Immunological profiling in long COVID:overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity

Background: Many patients with SARS-CoV-2 infection develop long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immune profiling of fatigued and non-fatigued long COVID patients and age- and sex-matched healthy controls (HCs). Methods:Long COVID symptoms were assessed using patient-reported outcome measures, including the fatigue assessment scale (FAS, scores ≥22 denote fatigue), and followed up to one year after hospital discharge. We assessed inflammation-related genes in circulating monocytes, serum levels of inflammation-regulating cytokines, and leukocyte and lymphocyte subsets, including major monocyte subsets and senescent T-lymphocytes, at 3-6 months post-discharge. Results: We included 37 fatigued and 36 non-fatigued long COVID patients and 42 HCs. Fatigued long COVID patients represented a more severe clinical profile than non-fatigued patients, with many concurrent symptoms (median 9 [IQR 5.0-10.0] vs 3 [1.0-5.0] symptoms, p&lt;0.001), and signs of cognitive failure (41%) and depression (&gt;24%). Immune abnormalities that were found in the entire group of long COVID patients were low grade inflammation (increased inflammatory gene expression in monocytes, increased serum pro-inflammatory cytokines) and signs of T-lymphocyte senescence (increased exhausted CD8+ TEMRA-lymphocytes). Immune profiles did not significantly differ between fatigued and non-fatigued long COVID groups. However, the severity of fatigue (total FAS score) significantly correlated with increases of intermediate and non-classical monocytes, upregulated gene levels of CCL2, CCL7, and SERPINB2 in monocytes, increases in serum Galectin-9, and higher CD8+ T-lymphocyte counts. Conclusion: Long COVID with fatigue is associated with many concurrent and persistent symptoms lasting up to one year after hospitalization. Increased fatigue severity associated with stronger signs of monocyte activation in long COVID patients and potentially point in the direction of monocyte-endothelial interaction. These abnormalities were present against a background of immune abnormalities common to the entire group of long COVID patients.</p

Retrospective French nationwide survey of childhood aggressive vascular anomalies of bone, 1988-2009

<p>Abstract</p> <p>Objective</p> <p>To document the epidemiological, clinical, histological and radiological characteristics of aggressive vascular abnormalities of bone in children.</p> <p>Study design</p> <p>Correspondents of the French Society of Childhood Malignancies were asked to notify all cases of aggressive vascular abnormalities of bone diagnosed between January 1988 and September 2009.</p> <p>Results</p> <p>21 cases were identified; 62% of the patients were boys. No familial cases were observed, and the disease appeared to be sporadic. Mean age at diagnosis was 8.0 years [0.8-16.9 years]. Median follow-up was 3 years [0.3-17 years]. The main presenting signs were bone fracture (n = 4) and respiratory distress (n = 7), but more indolent onset was observed in 8 cases. Lung involvement, with lymphangiectasies and pleural effusion, was the most frequent form of extraosseous involvement (10/21). Bisphosphonates, alpha interferon and radiotherapy were used as potentially curative treatments. High-dose radiotherapy appeared to be effective on pleural effusion but caused major late sequelae, whereas antiangiogenic drugs like alpha interferon and zoledrenate have had a limited impact on the course of pulmonary complications. The impact of bisphosphonates and alpha interferon on bone lesions was also difficult to assess, owing to insufficient follow-up in most cases, but it was occasionally positive. Six deaths were observed and the overall 10-year mortality rate was about 30%. The prognosis depended mainly on pulmonary and spinal complications.</p> <p>Conclusion</p> <p>Aggressive vascular abnormalities of bone are extremely rare in childhood but are lifethreatening. The impact of anti-angiogenic drugs on pulmonary complications seems to be limited, but they may improve bone lesions.</p

Budżetowanie działalności jednostek gospodarczych Teoria i praktyka. Część V

Z wprowadzenia: "Przekazujemy do rąk Czytelników część monografii dotyczącej budżetowania jednostek gospodarczych. Jej przygotowanie zbiegło się z ukazaniem się manifestu Precz z budżetami Jeremiego Норе’а i Robina Frasera. Autorzy poddają tam ostrej krytyce dotychczasowe praktyki stosowania budżetowania kosztowego. Stąd niniejsza publikacja - między innymi - dlatego różni się istotnie od poprzednich. Od pewnego czasu - także w Polsce - pojawiały się głosy wskazujące na istotne niedoskonałości budżetowania kosztowego, na przykład J. Gierusz [Materiały konferencyjne 2001], G. H. Świderska [Rachunkowośćzarządcza i rachunek kosztów, 2002]. Nie odnosiły one jednak skutku. Nie zauważono też dotąd narastającej listy zarzutów wytaczanych przeciw finansowym jednostkom miary stosowanym w budżetowaniu kosztowym, na przykład G. K. Świderska [jak wyżej], M. Sierpińska, B. Niedbała [Controllingoperacyjny wpnedsiębiorstwie, 2003]. Bez echa pozostało postawione przez autora pytanie: „zmierzch czy rozwój budżetowania?” [„Controlling i rachunkowość zarządcza” 9/2002], gdzie jednoznacznie wskazano, że budżetowanie kosztowe obejmuje jedynie jedną sferę działalności przedsiębiorstwa i tym samym nie może stanowić wystarczającej podstawy do sterowania przedsiębiorstwem. Zwolennicy budżetowania kosztowego nawet zgadzali się ze stawianymi zarzutami, jednak nie reagowali na propozycje zmian w filozofii i metodologii budżetowania."(...

Motor imagery during action observation: A brief review of evidence, theory and future research opportunities

Motor imagery (MI) and action observation (AO) have traditionally been viewed as two separate techniques, which can both be used alongside physical practice to enhance motor learning and rehabilitation. Their independent use has been shown to be effective, and there is clear evidence that the two processes can elicit similar activity in the motor system. Building on these well-established findings, research has now turned to investigate the effects of their combined use. In this article, we first review the available neurophysiological and behavioral evidence for the effects of combined action observation and motor imagery (‘AO+MI’) on motor processes. We next describe a conceptual framework for their combined use, and then discuss several areas for future research into AO+MI processes. In this review, we advocate a more integrated approach to AO+MI techniques than has previously been adopted by movement scientists and practitioners alike. We hope this early review of an emergent body of research, along with a related set of research questions, can inspire new work in this area. We are optimistic that future research will further confirm if, how, and when this combined approach to AO+MI can be more effective in motor learning and rehabilitation settings, relative to the more traditional application of AO or MI independently

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Nationalization processes in Czechoslovakia on the example of CKD

The work deals with the nationalization in 1945 and its subsequent effects on the example of Czechoslovakia industrial company CKD. The paper presents the results of research in which I discovered that it was nationalized CKD did not help. The main blame for this are insensitive, politically motivated interference in the structure of CKD. When CKD is becoming a tool for achieving political goals. Another important reason is the limitation of the market economy and competition. The internal reason is too high wages, which did not correspond with work productivity. At work I perform comparison operations CKD before the war and after nationalization in order to get information on how to lead economically. The work is not forgotten page of the legislative framework and assumptions nationalization nationalization in Czechoslovakia. The work compares theoretical and practical side of the page nationalizatio