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6 [2.2-4.6] vs 1.4 [0.9-2.4], <br /><br /> &lt; .001) and the validation cohort (2.6 [2.3-4.4] vs 2.2 [1.0-2.8], <br /><br /> &lt; .001). On multivariate analysis of the derivation cohort, admission for hemorrhagic shock (odds ratio 13.98), IC-RDOS (odds ratio 1.77), and Simplified Acute Physiology Score II (odds ratio 1.10) was associated with ICU mortality. Areas under the receiving operating characteristic curve of IC-RDOS to predict ICU mortality were 0.785 and 0.794 in the derivation and validation cohorts, respectively.<br /><br /> IC-RDOS, an observational correlate of dyspnea, but not dyspnea itself, was associated with higher mortality in ICU subjects.<br /><br />IC-RDOS, an observational correlate of dyspnea, but not dyspnea itself, was associated with higher mortality in ICU subjects.<br /><br /> Pulmonary rehabilitation (PR) is useful in survivors of COVID-19-associated acute respiratory failure (ARF). The aim of this retrospective study on in-patient PR was to report rehabilitative trajectories and effects of cycle training.<br /><br /> According to the Short Physical Performance Battery (SPPB) score at admission (T0), participants were allocated to stage 1 (SPPB &lt; 6), stage 2 (SPPB ≥ 6 and &lt; 10), or stage 3 (SPPB ≥ 10) and performed increasing level of activities from passive exercises to free walking, balance exercises, strength exercises, and tailored cycle-ergometer endurance training. The primary outcome was SPPB. 6-min walk distance (6MWD), Medical Research Council score, Barthel dyspnea index, and rate of subjects able to cycling were also assessed.<br /><br /> Data of 123 participants were analyzed. At T0, 44 (35.8%), 50 (40.6%), and 29 (23.6%) participants were allocated to stages 1-3, respectively. At discharge, participants showed significant improvements in SPPB, independent of the initial stage, 81. Benefits were independent of initial stage of physical performance and allowed participants to move from lower to higher levels of activities.<br /><br /> The management of mechanical ventilation critically impacts outcome for patients with acute respiratory failure. Ventilator settings in the early post-intubation period may be especially influential on outcome. Low tidal volume ventilation in the prehospital setting has been shown to impact the provision of low tidal volume after admission and influence outcome. However, there is an overall paucity of data on mechanical ventilation for air medical transport patients. The objectives of this study were to characterize air medical transport ventilation practices and assess variables associated with nonprotective ventilation.<br /><br /> This was a multi-center, nationwide (approximately 130 bases) retrospective cohort study conducted on consecutive, adult mechanically ventilated air medical transport patients treated in the prehospital environment. Descriptive statistics were used to assess the cohort; the chi-square test compared categorical variables, and continuous variables were compared using independent samples <br /><br /> overwhelming majority of air medical transport subjects had tidal volume set empirically, which may be exposing patients to nonprotective ventilator settings. Given a lack of PBW assessments, the frequency of low tidal volume use remains unknown. Performance improvement initiatives aimed at indexing tidal volume to PBW are easy targets to improve the delivery of mechanical ventilation in the prehospital arena, especially for females.<br /><br />The overwhelming majority of air medical transport subjects had tidal volume set empirically, which may be exposing patients to nonprotective ventilator settings. Given a lack of PBW assessments, the frequency of low tidal volume use remains unknown. Performance improvement initiatives aimed at indexing tidal volume to PBW are easy targets to improve the delivery of mechanical ventilation in the prehospital arena, especially for females.<br /><br /> Adults with chronic lung disease use electronic cigarettes (e-cigarette) at higher rates than those without chronic lung disease. Because e-cigarettes have now been shown to cause adverse pulmonary effects and impair immune responses, it is particularly important to identify the factors that contribute to e-cigarette use in individuals with chronic lung disease. We tested whether mental health explains the association between chronic lung disease and e-cigarette use, and whether the association between chronic lung disease and e-cigarette use is conditional on the presence of respiratory symptoms.<br /><br /> Data were obtained from the 2018 Behavioral Risk Factor Surveillance System. Logistic regression was used to test the association between chronic lung disease status and e-cigarette use when controlling for demographic variables and comorbidities. Structural equation modeling was then used to evaluate (a) whether the number of bad mental health days in the past 30 days explained the association between chronic llation.<br /><br />The association between chronic lung disease and e-cigarette use may be due, in part, to poorer mental health among individuals with chronic lung disease. These findings provide preliminary evidence that improving the mental health of individuals with chronic lung disease could reduce e-cigarette use in this vulnerable population.The evolutionarily conserved extended synaptotagmin (E-Syt) proteins are calcium-activated lipid transfer proteins that function at contacts between the ER and plasma membrane (ER-PM contacts). However, roles of the E-Syt family members in PM lipid organisation remain incomplete. Among the E-Syt family, the yeast tricalbin (Tcb) proteins are essential for PM integrity upon heat stress, but it is not known how they contribute to PM maintenance. Using quantitative lipidomics and microscopy, we find that the Tcb proteins regulate phosphatidylserine homeostasis at the PM. Moreover, upon heat-induced membrane stress, Tcb3 co-localises with the PM protein Sfk1 that is implicated in PM phospholipid asymmetry and integrity. The Tcb proteins also control the PM targeting of the known phosphatidylserine effector Pkc1 upon heat-induced stress. Phosphatidylserine has evolutionarily conserved roles in PM organisation, integrity, and repair. We propose that phospholipid regulation is an ancient essential function of E-Syt family members required for PM integrity.Luciferase reporter assays represent a simple and sensitive experimental system in cell and molecular biology to study multiple biological processes. However, the application of these assays is often limited by the costs of conventional luminometer instruments and the versatility of their use in different experimental conditions. Therefore, we aimed to develop a small, affordable luminometer allowing continuous measurement of luciferase activity, designed for inclusion into various kinds of tissue culture incubators. Here, we introduce LuminoCell-an open-source platform for the construction of an affordable, sensitive, and portable luminometer capable of real-time monitoring in-cell luciferase activity. The LuminoCell costs $40, requires less than 1 h to assemble, and it is capable of performing real-time sensitive detection of both magnitude and duration of the activity of major signalling pathways in cell cultures, including receptor tyrosine kinases (EGF and FGF), WNT/β-catenin, and NF-κB. In addition, we show that the LuminoCell is suitable to be used in cytotoxicity assays as well as for monitoring periodic circadian gene expression.Spinal muscular atrophy, the leading genetic cause of infant mortality, is a motor neuron disease caused by low levels of survival motor neuron (SMN) protein. SMN is a multifunctional protein that is implicated in numerous cytoplasmic and nuclear processes. Recently, increasing attention is being paid to the role of SMN in the maintenance of DNA integrity. DNA damage and genome instability have been linked to a range of neurodegenerative diseases. [https://www.selleckchem.com/products/mm-102.html MM-102 purchase] The ribosomal DNA (rDNA) represents a particularly unstable locus undergoing frequent breakage. Instability in rDNA has been associated with cancer, premature ageing syndromes, and a number of neurodegenerative disorders. Here, we report that SMN-deficient cells exhibit increased rDNA damage leading to impaired ribosomal RNA synthesis and translation. We also unravel an interaction between SMN and RNA polymerase I. Moreover, we uncover an spinal muscular atrophy motor neuron-specific deficiency of DDX21 protein, which is required for resolving R-loops in the nucleolus. Taken together, our findings suggest a new role of SMN in rDNA integrity.Odors are transported by turbulent air currents, creating complex temporal fluctuations in odor concentration that provide a potentially informative stimulus dimension. We have shown that mice are able to discriminate odor stimuli based on their temporal structure, indicating that information contained in the temporal structure of odor plumes can be extracted by the mouse olfactory system. Here, using in vivo extracellular and intracellular electrophysiological recordings, we show that mitral cells (MCs) and tufted cells (TCs) of the male C57BL/6 mouse olfactory bulb can encode the dominant temporal frequencies present in odor stimuli up to at least 20 Hz. A substantial population of cell-odor pairs showed significant coupling of their subthreshold membrane potential with the odor stimulus at both 2 Hz (29/70) and the suprasniff frequency 20 Hz (24/70). Furthermore, mitral/tufted cells (M/TCs) show differential coupling of their membrane potential to odor concentration fluctuations with tufted cells coupling but strongly modulated by local inhibitory circuits. In summary, this study provides insight into how both cellular and circuit properties modulate encoding of odor temporal features in the mouse olfactory bulb.Torpor is a naturally occurring, hypometabolic, hypothermic state engaged by a wide range of animals in response to imbalance between the supply and demand for nutrients. Recent work has identified some of the key neuronal populations involved in daily torpor induction in mice, in particular, projections from the preoptic area of the hypothalamus to the dorsomedial hypothalamus (DMH). The DMH plays a role in thermoregulation, control of energy expenditure, and circadian rhythms, making it well positioned to contribute to the expression of torpor. We used activity-dependent genetic TRAPing techniques to target DMH neurons that were active during natural torpor bouts in female mice. Chemogenetic reactivation of torpor-TRAPed DMH neurons in calorie-restricted mice promoted torpor, resulting in longer and deeper torpor bouts. Chemogenetic inhibition of torpor-TRAPed DMH neurons did not block torpor entry, suggesting a modulatory role for the DMH in the control of torpor. This work adds to the evidence that the preoptic area of the hypothalamus and the DMH form part of a circuit within the mouse hypothalamus that controls entry into daily torpor.SIGNIFICANCE STATEMENT Daily heterotherms, such as mice, use torpor to cope with environments in which the supply of metabolic fuel is not sufficient for the maintenance of normothermia. Daily torpor involves reductions in body temperature, as well as active suppression of heart rate and metabolism. How the CNS controls this profound deviation from normal homeostasis is not known, but a projection from the preoptic area to the dorsomedial hypothalamus has recently been implicated. We demonstrate that the dorsomedial hypothalamus contains neurons that are active during torpor. Activity in these neurons promotes torpor entry and maintenance, but their activation alone does not appear to be sufficient for torpor entry.