Connerhjort4168

Addition of miR-34a-5p or miR-125b-5p attenuated Aβ-induced apoptosis and oxidative stress. BACE1 acted as a target of miR-34a-5p and miR-125b-5p and its restoration weakened the effect of miR-34a-5p or miR-125b-5p on Aβ-induced neurotoxicity. Moreover, EGCG could mitigate Aβ-induced neurotoxicity, which might be associated with miR-34a-5p and miR-125b-5p. CONCLUSION miR-34a-5p and miR-125b-5p inhibited Aβ-induced neurotoxicity by decreasing apoptosis and oxidative stress via targeting BACE1, providing novel targets for treatment of AD. BACKGROUND It is poorly understood how public perception of the difference between brain death and circulatory death may influence attitudes towards organ donation. We investigated the public opinion on brain death versus circulatory death and documented inconsistencies in the legislations of countries with different cultural and socioeconomic backgrounds. METHODS Using a crowdsourcing approach, we randomized 1072 participants from 30 countries to a case report of organ donation after brain death or to one following circulatory death. Further, we sampled guidelines from 24 countries and 5 continents. RESULTS Of all participants, 73% stated they would be willing to donate all organs, while 16% would want to donate some of their organs. To increase the rate of donations, 47% would agree with organ donation without family consent as the default. Exposure to "brain death" was not associated with a lesser likelihood of participants agreeing with organ donation (82.1%) compared to "circulatory death" (81.9%; relative risk 1.02, 95% CI 0.99 to 1.03; p = .11). However, participants exposed to "circulatory death" were more certain that the patient was truly dead (87.9% ± 19.7%) than participants exposed to "brain death" (84.1% ± 22.7%; Cohen's d 0.18; p = 0004). Sampling of guidelines revealed large differences between countries regarding procedures required to confirm brain death and circulatory death, respectively. CONCLUSIONS Implementation of organ donation after circulatory death is unlikely to negatively influence the willingness to donate organs, but legislation is still brain death-based in most countries. The time seems ripe to increase the rate of circulatory death-based organ donation. OBJECTIVE Aneurysm growth is a risk factor for rupture, however the detailed mechanism remains unclear. The present study was performed to identify whether hemodynamic insult could prompt small unruptured aneurysms to grow. METHODS Six pairs of unruptured small (50% volume increase; n = 6) and an angiographic stable group (with ±10% volume changes; n = 6). Patient-specific computational fluid dynamic models were created and run under pulsatile flow conditions. Reverse reconstruction technique was used to simulate the status of before aneurysm generation. Relevant hemodynamic variables were calculated and compared between the two groups. RESULTS In the enlarged group, wall shear stress (WSS) decreased from aneurysm neck to dome, whereas WSS at the aneurysm neck (58.68 ± 34.45 Pa) and body (52.68 ± 46.37 Pa) was significantly higher than the stable group (neck 36.83 ± 18.20 Pa and body 30.77 ± 18.85 Pa) (P  less then  .05). Nutlin-3 WSS decreased at the neck, body, and dome and flow patent became stable after aneurysm growth (P  less then  .05). Reverse reconstruction revealed an elevated WSS at the site of aneurysm formation compared with other sites in the parent artery, and WSS at the formation site significantly decreased after aneurysm growth and further enlargement (P  less then  .05). CONCLUSION Local elevated WSS to the arterial wall contributed to cerebral aneurysm generation, whereas turbulent flow patterns and elevated WSS at the aneurysm neck and body worked together to result in further growth of small aneurysms. INTRODUCTION There is scarce evidence comparing the behavior in magnetic resonance (MRI) between positive and negative aquaporin-4 antibody neuromyelitis optica spectrum disorders (P-NMOSD and NNMOSD, respectively). The aim of this study was to describe and compare MRI features through a quantitative and qualitative analysis between P-NMOSD and NNMOSD patients in a cohort from Latin American (LATAM) patients. METHODS We retrospectively reviewed the MRI and medical records of NMOSD patients as defined by the 2015 validated diagnostic criteria, and with at least 3 years of follow-up from disease onset (first symptom). We included patients from Argentina, Brazil and Venezuela. To be included, NMOSD patients must have had AQP4-ab status measured by a cell-based assay. Brain MRIs were obtained for each participant at disease onset and every 12 months for 3 years. Demographics, clinical and MRI variables (T2 lesion volume [T2LV], lesion distribution, cortical thickness [CT] and percentage of brain volume loss [PBVL]) were analyzed and compared between groups (P-NMOSD; NNMOSD) at disease onset and follow-up. A multiple sclerosis (MS) control group of patients was also included. RESULTS We included 24 P-NMOSD, 15 NNMOSD and 35 MS patients. No differences in age, gender and follow-up time were observed between groups. Nor were differences found in lesion distribution at disease onset or in brain volumes during follow-up between P-NMOSD and NNMOSD patients (T2LV = 0.43, CT = 0.12, PBVL p = 0.45). Significant differences were observed in lesion distribution at disease onset, as well as in brain volumes during follow-up between NMOSD and MS (T2LV = p less then 0.001, CT = p less then 0.001, PBVL p = 0.01). CONCLUSION Different MRI features were observed between MS and NMOSD. However, no quantitative nor qualitative differences were observed between P-NMOSD and NNMOSD, not allowing us to differentiate NMOSD conditions by MRI. OBJECTIVES In the pre-azole era, central nervous system (CNS) infections with Aspergillus had a dismal outcome. Survival improved with voriconazole but CNS infections caused by azole-resistant A. fumigatus is precluding its use. Intravenous liposomal-amphotericin B (L-AmB) is the preferred treatment option for azole-resistant CNS infections but has suboptimal brain concentrations. METHODS We describe three patients with biopsy proven CNS aspergillosis where intraventricular L-AmB is added to systemic therapy. 2 patients with azole-resistant and 1 patient with azole-susceptible CNS aspergillosis were treated with intraventricular L-AmB at a dose of 1 mg weekly. RESULTS We describe 3 patients successfully treated with a combination of intravenous and intraventricular L-AmB. All three patients survived but one patient has serious headache, most likely not related to this treatment. CONCLUSIONS Intraventricular L-AmB may have a role in the treatment of therapy-refractory CNS aspergillosis when added to systemic therapy.