Notes

Mitochondrial links among mental faculties aging and Alzheimer's disease.
05). However, there was no significant difference in edema in the majority of muscle groups, except the adductor magnus (p = 0.012) and soleus (p = 0.009) with higher grade edema in IIM. Additionally, all the adductor magnus muscles in LGMD (100%) showed high-grade fat substitution, but none of them showed high-grade edema. Conclusions MRI could be a valuable tool to differentiate LGMD from IIM based on the discrepancy in muscle fat substitution, and the adductor magnus muscle could provide a biosignature to categorizing LGMD.Multiple sclerosis is a neurodegenerative disease associated with demyelination and neuroinflammation in the central nervous system. There is an urgent need to develop remyelinating therapies to better treat multiple sclerosis and other demyelinating diseases. The kappa opioid receptor (KOR) has been identified as a potential target for the development of remyelinating therapies; however, prototypical KOR agonists, such as U50,488 have side effects, which limit clinical use. In the current study, we investigated a Salvinorin A analog, ethoxymethyl ether Salvinorin B (EOM SalB) in two preclinical models of demyelination in C57BL/6J mice. We showed that in cellular assays EOM SalB was G-protein biased, an effect often correlated with fewer KOR-mediated side effects. In the experimental autoimmune encephalomyelitis model, we found that EOM SalB (0.1-0.3 mg/kg) effectively decreased disease severity in a KOR-dependent manner and led to a greater number of animals in recovery compared to U50,488 treatment. Furthermore, EOM SalB treatment decreased immune cell infiltration and increased myelin levels in the central nervous system. In the cuprizone-induced demyelination model, we showed that EOM SalB (0.3 mg/kg) administration led to an increase in the number of mature oligodendrocytes, the number of myelinated axons and the myelin thickness in the corpus callosum. Overall, EOM SalB was effective in two preclinical models of multiple sclerosis and demyelination, adding further evidence to show KOR agonists are a promising target for remyelinating therapies.Background The role of tranexamic acid (TXA) in preventing hematoma expansion (HE) in patients with acute spontaneous intracerebral hemorrhage (ICH) remains unclear. We aim to investigate the efficacy and safety of TXA in acute spontaneous ICH with a particular focus on subgroups. Methods Randomized controlled trials (RCTs) were retrieved from CENTRAL, Clinicaltrials.gov, EMBASE, PubMed, and WHO ICTRP. The primary outcome measurement was HE. The secondary outcome measurements included 3-month poor functional outcome (PFO), 3-month mortality, and major thromboembolic events (MTE). We conducted subgroup analysis according to the CT markers of HE (standard-risk population and high-risk population) and the time from onset to randomization (>4.5 and ≤4.5 h). Results We identified seven studies (representing five RCTs) involving 2,650 participants. Compared with placebo, TXA may reduce HE on subsequent imaging (odd ratio [OR] 0.825; 95% confidence interval [CI] 0.692-0.984; p = 0.033; I2 = 0%; GRADE moderate certainty). TXA and placebo arms did not differ in the rates of 3-month PFO, 3-month mortality, and MTE. Subgroup analysis indicated that TXA reduced the risk of HE in the high-risk population with CT markers of HE (OR 0.646; 95% CI 0.503-0.829; p = 0.001; I2 = 0 %) and in patients who were treated within 4.5 h of symptom onset (OR 0.823; 95% CI 0.690-0.980; p = 0.029; I2 = 0%), but this protective effect was not observed in the standard-risk population and patients who were treated over 4.5 h of symptom onset. Conclusions Tranexamic acid (TXA) may decrease the risk of HE in patients with acute spontaneous ICH. Importantly, the decreased risk was observed in patients who were treatable within 4.5 h and with a high risk of HE, but not in those who were treatable over 4.5 h and in standard-risk population. However, PFO or mortality at 3 months did not significantly differ between patients who received TXA and those who received placebo. TXA is safe for acute spontaneous ICH without increasing MTE.Background and Purpose The aim of this study was to determine the relationship between the heart rate-corrected QT (QTc) interval and the risk of incident long-term mortality in patients with acute ischemic stroke (AIS), considering the impact of sex differences on clinical characteristics, outcomes, and QTc intervals. Methods We analyzed prospectively registered data included patients with AIS who visited the emergency room within 24 h of stroke onset and underwent routine cardiac testing, such as measurements of cardiac enzymes and 12-lead ECG. QTc interval was corrected for heart rate using Fridericia's formula and was stratified by sex-specific quartiles. Cox proportional hazards models were used to examine the association between baseline QTc interval and incident all-cause death. Results A total of 1,668 patients with 1,018 (61.0%) men and mean age 66.0 ± 12.4 years were deemed eligible. Based on the categorized quartiles of the QTc interval, cardiovascular risk profile, and stroke severity increased with prolonged QTc interval, and the risk of long-term mortality increased over a median follow-up of 33 months. Cox proportional hazard model analysis showed that the highest quartile of QTc interval (≥479 msec in men and ≥498 msec in women; hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.07-2.08) was associated with all-cause death. Furthermore, dichotomized QTc interval prolongation, defined by the highest septile of the QTc interval (≥501 ms in men and ≥517 m in women HR 1.33, 95% CI 1.00-1.80) was significantly associated with all-cause mortality after adjusting for all clinically relevant variables, such as stroke severity. Conclusions Prolonged QTc interval was associated with increased risk of long-term mortality, in parallel with the increasing trend of prevalence of cardiovascular risk profiles and stroke severity, across sex differences in AIS patients.Introduction We investigated whether the toe-brachial index (TBI) is associated with stroke prognosis and evaluated this association in patients with normal ankle-brachial index (ABI). Methods Acute ischemic stroke patients who underwent TBI measurements were enrolled. Poor functional outcome was defined as modified Rankin Scale score ≥3. Major adverse cardiovascular event (MACE) was defined as stroke recurrence, myocardial infarction, or death. Normal ABI was defined as 0.9 ≤ ABI ≤ 1.4. Results A total of 1,697 patients were enrolled and followed up for a median 39.7 (interquartile range, 25.7-54.6) months. During the period, 305 patients suffered MACE (18.0%), including 171 (10.1%) stroke recurrences. TBI was associated with hypertension, diabetes, atrial fibrillation, aortic plaque score, ABI, and brachial-ankle pulse wave velocity (all p less then 0.05). In multivariable logistic regression, TBI was inversely associated with poor functional outcome in all patients [odds ratio (OR) 0.294, 95% confidence interval (CI) 0.114-0.759], even in patients with normal ABI (OR 0.293, 95% CI 0.095-0.906). In multivariable Cox regression, TBI less then 0.6 was associated with stroke recurrence [hazard ratio (HR) 1.651, 95% CI 1.135-2.400], all-cause mortality (HR 2.105, 95% CI 1.343-3.298), and MACE (HR 1.838, 95% CI 1.396-2.419) in all patients. TBI less then 0.6 was also associated with stroke recurrence (HR 1.681, 95% CI 1.080-2.618), all-cause mortality (HR 2.075, 95% CI 1.180-3.651), and MACE (HR 1.619, 95% CI 1.149-2.281) in patients with normal ABI. Conclusions Low TBI is independently associated with poor short- and long-term outcomes in acute ischemic stroke patients despite normal ABI.Introduction The role of near-infrared spectroscopy (NIRS) for the evaluation of cerebral haemodynamics is gaining increasing popularity because of its noninvasive nature. The aim of this study was to evaluate the role of the integral components of regional cerebral oxygenation (rSO2) measured by NIRS [i.e., arterial-oxyhemoglobin (O2Hbi) and venous-deoxyhemoglobin (HHbi)-components], as indirect surrogates of cerebral blood flow (CBF) in a cohort of critically ill patients with coronavirus disease 2019 (COVID-19). We compared these findings to the gold standard technique for noninvasive CBF assessment, Transcranial Doppler (TCD). Methods Mechanically ventilated patients with COVID-19 admitted to the Intensive Care Unit (ICU) of Policlinico San Martino Hospital, Genova, Italy, who underwent multimodal neuromonitoring (including NIRS and TCD), were included. rSO2 and its components [relative changes in O2Hbi, HHbi, and total haemoglobin (cHbi)] were compared with TCD (cerebral blood flow velocity, CBFV). Changed patients with COVID-19.Background and Purpose Butylphtalide increases the vascular endothelial growth factor (VEGF) and decreases matrix metalloproteinase (MMP)-9 in animal models of stroke and might be of use in the management of stroke. To explore whether butylphthalide combined with conventional treatment can change the levels of MMP-9 and VEGF and the National Institutes of Health Stroke Scale (NIHSS) scores of patients with stroke. Methods This was a prospective cohort study involving inpatients admitted to the Jiangxi Provincial People's Hospital (January-June 2019) due to acute cerebral infarction. The patients received conventional treatments with or without butylphthalide. The changes in the NIHSS scores were compared between groups. Plasma MMP-9 and VEGF were measured by enzyme-linked immunosorbent assay. Results A total of 24 patients were included in the conventional treatment group and 46 in the butylphthalide group. The butylphthalide group showed lower MMP-9 (130 ± 59 vs. 188 ± 65, p = 0.001) and higher VEGF (441 ± 121 vs. 378 ± 70, p = 0.034) levels on day 6 compared with the conventional treatment group. The changes in MMP-9 and VEGF were significant, starting on day 3 in the butylphthalide group but on day 6 in the conventional treatment group. There were no differences between the two groups in the NIHSS scores at admission and at discharge (p > 0.05). The overall response rate was higher in the butylphthalide group compared with the conventional treatment group (63.0 vs. 37.5%, p = 0.042). Conclusion Butylphthalide combined with conventional treatment can decrease MMP-9 levels and increase VEGF levels. The patients showed the reduced NIHSS scores, possibly suggesting some improvement in prognosis after stroke. Still, the conclusions need to be confirmed in a larger sample and in different etiological subtypes of stroke.This study examines the effect of CEOs' early-life traumatic experience on firm-specific stock price crash risk. Drawing on the idea of natural experiments, we take the Great Famine in China as an external traumatic event which cannot be selected or controlled by human. The analysis points out that compensation psychology and irrational defense psychology after the trauma of Great Famine are important factors that cause CEOs to hoard bad news. Based on a large sample of Chinese companies from 2007 to 2017, we find evidence that CEOs who experienced the Great Famine during early-life tend to hoard bad news, which result in higher stock price crash risk. The more severe and prolonged the Great Famine that the CEOs experienced, the greater the effect of this traumatic experience. CEOs decision-making power enhances the adverse effect of CEOs' early-life traumatic experiences on crash risk. Findings of this study contributes to the literature by providing a new explanation for the stock price crash risk, which is of great significance for the sustained and healthy development of capital markets.
Here's my website: