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001). Manual rib cage compression combined with endotracheal suctioning increased mucus clearance compared with closed suctioning alone (mucus amounts, 5.5 [3.4-9.4] g vs 0.7 [0.5-2.0] g; P = .004); however, it did not improve gas exchange and radiologic findings. There were no significant differences in hemodynamic variables between the 2 groups. CONCLUSIONS Our findings indicated that hard and brief manual rib cage compression combined with closed suctioning was safe and led to improvement of mucus clearance; however, no effectiveness was confirmed with regard to oxygenation and ventilation. Copyright © 2020 by Daedalus Enterprises.Oxygen has long been considered a vital and potentially life-saving component of emergency care. Given this, there is widespread and liberal use of supplemental oxygen in hospitals across the United States and throughout the world. Recent research, however, delineates serious deleterious effects at the cellular level, inducing damage to the cardiovascular system, the central nervous system, the pulmonary system, and beyond. A scoping review was conducted to identify and synthesize available research data as it pertains to the clinical effects of hyperoxia in critically ill adult patients in acute care settings. We searched PubMed, MEDLINE, CINAHL, and Scopus databases. We also reviewed the reference lists of included publications. The selection of relevant articles was conducted by 2 researchers at 2 levels of screening. The review identified 30 studies, of which 5 were randomized controlled trials, 2 were prospective cohort studies, and 23 were retrospective cohort studies. A descriptive analysis of study results was performed. Current evidence suggests an association between hyperoxia and increased mortality after cardiac arrest, stroke, and traumatic brain injury, as well as in the setting of sepsis, although there is insufficient evidence to conclude concretely that hyperoxia effects clinical outcomes. As such, there exists a need for additional large-scale randomized controlled trials with well-defined parameters for the evaluation of clinical outcomes. Until the completion of such trials, titration of supplemental O2 to normoxia is advised to avoid the negative effects of both hyperoxia and hypoxia in acutely ill adult patients. Copyright © 2020 by Daedalus Enterprises.BACKGROUND Clinical observations on the potential of pre-hospital antiplatelet therapy in preventing ARDS have been inconsistent. To further the correlation between antiplatelet therapy and ARDS, we conducted a meta-analysis to evaluate the effects of pre-hospital antiplatelet therapy on subjects with ARDS. METHODS A literature search in major data banks was performed. We included prospective and retrospective cohorts, case-control trials, and randomized controlled trials that compared the ARDS incidence in subjects with or without pre-hospital antiplatelet agents. RESULTS Meta-analysis of 7 studies (a total of 30,291 subjects) showed significantly lower odds of ARDS in the pre-hospital antiplatelet therapy group compared with subjects with no pre-hospital antiplatelet therapy (odds ratio 0.68, 95% CI 0.56-0.83; P less then .001). However, ARDS mortalities in the hospital and ICUs were not affected. CONCLUSIONS These findings indicated that pre-hospital antiplatelet therapy was associated with a reduced rate of ARDS but had no effect on the mortality in the subjects at high risk. Copyright © 2020 by Daedalus Enterprises.BACKGROUND Switching patients affected by early severe ARDS and undergoing extracorporeal membrane oxygenation (ECMO) from controlled ventilation to spontaneous breathing can be either beneficial or harmful, depending on how effectively the breathing pattern is controlled with ECMO. Identifying the factors associated with ineffective control of spontaneous breathing with ECMO may advance our pathophysiologic understanding of this syndrome. METHODS We conducted a prospective study in subjects with severe ARDS who were on ECMO support ≤ 7 d. Subjects were switched to minimal sedation and pressure-support ventilation while extracorporeal CO2 removal was increased to approximate the subject's total CO2 production (V̇CO2 ). We calculated the rapid shallow breathing index (RSBI) as breathing frequency divided by tidal volume. We explored the correlation between certain characteristics recorded during pretest controlled ventilation and the development of apnea (ie, expiratory pause lasting > 10 s; n = 3), normal breathing pattern (ie, apnea to RSBI ≤ 105 breaths/min/L; n = 6), and rapid shallow breathing (RSBI > 105 breaths/min/L; n = 6) that occurred during the test study. RESULTS The ratio of extracorporeal CO2 removal to the subjects' V̇CO2 was >90% in all 15 subjects, and arterial blood gases remained within normal ranges. Baseline pretest Sequential Organ Failure Assessment score, total V̇CO2 and ventilatory ratio increased steadily, whereas PaO2 /FIO2 was higher in subjects with apnea compared to intermediate RSBI ≤105 breaths/min/L and elevated RSBI >105 breaths/min/L. In subjects with rapid shallow breathing, baseline lung weight measured with quantitative computed tomography scored higher, as well. CONCLUSIONS In early severe ARDS, the factors associated with rapid shallow breathing despite maximum extracorporeal CO2 extraction include less efficient CO2 and O2 exchange by the natural lung, higher severity of organ failure, and greater magnitude of lung edema. CID755673 concentration Copyright © 2020 by Daedalus Enterprises.BACKGROUND In the limited literature on cleaning tracheostomy stoma sites, there is no standard guideline for the cleaning solution. The objective of this study was to determine whether signs of stoma-site infection were different among a hospitalized pediatric population when using sterile water, sterile saline solution, or 0.25% acetic acid solution for tracheostomy stoma cleaning. METHODS A retrospective chart review was completed and included nursing and physician notes. The subjects were less then 1 y of age, in the neonatal ICU, and received a tracheostomy within the previous 30 days. Clinical signs of infection were visually observed by the providers and documented in the medical record. The subjects were divided into 3 groups, those prescribed 0.25% acetic acid, those prescribed sterile water, and those prescribed sterile saline solution for twice daily tracheostomy stoma care. We compared the rate of signs of infection of the tracheostomy stoma site across the 3 treatments by using a chi-square test. RESULTS In the 102 subjects included, there were significantly more signs of infection in the subjects for whom 0.25% acetic acid was not used for daily stoma cleaning (P = .03). There were no differences in signs of infection between those cleaned with saline solution (39%) and those cleaned with sterile water (31%) for daily stoma cleaning. Overall, there were 29% fewer signs of infection when 0.25% acetic acid was used than either sterile water or saline solution. CONCLUSIONS Analysis of our findings indicated that a 0.25% acetic acid solution used for stoma cleaning may be associated with fewer signs of infection than sterile water or sterile saline solution. More research is warranted toward establishing a standard practice. Copyright © 2020 by Daedalus Enterprises.BACKGROUND Patients with cystic fibrosis develop decreased exercise capacity. However, the main factors responsible for this decline are still unclear. Thus, the objective of this study was to evaluate the factors influencing exercise capacity assessed with the modified shuttle test (MST) in individuals with cystic fibrosis. METHODS A cross-sectional study was carried out in subjects with a diagnosis of cystic fibrosis who were 6-26 y old and were regularly monitored at 2 cystic fibrosis reference centers in Brazil. Individuals who were unable to perform the tests or who exhibited hemodynamic instability and exacerbation of respiratory symptoms were excluded. Anthropometric, clinical, and genotype data were collected. In addition, lung function and exercise capacity were evaluated with the MST. RESULTS 73 subjects (mean age 12.2 ± 4.9 y and FEV1 76.8 ± 23.3%) were included. The mean distance achieved in the MST was 765 ± 258 m (71.6% of predicted). The distance achieved on the MST correlated significantly with age (r = 0.49, P 67% of predicted (P = .02) and those with resting heart rate less then 100 beats/min (P = .01) had a greater exercise capacity. Resting heart rate, age, and FEV1 (%) were found as significant variables to explain the distance achieved on the MST (R2 = 0.48, standard error = 191.0 m). CONCLUSIONS The main determinants of exercise capacity assessed with the MST in individuals with cystic fibrosis were resting heart rate, age, and lung function. Copyright © 2020 by Daedalus Enterprises.The serotonin (5-hydroxytrypatmine) receptor 5-HT6 (5-HT6R) has emerged as a promising target to alleviate the cognitive symptoms of neurodevelopmental diseases. We previously demonstrated that 5-HT6R finely controls key neurodevelopmental steps, including neuronal migration and the initiation of neurite growth, through its interaction with cyclin-dependent kinase 5 (Cdk5). Here, we showed that 5-HT6R recruited G protein-regulated inducer of neurite outgrowth 1 (GPRIN1) through a Gs-dependent mechanism. Interactions between the receptor and either Cdk5 or GPRIN1 occurred sequentially during neuronal differentiation. The 5-HT6R-GPRIN1 interaction enhanced agonist-independent, receptor-stimulated cAMP production without altering the agonist-dependent response in NG108-15 neuroblastoma cells. This interaction also promoted neurite extension and branching in NG108-15 cells and primary mouse striatal neurons through a cAMP-dependent protein kinase A (PKA)-dependent mechanism. This study highlights the complex allosteric modulation of GPCRs by protein partners and demonstrates how dynamic interactions between GPCRs and their protein partners can control the different steps of highly coordinated cellular processes, such as dendritic tree morphogenesis. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.L-type voltage-gated Ca2+ channels (LTCCs) are implicated in neurodegenerative processes and cell death. Accordingly, LTCC antagonists have been proposed to be neuroprotective, although this view is disputed, because intentional LTCC activation can also have beneficial effects. LTCC-mediated Ca2+ influx influences mitochondrial function, which plays a crucial role in the regulation of cell viability. Hence, we investigated the effect of modulating LTCC-mediated Ca2+ influx on mitochondrial function in cultured hippocampal neurons. To activate LTCCs, neuronal activity was stimulated by increasing extracellular K+ or by application of the GABAA receptor antagonist bicuculline. The activity of LTCCs was altered by application of an agonistic (Bay K8644) or an antagonistic (isradipine) dihydropyridine. Our results demonstrated that activation of LTCC-mediated Ca2+ influx affected mitochondrial function in a bimodal manner. At moderate stimulation strength, ATP synthase activity was enhanced, an effect that involved Ca2+-induced Ca2+ release from intracellular stores.
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