulated all adipogenic genes and resveratrol did not modify them. In the HF group, the activity of FAS tended to increase, while resveratrol decreased. In conclusion, resveratrol reverses the change induced by high-fat feeding in the expression of Rev-Erbα in adipose tissue, which means that clock machinery is a target for this polyphenol. This change seems to be related to reduced lipogenesis, which might be involved in the body fat-lowering effect of this molecule.

A Comparison of B16 Melanoma Cells and 3T3 Fibroblasts Concerning Cell Viability and ROS Production in the Presence of Melatonin, Tested Over a Wide Range of Concentrations.

Melatonin is a pleiotropic molecule with many cellular and systemic actions, including chronobiotic effects. Beneficial effects are widely documented concerning the treatment of neoplastic diseases in vivo as well as reductions in viability of cultured cells from melanoma, one of the most aggressive cancers in humans. However, studies of its effects on non-tumor cells in vitro have not focused on viability, except for experiments aiming to protect against oxidotoxicity or other toxicological insults. Furthermore, there is no agreement on the range of effective melatonin concentrations in vitro, and the mechanisms that reduce cell viability have remained unclear. Tumor cell-specific increases in the production of reactive oxygen and nitrogen species (ROS/RNS) may provide a possible explanation. Our aim was to analyze the potential inhibition of tumor (B16 melanoma 4A5) and non-tumor cell (3T3 Swiss albino) viability using a wide range of melatonin concentrations (10-11-10-2 M), and to determine whether intracellular ROS enhancement was involved in this process. In the absence of fetal bovine serum (FBS), low melatonin concentrations (10-9-10-5 M) reduced the proliferation of melanoma cells with no effect in fibroblasts, whereas, in the presence of FBS, they had no effect or even increased the proliferation of both fibroblast and melanoma cells. Melatonin concentrations in the upper millimolar range increased ROS levels and reduced the viability of both cell types, but more markedly so in non-tumor cells. Thus, low melatonin concentrations reduce proliferation in this specific melanoma cell line, whereas high concentrations affect the viability of both tumor (B16 4A5 melanoma) and non-tumor (3T3 fibroblasts) cells. Increased ROS levels in both lines indicate a role for ROS production in the reduction of cell viability at high-but not low-melatonin concentrations, although the mechanism of action still remains to be elucidated.

Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women.

Menopausal women exhibit a loss of circadian coordination, a process that runs parallel with a redistribution of adipose tissue. However, the specific genetic mechanisms underlying these alterations have not been studied. Thus, the aim of the present study was to determine whether the development of menopause induces an alteration of the genes that control biological rhythms in human subcutaneous (SAT) and visceral (VAT) adipose tissue, and whether changes in clock gene expression are involved in the increased risk of developing metabolic syndrome (MetS), which is frequently associated with menopause. To this end, VAT and SAT biopsies were taken in pre- (n = 7) and postmenopausal (n = 7) women at similar hours in the morning. RNA was extracted, and a microarray analysis was made. Data were confirmed by quantitative real-time polymerase chain reaction. Western blot and immunohistochemical analysis were also performed. When clock gene expression was compared between both groups of women, data in SAT showed that expression of the core clock gene period3 was significantly higher in postmenopausal women, while casein kinase-1δ, E1A-binding protein and cAMP-responsive element were preferentially expressed in the premenopausal group. In VAT, period2 (PER2) and v-myc myelocytomatosis viral oncogene expressions were significantly higher in the postmenopausal group. Western blot analysis indicated that PER2 and PER3 protein expression was also increased in postmenopausal women. In addition, several genes, including PER2, were differentially expressed depending on whether or not the patient met the MetS criteria. We conclude that menopause transition induces several changes in the genotype of the adipose tissue chronobiological machinery related to an increased risk of developing MetS.

[Chronobiological aspects of obesity and metabolic syndrome]. / Aspectos cronobiológicos de la obesidad y el síndrome metabólico.

Circadian rhythms (approximately 24h) are widely characterized at molecular level and their generation is acknowledged to originate from oscillations in expression of several clock genes and from regulation of their protein products. While general entrainment of organisms to environmental light-dark cycles is mainly achieved through the master clock of the suprachiasmatic nucleus in mammals, this molecular clockwork is functional in several organs and tissues. Some studies have suggested that disruption of the circadian system (chronodisruption (CD)) may be causal for manifestations of the metabolic syndrome. This review summarizes (1) how molecular clocks coordinate metabolism and their specific role in the adipocyte; (2) the genetic aspects of and scientific evidence for obesity as a chronobiological illness; and (3) CD and its causes and pathological consequences. Finally, ideas about use of chronobiology for the treatment of obesity are discussed.

Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling.

Evidence is accumulating regarding the importance of circadian core oscillators, several associated factors, and melatonin signaling in the maintenance of health. Dysfunction of endogenous clocks, melatonin receptor polymorphisms, age- and disease-associated declines of melatonin likely contribute to numerous diseases including cancer, metabolic syndrome, diabetes type 2, hypertension, and several mood and cognitive disorders. Consequences of gene silencing, overexpression, gene polymorphisms, and deviant expression levels in diseases are summarized. The circadian system is a complex network of central and peripheral oscillators, some of them being relatively independent of the pacemaker, the suprachiasmatic nucleus. Actions of melatonin on peripheral oscillators are poorly understood. Various lines of evidence indicate that these clocks are also influenced or phase-reset by melatonin. This includes phase differences of core oscillator gene expression under impaired melatonin signaling, effects of melatonin and melatonin receptor knockouts on oscillator mRNAs or proteins. Cross-connections between melatonin signaling pathways and oscillator proteins, including associated factors, are discussed in this review. The high complexity of the multioscillator system comprises alternate or parallel oscillators based on orthologs and paralogs of the core components and a high number of associated factors with varying tissue-specific importance, which offers numerous possibilities for interactions with melatonin. It is an aim of this review to stimulate research on melatonin signaling in peripheral tissues. This should not be restricted to primary signal molecules but rather include various secondarily connected pathways and discriminate between direct effects of the pineal indoleamine at the target organ and others mediated by modulation of oscillators.

Nocturnalism induced by scheduled feeding in diurnal Octodon degus.

Octodon degus, a mainly diurnal rodent, characterized by its ability to shift to a nocturnal locomotor pattern under laboratory conditions, was studied to determine whether restricted food access during the scotophase could induce nocturnalism. To address this question, wheel running activity, feeding, and body temperature rhythms were analyzed for diurnal degus housed with a wheel and subjected to either long (12 h) or short (2 h) food availability periods, in the latter case with random or scheduled food access times. The results show that allowing nocturnal feeding for 2 h, but not 12 h, can shift a previous diurnal phase preference for wheel running activity and body temperature to the scotophase, with random feeding being more effective than scheduled food availability. However, this behavioral inversion proved to be unstable, as the degus returned to the diurnal phase within only a few days after the restricted feeding was discontinued. In addition, the negative masking effect induced by light, which is characteristic of the degus' nocturnal chronotype, was not observed when the animals were forced to feed at night. Thus, neither long, short, random, nor scheduled food-availability during the scotophase was able to induce all the characteristics of the nocturnal chronotype in Octodon degus.