Micromotors of MnO2 for the Recovery of Microplastics.

Plastics, primarily microplastics, are among the greatest pollutants in aquatic environments. Their removal and/or degradation in these environments are crucial to ensure an optimal future of these ecosystems. In this work, MnO2 particles were synthesized and characterized for the removal of polystyrene microplastics as a model. MnO2 catalyzes the peroxide reaction, resulting in the formation of oxygen bubbles that propel the pollutants to the surface, achieving removal efficiencies of up to 80%. To achieve this, hydrothermal synthesis was employed using various methods. Parameters such as MnO2, pH, microplastics, and H2O2 concentrations were varied to determine the optimal conditions for microplastics recovering. The ideal conditions for a low microplastic concentrations (10 mg L-1) are 0.2 g L-1 MnO2, 1.6% of H2O2 and 0.01 triton as a surfactant. In these conditions, the micromotors can recover approximately 80% of 300 nm sized polystyrene microplastic within 40 min.

Uncovering Novel Biomarkers of Inflammation as Potential Screening Targets of Disease Risk in Healthcare Shift Workers: A Pilot Study.

Shift work, experienced by nearly 30% of the U.S. workforce, is hazardous to health and has become a pervasive labor practice in the healthcare sector worldwide. It increases the risk of stroke, diabetes, cancer, and cardiovascular disease. Nonetheless, specific screening targets for shift workers still need to be defined. In this study, we have begun uncovering these targets as specific low-grade systemic inflammation markers and functional endotoxin-elicited responses that may foreshadow disease risk in shift workers. One hundred four participants (normothermic and normotensive) were healthy, non-smoking, and drug- and medication-free volunteers recruited from Atlanta area hospitals and medical schools. We assessed the concentration of three proteins in plasma samples from day workers and shift workers (lipopolysaccharide-binding protein, IL-10, and TNF-α), and the relationship between these baseline biomarkers and their response to an ex-vivo endotoxin challenge. We show that shift work increases low-grade systemic inflammation and disrupts discrete endotoxin responses. As shift work exposure increases, the correlation between low-grade systemic inflammation markers and their endotoxin responses was disrupted; this effect was more robust for TNF-α than for IL-10. With increased shift work exposure, these events, alone or combined, represent potential systemic and functional signals that may be harnessed to develop screening tools to identify at-risk individuals.

A Novel Approach to Obtain Vaccine Effectiveness Continuous Profiles. Example Case: COVID-19 in Elderly Mexicans.

Population-wide vaccination is the most promising long-term COVID-19 disease management strategy. However, the protection offered by the currently available COVID-19 vaccines wanes over time, requiring boosters to be periodically given, which represents an unattainable challenge, especially if it is necessary to apply several doses per year. Therefore, it is essential to design strategies that contribute to maximizing the control of the pandemic with the available vaccines. Achieving this objective requires knowing, as precisely and accurately as possible, the changes in vaccine effectiveness over time in each population group, considering the eventual dependence on age, sex, etc. Thus, the present work proposes a novel approach to calculating realistic effectiveness profiles against symptomatic disease. In addition, this strategy can be adapted to estimate realistic effectiveness profiles against hospitalizations or deaths. All such time-dependent profiles allow the design of improved vaccination schedules, where each dose can be administrated to the population groups so that the fulfillment of the containment objectives is maximized. As a practical example for this analysis, vaccination against COVID-19 in Mexico was considered. However, this methodology can be applied to other countries' data or to characterize future vaccines with time-dependent effectiveness values. Since this strategy uses aggregated observational data collected from massive databases, assumptions about the data validity and the course of the studied epidemic could eventually be necessary.

A Ferrofluid with Surface Modified Nanoparticles for Magnetic Hyperthermia and High ROS Production.

A ferrofluid with 1,2-Benzenediol-coated iron oxide nanoparticles was synthesized and physicochemically analyzed. This colloidal system was prepared following the typical co-precipitation method, and superparamagnetic nanoparticles of 13.5 nm average diameter, 34 emu/g of magnetic saturation, and 285 K of blocking temperature were obtained. Additionally, the zeta potential showed a suitable colloidal stability for cancer therapy assays and the magneto-calorimetric trails determined a high power absorption density. In addition, the oxidative capability of the ferrofluid was corroborated by performing the Fenton reaction with methylene blue (MB) dissolved in water, where the ferrofluid was suitable for producing reactive oxygen species (ROS), and surprisingly a strong degradation of MB was also observed when it was combined with H2O2. The intracellular ROS production was qualitatively corroborated using the HT-29 human cell line, by detecting the fluorescent rise induced in 2,7-dichlorofluorescein diacetate. In other experiments, cell metabolic activity was measured, and no toxicity was observed, even with concentrations of up to 4 mg/mL of magnetic nanoparticles (MNPs). When the cells were treated with magnetic hyperthermia, 80% of cells were dead at 43 °C using 3 mg/mL of MNPs and applying a magnetic field of 530 kHz with 20 kA/m amplitude.

Shift Work Predicts Increases in Lipopolysaccharide-Binding Protein, Interleukin-10, and Leukocyte Counts in a Cross-Sectional Study of Healthy Volunteers Carrying Low-Grade Systemic Inflammation.

The disruption of inflammatory responses is a potential mechanism behind the harmful effects of shift work and is associated with increased risk of hypertension, stroke, obesity, diabetes, and cancer. These responses are linked to the proliferation of leukocytes in shift workers, suggesting a systemic signal as a potential mediator. The purpose of this study was to assess the relationship between systemic inflammation, leukocyte counts, and systemic endotoxemia in samples from a diverse cohort of day workers and shift workers. Participants (normothermic and normotensive) were healthy volunteers, non-smoking, and drug- and medication-free. The following outcomes were measured: C-reactive protein, TNF-α, IL-6, IL-1ß, IL-10, leukocyte counts (monocytes, lymphocytes, and neutrophils), and lipopolysaccharide-binding protein (LBP). Risk factors that increase systemic inflammation, such as blood pressure, sleep loss, and cortisol, were also assessed. The results indicated that shift workers slept significantly less than day workers and had significantly increased concentrations of all of the cytokines measured as well as plasma cortisol. Regression models found that after controlling for covariates, shift-work exposure predicted the significant increase observed in IL-10, leukocyte counts, and LBP. Our results suggest that acute increases in low-grade systemic endotoxemia are unresolved during chronic shift-work exposure. This ongoing immune challenge may underlie the disrupted inflammatory responses characteristic of shift-work-related pathologies. Systemic endotoxemia may represent a novel target to investigate the early effects of exposure to shift-work schedules.

Environmental circadian disruption suppresses rhythms in kidney function and accelerates excretion of renal injury markers in urine of male hypertensive rats.

Nontraditional work schedules, such as shift work, have been associated with numerous health issues, including cardiovascular and metabolic disease. These work schedules can chronically misalign environmental timing cues with internal circadian clock systems in the brain and in peripheral organs, leading to dysfunction of those systems and their associated biological processes. Environmental circadian disruption in the kidney may be an important factor in the increased incidence of hypertension and adverse health outcomes in human shift workers. The relationship between renal rhythmicity and injury resilience is not well understood, especially in the context of environmental, rather than genetic, manipulations of the circadian system. We conducted a longitudinal study to determine whether chronic shifting of the light cycle that mimics shift work schedules would disrupt output rhythms of the kidney and accelerate kidney injury in salt-loaded male spontaneously hypertensive, stroke-prone rats. We observed that chronic shifting of the light-dark (LD) cycle misaligned and decreased the amplitude of urinary volume rhythms as the kidney phase-shifted to match each new lighting cycle. This schedule also accelerated glomerular and tubular injury marker excretion, as quantified by nephrin and KIM-1 compared with rats kept in a static LD cycle. These data suggest that disrupted rhythms in the kidney may decrease resilience and contribute to disease development in systems dependent on renal and cardiovascular functions.

Environmental Circadian Disruption Increases Stroke Severity and Dysregulates Immune Response.

Understanding the health consequences of chronic disruption of circadian rhythms can contribute to improving prevention strategies for shift workers. Chronic circadian disruption in shift work has been linked to a higher risk of stroke. Dysregulated immune responses are also linked to circadian disruption and may be a factor in stroke outcomes in shift workers. In this study, we test the hypotheses that specific schedules of circadian disruption exacerbate inflammatory responses in the brain, causing an increase in infarct size after experimentally induced ischemic stroke. Mice were exposed to 1 of 5 different lighting schedules followed by a 30-min middle cerebral artery occlusion, then reperfusion and 3-day recovery. A history of weekly phase advances resulted in an increased infarct volume versus the control lighting schedule. These effects were shift-direction specific, nonpermanent, and required multiple shifts to occur. In a separate cohort, stereotaxic injections of lipopolysaccharide were given bilaterally after exposure to 1 of 3 different lighting schedules. Ratios of pro- to anti-inflammatory cytokine expression show dysregulated responses after a history of phase advances. We conclude that chronic circadian disruption leads to worsened stroke outcome in a direction- and schedule-specific manner likely because of priming of the inflammatory response in the brain. These pieces of evidence suggest that the health impacts of shift work may be improved by targeting shift work scheduling, inflammatory mediators, or both.

A reductionist, in vitro model of environmental circadian disruption demonstrates SCN-independent and tissue-specific dysregulation of inflammatory responses.

Environmental circadian disruption (ECD), characterized by repeated or long-term disruption in environmental timing cues which require the internal circadian clock to change its phase to resynchronize with the environment, is associated with numerous serious health issues in humans. While animal and isolated cell models exist to study the effects of destabilizing the relationship between the circadian system and the environment, neither approach provides an ideal solution. Here, we developed an in vitro model which incorporates both elements of a reductionist cellular model and disruption of the clock/environment relationship using temperature as an environmental cue, as occurs in vivo. Using this approach, we have demonstrated that some effects of in vivo ECD can be reproduced using only isolated peripheral oscillators. Specifically, we report exaggerated inflammatory responses to endotoxin following repeated environmental circadian disruption in explanted spleens. This effect requires a functional circadian clock but not the master brain clock, the suprachiasmatic nucleus (SCN). Further, we report that this is a result of cumulative, rather than acute, circadian disruption as has been previously observed in vivo. Finally, such effects appear to be tissue specific as it does not occur in lung, which is less sensitive to the temperature cycles employed to induce ECD. Taken together, the present study suggests that this model could be a valuable tool for dissecting the causes and effects of circadian disruption both in isolated components of physiological systems as well as the aggregated interactions of these systems that occur in vivo.

The Protective Effect of Trichoderma asperellum on Tomato Plants against Fusarium oxysporum and Botrytis cinerea Diseases Involves Inhibition of Reactive Oxygen Species Production.

Trichoderma species are fungi widely employed as plant-growth-promoting agents and for biological control. Several commercial and laboratory-made solid formulations for mass production of Trichoderma have been reported. In this study, we evaluated a solid kaolin-based formulation to promote the absortion/retention of Trichoderma asperellum in the substrate for growing tomato plants. The unique implementation of this solid formulation resulted in an increased growth of the tomato plants, both in roots and shoots after 40 days of its application. Plants were challenged with two fungal pathogens, Fusarium oxysporum and Botrytis cinerea, and pretreatment with T. asperellum resulted in less severe wilting and stunting symptoms than non-treated plants. Treatment with T. asperellum formulation inhibited Reactive Oxygen Species (ROS) production in response to the pathogens in comparison to plants that were only challenged with both pathogens. These results suggest that decrease in ROS levels contribute to the protective effects exerted by T. asperellum in tomato.

Kidney Transplant in Pediatric Patient With Heart Failure: Case Report.

Chronic kidney disease is defined as irreversible and progressive damage of the kidney. Chronicity is defined by the presence of renal dysfunction for at least 3 months, and renal dysfunction is defined through combinations of investigation (abnormal radiologic findings, abnormal urine or abnormal biochemistry reflecting renal dysfunction) and/or documentation of glomerular filtration rate below 60 mL/min/1.73 m². The case patient was a girl of 11 years of age, with diagnosis of chronic renal disease, of unknown cause, under renal replacement therapy with peritoneal dialysis, with progressive deterioration of general status and decrease of functional capacity and tolerance to physical activity, presence of fatigue, pulmonary congestion, retention of liquids, and edema in lower extremities, even with adjustment of medical treatment. Transplant was performed from a related living donor, without incidents or complications. The results of pediatric kidney trans plant are excellent, offering a high quality of life for recipients; many patients return to school. It is consi dered the criterion standard for the treatment of pediatric endstage renal disease with excellent allograft function and subsequent resolution of systolic dysfunction.

The endophytic capacity of the entomopathogenic fungus Beauveria bassiana caused inherent physiological response in two barley (Hordeum vulgare) varieties.

In this study, the endophytic capacity of B. bassiana was determined for two barley (Hordeum vulgare) varieties, Josefa and Esmeralda, inoculated with a seedling immersion at three different concentrations (1 × 106, 1 × 107 and 1 × 108 conidia/mL). Seedling length and chlorophyll content were found to be not affected when inoculated with the entomopathogenic fungus, in both barley varieties. However, the colonisation percentage was found to be significantly lower with the inoculum concentration 1 × 106 conidia/mL for both barley varieties (P < 0.05) when compared to the other concentrations. Furthermore, a principal component analysis indicated that 96.23% of the variability in the data could be explained with two components. This analysis showed that the seedling length and chlorophyll content were positively correlated in both barley varieties for the 1 × 107 conidia/mL concentration. Likewise, a positive correlation was observed for colonisation percentage and treatment with 1 × 108 conidia/mL in the Josefa variety only. This is the first study in which the endophytic capacity of B. bassiana was evaluated in two different barley varieties, with the Josefa variety found to be the most susceptible.

Use of lignocellulosic wastes of pecan (Carya illinoinensis) in the cultivation of Ganoderma lucidum / Utilización de residuos lignocelulósicos de la pacana (Carya illinoinensis) para el cultivo del hongo Ganoderma lucidum

Background: The wastes of pecan nut (Carya illinoinensis (Wangenh.) K. Koch) production are increasing worldwide and have high concentrations of tannins and phenols. Aims: To study the biodegradation of lignocellulosic wastes of pecan used as solid substrate for the cultivation of the white-rot fungus Ganoderma lucidum (Curtis) P. Karst. Methods: Six formulations of pecan wastes were used as solid substrate: pecan shells (PS100), pecan pericarp (PP100), pecan wood-chips (PB100), and the combinations PS50+PP50, PB50+PS50 and PB50+PP50. The substrates were inoculated with a wild strain of G. lucidum collected in the Iberian Peninsula. The biodegradation capability of G. lucidum was estimated by using the mycelial growth rate, the biological efficiency, the production and the dry biological efficiency. Results: Notably, all solid substrates were suitable for G. lucidum growth and mushroom yield. The best performance in mushroom yield was obtained with PB100 (55.4% BE), followed by PB50+PP50 (31.7% BE) and PB50+PS50 (25.4% BE). The mushroom yield in the substrates containing pecan wood-chips (PB) was significantly higher. Conclusions: Our study is leading the way in attempting the cultivation of G. lucidum on lignocellulosic pecan waste. These results show an environmentally friendly alternative that increases the benefits for the global pecan industry, especially in rural areas, and transforms biomass into mushrooms with nutraceutical properties and biotechnological applications

Antecedentes: Los residuos de la producción de pacana (Carya illinoinensis [Wangenh.] K. Koch) se distribuyen por todo el mundo y poseen elevadas concentraciones de taninos y fenoles. Objetivos: Estudiar la biodegradación de los residuos lignocelulósicos de la pacana usados como sustrato sólido para el cultivo de Ganoderma lucidum (Curtis) P. Karst. Métodos: Se utilizaron seis formulaciones de sustratos sólidos a partir de los residuos: cáscara de la nuez (PS100), pericarpio de la nuez (PP100), astillas de ramas de poda (PB100) y las combinaciones PS50+PP50, PB50+PS50 y PB50+PP50. Los sustratos se inocularon con las hifas de una cepa silvestre de G. lucidum procedente de la península ibérica. La capacidad de biodegradación de G. lucidum se estimó mediante el ratio de crecimiento micelial, la eficiencia biológica, la producción de carpóforos y la eficiencia biológica en seco. Resultados: Notablemente, todos los sustratos sólidos utilizados resultaron adecuados para ser colonizados por G. lucidum y producir carpóforos. Los mejores rendimientos en cultivo se obtuvieron con la formulación PB100 (55,4% BE), seguida por PB50+PP50 (31,7% BE) y PB50+PS50 (25,4% BE). La producción de carpóforos en sustratos con astillas de ramas del árbol (PB) fue considerablemente más elevada que en aquellos que no contenían este residuo. Conclusiones: Este estudio muestra la posibilidad de cultivar G. lucidum sobre residuos lignocelulósicos de pacana. Los resultados obtenidos sugieren una alternativa respetuosa con el medio ambiente para el incremento de los beneficios en la industria de la pacana a nivel internacional, especialmente en zonas rurales, al convertir biomasa en la producción de un hongo de interés nutracéutico y con aplicaciones biotecnológicas

Use of lignocellulosic wastes of pecan (Carya illinoinensis) in the cultivation of Ganoderma lucidum.

BACKGROUND: The wastes of pecan nut (Carya illinoinensis (Wangenh.) K. Koch) production are increasing worldwide and have high concentrations of tannins and phenols. AIMS: To study the biodegradation of lignocellulosic wastes of pecan used as solid substrate for the cultivation of the white-rot fungus Ganoderma lucidum (Curtis) P. Karst. METHODS: Six formulations of pecan wastes were used as solid substrate: pecan shells (PS100), pecan pericarp (PP100), pecan wood-chips (PB100), and the combinations PS50+PP50, PB50+PS50 and PB50+PP50. The substrates were inoculated with a wild strain of G. lucidum collected in the Iberian Peninsula. The biodegradation capability of G. lucidum was estimated by using the mycelial growth rate, the biological efficiency, the production and the dry biological efficiency. RESULTS: Notably, all solid substrates were suitable for G. lucidum growth and mushroom yield. The best performance in mushroom yield was obtained with PB100 (55.4% BE), followed by PB50+PP50 (31.7% BE) and PB50+PS50 (25.4% BE). The mushroom yield in the substrates containing pecan wood-chips (PB) was significantly higher. CONCLUSIONS: Our study is leading the way in attempting the cultivation of G. lucidum on lignocellulosic pecan waste. These results show an environmentally friendly alternative that increases the benefits for the global pecan industry, especially in rural areas, and transforms biomass into mushrooms with nutraceutical properties and biotechnological applications.

Neural correlates of individual differences in circadian behaviour.

Daily rhythms in mammals are controlled by the circadian system, which is a collection of biological clocks regulated by a central pacemaker within the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. Changes in SCN function have pronounced consequences for behaviour and physiology; however, few studies have examined whether individual differences in circadian behaviour reflect changes in SCN function. Here, PERIOD2::LUCIFERASE mice were exposed to a behavioural assay to characterize individual differences in baseline entrainment, rate of re-entrainment and free-running rhythms. SCN slices were then collected for ex vivo bioluminescence imaging to gain insight into how the properties of the SCN clock influence individual differences in behavioural rhythms. First, individual differences in the timing of locomotor activity rhythms were positively correlated with the timing of SCN rhythms. Second, slower adjustment during simulated jetlag was associated with a larger degree of phase heterogeneity among SCN neurons. Collectively, these findings highlight the role of the SCN network in determining individual differences in circadian behaviour. Furthermore, these results reveal novel ways that the network organization of the SCN influences plasticity at the behavioural level, and lend insight into potential interventions designed to modulate the rate of resynchronization during transmeridian travel and shift work.

Shell neurons of the master circadian clock coordinate the phase of tissue clocks throughout the brain and body.

BACKGROUND: Daily rhythms in mammals are programmed by a master clock in the suprachiasmatic nucleus (SCN). The SCN contains two main compartments (shell and core), but the role of each region in system-level coordination remains ill defined. Herein, we use a functional assay to investigate how downstream tissues interpret region-specific outputs by using in vivo exposure to long day photoperiods to temporally dissociate the SCN. We then analyze resulting changes in the rhythms of clocks located throughout the brain and body to examine whether they maintain phase synchrony with the SCN shell or core. RESULTS: Nearly all of the 17 tissues examined in the brain and body maintain phase synchrony with the SCN shell, but not the SCN core, which indicates that downstream oscillators are set by cues controlled specifically by the SCN shell. Interestingly, we also found that SCN dissociation diminished the amplitude of rhythms in core clock gene and protein expression in brain tissues by 50-75 %, which suggests that light-driven changes in the functional organization of the SCN markedly influence the strength of rhythms in downstream tissues. CONCLUSIONS: Overall, our results reveal that body clocks receive time-of-day cues specifically from the SCN shell, which may be an adaptive design principle that serves to maintain system-level phase relationships in a changing environment. Further, we demonstrate that lighting conditions alter the amplitude of the molecular clock in downstream tissues, which uncovers a new form of plasticity that may contribute to seasonal changes in physiology and behavior.

Long-chain bases, phosphatidic acid, MAPKs, and reactive oxygen species as nodal signal transducers in stress responses in Arabidopsis.

Due to their sessile condition, plants have developed sensitive, fast, and effective ways to contend with environmental changes. These mechanisms operate as informational wires conforming extensive and intricate networks that are connected in several points. The responses are designed as pathways orchestrated by molecules that are transducers of protein and non-protein nature. Their chemical nature imposes selective features such as specificity, formation rate, and generation site to the informational routes. Enzymes such as mitogen-activated protein kinases and non-protein, smaller molecules, such as long-chain bases, phosphatidic acid, and reactive oxygen species are recurrent transducers in the pleiotropic responses to biotic and abiotic stresses in plants. In this review, we considered these four components as nodal points of converging signaling pathways that start from very diverse stimuli and evoke very different responses. These pleiotropic effects may be explained by the potentiality that every one of these four mediators can be expressed from different sources, cellular location, temporality, or magnitude. Here, we review recent advances in our understanding of the interplay of these four specific signaling components in Arabidopsis cells, with an emphasis on drought, cold and pathogen stresses.

Endogenous circadian regulation of pro-inflammatory cytokines and chemokines in the presence of bacterial lipopolysaccharide in humans.

Various aspects of immune response exhibit 24-h variations suggesting that infection susceptibility and treatment efficacy may vary by time of day. Whether these 24-h variations are endogenous or evoked by changes in environmental or behavioral conditions is not known. We assessed the endogenous circadian control and environmental and behavioral influences on ex-vivo lipopolysaccharide stimulation of whole blood in thirteen healthy participants under 48h of baseline conditions with standard sleep-wake schedules and 40-50h of constant environmental and behavioral (constant routine; CR) conditions. Significant 24-h rhythms were observed under baseline conditions in Monocyte Chemotactic Protein, Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin 8 but not Tumor Necrosis Factor alpha whereas significant 24-h rhythms were observed in all four immune factors under CR conditions. The rhythm amplitudes, expressed as a percentage of mean, were comparable between immune factors and across conditions. In contrast, the acrophase time (time of the fitted peak) was different between immune factors, and included daytime and nighttime peaks and changes across behavioral conditions. These results suggest that the endogenous circadian system underpins the temporal organization of immune responses in humans with additional effects of external environmental and behavioral cycles. These findings have implications for understanding the adverse effects of recurrent circadian disruption and sleep curtailment on immune function.

Prevención para la exacerbación aguda en la Enfermedad Pulmonar Obstructiva Crónica / Prevention of acute exacerbation in chronic obstructive pulmonary disease

La enfermedad Pulmonar Obstructiva Crónica (EPOC), causa importante de muerte en los paises desarrollados (ocupa el cuarto lugar en EUA), es tan ó más frecuente en países en desarrollo. La exacerbación aguda de la enfermedad (EABC) causa número importante de hospitalizaciones y consultas. Un paciente con EPOC presenta de una a tres EABC por año, el número de exacerbaciones es marcador de severidad de la condición y determina la calidad de vida y mortalidad del paciente, 3 a 16% de casos se hospitalizan. La mortalidad hospitalaria es elevada, 10% en casos de EPOC severos y mayor si el paciente ingresa a una Unidad de Cuidado Intensivo. La etiología subyacente en la descompensación de un paciente co EPOC, es infecciosa, (hasta 80%), otras condiciones como Embolia Pulmonar, Neutórax, Isuficiencia Cardíaca, Fracturas en la caja torácica e Infecciones no pulmonares, descompensan también al paciente. La prevención de la exacerbación es un objetivo principal de la EPOC, en la actualidad las medidas que pueden disminuir la frecuencia de EABC se ha incrementado y existe evidencia que sustenta intervenciones de tipo preventivo eficaces. Estas medidas pueden ser farmacológicas, están disponibles para el beneficio de nuestros pacientes. El paciente con EABC debe recibir tratamiento proporcional a la severidad de su condición, se debe tratar las comorbilidades y instalar desde el momento agudo el inicio de la estrategia preventiva para el futuro. La presencia de EABC es un evento que puede deberse a múltiples causas, por lo que un enfoque individual del paciente es primordial.

Dynamic interactions mediated by nonredundant signaling mechanisms couple circadian clock neurons.

Interactions among suprachiasmatic nucleus (SCN) neurons are required for robust circadian rhythms entrained to local time. To investigate these signaling mechanisms, we developed a functional coupling assay that uniquely captures the dynamic process by which SCN neurons interact. As a population, SCN neurons typically display synchronized rhythms with similar peak times, but will peak 6-12 hr apart after in vivo exposure to long days. Once they are removed from these conditions, SCN neurons resynchronize through a phase-dependent coupling process mediated by both vasoactive intestinal polypeptide (VIP) and GABAA signaling. Notably, GABAA signaling contributes to coupling when the SCN network is in an antiphase configuration, but opposes synchrony under steady-state conditions. Further, VIP acts together with GABAA signaling to couple the network in an antiphase configuration, but promotes synchrony under steady-state conditions by counteracting the actions of GABAA signaling. Thus, SCN neurons interact through nonredundant coupling mechanisms influenced by the state of the network.