Photolytic splitting of homodimeric quinone-derived oxetanes studied by ultrafast transient absorption spectroscopy and quantum chemistry.

The photoinduced cycloreversion of oxetane derivatives is of considerable biological interest since these compounds are involved in the photochemical formation and repair of the highly mutagenic pyrimidine (6-4) pyrimidone DNA photoproducts ((6-4)PPs). Previous reports have dealt with the photoreactivity of heterodimeric oxetanes composed mainly of benzophenone (BP) and thymine (Thy) or uracil (Ura) derivatives. However, these models are far from the non-isolable Thy〈ºã€‰Thy dimers, which are the real precursors of (6-4)PPs. Thus, we have synthesized two chemically stable homodimeric oxetanes through the Paternò-Büchi reaction between two identical enone units, i.e. 1,4-benzoquinone (BQ) and 1,4-naphthoquinone (NQ), that led to formation of BQ-Ox and NQ-Ox, respectively. Their photoreactivity has been studied by means of steady-state photolysis and transient absorption spectroscopy from the femtosecond to the microsecond time scale. Thus, photolysis of BQ-Ox and NQ-Ox led to formation of the monomeric BQ or NQ, respectively, through ring opening in a "non-adiabatic" process. Accordingly, the transient absorption spectra of the triplet excited quinones (3BQ* and 3NQ*) were not observed as a result of direct photolysis of the quinone-derived oxetanes. In the case of NQ-Ox, a minor signal corresponding to 3NQ* was detected; its formation was ascribed to minor photodegradation of the oxetane during acquisitions of the spectra during the laser experiments. These results are supported by computational analyses based on density functional theory and multiconfigurational quantum chemistry (CASSCF/CASPT2); here, an accessible conical intersection between the ground and excited singlet states has been characterized as the main structure leading to deactivation of excited BQ-Ox or NQ-Ox. This behavior contrasts with those previously observed for heterodimeric thymine-derived oxetanes, where a certain degree of ring opening into the excited triplet state is observed.

Quantum-Chemistry Study of the Photophysical Properties of 4-Thiouracil and Comparisons with 2-Thiouracil.

DNA in living beings is constantly damaged by exogenous and endogenous agents. However, in some cases, DNA photodamage can have interesting applications, as it happens in photodynamic therapy. In this work, the current knowledge on the photophysics of 4-thiouracil has been extended by further quantum-chemistry studies to improve the agreement between theory and experiments, to better understand the differences with 2-thiouracil, and, last but not least, to verify its usefulness as a photosensitizer for photodynamic therapy. This study has been carried out by determining the most favorable deactivation paths of UV-vis photoexcited 4-thiouracil by means of the photochemical reaction path approach and an efficient combination of the complete-active-space second-order perturbation theory//complete-active-space self-consistent field (CASPT2//CASSCF), (CASPT2//CASPT2), time-dependent density functional theory (TDDFT), and spin-flip TDDFT (SF-TDDFT) methodologies. By comparing the data computed herein for both 4-thiouracil and 2-thiouracil, a rationale is provided on the relatively higher yields of intersystem crossing, triplet lifetime and singlet oxygen production of 4-thiouracil, and the relatively higher yield of phosphorescence of 2-thiouracil.

Situational and Victim Correlates of Increased Case Fatality Rates in Los Angeles Shootings, 2005-2021.

The gun assault case fatality rate measures the fraction of shooting victims who die from their wounds. Considerable debate has surrounded whether gun assault case fatality rates have changed over time and what factors may be involved. We use crime event data from Los Angeles to examine the victim and situational correlates of gun assault case fatality rates over time. We estimated log binomial regression models for the probability of death in each year from 2005 to 2021, conditioned on situational and victim characteristics of the crime. Case fatality rates increased by around 1.3% per year between 2005 and 2021 from around 15.9 to 19.7%. Baseline case fatality rates differed systematically by most situational and victim but followed similar temporal trends. Only victim age significantly covaried with the temporal trend in case fatality rates. An individual shot in Los Angeles in 2021 was 23.7% more likely to die than the equivalent victim in 2005. The steady increase in case fatality rates suggests that there were around 394 excess fatalities over what would have occurred if case fatality rates remained at the 2005 level. Increases in the average age of victims over time may contribute to the general temporal trend. We hypothesize that older victims are more likely to be shot indoors where lethal close-range wounds are more likely.

Auditory stimulation during REM sleep modulates REM electrophysiology and cognitive performance.

REM sleep is critical for memory, emotion, and cognition. Manipulating brain activity during REM could improve our understanding of its function and benefits. Earlier studies have suggested that auditory stimulation in REM might modulate REM time and reduce rapid eye movement density. Building on this, we studied the cognitive effects and electroencephalographic responses related to such stimulation. We used acoustic stimulation locked to eye movements during REM and compared two overnight conditions (stimulation and no-stimulation). We evaluated the impact of this stimulation on REM sleep duration and electrophysiology, as well as two REM-sensitive memory tasks: visual discrimination and mirror tracing. Our results show that this auditory stimulation in REM decreases the rapid eye movements that characterize REM sleep and improves performance on the visual task but is detrimental to the mirror tracing task. We also observed increased beta-band activity and decreased theta-band activity following stimulation. Interestingly, these spectral changes were associated with changes in behavioural performance. These results show that acoustic stimulation can modulate REM sleep and suggest that different memory processes underpin its divergent impacts on cognitive performance.

Reductive Photocycloreversion of Cyclobutane Dimers Triggered by Guanines.

The quest for simple systems achieving the photoreductive splitting of four-membered ring compounds is a matter of interest not only in organic chemistry but also in biochemistry to mimic the activity of DNA photorepair enzymes. In this context, 8-oxoguanine, the main oxidatively generated lesion of guanine, has been shown to act as an intrinsic photoreductant by transferring an electron to bipyrimidine lesions and provoking their cycloreversion. But, in spite of appropriate photoredox properties, the capacity of guanine to repair cyclobutane pyrimidine dimer is not clearly established. Here, dyads containing the cyclobutane thymine dimer and guanine or 8-oxoguanine are synthesized, and their photoreactivities are compared. In both cases, the splitting of the ring takes place, leading to the formation of thymine, with a quantum yield 3.5 times lower than that for the guanine derivative. This result is in agreement with the more favored thermodynamics determined for the oxidized lesion. In addition, quantum chemistry calculations and molecular dynamics simulations are carried out to rationalize the crucial aspects of the overall cyclobutane thymine dimer photoreductive repair triggered by the nucleobase and its main lesion.

Extreme Violence and Weight-Related Outcomes in Mexican Adults.

Sociological research suggests that violent environments contribute to excess weight, a pressing health issue worldwide. However, this research has neglected extreme forms of violence, such as armed conflicts, a theoretically significant omission because armed conflict could reasonably lead to weight loss, not weight gain. I examine the weight-related, short-term consequences of the Mexican "War on Organized Crime." I combine body mass index (N = 3,341) and waist circumference (N = 3,509) measures from the Mexico Family Life Survey with a novel data set on aggressions, confrontations, and executions between 2009 and 2011 (CIDE-PPD database) and exploit variation in the timing of the outcome relative to violent events taking place in the same residential environment. I find a robust and large positive association between armed conflict events and weight gain in adults and suggestive evidence of the behavioral, emotional, and physiological/biochemical pathways connecting those variables.

Response of sleep slow oscillations to acoustic stimulation is evidenced by distinctive synchronization processes.

Closed-loop acoustic stimulation (CLAS) during sleep has shown to boost slow wave (SW) amplitude and spindle power. Moreover, sleep SW have been classified based on different processes of neuronal synchronization. Thus, different types of SW events may have distinct functional roles and be differentially affected by external stimuli. However, the SW synchronization processes affected by CLAS are not well understood. Here, we studied the effect of CLAS on the dissociation of SW events based on two features of neuronal synchronization in the electroencephalogram (topological spread and wave slope). We evaluated and classified individual SW events of 14 healthy subjects during a CLAS stimulated (STM) and a control night (CNT). Three main categories of SW events were found denoting (C1) steep slope SW with global spread, (C2) flat-slope waves with localized spread and homeostatic decline, and (C3) multipeaked flat-slope events with global spread. Comparing between conditions, we found a consistent increase of event proportion and trough amplitudes for C1 events during the time of stimulation. Furthermore, we found similar increases in post-stimulus spectral power in θ, ß, and σ frequencies for CNT vs STIM condition independently of sleep stage or SW categories. However, topological analysis showed differentiated spatial dynamics in N2 and N3 for SW categories and the co-occurrence with spindle events. Our findings support the existence of multiple types of SW with differential response to external stimuli and possible distinct neuronal mechanisms.

Effects of Anti-Seizure Medication on Sleep Spindles and Slow Waves in Drug-Resistant Epilepsy.

There is a close bidirectional relationship between sleep and epilepsy. Anti-seizure medications (ASM) act to reduce seizure frequency but can also impact sleep; this remains a relatively unexplored field given the importance of sleep on seizure occurrence, memory consolidation, and quality of life. We compared the effect of poly-ASM treatment on a night of sleep compared to an unmedicated night in patients with drug-resistant epilepsy, where ASMs were withdrawn and later restored as part of their pre-surgical evaluation. Within-subject analysis between medicated and unmedicated nights showed ASMs increased spindle (11-16 Hz) power and decreased slow wave (0.1-2 Hz) amplitude. Spindles became less strongly coupled to slow waves in the ASM night compared to no-ASM night, with effects to both the phase and strength of coupling and correlated with slow wave reduction. These effects were not seen in age-matched controls from the same unit where ASMs were not changed between two nights. Overall, we found that ASM polytherapy not only changed specific sleep waveforms, but also the fine interplay of spindle/slow wave coupling. Since these sleep oscillations impact both seizure occurrence and memory consolidation, our findings provide evidence towards a decoupling impact of ASMs on sleep that should be considered in future studies of sleep and memory disruption in people with epilepsy.

Weight changes after first-line antiretroviral initiation in a cohort of HIV-positive patients in Southern Spain (CAPOTA study).

BACKGROUND: Obesity among persons living with HIV (PLWH) has increased and weight gain after antiretroviral therapy (ART) can lead to metabolic disorders and impact survival. Our objective was to analyze weight and metabolic changes in HIV näive patients after 48 weeks of ART. METHODS: Observational, retrospective, multicentered cohort study comprising naïve-patients who started tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) or abacavir/lamivudine/dolutegravir (ABC/3TC/DTG), with no change in treatment for 48 weeks. Clinical and metabolic parameters were collected at baseline and week-48. Statistical program used was SPSS 21.0.0. RESULTS: The study included 329 participants from 6 hospitals. Participants were 89% male and 10% had AIDS diagnosis. Median age was 35 (IQR 27-43) years. Median baseline CD4 count was 417 (IQR 250-569) cell/mm3 and HIV viral load 4.65 (IQR 4.21-5.18) log10 copies/ml. Baseline median weight was 70 (IQR 62-79) kg, body mass index 23.4 (IQR 21.2-26.0) kg/m2; 22.7% overweight and 6.4% obese. ART regimens: ABC/3TC/DTG (196), TAF/FTC/EVG/c (133). Baseline characteristics were similar in both ART groups. Average weight gain at week-48 was 2.9 (SD 5.5) kg (p < 0.0001) with no differences between both groups. There was an increase in obesity (6.4%-8%; p < 0.003) and overweight (22.7%-28.9%; p < 0.0001). Weight increase was associated with AIDS: OR 3.05 (95%; CI 1.009-9.22), p = 0.048; and lower baseline weight: OR 1.032 (95% CI 1.009-1.05), p = 0.006. CONCLUSIONS: After ART initiation patients gain weight regardless of the regimen they take. Weight gain is associated with AIDS and the use of TAF/FTC/EVG/c.

Optimising sounds for the driving of sleep oscillations by closed-loop auditory stimulation.

Recent studies have shown that slow oscillations (SOs) can be driven by rhythmic auditory stimulation, which deepens slow-wave sleep (SWS) and improves memory and the immune-supportive hormonal milieu related to this sleep stage. While different attempts have been made to optimise the driving of the SOs by changing the number of click stimulations, no study has yet investigated the impact of applying more than five clicks in a row. Likewise, the importance of the type of sounds in eliciting brain responses is presently unclear. In a study of 12 healthy young participants (10 females; aged 18-26 years), we applied an established closed-loop stimulation method, which delivered sequences of 10 pink noises, 10 pure sounds (B note of 247 Hz), 10 pronounced "a" vowels, 10 sham, 10 variable sounds, and 10 "oddball" sounds on the up phase of the endogenous SOs. By analysing area under the curve, amplitude, and event related potentials, we explored whether the nature of the sound had a differential effect on driving SOs. We showed that every stimulus in a 10-click sequence, induces a SO response. Interestingly, all three types of sounds that we tested triggered SOs. However, pink noise elicited a more pronounced response compared to the other sounds, which was explained by a broader topographical recruitment of brain areas. Our data further suggest that varying the sounds may partially counteract habituation.

Ongoing neural oscillations predict the post-stimulus outcome of closed loop auditory stimulation during slow-wave sleep.

Large slow oscillations (SO, 0.5-2 Hz) characterise slow-wave sleep and are crucial to memory consolidation and other physiological functions. Manipulating slow oscillations may enhance sleep and memory, as well as benefitting the immune system. Closed-loop auditory stimulation (CLAS) has been demonstrated to increase the SO amplitude and to boost fast sleep spindle activity (11-16 Hz). Nevertheless, not all such stimuli are effective in evoking SOs, even when they are precisely phase locked. Here, we studied what factors of the ongoing activity patterns may help to determine what oscillations to stimulate to effectively enhance SOs or SO-locked spindle activity. Hence, we trained classifiers using the morphological characteristics of the ongoing SO, as measured by electroencephalography (EEG), to predict whether stimulation would lead to a benefit in terms of the resulting SO and spindle amplitude. Separate classifiers were trained using trials from spontaneous control and stimulated datasets, and we evaluated their performance by applying them to held-out data both within and across conditions. We were able to predict both when large SOs occurred spontaneously, and whether a phase-locked auditory click effectively enlarged them with good accuracy for predicting the SO trough (∼70%) and SO peak values (∼80%). Also, we were able to predict when stimulation would elicit spindle activity with an accuracy of ∼60%. Finally, we evaluate the importance of the various SO features used to make these predictions. Our results offer new insight into SO and spindle dynamics and may suggest techniques for developing future methods for online optimization of stimulation.

Auditory closed-loop stimulation on sleep slow oscillations using in-ear EEG sensors.

Acoustic stimulation synchronized to slow oscillations in scalp electroencephalograms has been shown to enhance sleep features, which makes it promising in boosting cognitive functions as well as in the treatment of some sleep disturbances. Nevertheless, scalp electrode sensors are resource intensive and poorly tolerated by sleeping patients. The aim of this study was to investigate the potential usability of in-the-ear electroencephalography to implement auditory closed-loop stimulation during sleep. For this, we evaluated the agreement between slow oscillation recordings obtained through the in-ear sensor and those obtained simultaneously from standard scalp electrodes during naps of 13 healthy subjects. We found that in-ear activity provided enough information to automatically detect sleep slow oscillations in real-time. Based on this, we successfully enhanced scalp slow oscillations using auditory single-cycle closed-loop brain-state-dependent stimulation based on in-ear signals acquired in 11 further subjects. We conclude that in-ear sensors provide a feasible technology for the enhancement of sleep patterns, and could pave the way for new clinical applications in the near future.

Long term effects of cueing procedural memory reactivation during NREM sleep.

Targeted memory reactivation (TMR) has recently emerged as a promising tool to manipulate and study the sleeping brain. Although the technique is developing rapidly, only a few studies have examined how the effects of TMR develop over time. Here, we use a bimanual serial reaction time task (SRTT) to investigate whether the difference between the cued and un-cued sequence of button presses persists long-term. We further explore the relationship between the TMR benefit and sleep spindles, as well as their coupling with slow oscillations. Our behavioural analysis shows better performance for the dominant hand. Importantly, there was a strong effect of TMR, with improved performance on the cued sequence after sleep. Closer examination revealed a significant benefit of TMR at 10 days post-encoding, but not 24 h or 6 weeks post-encoding. Time spent in stage 2, but not stage 3, of NREM sleep predicted cueing benefit. We also found a significant increase in spindle density and SO-spindle coupling during the cue period, when compared to the no-cue period. Together, our results demonstrate that TMR effects evolve over several weeks post-cueing, as well as emphasising the importance of stage 2, spindles and the SO-spindle coupling in procedural memory consolidation.

Theoretical Study on the Photo-Oxidation and Photoreduction of an Azetidine Derivative as a Model of DNA Repair.

Photocycloreversion plays a central role in the study of the repair of DNA lesions, reverting them into the original pyrimidine nucleobases. Particularly, among the proposed mechanisms for the repair of DNA (6-4) photoproducts by photolyases, it has been suggested that it takes place through an intermediate characterized by a four-membered heterocyclic oxetane or azetidine ring, whose opening requires the reduction of the fused nucleobases. The specific role of this electron transfer step and its impact on the ring opening energetics remain to be understood. These processes are studied herein by means of quantum-chemical calculations on the two azetidine stereoisomers obtained from photocycloaddition between 6-azauracil and cyclohexene. First, we analyze the efficiency of the electron-transfer processes by computing the redox properties of the azetidine isomers as well as those of a series of aromatic photosensitizers acting as photoreductants and photo-oxidants. We find certain stereodifferentiation favoring oxidation of the cis-isomer, in agreement with previous experimental data. Second, we determine the reaction profiles of the ring-opening mechanism of the cationic, neutral, and anionic systems and assess their feasibility based on their energy barrier heights and the stability of the reactants and products. Results show that oxidation largely decreases the ring-opening energy barrier for both stereoisomers, even though the process is forecast as too slow to be competitive. Conversely, one-electron reduction dramatically facilitates the ring opening of the azetidine heterocycle. Considering the overall quantum-chemistry findings, N,N-dimethylaniline is proposed as an efficient photosensitizer to trigger the photoinduced cycloreversion of the DNA lesion model.

On Lethal Interactions: Differences Between Expressive and Instrumental Homicides in Mexico City.

Research on violence in Mexico and Latin America suggests that, in part, due to state attempts to fight organized crime and the widespread availability of firearms, violence and homicides in general have experienced a recent shift from expressive to instrumental. Despite this transformation, however, socioeconomically disadvantaged young males continue to be overwhelmingly present in homicide events. We argue that both the use of a firearm and demographic and traditional socioeconomic factors should independently predict instrumental homicide; however, the association between the use of a firearm and instrumentality should be moderated by the level or category of these traditional characteristics (i.e., socioeconomic status, age, and gender). Our findings are broadly consistent with these claims. We show that the relationship between the use of a firearm and instrumental homicides is larger for homicides involving disadvantaged males as victims because this group is more at risk of suffering homicidal violence to begin with, despite the fact that independently (i.e., with no interactions), higher socioeconomic status, age, and female victimhood are positively associated with instrumentality. We discuss the implications of these findings for research on Latin American violence and the expressive/instrumental distinction.

Identification of parasitic arthropods collected from domestic and wild animals in Yucatan, Mexico.

The morphological characterization of ectoparasites from domestic and wild animals is crucial to distinguish those that may be involved in the transmission of zoonotic pathogens. The objectives of this work were to identify parasitic arthropods collected from several hosts in Yucatan State, Mexico and to determine the prevalence of the parasite Trypanosoma cruzi in sylvatic specimens of Triatoma dimidiata. Morphological traits and scanning electron microscopy were used to confirm some parasitic identities. In total, 834 parasitic arthropods of various taxa were identified. Amblyomma americanum, Amblyomma maculatum, Amblyomma parvum, Dermacentor variabilis, and Rhipicephalus sanguineus were identified from dogs, horses, sheep, and deer. The flea Ctenocephalides felis was identified from dogs and the human flea, Pulex irritans was found on horses and sheep. The Neotropical deer ked Lipoptena mazamae was identified from brown brocket deer Mazama pandora. The chewing lice Chelopistes meleagridis, Menacanthus stramineus, Menopon gallinae, Myrsidea sp. and Lipeurus caponis were identified from poultry (Meleagris gallopavo and Gallus gallus). Other chewing lice, Tyranniphilopterus sp., Columbicola columbae, and Physconelloides eurysema were identified from wild birds Pachyramphus aglaiae, Patagioenas flavirostris and Zenaida asiatica, respectively. Trypanosoma cruzi was present in 52.5% of sylvatic adult T. dimidiata. Several of these findings represent new records of ectoparasites for Yucatan and new distribution areas in Mexico. The implications for human and animal health are discussed.

Automatic seizure detection based on imaged-EEG signals through fully convolutional networks.

Seizure detection is a routine process in epilepsy units requiring manual intervention of well-trained specialists. This process could be extensive, inefficient and time-consuming, especially for long term recordings. We proposed an automatic method to detect epileptic seizures using an imaged-EEG representation of brain signals. To accomplish this, we analyzed EEG signals from two different datasets: the CHB-MIT Scalp EEG database and the EPILEPSIAE project that includes scalp and intracranial recordings. We used fully convolutional neural networks to automatically detect seizures. For our best model, we reached average accuracy and specificity values of 99.3% and 99.6%, respectively, for the CHB-MIT dataset, and corresponding values of 98.0% and 98.3% for the EPILEPSIAE patients. For these patients, the inclusion of intracranial electrodes together with scalp ones increased the average accuracy and specificity values to 99.6% and 58.3%, respectively. Regarding the other metrics, our best model reached average precision of 62.7%, recall of 58.3%, F-measure of 59.0% and AP of 54.5% on the CHB-MIT recordings, and comparatively lowers performances for the EPILEPSIAE dataset. For both databases, the number of false alarms per hour reached values less than 0.5/h for 92% of the CHB-MIT patients and less than 1.0/h for 80% of the EPILEPSIAE patients. Compared to recent studies, our lightweight approach does not need any estimation of pre-selected features and demonstrates high performances with promising possibilities for the introduction of such automatic methods in the clinical practice.

Regiochemical memory in the adiabatic photolysis of thymine-derived oxetanes. A combined ultrafast spectroscopic and CASSCF/CASPT2 computational study.

The photoinduced cycloreversion of oxetanes has been thoroughly investigated in connection with the photorepair of the well-known DNA (6-4) photoproducts. In the present work, the direct photolysis of the two regioisomers arising from the irradiation of benzophenone (BP) and 1,3-dimethylthymine (DMT), namely the head-to-head (HH-1) and head-to-tail (HT-1) oxetane adducts, has been investigated by combining ultrafast spectroscopy and theoretical multiconfigurational quantum chemistry analysis. Both the experimental and computational results agree with the involvement of an excited triplet exciplex 3[BPDMT]* for the photoinduced oxetane cleavage to generate 3BP* and DMT through an adiabatic photochemical reaction. The experimental signature of 3[BPDMT]* is the appearance of an absorption band at ca. 400 nm, detected by femtosecond transient absorption spectroscopy. Its formation is markedly regioselective, as it is more efficient and proceeds faster for HH-1 (∼2.8 ps) than for HT-1 (∼6.3 ps). This is in line with the theoretical analysis, which predicts an energy barrier to reach the triplet exciplex for HT-1, in contrast with a less hindered profile for HH-1. Finally, the more favorable adiabatic cycloreversion of HH-1 compared to that of HT-1 is explained by its lower probability to reach the intersystem crossing with the ground state, which would induce a radiationless deactivation process leading either to a starting adduct or to a dissociated BP and DMT.

Characterization of Locally Excited and Charge-Transfer States of the Anticancer Drug Lapatinib by Ultrafast Spectroscopy and Computational Studies.

Lapatinib (LAP) is an anticancer drug, which is metabolized to the N- and O-dealkylated products (N-LAP and O-LAP, respectively). In view of the photosensitizing potential of related drugs, a complete experimental and theoretical study has been performed on LAP, N-LAP and O-LAP, both in solution and upon complexation with human serum albumin (HSA). In organic solvents, coplanar locally excited (LE) emissive states are generated; they rapidly evolve towards twisted intramolecular charge-transfer (ICT) states. By contrast, within HSA only LE states are detected. Accordingly, femtosecond transient absorption reveals a very fast switching (ca. 2 ps) from LE (λmax =550 nm) to ICT states (λmax =480 nm) in solution, whereas within HSA the LE species become stabilized and live much longer (up to the ns scale). Interestingly, molecular dynamics simulation studies confirm that the coplanar orientation is preferred for LAP (or to a lesser extent N-LAP) within HSA, explaining the experimental results.

Chocolate for breakfast prevents circadian desynchrony in experimental models of jet-lag and shift-work.

Night-workers, transcontinental travelers and individuals that regularly shift their sleep timing, suffer from circadian desynchrony and are at risk to develop metabolic disease, cancer, and mood disorders, among others. Experimental and clinical studies provide evidence that food intake restricted to the normal activity phase is a potent synchronizer for the circadian system and can prevent the detrimental metabolic effects associated with circadian disruption. As an alternative, we hypothesized that a timed piece of chocolate scheduled to the onset of the activity phase may be sufficient stimulus to synchronize circadian rhythms under conditions of shift-work or jet-lag. In Wistar rats, a daily piece of chocolate coupled to the onset of the active phase (breakfast) accelerated re-entrainment in a jet-lag model by setting the activity of the suprachiasmatic nucleus (SCN) to the new cycle. Furthermore, in a rat model of shift-work, a piece of chocolate for breakfast prevented circadian desynchrony, by increasing the amplitude of the day-night c-Fos activation in the SCN. Contrasting, chocolate for dinner prevented re-entrainment in the jet-lag condition and favored circadian desynchrony in the shift-work models. Moreover, chocolate for breakfast resulted in low body weight gain while chocolate for dinner boosted up body weight. Present data evidence the relevance of the timing of a highly caloric and palatable meal for circadian synchrony and metabolic function.