During the coronavirus disease 2019 (COVID-19) pandemic, Long COVID syndrome, which impairs patients through cognitive deficits, fatigue, and exhaustion, has become increasingly relevant. Its ...underlying pathophysiology, however, is unknown. In this study, we assessed cognitive profiles and regional cerebral glucose metabolism as a biomarker of neuronal function in outpatients with long-term neurocognitive symptoms after COVID-19. Methods: Outpatients seeking neurologic counseling with neurocognitive symptoms persisting for more than 3 mo after polymerase chain reaction (PCR)–confirmed COVID-19 were included prospectively between June 16, 2020, and January 29, 2021. Patients (n = 31; age, 53.6 ± 2.0 y) in the long-term phase after COVID-19 (202 ± 58 d after positive PCR) were assessed with a neuropsychologic test battery. Cerebral 18F-FDG PET imaging was performed in 14 of 31 patients. Results: Patients self-reported impaired attention, memory, and multitasking abilities (31/31), word-finding difficulties (27/31), and fatigue (24/31). Twelve of 31 patients could not return to the previous level of independence/employment. For all cognitive domains, average group results of the neuropsychologic test battery showed no impairment, but deficits (z score < −1.5) were present on a single-patient level mainly in the domain of visual memory (in 7/31; other domains ≤ 2/31). Mean Montreal Cognitive Assessment performance (27/30 points) was above the cutoff value for detection of cognitive impairment (<26 points), although 9 of 31 patients performed slightly below this level (23–25 points). In the subgroup of patients who underwent 18F-FDG PET, we found no significant changes of regional cerebral glucose metabolism. Conclusion: Long COVID patients self-report uniform symptoms hampering their ability to work in a relevant fraction. However, cognitive testing showed minor impairments only on a single-patient level approximately 6 mo after the infection, whereas functional imaging revealed no distinct pathologic changes. This clearly deviates from previous findings in subacute COVID-19 patients, suggesting that underlying neuronal causes are different and possibly related to the high prevalence of fatigue.
While neuropathological examinations in patients who died from COVID-19 revealed inflammatory changes in cerebral white matter, cerebral MRI frequently fails to detect abnormalities even in the ...presence of neurological symptoms. Application of multi-compartment diffusion microstructure imaging (DMI), that detects even small volume shifts between the compartments (intra-axonal, extra-axonal and free water/CSF) of a white matter model, is a promising approach to overcome this discrepancy. In this monocentric prospective study, a cohort of 20 COVID-19 inpatients (57.3 ± 17.1 years) with neurological symptoms (e.g. delirium, cranial nerve palsies) and cognitive impairments measured by the Montreal Cognitive Assessment (MoCA test; 22.4 ± 4.9; 70% below the cut-off value <26/30 points) underwent DMI in the subacute stage of the disease (29.3 ± 14.8 days after positive PCR). A comparison of whole-brain white matter DMI parameters with a matched healthy control group (n = 35) revealed a volume shift from the intra- and extra-axonal space into the free water fraction (V-CSF). This widespread COVID-related V-CSF increase affected the entire supratentorial white matter with maxima in frontal and parietal regions. Streamline-wise comparisons between COVID-19 patients and controls further revealed a network of most affected white matter fibres connecting widespread cortical regions in all cerebral lobes. The magnitude of these white matter changes (V-CSF) was associated with cognitive impairment measured by the MoCA test (r = -0.64, P = 0.006) but not with olfactory performance (r = 0.29, P = 0.12). Furthermore, a non-significant trend for an association between V-CSF and interleukin-6 emerged (r = 0.48, P = 0.068), a prominent marker of the COVID-19 related inflammatory response. In 14/20 patients who also received cerebral 18F-FDG PET, V-CSF increase was associated with the expression of the previously defined COVID-19-related metabolic spatial covariance pattern (r = 0.57; P = 0.039). In addition, the frontoparietal-dominant pattern of neocortical glucose hypometabolism matched well to the frontal and parietal focus of V-CSF increase. In summary, DMI in subacute COVID-19 patients revealed widespread volume shifts compatible with vasogenic oedema, affecting various supratentorial white matter tracts. These changes were associated with cognitive impairment and COVID-19 related changes in 18F-FDG PET imaging.
Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits T-cell activation and is expressed on T-regulatory cells. Human CTLA-4 deficiency results in severe immune dysregulation. Abatacept (CTLA-4 Ig) is ...approved for the treatment of rheumatoid arthritis (RA) and its mechanism of action is attributed to effects on T-cells. It is known that CTLA-4 modulates the expression of its ligands CD80 and CD86 on antigen presenting cells (APC) by transendocytosis. As B-cells express CD80/CD86 and function as APC, we hypothesize that B-cells are a direct target of abatacept.
To investigate direct effects of abatacept on human B-lymphocytes in vitro and in RA patients.
The effect of abatacept on healthy donor B-cells’ phenotype, activation and CD80/CD86 expression was studied in vitro. Nine abatacept-treated RA patients were studied. Seven of these were followed up to 24 months, and two up to 12 months only and treatment response, immunoglobulins, ACPA, RF concentrations, B-cell phenotype and ACPA-specific switched memory B-cell frequency were assessed.
B-cell development was unaffected by abatacept. Abatacept treatment resulted in a dose-dependent decrease of CD80/CD86 expression on B-cells in vitro, which was due to dynamin-dependent internalization. RA patients treated with abatacept showed a progressive decrease in plasmablasts and serum IgG. While ACPA-titers only moderately declined, the frequency of ACPA-specific switched memory B-cells significantly decreased.
Abatacept directly targets B-cells by reducing CD80/CD86 expression. Impairment of antigen presentation and T-cell activation may result in altered B-cell selection, providing a new therapeutic mechanism and a base for abatacept use in B-cell mediated autoimmunity.
•CTLA-4 contributes to the maintenance of B-cell tolerance.•Abatacept directly modulates CD80/CD86 expression.•Abatacept treatment results in a decrease of self-antigen specific memory B-cells in vivo.
Abatacept impairs expression of CD80 and CD86 on B-cells thereby modulating their antigen presenting cell function, leading to a reduced autoantigen-specific memory B-cell frequency in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
sp. nov. has recently been reported as a novel human pathogenic spirochete causing Lyme disease (LD) in North America. Previous data reveal a higher spirochaetemia in the blood compared to patients ...infected by LD spirochetes belonging to the
sensu lato complex, suggesting that this novel genospecies must exploit strategies to overcome innate immunity, in particular complement. To elucidate the molecular mechanisms of immune evasion, we utilized various methodologies to phenotypically characterize
and to identify determinants involved in the interaction with complement. Employing serum bactericidal assays, we demonstrated that
resists complement-mediated killing. To further elucidate the role of the key regulators of the alternative pathway (AP), factor H (FH), and FH-like protein 1 (FHL-1) in immune evasion of
, serum adsorption experiments were conducted. The data revealed that viable spirochetes recruit both regulators from human serum and FH retained its factor I-mediated C3b-inactivating activity when bound to the bacterial cells. In addition, two prominent FH-binding proteins of approximately 30 and 18 kDa were detected in
strain MN14-1420. Bioinformatics identified a gene, exhibiting 60% identity at the DNA level to the
encoding gene of
. Following PCR amplification, the gene product was produced as a His-tagged protein. The CspA-orthologous protein of
interacted with FH and FHL-1, and both bound regulators promoted inactivation of C3b in the presence of factor I. Additionally, the CspA ortholog counteracted complement activation by inhibiting the alternative and terminal but not the classical and Lectin pathways, respectively. Increasing concentrations of CspA of
also strongly affected C9 polymerization, terminating the formation of the membrane attack complex. To assess the role of CspA of
in facilitating serum resistance, a gain-of-function strain was generated, harboring a shuttle vector allowing expression of the CspA encoding gene under its native promotor. Spirochetes producing the native protein on the cell surface overcame complement-mediated killing, indicating that CspA facilitates serum resistance of
. In conclusion, here we describe the molecular mechanism utilized by
to resists complement-mediated killing by capturing human immune regulators.
Résumé: Cet article a pour but de présenter comment les apports du modèle psychophysiologique bio-existentialiste élaboré par Vezio Ruggieri et ses collaborateurs peuvent jeter une lumière nouvelle ...sur les processus sous-jacents le jeu de l'acteur tels que la présence scénique, le processus d'identification avec un personnage et le complexe mécanisme de la prosodie. Cet encadrement théorique, qui voit le rapport corps-esprit dans une relation circulaire, éclairera le lecteur sur les bases physiologiques de la perception et de l'imagination ainsi que sur le rôle fondamental que la structure musculaire joue dans la construction de ces phénomènes.
Abstract: This article aims at presenting how the contributions of the bio-existentialist psychophysiological model conceptualized by Vezio Ruggieri and his collaborators can bring a new light on some core elements underlying acting such as stage presence, identification process with a character and the complex mechanism of prosody. This theoretical mark, which sees the connection body-mind in a circular relation, will enlighten the reader on the physiological basis of perception and imagination as well as on the fundamental role that the muscular structure plays within the construction of these phenomena.
Resumo: Este artigo tem como objetivo apresentar a forma como as contribuições do modelo psicofisiológico bioexistencialista desenvolvido por Vezio Ruggieri e seus colaboradores podem trazer uma nova compreensão sobre os processos subjacentes do jogo do ator, como a presença cênica, o processo de identificação com um personagem e o mecanismo complexo da prosódia. Esse contexto teórico, que considera a conexão corpo-mente como uma relação circular, esclarece ao leitor as bases fisiológicas da percepção e da imaginação, bem como o papel fundamental que a estrutura muscular desempenha na construção desses fenômenos.
ABSTRACT - A New Psychophysical Approach in Contemporary Theater Pedagogy - This article aims at presenting how the contributions of the bio-existentialist psychophysiological model conceptualized by ...Vezio Ruggieri and his collaborators can bring a new light on some core elements underlying acting such as stage presence, identification process with a character and the complex mechanism of prosody. Ramener sur le même plan physiologique les processus perceptifs et imaginatifs ouvre des possibilités d'application dans l'art théâtral en travaillant sur les connexions entre la construction des expériences liées à la relation avec le monde extérieur, et la formation des représentations internes auto-générées par le texte par exemple. The Running Horse Stops: the hypothetical role of the eyes in imagery movement, Perceptual and Motor Skills, Missoula, AmSci Publications, n. 89, p. 1088-1092, 1999. ABSTRACT - A New Psychophysical Approach in Contemporary Theater Pedagogy - This article aims at presenting how the contributions of the bio-existentialist psychophysiological model conceptualized by Vezio Ruggieri and his collaborators can bring a new light on some core elements underlying acting such as stage presence, identification process with a character and the complex mechanism of prosody. RÉSUMÉ - Une Nouvelle Orientation Psychophysique dans la Pédagogie Théâtrale Contemporaine - Cet article a pour but de présenter comment les apports du modèle psychophysiologique bio-existentialiste élaboré par Vezio Ruggieri et ses collaborateurs peuvent jeter une lumière nouvelle sur les processus sous-jacents le jeu de l'acteur tels que la présence scénique, le processus d'identification avec un personnage et le complexe mécanisme de la prosodie. The Running Horse Stops: the hypothetical role of the eyes in imagery movement, Perceptual and Motor Skills, Missoula, AmSci Publications, n. 89, p. 1088-1092, 1999.
While it is acknowledged that child obesity interventions should cover multiple ecological levels (downstream, midstream and upstream) to maximize their effectiveness, there is a lack of evaluation ...data to guide the development and implementation of such efforts. To commence addressing this knowledge gap, the present study provides process evaluation data relating to the experiences of groups implementing the EPODE approach to child obesity prevention in various locations around the world. The aim of this exploratory study was to investigate the barriers and facilitators to program implementation in program sites around the world to assist in developing strategies to enhance program outcomes.
An online survey that included open-ended questions was distributed to the 25 EPODE programs in operation at the time of the survey (May 2012). The survey items asked respondents to comment on those aspects of program implementation that they found challenging and to suggest areas for future improvement. Eighteen programs representing 14 countries responded to the request to participate in the survey, yielding a 72% response rate. The responses were analyzed via the constant comparative method using NVivo qualitative data analysis software.
The main concerns of the various EPODE programs were their ability to secure ongoing funding and their access to evidence-based intervention methods and policy advice relating to relationships with third parties. These issues were in turn impacted by other factors, including (i) access to user-friendly information relating to the range of intervention strategies available and appropriate evaluation measures; (ii) assistance with building and maintaining stakeholder relationships; and (iii) assurance of the quality, independence, and transparency of policies and practices.
The findings are facilitating the ongoing refinement of the EPODE approach. In particular, standardized and tailored information packages are being made available to advise program members of (i) the various evaluation methods and tools at their disposal and (ii) methods of acquiring private partner support. Overall, the study results relating to the types of issues encountered by program members are likely to be useful in guiding the future design and implementation of multi-level initiatives seeking to address other complex and intractable health-related problems.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Uma Nova Abordagem Psicofísica na Pedagogia Teatral Contemporânea Vezio Ruggieri (Università degli Studi di Roma La Sapienza – Roma, Itália); Lea Walter (Associazione Psicofisiologi Clinici per l’Integrazione Sociale – Roma, Itália)
Revista Brasileira de Estudos da Presença,
08/2015, Volume:
5, Issue:
3
Journal Article
Open access
Este artigo tem como objetivo apresentar a forma como as contribuições do modelo psicofisiológico bioexistencialista desenvolvido por Vezio Ruggieri e seus colaboradores podem trazer uma nova ...compreensão sobre os processos subjacentes do jogo do ator, como a presença cênica, o processo de identificação com um personagem e o mecanismo complexo da prosódia. Esse contexto teórico, que considera a conexão corpo-mente como uma relação circular, esclarece ao leitor as bases fisiológicas da percepção e da imaginação, bem como o papel fundamental que a estrutura muscular desempenha na construção desses fenômenos.
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