Interferon-alpha or -beta facilitates SARS-CoV-2 pulmonary vascular infection by inducing ACE2

Severe viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a hyperinflammatory state typified by elevated circulating pro-inflammatory cytokines, frequently leading to potentially lethal vascular complications including thromboembolism, disseminated intracellular coagulopathy and vasculitis. Though endothelial infection and subsequent endothelial damage have been described in patients with fatal COVID-19, the mechanism by which this occurs remains elusive, particularly given that, under naïve conditions, pulmonary endothelial cells demonstrate minimal cell surface expression of the SARS-CoV-2 binding receptor ACE2. Herein we describe SARS-CoV-2 infection of the pulmonary endothelium in postmortem lung samples from individuals who died of COVID-19, demonstrating both heterogeneous ACE2 expression and endothelial damage. In primary endothelial cell cultures, we show that SARS-CoV-2 infection is dependent on the induction of ACE2 protein expression and that this process is facilitated by type 1 interferon-alpha (IFNα) or -beta(β)—two of the main anti-viral cytokines induced in severe SARS-CoV-2 infection—but not significantly by other cytokines (including interleukin 6 and interferon γ/λ). Our findings suggest that the stereotypical anti-viral interferon response may paradoxically facilitate the propagation of COVID-19 from the respiratory epithelium to the vasculature, raising concerns regarding the use of exogenous IFNα/β in the treatment of patients with COVID-19.

     

The Bright Side of Grit in Burnout-Prevention: Exploring Grit in the Context of Demands-Resources Model among Chinese High School Students

This study contributes to understanding students’ emotional responses to academic stressors by integrating grit into the well-established Job Demands-Resources Model and by examining the relationship between academic demands, grit (consistency of interests, perseverance of effort), burnout, engagement, academic achievement, depression, and life satisfaction in Chinese students. We conducted a self-report study with N?=?1527 Chinese high school students (M_age?=?16.38 years, SD?=?1.04). The results of structural equation modeling showed that after controlling for gender, socio-economic status, and school types, demands positively related to burnout and negatively related to engagement. Both facets of grit negatively related to exhaustion, whereas only perseverance of effort positively related to engagement. Burnout positively related to depression and negatively related to life satisfaction, whereas engagement positively related to life satisfaction. However, neither burnout nor engagement was related to academic achievement. Our findings indicate that grit may be protective against school burnout.

     

DSC perfusion-based collateral imaging and quantitative T2 mapping to assess regional recruitment of leptomeningeal collaterals and microstructural cortical tissue damage in unilateral steno-occlusive vasculopathy

Leptomeningeal collateral supply is considered pivotal in steno-occlusive vasculopathy to prevent chronic microstructural ischaemic tissue damage. The aim of this study was to assess the alleged protective role of leptomeningeal collaterals in patients with unilateral high-grade steno-occlusive vasculopathy using quantitative (q)T2 mapping and perfusion-weighted imaging (PWI)-based collateral abundance. High-resolution qT2 was used to estimate microstructural damage of the segmented normal-appearing cortex. Volumetric abundance of collaterals was assessed based on PWI source data. The ratio relative cerebral blood flow/relative cerebral blood volume (rCBF/rCBV) as a surrogate of relative cerebral perfusion pressure (rCPP) was used to investigate the intravascular hemodynamic competency of pial collateral vessels and the hemodynamic state of brain parenchyma. Within the dependent vascular territory with increased cortical qT2 values (P = 0.0001) compared to the contralateral side, parenchymal rCPP was decreased (P = 0.0001) and correlated negatively with increase of qT2 (P  < 0.05). Furthermore, volumetric abundance of adjacent leptomeningeal collaterals was significantly increased (P < 0.01) and negatively correlated with changes of parenchymal rCPP (P = 0.01). Microstructural cortical damage is closely related to restrictions of antegrade blood flow despite increased pial collateral vessel abundance. Therefore, increased leptomeningeal collateral supply cannot necessarily be regarded as a sign of effective compensation in patients with high-grade steno-occlusive vasculopathy.     

Nusinersen treatment significantly improves hand grip strength,hand motor function and MRC sum scores in adult patients with spinal muscular atrophy types 3 and 4

Journal of Neurology - Nusinersen recently became available as the first treatment for Spinal Muscular Atrophy (SMA) and data on its effectiveness and safety in adult SMA patients are still scarce....     

Endurance running acutely raises plasma osteoprotegerin and lowers plasma receptor activator of nuclear factor kappa B ligand

Abstract The balance of the 2 cytokines, osteoprotegerin (OPG) and the receptor activator of nuclear factor kappa B ligand (soluble (s)RANKL), is known to have considerable influence on bone formation and degradation. Plasma concentrations of OPG and (s)RANKL were determined in a total of 31 long-distance runners before and immediately after running distances of either 15 or 42.195 km, respectively. In both groups of endurance runners, a significant decrease of sRANKL was observed during the run, the extent of which correlated to the running distance. Furthermore, OPG increased only in runners covering the marathon distance of 42.195 km. We hypothesize that the known positive effect of long-distance running on the skeletal mass may be mediated by the OPG/sRANKL system.     

A Lifetime of Allograft Function with Kidneys from Older Donors

Strategies to increase expanded criteria donor (ECD) transplantation are needed. We quantified the extent to which ECD kidneys provide recipients with a lifetime of allograft function by determining the difference between patient survival and death-censored allograft survival (graft survival). Initial analyses compared 5-year outcomes in the Eurotransplant Senior Program (European) and the United States Renal Data System. Among European recipients ≥65 years, patient survival exceeded graft survival, and ECD recipients returned to dialysis for an average of 5.2 months after transplant failure. Among United States recipients ≥60 years, graft survival exceeded patient survival. Although patient survival in elderly recipients in the United States was low (49% at 5 years), the average difference in patient survival at 10 years in elderly recipients in the United States with an ECD versus non-ECD transplant was only 7 months. The probability of patient survival with a functioning allograft at 5 years was higher with ECD transplantation within 1 year after activation to the waiting list than with delayed non-ECD transplantation ≥3 years after activation to the waiting list. Subsequent analyses demonstrated that ECD transplants do not provide a lifetime of allograft function in recipients <50 years in the United States. These findings should encourage ECD transplantation in patients ≥60 years, demonstrate that rapid ECD transplantation is superior to delayed non-ECD transplantation, and challenge the policy in the United States of allowing patients <50 years to receive an ECD transplant.     

Treatment options in painful chronic pancreatitis: a systematic review

Background

Longlasting and unbearable pain is the most common and striking symptom of chronic pancreatitis. Accordingly, pain relief and improvement in patients'' quality of life are the primary goals in the treatment of this disease. This systematic review aims to summarize the available data on treatment options.

Methods

A systematic search of MEDLINE/PubMed and the Cochrane Library was performed according to the PRISMA statement for reporting systematic reviews and meta-analysis. The search was limited to randomized controlled trials and meta-analyses. Reference lists were then hand-searched for additional relevant titles. The results obtained were examined individually by two independent investigators for further selection and data extraction.

Results

A total of 416 abstracts were reviewed, of which 367 were excluded because they were obviously irrelevant or represented overlapping studies. Consequently, 49 full-text articles were systematically reviewed.

Conclusions

First-line medical options include the provision of pain medication, adjunctive agents and pancreatic enzymes, and abstinence from alcohol and tobacco. If medical treatment fails, endoscopic treatment offers pain relief in the majority of patients in the short term. However, current data suggest that surgical treatment seems to be superior to endoscopic intervention because it is significantly more effective and, especially, lasts longer.