17 research outputs found
Infection of brain pericytes underlying neuropathology of covidâ19 patients
A wide range of neurological manifestations have been associated with the development of COVIDâ19 following SARSâCoVâ2 infection. However, the etiology of the neurological sympto-matology is still largely unexplored. Here, we used stateâofâtheâart multiplexed immunostaining of human brains (n = 6 COVIDâ19, median age = 69.5 years; n = 7 control, median age = 68 years) and demonstrated that expression of the SARSâCoVâ2 receptor ACE2 is restricted to a subset of neuro-vascular pericytes. Strikingly, neurological symptoms were exclusive to, and ubiquitous in, patients that exhibited moderate to high ACE2 expression in perivascular cells. Viral dsRNA was identified in the vascular wall and paralleled by perivascular inflammation, as signified by T cell and macro-phage infiltration. Furthermore, fibrinogen leakage indicated compromised integrity of the bloodâ brain barrier. Notably, cerebrospinal fluid from additional 16 individuals (n = 8 COVIDâ19, median age = 67 years; n = 8 control, median age = 69.5 years) exhibited significantly lower levels of the pericyte marker PDGFRÎČ in SARSâCoVâ2âinfected cases, indicative of disrupted pericyte homeostasis. We conclude that pericyte infection by SARSâCoVâ2 underlies virus entry into the privileged central nervous system space, as well as neurological symptomatology due to perivascular inflammation and a locally compromised bloodâbrain barrier
Coding Early Naturalists' Accounts into Long-Term Fish Community Changes in the Adriatic Sea (1800â2000)
The understanding of fish communities' changes over the past centuries has important implications for conservation policy and marine resource management. However, reconstructing these changes is difficult because information on marine communities before the second half of the 20th century is, in most cases, anecdotal and merely qualitative. Therefore, historical qualitative records and modern quantitative data are not directly comparable, and their integration for long-term analyses is not straightforward. We developed a methodology that allows the coding of qualitative information provided by early naturalists into semi-quantitative information through an intercalibration with landing proportions. This approach allowed us to reconstruct and quantitatively analyze a 200-year-long time series of fish community structure indicators in the Northern Adriatic Sea (Mediterranean Sea). Our analysis provides evidence of long-term changes in fish community structure, including the decline of Chondrichthyes, large-sized and late-maturing species. This work highlights the importance of broadening the time-frame through which we look at marine ecosystem changes and provides a methodology to exploit, in a quantitative framework, historical qualitative sources. To the purpose, naturalists' eyewitness accounts proved to be useful for extending the analysis on fish community back in the past, well before the onset of field-based monitoring programs
Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias
BackgroundCardiac sympathetic denervation (CSD) has been shown to reduce the burden of implantable cardioverter-defibrillator (ICD) shocks in small series of patients with structural heart disease (SHD) and recurrent ventricular tachyarrhythmias (VT).ObjectivesThis study assessed the value of CSD and the characteristics associated with outcomes in this population.MethodsPatients with SHD who underwent CSD for refractory VT or VT storm at 5 international centers were analyzed by the International Cardiac Sympathetic Denervation Collaborative Group. Kaplan-Meier analysis was used to estimate freedom from ICD shock, heart transplantation, and death. Cox proportional hazards models were used to analyze variables associated with ICD shock recurrence and mortality after CSD.ResultsBetween 2009 and 2016, 121 patients (age 55 ± 13 years, 26% female, mean ejection fraction of 30 ± 13%) underwent left or bilateral CSD. One-year freedom from sustained VT/ICD shock and ICD shock, transplant, and death were 58% and 50%, respectively. CSD reduced the burden of ICD shocks from a mean of 18 ± 30 (median 10) in the year before study entry to 2.0 ± 4.3 (median 0) at a median follow-up of 1.1 years (p < 0.01). On multivariable analysis, pre-procedure New York Heart Association functional class III and IV heart failure and longer VT cycle lengths were associated with recurrent ICD shocks, whereas advanced New York Heart Association functional class, longer VT cycle lengths, and a left-sided-only procedure predicted the combined endpoint of sustained VT/ICD shock recurrence, death, and transplantation. Of the 120 patients taking antiarrhythmic medications before CSD, 39 (32%) no longer required them at follow-up.ConclusionsCSD decreased sustained VT and ICD shock recurrence in patients with refractory VT. Characteristics independently associated with recurrence and mortality were advanced heart failure, VT cycle length, and a left-sided-only procedure