Notes

RPE necroptosis in response to oxidative stress plus AMD.
Individuals with multiple sclerosis (MS) experience progressive declines in movement capabilities, especially walking performance. The purpose of our study was to compare the amount of variance in walking performance that could be explained by the functional capabilities of lower leg muscles in persons with MS and a sex- and age-matched control group. Participants performed two walking tests (6-min walk and 25-ft walk), strength tests for the plantar flexor and dorsiflexor muscles, and steady submaximal (10% and 20% maximum) isometric contractions. High-density electromyography (EMG) was recorded during the steady contractions and the signals were decomposed to identify the discharge times of concurrently active motor units. There were significant differences between the two groups in the force fluctuations during the steady contractions (force steadiness), the strength of the plantar flexor and dorsiflexor muscles, and the discharge characteristics during the steady contractions. Performance on the two walking tests by the MS group was moderately associated with force steadiness of the plantar flexor and dorsiflexor muscles; worse force steadiness was associated with poorer walking performance. In contrast, the performance of the control group was associated with muscle strength (25-ft test) and force steadiness of the dorsiflexors and variance in common input of motor units to the plantar flexors (6-min test). These findings indicate that a reduction in the ability to maintain a steady force during submaximal isometric contractions is moderately associated with walking performance of persons with MS.Background E-cigarette use is on the rise and many adult e-cigarette users also smoke combustible cigarettes. Past work suggests that dual use (i.e. use of both electronic and combustible cigarettes) is associated with greater rates of cannabis use, yet little is known about the nature of cannabis use among dual users. Objectives The current study examined 414 adult dual users (48.3% female, Mage = 35.1 years), half of whom endorsed current (past month) cannabis use. Results Results indicated that cannabis users reported more severe pain, greater pain interference, and more hazardous drinking. In addition, cannabis use was robustly related to hazardous drinking after statistically controlling for demographic and pain-related variables. Cannabis use was also associated with hazardous drinking indirectly via pain interference at greater levels of pain severity. Conclusions/Importance These results highlight several clinical correlates of cannabis use among adult dual users, and also suggest that pain may play an important role in hazardous drinking among these individuals.Peripheral viscerosensory afferent signals are transmitted to the nucleus tractus solitarii (nTS) via release of glutamate. Following release, glutamate is removed from the extrasynaptic and synaptic cleft via excitatory amino acid transporters (EAATs), thus limiting glutamate receptor activation or over activation, and maintaining its working range. We have shown that EAAT block with the antagonist threo-β-Benzyloxyaspartic acid (TBOA) depolarized nTS neurons and increased spontaneous excitatory postsynaptic current (sEPSC) frequency yet reduced the amplitude of afferent (TS)-evoked EPSCs (TS-EPSCs). Interestingly, chronic intermittent hypoxia (CIH), a model of obstructive sleep apnea, produces similar synaptic responses as EAAT block. We hypothesized EAAT expression or function are downregulated after CIH, and this reduction in glutamate removal contributes to the observed neurophysiological responses. To test this hypothesis, we used brain slice electrophysiology and imaging of glutamate release and TS-afferent Ca2+ to compare nTS properties of rats exposed to 10 days of normoxia (Norm, 21%O2) or CIH. Results show that EAAT blockade with TFB-TBOA in Norm caused neuronal depolarization, generation of an inward current, and increased spontaneous synaptic activity. The latter augmentation was eliminated by inclusion of tetrodotoxin in the perfusate. TS stimulation during TFB-TBOA also elevated extracellular glutamate and decreased presynaptic Ca2+ and TS-EPSC amplitude. Selleck (E/Z)-BCI In CIH, the effects of EAAT block are eliminated or attenuated. CIH reduced EAAT expression in nTS, which may contribute to the attenuated function seen is this condition. Therefore, CIH reduces EAAT influence on synaptic and neuronal activity which may lead to the physiological consequences seen in OSA and CIH.BACKGROUND Outcomes from extracorporeal cardiopulmonary resuscitation (ECPR) are felt to be influenced by selective use, but the characteristics of those receiving ECPR are undefined. We demonstrate the relationship between individual patient and hospital characteristics and the probability of ECPR use. METHODS AND RESULTS We performed an observational analysis of adult inpatient cardiac arrests in the United States from 2000 to 2018 reported to the American Heart Association's Get With The Guidelines-Resuscitation registry restricted to hospitals that provided ECPR. We calculated case mix adjusted relative risk (RR) of receiving ECPR for individual characteristics. From 2000 to 2018, 129 736 patients had a cardiac arrest (128 654 conventional cardiopulmonary resuscitation and 1082 ECPR) in 224 hospitals that offered ECPR. ECPR use was associated with younger age (RR, 1.5 for less then 40 vs. 40-59 years; 95% CI, 1.2-1.8), no pre-existing comorbidities (RR, 1.4; 95% CI, 1.1-1.8) or cardiac-specific comorbidities (congestive heart failure [RR, 1.3; 95% CI, 1.2-1.5], prior myocardial infarction [RR, 1.4; 95% CI, 1.2-1.6], or current myocardial infarction [RR, 1.5; 95% CI, 1.3-1.8]), and in locations of procedural areas at the times of cardiac arrest (RR, 12.0; 95% CI, 9.5-15.1). ECPR decreased after hours (3-11 pm [RR, 0.8; 95% CI, 0.7-1.0] and 11 pm-7 am [RR, 0.6; 95% CI, 0.5-0.7]) and on weekends (RR, 0.7; 95% CI, 0.6-0.9). CONCLUSIONS Less than 1% of in-hospital cardiac arrest patients are treated with ECPR. ECPR use is influenced by patient age, comorbidities, and hospital system factors. Randomized controlled trials are needed to better define the patients in whom ECPR may provide a benefit.
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