Cerebrospinal fluid findings in patients with neurological manifestations in post-COVID-19 syndrome

BACKGROUND: Information on cerebrospinal fluid (CSF) findings in patients with neurological manifestations in post-COVID-19 syndrome is scarce. METHODS: Retrospective evaluation of 84 CSF samples in patients fulfilling post-COVID-19 criteria in two neurological post-COVID-19 outpatient clinics. RESULTS: In 68% of samples, all CSF parameters were normal. The most frequent pathological CSF finding was elevation of total protein (median total protein 33.3 mg/dl [total range 18.5-116.2]) in 20 of 83 (24%) samples. The second most prevalent pathological finding was a blood-CSF barrier dysfunction as measured by elevation of QAlb (median QAlb 4.65 [2.4-13.2]) in 11/84 (13%). Pleocytosis was found in only 5/84 (6%) samples and was mild in all of them. CSF-restricted oligoclonal bands were found in 5/83 (6%) samples. Anti-neuronal autoantibodies in CSF were negative in most cases, whilst 12/68 (18%) samples were positive for anti-myelin autoantibodies in serum. PCR for herpesviridae (HSV-1/-2, VZV, EBV, CMV, HHV6) showed, if at all, only weakly positive results in CSF or EDTA whole blood/plasma. CONCLUSIONS: The majority of samples did not show any pathologies. The most frequent findings were elevation of total protein and blood-CSF barrier dysfunction with no signs of intrathecal inflammation. CSF analysis still keeps its value for exclusion of differential diagnoses

Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity

Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels targeting several G-protein coupled receptors (GPCR). In this exploratory study, we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and asymptomatic post COVID-19 controls (n=40) were also included in the study as control groups. We found lower levels for various AABs in PCS compared to at least one control group, accompanied by alterations in the correlations among AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1, and ADRA2A as the strongest classifiers (AABs stratifying patients according to disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms were associated with ADRB2 AAB levels in PCS/ME/CFS patients. Our study identified dysregulation of AAB against various receptors involved in the autonomous nervous system (ANS), vaso-, and immunoregulation and their correlation with symptom severity, pointing to their role in the pathogenesis of PCS

The Governance of Global Innovation Systems: Putting Knowledge in Context

Technological innovation increasingly depends on multiscalar actor networks and institutions. However, the developers of many conceptual frameworks explaining innovation success have paid only limited attention to this new reality, due to their focus on regions and countries as agents that shape innovation governance and as containers that provide institutional conditions for innovation success. In particular, innovation systems literature has been criticized in this respect. In the present chapter, we refer to the recently formulated Global Innovation Systems approach, which enables researchers to capture the emergence of system resources across spatial scales. With this framework, we emphasize that beyond the focus on knowledge generation processes, a better understanding of valuation processes is necessary to guide governance structures for generating new technologies and products. This is particularly true for sectors that are oriented towards confronting grand challenges, such as cleantech industries

Exploring the role of instrument design and instrument interaction for eco-innovation: a survey-based analysis of renewable energy innovation in Germany

Empirical research on eco-innovation has produced a substantive body of literature on the relevance of regulation for stimulating such innovation. Much of this work on the role of policy for eco-innovation relies on econometric analyses of company survey data. In this regard, the eco-innovation module introduced in 2008/9 in the Community Innova-tion Survey serves as an important data source that has helped improve our under-standing of the role of environmental and innovation policy for eco-innovation in the Eu-ropean Union (EU). However, so far, this data source has provided only limited oppor-tunities to generate insights into the role of instrument design and instrument interaction for eco-innovation. In this chapter, we present a first attempt to measure such aspects in a company innovation survey based on the example of renewable energy innovation in Germany. In particular, we explore to what extent the design of the German Renewa-ble Energy Sources Act (and the interaction of its feed-in tariffs with the EU emissions trading system) correlates with innovation in renewable power generation technologies. We find instrument design features but not instrument type to be related to eco-innovation. In addition, our exploratory study provides evidence for an interaction effect between climate policy and renewables support policy. Based on these findings, we discuss implications for future research on the role of policy in eco-innovation

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.</p

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Neuroticism and conscientiousness are associated with cortisol diurnal profiles in adults-Role of positive and negative affect

A substantial body of research on the pathophysiology of negative health outcomes has focused on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Maladaptive and adaptive personality features have been discussed to be associated with health outcomes. In the current study, we investigated the association of neuroticism (N) and conscientiousness (C) with diurnal cortisol levels in 102 working parents (M age=37 years; 50% female). Further, we examined the impact of daily positive and negative affect on this association. During a 6-day time-sampling phase, cortisol was measured at awakening and after that within intervals of 3h. We found a positive association of N with cortisol levels throughout the measurement period, but no association of C with daily cortisol. When accounting for daily positive and negative affect, individuals with high scores on C displayed reductions in daily cortisol concentrations that were driven by positive affect compared to individuals with low C scores. No such association emerged for N. Our findings might further elucidate the role of personality in HPA axis regulation and improve our understanding of the association of endocrine states and health outcomes