While there was no difference in the CGRP expression between the two groups, FTY720 significantly preserved the MOR in both the caudal and rostral areas of the spinal dorsal horn. While HTT was preserved in the FTY720 group, it was significantly increased in the rostral side and decreased in the caudal side of the injury in the vehicle group. These results suggest that FTY720 ameliorates post-traumatic allodynia through regulation of neuro-inflammation, maintenance of the blood brain barrier, and inhibition of glial scar formation, thereby preserving the connectivity of the descending inhibitory pathway and reducing neuropathic pain.Background and Purpose- Aortic valve stenosis may lead to atrial and ventricular remodeling, predisposes to atrial fibrillation, and may also be an independent risk factor of ischemic stroke. However, information on stroke rates among persons with aortic valve stenosis are sparse. We aimed to determine the incidence rates and relative risks of ischemic stroke in individuals with diagnosed aortic valve stenosis compared with age- and sex-matched controls. Methods- All patients with incident aortic valve stenosis aged >18 years (n=79 310) and age- and sex-matched controls were identified using the Danish nationwide registries (1997-2017). Incidence rates per 1000 person-years (PY) and multivariable adjusted hazard ratios with 95% CIs were reported. Results- In total, 873 373 individuals (median age 77 years, 51.5% men, 9.1% with aortic valve stenosis) were included. Ischemic stroke occurred in 70 205 (8.0%) individuals during 4 880 862 PY of follow-up. Incidence rates of ischemic stroke were 13.3/1000 PY among cial in some individuals.Background and Purpose- MRproANP (midregional proatrial natriuretic peptide) is known to be independently associated with cardioembolic stroke cause and to improve risk stratification for 90-day mortality when measured within 24 to 72 hours after symptom onset in patients with acute ischemic stroke. However, the optimal time point for assessment remains unclear. This study aimed to evaluate prognostic utility of MRproANP at different time points during the first 5 days of hospitalization in patients with acute ischemic stroke. Methods- Samples of MRproANP were collected on admission ( less then 72 hours after onset) and at multiple time points during the first 5 days of hospitalization in 348 consecutively enrolled patients with acute ischemic stroke. The prognostic value for 90-day mortality, 90-day functional outcome, and the association with cardioembolic stroke cause was assessed regarding the time of measurement, and change over time was modeled using generalized estimating equations. Results- MRproANP levels modestly decease over the initial 5 days but remain highly predictive for cardioembolic stroke cause (odds ratio, 9.75 [95% CI, 3.2-29]; 10.62 [95% CI, 3.4-33.3]; 10.8 [95% CI, 3.1-37.1]; 19.4 [95% CI, 5.49-68.7] on admission, day 1, 3 and 5) and 90-day mortality (odds ratio, 59.4 [95% CI, 7.4-480.7]; 78.3 [95% CI, 7.9-772.6]; 14.5 [95% CI, 1.4-145]; 19.81 [95% CI, 2.7-143.4] on admission, day 1, 3, and 5). Change over time does not significantly modify the prognostic value of MRproANP (P=0.65 and P=0.56 for the interaction term in the multivariate model). Conclusions- Independent prognostic value of MRproANP remains unaltered in the acute phase of stroke at least up to 5 days; repeated measurements do not improve the prognostic value.Rationale Right ventricular (RV) fibrosis in pulmonary arterial hypertension (PAH) contributes to RV failure (RVF). While RV fibrosis reflects changes in the function of resident RV fibroblasts (RVfib), these cells are understudied. Objective Examine the role of mitochondrial metabolism of RVfib in RV fibrosis in human and experimental PAH. Methods and Results Male Sprague-Dawley rats received monocrotaline (MCT; 60 mg/kg) or saline. Drinking water containing no supplement or the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate was started 7-days post MCT. At week-4, treadmill testing, echocardiography and right heart catheterization were performed. The effects of PDK activation on mitochondrial dynamics and metabolism, RVfib proliferation, and collagen production were studied in RVfib in cell culture. Epigenetic mechanisms for persistence of the profibrotic RVfib phenotype in culture were evaluated. PDK expression was also studied in the RVfib of patients with decompensated RVF (n=11) versus con therapeutic levels in the RV, reduced phospho-PDH expression, RV fibrosis and hypertrophy, and improved RV function. In patients with PAH and RVF, RVfib had increased PDK1 expression. Conclusions MCT-RVfib manifest a DNMT1-HIF-1α-PDK-mediated, chamber-specific, metabolic memory that promotes collagen production and RV fibrosis. This epigenetic mitochondrial-metabolic pathway is a potential antifibrotic therapeutic target.Purpose This study aims to provide insights into the impact of organizational family-centered care characteristics at German neonatal intensive care units (NICUs) on the satisfaction of parents of very low birthweight (VLBW) infants.Materials and methods Using multilevel modeling, this study analyzed whether organizational characteristics of NICUs fostering parent-infant interaction (by way of the existence of a recreation room, possibility of rooming in, existence of unrestricted visiting hours for parents, existence of parental classes, and the connection to parent associations as well as the existence of standards on developmentally supportive care) increase the satisfaction of parents after the infants’ high-intensive care phase within the NICU.Results Nine hundred and twenty-three VLBW infants from 66 NICUs in Germany born between May and October 2013 were enrolled in this multicenter study. We retrieved 1493 questionnaires completed by 1277 parents. The existence of unrestricted visiting hours (adjusted odds ratio (AOR) 1.967; 95% CI [1.118, 3.459]) and standardized procedures for developmentally supportive care (AOR 1.775; 95% CI [1.166, 2.704]) were positively associated with parental satisfaction.Conclusions Fostering the parent-infant interaction through the provision of developmentally supportive care and unrestricted visiting hours for parents whose infants are hospitalized within an NICU significantly contributes to the satisfaction of parents.Rationale microRNAs (miRNAs) are small non-coding RNAs that modulate gene expression by negatively regulating translation of target genes. While the role of several miRNAs in vascular smooth muscle cells (VSMCs) has been extensively characterized, the function of miR-128-3p (miR-128) is still unknown. Objective To determine if miR-128 modulates VSMC phenotype, and to define the underlying mechanisms. Methods and Results We screened for miRNAs whose expression is modulated by an altered DNA methylation status in VSMCs, and among the hits we selected miR-128. We found that miR-128 was expressed in various tissues, primary murine cells, and pathological murine and human vascular specimens. Through gain- and loss-of-function approaches, we determined that miR-128 affects VSMC proliferation, migration, differentiation, and contractility. The alterations of those properties were dependent upon epigenetic regulation of key VSMC differentiation genes; notably, Kruppel-like factor 4 was found to be a direct target of miR-128 and able to modulate the methylation status of the pivotal VSMC gene Myosin Heavy Chain 11 (Myh11). Finally, in vivo lentiviral delivery of miR-128 prevented intimal hyperplasia in a mouse model of carotid restenosis without modifying vital cardiovascular parameters. Conclusions miR-128 is a critical modulator of VSMCs and is regulated by epigenetic modifications upon stress. Its modulation in the context of disease could be exploited for therapeutic purposes.The dopaminergic (DA) system function is frequently disrupted after traumatic brain injury (TBI). However, published interventions that target the DA system with the hope of enhancing functional outcomes are inconclusive, partially due to the lack of DA signaling biomarkers that can be used to select patients likely to benefit from DA-directed therapies or to monitor treatment efficacy. The goal of this study was to evaluate the feasibility of using I-iofluopane SPECT is a promising tool to determine the severity of presynaptic DA terminal disruption and for monitoring pharmacokinetics and pharmacodynamics of therapeutic interventions targeting the DA system.The purpose of this systematic review with meta-analysis was to examine the effects of strength training (ST) on selected components of physical fitness (e.g., lower/upper limb maximal strength, muscular endurance, jump performance, cardiorespiratory endurance) and sport-specific performance in rowers. Only studies with an active control group were included if they examined the effects of ST on at least one proxy of physical fitness and/or sport-specific performance in rowers. Weighted and averaged standardized mean differences (SMD) were calculated using random-effects models. Subgroup analyses were computed to identify effects of ST type or expertise level on sport-specific performance. Our analyses revealed significant small effects of ST on lower limb maximal strength (SMD = 0.42, p = 0.05) and on sport-specific performance (SMD = 0.32, p = 0.05). Non-significant effects were found for upper limb maximal strength, upper/lower limb muscular endurance, jump performance, and cardiorespiratory endurance. Subgroup analyses for ST type and expertise level showed non-significant differences between the respective subgroups of rowers (p ≥ 0.32). Our systematic review with meta-analysis indicated that ST is an effective means for improving lower limb maximal strength and sport-specific performance in rowers. However, ST-induced effects are neither modulated by ST type nor rowers’ expertise level.Abbreviations CON control group; ICC intraclass correlation coefficient; CRE cardiorespiratory endurance; F female; IG intervention group; INT intervention group; M male; Sets number of sets per exercise; SMD standardized mean differences; SMDwm weighted mean SMD; ST strength training; RCT randomized controlled trial; Reps repetitions; RM repetition maximum; TF training frequency (times per week); TI training intensity (eg., % of 1 repetition maximum); TP training periods (weeks).The purpose of this study was to assess the results of dorsal intercarpal ligament capsulodesis (Mayo technique) for cases of chronic scapholunate instability and to specify the indications according to the severity of instability. A retrospective analysis was conducted and examined dorsal intercarpal ligament capsulodesis procedures performed for chronic scapholunate instability without intercarpal or radiocarpal arthritis. One-hundred and twenty patients were examined by an independent observer (48 predynamic, 48 dynamic and 24 static scapholunate instabilities). The follow-up period averaged 54 months (range 24-127). Mean final Mayo wrist score was 70, mean final Patient-Rated Wrist Evaluation was 27 and mean final QuickDASH score was 26. Functional, clinical and radiological data were improved for the operated patients. We concluded that dorsal intercarpal ligament capsulodesis is a good option for treating early stages of scapholunate instability. Level of evidence IV.