Generalized Green's functions for higher order boundary value matrix differential systems

In this paper, a Green's matrix function for higher order two point boundary value differential matrix problems is constructed. By using the concept of rectangular co-solution of certain algebraic matrix equation associated to the problem, an existence condition as well as an explicit closed form expression for the solution of possibly not well-posed boundary value problems is given avoiding the increase of the problem dimension

Preliminary Water Assessment Reports of The Test Basins of The Watch Project

This report presents the initial plans of the case studies how they link to rest of the Watch project and on which water resources they will focus. This report will function as the basis for further discussions on how to improve the integration of the case studies within the project and to develop a more general protocol for each of the case studies. Currently 5 catchments are used within the Watch project, they differ in climatic and hydro-geological features and expected climate changes: the Glomma River basin (Eastern Norway), the upper Guadiana basin (Central Spanish Plateau), the Nitra River basin (central Slovakia), the Upper-Elbe basin (part of the Elbe River) and the island of Crete. Also the water resources issues vary over these cases. Agricultural (and domestic) water use is under pressure in the Mediterranean catchments probably aggravating with the expected increase in drought frequency under future climate. The Norwegian catchment provides hydropower services under threat of precipitation increase rather than decrease. The central European catchments are threatened mainly by increased variability, i.e. increased frequencies of extremes in a densely populated environment, and river flow may need additional buffers (reservoirs) to reduce floodrisk and store water for dry period

Two-Photon Na+ Imaging Reports Somatically Evoked Action Potentials in Rat Olfactory Bulb Mitral and Granule Cell Neurites

Dendrodendritic synaptic interactions are a hallmark of neuronal processing in the vertebrate olfactory bulb. Many classes of olfactory bulb neurons including the principal mitral cells (MCs) and the axonless granule cells (GCs) dispose of highly efficient propagation of action potentials (AP) within their dendrites, from where they can release transmitter onto each other. So far, backpropagation in GC dendrites has been investigated indirectly via Ca2+ imaging. Here, we used two-photon Na+ imaging to directly report opening of voltage-gated sodium channels due to AP propagation in both cell types. To this end, neurons in acute slices from juvenile rat bulbs were filled with 1 mM SBFI via whole-cell patch-clamp. Calibration of SBFI signals revealed that a change in fluorescence Delta F/F by 10% corresponded to a Delta[Na+](i) of similar to 22 mM. We then imaged proximal axon segments of MCs during somatically evoked APs (sAP). While single sAPs were detectable in similar to 50% of axons, trains of 20 sAPs at 50 Hz always resulted in substantial Delta F/F of similar to 15% (similar to 33 mM Delta[Na+](i)). Delta F/F was significantly larger for 80 Hz vs. 50 Hz trains, and decayed with half-durations tau(1/2) similar to 0.6 s for both frequencies. In MC lateral dendrites, AP trains yielded small Delta F/F of similar to 3% (similar to 7 mM Delta[Na+](i)). In GC apical dendrites and adjacent spines, single sAPs were not detectable. Trains resulted in an average dendritic Delta F/F of 7% (16 mM Delta[Na+](i)) with tau(1/2) similar to 1 s, similar for 50 and 80 Hz. Na+ transients were indistinguishable between large GC spines and their adjacent dendrites. Cell-wise analysis revealed two classes of GCs with the first showing a decrease in Delta F/F along the dendrite with distance from the soma and the second an increase. These classes clustered with morphological parameters. Simulations of Delta[Na+](i) replicated these behaviors via negative and positive gradients in Na+ current density, assuming faithful AP backpropagation. Such specializations of dendritic excitability might confer specific temporal processing capabilities to bulbar principal cell-GC subnetworks. In conclusion, we show that Na+ imaging provides a valuable tool for characterizing AP invasion of MC axons and GC dendrites and spines

TBE vaccination breakthrough cases—Does age matter?

Funding Information: Funding: This study was sponsored by Pfizer Inc. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Tick-borne encephalitis (TBE) vaccines are highly effective in preventing TBE and vaccine failures (VF) are rare events. In this study, we compared the age distribution of TBE cases and TBE VF in three endemic countries: Sweden, Southern Germany, and Latvia. While the age distribution of TBE cases was similar for those <50 years versus those ≥50 years in all three countries, in Sweden, a higher proportion of VF cases was ≥50 years, whereas most VF cases in Latvia were <50 years of age and more evenly distributed between those <50 years versus those ≥50 in Southern Germany. Here, theoretical explanations were provided, including differences in diagnostic practices, vaccine uptake between age groups, behavioral patterns and underlying medical conditions, as to why VF were generally older in Sweden than the other countries. There is no scientific rationale to give an extra priming dose of TBE vaccine to subjects ≥50 years of age.publishersversionPeer reviewe

Virtual reality-based early neurocognitive stimulation in critically ill patients: A pilot randomized clinical trial

This study focuses on the application of a non-immersive virtual reality (VR)-based neurocognitive intervention in critically ill patients. Our aim was to assess the feasibility of direct outcome measures to detect the impact of this digital therapy on patients’ cognitive and emotional outcomes. Seventy-two mechanically ventilated adult patients were randomly assigned to the “treatment as usual” (TAU, n = 38) or the “early neurocognitive stimulation” (ENRIC, n = 34) groups. All patients received standard intensive care unit (ICU) care. Patients in the ENRIC group also received adjuvant neurocognitive stimulation during the ICU stay. Outcome measures were a full neuropsychological battery and two mental health questionnaires. A total of 42 patients (21 ENRIC) completed assessment one month after ICU discharge, and 24 (10 ENRIC) one year later. At onemonth follow-up, ENRIC patients had better working memory scores (p = 0.009, d = 0.363) and showed up to 50% less non-specific anxiety (11.8% vs. 21.1%) and depression (5.9% vs. 10.5%) than TAU patients. A general linear model of repeated measures reported a main effect of group, but not of time or group–time interaction, on working memory, with ENRIC patients outperforming TAU patients (p = 0.008, ¿p2 = 0.282). Our results suggest that non-immersive VR-based neurocognitive stimulation may help improve short-term working memory outcomes in survivors of critical illness. Moreover, this advantage could be maintained in the long term. An efficacy trial in a larger sample of participants is feasible and must be conducted. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Extracellular Vesicles (EVs) for discovering Biomarkers of Systemic Lupus Erythematosus (SLE) by using Proteomic techniques and Bioinformatics analyses.

Congresos y Conferencias: Comunicación de Congreso - Póster - En línea.Objectives: SLE is a multifactorial and heterogeneous disease, difficult to diagnose. The objective of this work is to discover possible non-invasive biomarkers in extracellular vesicles, to improve the diagnosis and monitoring of SLE. Methods: EVs from peritoneal exudates have been isolated from two groups of mice with pristane-induced lupus after 2 weeks: CD38-deficient (CD38ko) mice and wild type mice (WT). The purification of the EVs was carried out by exclusion chromatography. Protein identification was carried out by liquid chromatography coupled to MS/MS, and functional protein analyses were addressed using ClueGO v2.5.7 + CluePedia v1.5.7 applications within Cytoscape v3.8.0. For relative quantification of the common proteins we used the exponentially modified protein abundance index (emPAI) normalized to the sum of all emPAI values (% molar). Volcano plots and statistical analyses were performed with GraphPad Prism v8.4.3. Searching for homologous human proteins related with SLE and blood was performed with StringApp within Cytoscape. Results: The protein analysis has been approached from three perspectives: (i) proteins that are only expressed in EVs from CD38ko, (ii) proteins that are only expressed in EVs from WT, and (iii) proteins that are expressed in both groups (common proteins). Volcano plots showed that 45 out of 224 identified common proteins differed significantly in protein abundance between WT vs CD38ko, while 81 proteins were unique to either WT or CD38ko mice. Searching for homologous human serum proteins that were associated with SLE, 29 out of these 45+81 proteins gave a significant score using the StringApp. Conclusions: In this study we have identified 29 possible biomarkers from extracellular vesicles, detectable in plasma or serum, which could help to better classify SLE patients and study the progression of the disease. Future perspectives: To isolate EVs from plasma or urine of SLE patients, to look for reliable biomarkers for the diagnosis of a disease as heterogeneous and complex as SLE

Genealogical typing of Neisseria meningitidis

Despite the increasing popularity of multilocus sequence typing (MLST), the most appropriate method for characterizing bacterial variation and facilitating epidemiological investigations remains a matter of debate. Here, we propose that different typing schemes should be compared on the basis of their power to infer clonal relationships and investigate the utility of sequence data for genealogical reconstruction by exploiting new statistical tools and data from 20 housekeeping loci for 93 isolates of the bacterial pathogen Neisseria meningitidis. Our analysis demonstrated that all but one of the hyperinvasive isolates established by multilocus enzyme electrophoresis and MLST were grouped into one of six genealogical lineages, each of which contained substantial variation. Due to the confounding effect of recombination, evolutionary relationships among these lineages remained unclear, even using 20 loci. Analyses of the seven loci in the standard MLST scheme using the same methods reproduced this classification, but were unable to support finer inferences concerning the relationships between the members within each complex

Effect of an early neurocognitive rehabilitation on autonomic nervous system in critically ill patients

Introduction Recent clinical and electrophysiological studies reveal a high incidence of autonomic nervous system (ANS) dys- function in patients treated in ICU [1]. ANS disturbances may produce diverse and unexpected consequences. For instance, critically ill patients are at risk of neurocognitive impairments that may persist after hospital discharge. Among various pathophysiological mechanisms proposed, ANS dysfunction leading cholinergic deficiency seems one of the most viable to explain the development of long-term sequelae. Heart rate variability (HRV) has been related to the activity of the prefrontal cortex [2] hence, prefrontal activation could help to strengthen the auto- nomic nervous system integrity. We are interested in assessing the improvement of the ANS dysfunction through neural circuits’ activation. Thus, we propose a novel therapy that could allow the reinforcing of ANS through an early neurocognitive intervention targeted to improve prefrontal activation. Objectives The aim of this study was to explore if the integrity of the ANS, via cardiac vagal tone, measured by the HRV can be modified after early neurocognitive rehabilitation in ICU patients. Methods A total of 17 critically ill patients received a 20-minute Early Neurocognitive Rehabilitation (ENR) session in their own bed in the ICU. HRV was derived from the recorded ECG signal during pre-session, session and post-session. Power in the specific frequency bands related to sympathetic and parasympathetic systems was computed (PLF and PHF for low and high frequency bands, respectively). PLF was computed within the clas- sic band, while PHF was computed within a band cen- tered at respiratory rate. Changes in the HRV parameters from pre-session to session, and from pre- session to post-session were studied using Wilcoxon signed-rank test. Results Clinical data of the sample are summarized in table 1. Comparing with baseline values, 9 patients (53%) showed a decreased PLF in post-session, while 8 patients (47%) presented a higher PLF (p = .759). In 12 patients (71%), PHF increased after the ENR session, suggesting an increase of parasympathetic activity (p = .836). Conclusions Diagnosis, severity of illness or medication could explain the differential effect in the evolution of the HRV para- meters among different patients. Despite differences, an early neurocognitive rehabilitation seems to increase parasympathetic activity after the session in the majority of the patients. Clinical characteristics of the critical ill patients should be further studied to determinate which patients could be the best candidates for early neurocog- nitive intervention

Changes in serogroup and genotype prevalence among carried meningococci in the United Kingdom during vaccine implementation.

BACKGROUND: Herd immunity is important in the effectiveness of conjugate polysaccharide vaccines against encapsulated bacteria. A large multicenter study investigated the effect of meningococcal serogroup C conjugate vaccine introduction on the meningococcal population. METHODS: Carried meningococci in individuals aged 15-19 years attending education establishments were investigated before and for 2 years after vaccine introduction. Isolates were characterized by multilocus sequence typing, serogroup, and capsular region genotype and changes in phenotypes and genotypes assessed. RESULTS: A total of 8462 meningococci were isolated from 47 765 participants (17.7%). Serogroup prevalence was similar over the 3 years, except for decreases of 80% for serogroup C and 40% for serogroup 29E. Clonal complexes were associated with particular serogroups and their relative proportions fluctuated, with 12 statistically significant changes (6 up, 6 down). The reduction of ST-11 complex serogroup C meningococci was probably due to vaccine introduction. Reasons for a decrease in serogroup 29E ST-254 meningococci (from 1.8% to 0.7%) and an increase in serogroup B ST-213 complex meningococci (from 6.7% to 10.6%) were less clear. CONCLUSIONS: Natural fluctuations in carried meningococcal genotypes and phenotypes a can be affected by the use of conjugate vaccines, and not all of these changes are anticipatable in advance of vaccine introduction