Effect of ambient temperature on sleep breathing phenotype in mice: the role of orexins

The loss of orexinergic neurons, releasing orexins, results in narcolepsy. Orexins participate in the regulation of many physiological functions, and their role as wake-promoting molecules has been widely described. Less is known about the involvement of orexins in body temperature and respiratory regulation. The aim of this study was to investigate whether orexin peptides modulate respiratory regulation as a function of ambient temperature (T°a) during different sleep stages. Respiratory phenotype of male orexin knockout (KO-ORX, n=9) and wild-type (WT, n=8) mice was studied at thermoneutrality (T°a=30°C) or during mild cold exposure (T°a=20°C) inside a whole-body plethysmography chamber. The states of wakefulness (W), non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS) were scored non-invasively, using a previously validated technique. Both in WT and KO-ORX mice T°a strongly and significantly affected ventilatory period and minute ventilation values during NREMS and REMS; moreover, the occurrence rate of sleep apneas in NREMS was significantly reduced at T°a=20°C compared to T°a=30°C. Overall, there were no differences in respiratory regulation during sleep between WT and KO-ORX mice, except for sigh occurrence rate, which was significantly increased at T°a=20°C with respect to T°a =30°C in WT mice, but not in KO-ORX mice. These results do not support a main role for orexin peptides in the temperature-dependent modulation of respiratory regulation during sleep. However, we showed that the occurrence rate of sleep apneas critically depends on T°a, without any significant effect of orexin peptides

Sleep and Tibialis Anterior Muscle Activity in Mice With Mild Hypoxia and Iron Deficiency: Implications for the Restless Legs Syndrome

Restless legs syndrome (RLS) is a neurological disorder that entails an urge to move with a circadian pattern during the evening/night. RLS may be accompanied by decreased sleep time and increased occurrence of periodic leg movements during sleep (PLMS), which involve bursts of tibialis anterior (TA) muscle electromyogram (EMG). Mild hypoxia and non-anemic iron deficiency, a highly prevalent nutritional deficiency, are relatively unexplored factors in RLS pathophysiology. We tested whether mice exposed to mild hypoxia, alone or in combination with non-anemic iron deficiency, show decreased sleep time particularly in the light (rest) period and increased occurrence of TA EMG phasic events similar to human PLMS. Female C57BL/6J mice were fed diets with low or normal iron for 6 months from weaning and instrumented with electrodes to record the electroencephalogram and the EMG of both TA muscles. Mice were recorded in a whole-body plethysmograph while breathing a normoxic or mildly hypoxic (15% O2) gas mixture for 48 h. Hypoxia increased minute ventilation during sleep. The low-iron diet decreased liver and serum iron, leaving blood hemoglobin and brainstem iron levels unaffected. Hypoxia, either alone or in combination with non-anemic iron deficiency, decreased non-rapid-eye-movement (non-REM) sleep time, but this occurred irrespective of the light/dark period and was not associated with increased occurrence of TA EMG events during non-REM sleep. These results do not support the hypothesis that mild hypoxia is sufficient to cause signs of RLS, either alone or in combination with non-anemic iron deficiency, pointing to the necessity of further susceptibility factors

Aspectos epidemiológicos, clínicos e laboratoriais da Meningite viral: uma revisão de literatura

Infecções ocasionadas por vírus são capazes de afetar o Sistema Nervoso Central (SNC), desencadeando principalmente encefalites e meningites. O objetivo foi relatar os aspectos epidemiológicos, clínicos e laboratoriais da meningite viral. Foi realizado uma revisão de literatura narrativa, na qual foram analisados artigos científicos publicados na língua portuguesa e inglesa, utilizando os descritores: Meningites virais, líquido cefalorraquidiano, meningites. O período de coleta destas informações ocorreu entre janeiro e abril de 2022. O enterovírus é o agente etiológico mais comum nos quadros de meningite asséptica, tendo uma prevalência em pacientes infantis e adultos de até 90% dos casos, sendo mais incidentes no sexo masculino. O estudo realizado aponta que o agente etiológico com maior prevalência é o Enterovírus Echovirus, todavia na rotina clínica não é realizado um diagnóstico específico do vírus, realizando apenas um descarte de meningite bacteriana por meio da avaliação bioquímica e celular do LCR. A meningite viral, normalmente, não é grave, porém, como não há um tratamento específico, é de extrema importância o diagnóstico da doença, a fim de evitar um processo terapêutico errôneo e uma maior taxa de hospitalização, com aumento de morbimortalidade

Perspectiva escolar

Monográfico con el título: 'Educació pel desenvolupament sostenible'. Resumen basado en el de la publicaciónLa educación para el desarrollo sostenible o la educación ambiental han ayudado a entender que el modelo de desarrollo hegemónico no sólo está conduciendo al colapso ecológico, sino que se mantiene sobre la base de perpetuación de la pobreza y de la injusticia. Desde la Década de las Naciones Unidas de la Educación para el Desarrollo Sostenible (2005-2014), se han elaborado una serie de materiales educativos sobre algunos temas clave para la sostenibilidad que están dirigidos al profesorado catalán, desde el ciclo superior de Primaria hasta el Bachillerato. Se explican estos materiales y se da una visión práctica de algunos maestros y educadores que los han llevado a la práctica en el aula.CataluñaUniversitat de Barcelona. Biblioteca de Ciències de l'Educació; Passeig de la Vall d'Hebron, 171; 08035 Barcelona; +34934021035; +34934021034;ES

Influence of Culture Substrates on Morphology and Function of Pulmonary Alveolar Cells In Vitro

Cell’s microenvironment has been shown to exert influence on cell behavior. In particular, matrix-cell interactions strongly impact cell morphology and function. The purpose of this study was to analyze the influence of different culture substrate materials on phenotype and functional properties of lung epithelial adenocarcinoma (A549) cells. A549 cells were seeded onto two different biocompatible, commercially available substrates: a polyester coverslip (Thermanox™ Coverslips), that was used as cell culture plate control, and a polydimethylsiloxane membrane (PDMS, Elastosil® Film) investigated in this study as alternative material for A549 cells culture. The two substrates influenced cell morphology and the actin cytoskeleton organization. Further, the Yes-associated protein (YAP) and its transcriptional coactivator PDZ-binding motif (TAZ) were translocated to the nucleus in A549 cells cultured on polyester substrate, yet it remained mostly cytosolic in cells on PDMS substrate. By SEM analysis, we observed that cells grown on Elastosil® Film maintained an alveolar Type II cell morphology. Immunofluorescence staining for surfactant-C revealing a high expression of surfactant-C in cells cultured on Elastosil® Film, but not in cells cultured on Thermanox™ Coverslips. A549 cells grown onto Elastosil® Film exhibited morphology and functionality that suggest retainment of alveolar epithelial Type II phenotype, while A549 cells grown onto conventional plastic substrates acquired an alveolar Type I phenotype

Toxicological evaluation of airborne particulate matter. Are cell culture technologies ready to replace animal testing?

Exposure to atmospheric particulate matter (PM) can affect human health, causing asthma, atherosclerosis, renal disease and cancer. In the last few years, outdoor air pollution has increased globally, leading to a public health emergency. Epidemiological studies have reported a correlation between the development of severe respiratory and systemic diseases and exposure to PM. To evaluate the toxic effect of PM of different origins, conventional experimental toxicological investigations have been conducted in animals; however, animal experimentation poses major ethical issues and usually differs from human conditions. As an alternative, human cell cultures are increasingly being used to investigate cellular and molecular mechanisms of PM toxicity. Although 2D cell cultures have been proven helpful, they are far from being a valid alternative to animal tests. Recently, 3D cell culture and organ-on-chip technology have provided systems that are more complex and that can be more informative for toxicity studies. In this review, the results of the 2D systems that are most frequently used for PM toxicity evaluations are summarized with a special focus on their limitations. We also examined to which extent 3D cell culture and particularly the organ-on-chip technology may overcome these limitations and represent effective tools to improve airborne PM toxicity evaluations

An Internet of Medical Things System to Increase Continuous Positive Airway Pressure Usage in Patients with Sleep-Disordered Breathing

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder associated with increased daytime sleepiness and cardiovascular risk. Continuous positive airway pressure (CPAP), requiring a pressure-generating device connected via tubing to a mask during sleep, is an efective treatment. However, patients’ adherence to CPAP is often suboptimal. Behavioural interventions are efective in improving adherence to CPAP. We aimed to provide proof of principle for the operation of a low-cost, self-standing, internet-based system to measure and promote adherence to CPAP. The system is composed of triaxial acceleration sensors attached to the CPAP mask and to the wrist, able to record CPAP usage information, and a mobile app that collects such information and, thorough a chatbot, feeds back to the patient to improve adherence to treatment. The mask subsystem identifes time periods when the mask is put on based on relatively high values of the ratio between acceleration spectral power at frequencies < 0.35 Hz vs. 0.35–2 Hz over 1-min windows. Accuracy in identifcation may be increased taking account of the surges in the standard deviation of wrist accelerations over 1-min windows that accompany putting on and taking of the mask. The whole system can represent a unique tool capable of monitoring and improving patients’ adherence to CPAP treatment. Its main strength lies in its simplicity, low cost, and independence from the specifc CPAP device and mask employed

An Internet of Medical Things System to Increase Continuous Positive Airway Pressure Usage in Patients with Sleep-Disordered Breathing

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder associated with increased daytime sleepiness and cardiovascular risk. Continuous positive airway pressure (CPAP), requiring a pressure-generating device connected via tubing to a mask during sleep, is an efective treatment. However, patients\u2019 adherence to CPAP is often suboptimal. Behavioural interventions are efective in improving adherence to CPAP. We aimed to provide proof of principle for the operation of a low-cost, self-standing, internet-based system to measure and promote adherence to CPAP. The system is composed of triaxial acceleration sensors attached to the CPAP mask and to the wrist, able to record CPAP usage information, and a mobile app that collects such information and, thorough a chatbot, feeds back to the patient to improve adherence to treatment. The mask subsystem identifes time periods when the mask is put on based on relatively high values of the ratio between acceleration spectral power at frequencies < 0.35 Hz vs. 0.35\u20132 Hz over 1-min windows. Accuracy in identifcation may be increased taking account of the surges in the standard deviation of wrist accelerations over 1-min windows that accompany putting on and taking of the mask. The whole system can represent a unique tool capable of monitoring and improving patients\u2019 adherence to CPAP treatment. Its main strength lies in its simplicity, low cost, and independence from the specifc CPAP device and mask employed

Mesenchymal stem cells help pancreatic islet transplantation to control type 1 diabetes

Islet cell transplantation has therapeutic potential to treat type 1 diabetes, which is characterized by autoimmune destruction of insulin-producing pancreatic islet β cells. It represents a minimal invasive approach for β cell replacement, but long-term blood control is still largely unachievable. This phenomenon can be attributed to the lack of islet vasculature and hypoxic environment in the immediate post-transplantation period that contributes to the acute loss of islets by ischemia. Moreover, graft failures continue to occur because of immunological rejection, despite the use of potent immunosuppressive agents. Mesenchymal stem cells (MSCs) have the potential to enhance islet transplantation by suppressing inflammatory damage and immune mediated rejection. In this review we discuss the impact of MSCs on islet transplantation and focus on the potential role of MSCs in protecting islet grafts from early graft failure and from autoimmune attack

Modulation of sympathetic vasoconstriction is critical for the effects of sleep on arterial pressure in mice

While values of arterial pressure during sleep are predictive of cardiovascular risk, the autonomic mechanisms underlying the cardiovascular effects of sleep remain poorly understood. Here, we assess the autonomic mechanisms of the cardiovascular effects of sleep in C57Bl/6J mice, taking advantage of a novel technique for continuous intraperitoneal infusion of autonomic blockers. Our results indicate that non-REM sleep decreases arterial pressure by decreasing sympathetic vasoconstriction, decreases heart rate by balancing parasympathetic activation and sympathetic withdrawal, and increases cardiac baroreflex sensitivity mainly by increasing fluctuations in parasympathetic activity. Our results also indicate that REM sleep increases arterial pressure by increasing sympathetic activity to the heart and blood vessels, and increases heart rate, at least in part, by increasing cardiac sympathetic activity. These results provide a framework for generating and testing hypotheses on cardiovascular derangements during sleep in mouse models and human patients