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Article ; Online: The complement alternative pathway and hemostasis.

Noris, Marina / Galbusera, Miriam

2022 Volume 313, Issue 1, Page(s) 139–161

Abstract: The complement and hemostatic systems are complex systems, and both involve enzymatic cascades, regulators, and cell components-platelets, endothelial cells, and immune cells. The two systems are ancestrally related and are defense mechanisms that limit ... ...

Abstract	The complement and hemostatic systems are complex systems, and both involve enzymatic cascades, regulators, and cell components-platelets, endothelial cells, and immune cells. The two systems are ancestrally related and are defense mechanisms that limit infection by pathogens and halt bleeding at the site of vascular injury. Recent research has uncovered multiple functional interactions between complement and hemostasis. On one side, there are proteins considered as complement factors that activate hemostasis, and on the other side, there are coagulation proteins that modulate complement. In addition, complement and coagulation and their regulatory proteins strongly interact each other to modulate endothelial, platelet and leukocyte function and phenotype, creating a potentially devastating amplifying system that must be closely regulated to avoid unwanted damage and\or disseminated thrombosis. In view of its ability to amplify all complement activity through the C3b-dependent amplification loop, the alternative pathway of complement may play a crucial role in this context. In this review, we will focus on available and emerging evidence on the role of the alternative pathway of complement in regulating hemostasis and vice-versa, and on how dysregulation of either system can lead to severe thromboinflammatory events.
MeSH term(s)	Humans ; Endothelial Cells ; Hemostasis ; Blood Coagulation ; Blood Platelets/metabolism ; Thrombosis ; Complement System Proteins/metabolism
Chemical Substances	Complement System Proteins (9007-36-7)
Language	English
Publishing date	2022-10-22
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.13150
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Article ; Online: The complement alternative pathway and hemostasis

Noris, Marina / Galbusera, Miriam

Immunological Reviews 2023 Jan., v. 313, no. 1, p. 139-161

2023 , Page(s) 139–161

Abstract: The complement and hemostatic systems are complex systems, and both involve enzymatic cascades, regulators, and cell components—platelets, endothelial cells, and immune cells. The two systems are ancestrally related and are defense mechanisms that limit ... ...

Abstract	The complement and hemostatic systems are complex systems, and both involve enzymatic cascades, regulators, and cell components—platelets, endothelial cells, and immune cells. The two systems are ancestrally related and are defense mechanisms that limit infection by pathogens and halt bleeding at the site of vascular injury. Recent research has uncovered multiple functional interactions between complement and hemostasis. On one side, there are proteins considered as complement factors that activate hemostasis, and on the other side, there are coagulation proteins that modulate complement. In addition, complement and coagulation and their regulatory proteins strongly interact each other to modulate endothelial, platelet and leukocyte function and phenotype, creating a potentially devastating amplifying system that must be closely regulated to avoid unwanted damage and\or disseminated thrombosis. In view of its ability to amplify all complement activity through the C3b‐dependent amplification loop, the alternative pathway of complement may play a crucial role in this context. In this review, we will focus on available and emerging evidence on the role of the alternative pathway of complement in regulating hemostasis and vice‐versa, and on how dysregulation of either system can lead to severe thromboinflammatory events.
Keywords	coagulation ; complement ; hemostasis ; leukocytes ; phenotype ; thrombosis
Language	English
Dates of publication	2023-01
Size	p. 139-161.
Publishing place	John Wiley & Sons, Inc
Document type	Article ; Online
Note	REVIEW
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.13150
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Why Dialogue is Effective in Schizophrenia Treatment

Laura Galbusera / Miriam Kyselo

Humana.Mente: Journal of Philosophical Studies, Vol 12, Iss

Insights from the Open Dialogue Approach and Enactive Cognitive Science

2019 Volume 36

Abstract: In this paper we focus on the psychiatric approach of Open Dialogue (OD) and seek to explain why the intersubjective process of dialogue, one of OD’s core clinical principles, is effective in schizophrenia treatment. We address this question from an ... ...

Abstract	In this paper we focus on the psychiatric approach of Open Dialogue (OD) and seek to explain why the intersubjective process of dialogue, one of OD’s core clinical principles, is effective in schizophrenia treatment. We address this question from an interdisciplinary viewpoint, by linking the OD approach with a theoretical account of the self as endorsed by enactive cognitive science. The paper is structured as follows: first, we introduce the OD approach and focus in particular on the principles that are characteristic of the dialogical therapeutic attitude. Second, we clarify our stance on the concept of schizophrenia by relying on insights from phenomenological psychiatry. Third, we introduce an enactive perspective on mental disorders, which elaborates on phenomenological psychiatry and conceives of the self as a self-organizing system, brought forth through interactional processes. Based on this enactive approach, we draw clinical implications for schizophrenia. In the fourth and final part, we propose conceptual bridges between the OD and the enactive approach by bringing to attention the intersubjective nature of the human self and the inherent vulnerability entailed in both the self’s maintenance and in the practice of dialogue. We then propose that the dialogical stance adopted by OD is effective in supporting the recovery of a balanced sense of self precisely because it provides an intersubjective space in which clients can safely experience and maintain the basic structures underlying the socially constituted self. Since our analysis touches upon fundamental structures of the therapeutic relationship, we hope that it will also be useful to inform general psychiatric practice and help advancing a more integrative understanding of psychotherapy for schizophrenia.
Keywords	Schizophrenia ; Therapeutic Relationship ; Dialogical Stance ; Open Dialogue ; Enactive Cognitive Science ; Social Self ; Philosophy (General) ; B1-5802
Subject code	120
Language	English
Publishing date	2019-12-01T00:00:00Z
Publisher	Associazione Culturale Humana.Mente
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The difference that makes the difference

Galbusera, Laura / Kyselo, Miriam

Psychosis - Psychological, Social and Integrative Approaches

A conceptual analysis of the open dialogue approach

2018 Volume 10, Issue 1, Page(s) 47–54

Abstract: In this paper we focus on the Open Dialogue (OD) approach to acute psychosis with the aim of better understanding and clarifying the principles underlying its efficacy. To do this, we do a conceptual analysis of the OD literature. We introduce the basic ... ...

Title translation	Der Unterschied, der den Unterschied macht: Eine konzeptionelle Analyse des offenen Dialogansatzes
Abstract	In this paper we focus on the Open Dialogue (OD) approach to acute psychosis with the aim of better understanding and clarifying the principles underlying its efficacy. To do this, we do a conceptual analysis of the OD literature. We introduce the basic principles of the OD approach and focus on the dialogical process, which stands out as a core healing factor of this practice. In particular, we shed light on one element that yields and sustains dialogue: the dialogical therapeutic stance. We systematise and disentangle different descriptions of the dialogical therapeutic stance and derive some of its essential properties. Based on this, we finally propose a clear-cut definition of the dialogical therapeutic stance as comprising two necessary and constitutive aspects: openness and authenticity. We believe that this conceptualisation might usefully inform the OD practice and theory, and eventually contribute to advance research on the treatment of schizophrenia.
Keywords	Authenticity ; Authentizität ; Interpersonal Communication ; Interpersonal Interaction ; Interpersonale Interaktion ; Interpersonale Kommunikation ; Offenheit für Erfahrungen ; Openness to Experience ; Patient Centered Care ; Patientenzentrierte Versorgung ; Psychose ; Psychosis ; Psychotherapeutic Processes ; Psychotherapeutische Prozesse ; Psychotherapie ; Psychotherapy ; Schizophrenia ; Schizophrenie ; Therapieerfolgskontrolle ; Treatment Effectiveness Evaluation
Language	English
Document type	Article
ZDB-ID	2478582-9
ISSN	1752-2447 ; 1752-2439
ISSN (online)	1752-2447
ISSN	1752-2439
DOI	10.1080/17522439.2017.1397734
Database	PSYNDEX

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Article ; Online: Interpersonal synchrony feels good but impedes self-regulation of affect.

Galbusera, Laura / Finn, Michael T M / Tschacher, Wolfgang / Kyselo, Miriam

Scientific reports

2019 Volume 9, Issue 1, Page(s) 14691

Abstract: The social benefits of interpersonal synchrony are widely recognized. Yet, little is known about its impact on the self. According to enactive cognitive science, the human self for its stability and regulation needs to balance social attunement with ... ...

Abstract	The social benefits of interpersonal synchrony are widely recognized. Yet, little is known about its impact on the self. According to enactive cognitive science, the human self for its stability and regulation needs to balance social attunement with disengagement from others. Too much interpersonal synchrony is considered detrimental for a person's ability to self-regulate. In this study, 66 adults took part in the Body-Conversation Task (BCT), a dyadic movement task promoting spontaneous social interaction. Using whole-body behavioural imaging, we investigated the simultaneous impact of interpersonal synchrony (between persons) and intrapersonal synchrony (within a person) on positive affect and self-regulation of affect. We hypothesized that interpersonal synchrony's known tendency to increase positive affect would have a trade-off, decreasing a person's ability to self-regulate affect. Interpersonal synchrony predicted an increase in positive affect. Consistent with our hypothesis, it simultaneously predicted a weakening in self-regulation of affect. Intrapersonal synchrony, however, tended to oppose these effects. Our findings challenge the widespread belief that harmony with others has only beneficial effects, pointing to the need to better understand the impact of interaction dynamics on the stability and regulation of the human self.
MeSH term(s)	Adult ; Affect ; Berlin ; Cooperative Behavior ; Emotional Regulation ; Female ; Humans ; Interpersonal Relations ; Male ; Motor Activity ; Young Adult
Language	English
Publishing date	2019-10-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-50960-0
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Article ; Online: An

Gastoldi, Sara / Aiello, Sistiana / Galbusera, Miriam / Breno, Matteo / Alberti, Marta / Bresin, Elena / Mele, Caterina / Piras, Rossella / Liguori, Lucia / Santarsiero, Donata / Benigni, Ariela / Remuzzi, Giuseppe / Noris, Marina

Frontiers in immunology

2023 Volume 14, Page(s) 1112257

Abstract: Introduction: Comprehensive genetic analysis is essential to clinical care of patients with atypical haemolytic uremic syndrome (aHUS) to reinforce diagnosis, and to guide treatment. However, the characterization of complement gene variants remains ... ...

Abstract	Introduction: Comprehensive genetic analysis is essential to clinical care of patients with atypical haemolytic uremic syndrome (aHUS) to reinforce diagnosis, and to guide treatment. However, the characterization of complement gene variants remains challenging owing to the complexity of functional studies with mutant proteins. This study was designed: 1) To identify a tool for rapid functional determination of complement gene variants; 2) To uncover inherited complement dysregulation in aHUS patients who do not carry identified gene variants. Methods: To address the above goals, we employed an ex-vivo assay of serum-induced C5b-9 formation on ADP-activated endothelial cells in 223 subjects from 60 aHUS pedigrees (66 patients and 157 unaffected relatives). Results: Sera taken from all aHUS patients in remission induced more C5b-9 deposition than control sera, independently from the presence of complement gene abnormalities. To avoid the possible confounding effects of chronic complement dysregulation related to aHUS status, and considering the incomplete penetrance for all aHUS-associated genes, we used serum from unaffected relatives. In control studies, 92.7% of unaffected relatives with known pathogenic variants exhibited positive serum-induced C5b-9 formation test, documenting a high sensitivity of the assay to identify functional variants. The test was also specific, indeed it was negative in all non-carrier relatives and in relatives with variants non-segregating with aHUS. All but one variants in aHUS-associated genes predicted in-silico as likely pathogenic or of uncertain significance (VUS) or likely benign resulted as pathogenic in the C5b-9 assay. At variance, variants in putative candidate genes did not exhibit a functional effect, with the exception of a Discussion: In conclusion, the serum-induced C5b-9 formation test in unaffected relatives of aHUS patients may be a tool for rapid functional evaluation of rare complement gene variants. When combined with exome sequencing the assay might be of help in variant selection, to identify new aHUS-associated genetic factors.
MeSH term(s)	Humans ; Complement Membrane Attack Complex/genetics ; Complement Membrane Attack Complex/metabolism ; Endothelial Cells/metabolism ; Atypical Hemolytic Uremic Syndrome/diagnosis ; Atypical Hemolytic Uremic Syndrome/genetics ; Complement System Proteins/genetics ; Complement System Proteins/therapeutic use ; Pedigree
Chemical Substances	Complement Membrane Attack Complex ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2023-02-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1112257
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Interpersonal synchrony feels good but impedes self-regulation of affect

Laura Galbusera / Michael T. M. Finn / Wolfgang Tschacher / Miriam Kyselo

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 12

Abstract: Abstract The social benefits of interpersonal synchrony are widely recognized. Yet, little is known about its impact on the self. According to enactive cognitive science, the human self for its stability and regulation needs to balance social attunement ... ...

Abstract	Abstract The social benefits of interpersonal synchrony are widely recognized. Yet, little is known about its impact on the self. According to enactive cognitive science, the human self for its stability and regulation needs to balance social attunement with disengagement from others. Too much interpersonal synchrony is considered detrimental for a person’s ability to self-regulate. In this study, 66 adults took part in the Body-Conversation Task (BCT), a dyadic movement task promoting spontaneous social interaction. Using whole-body behavioural imaging, we investigated the simultaneous impact of interpersonal synchrony (between persons) and intrapersonal synchrony (within a person) on positive affect and self-regulation of affect. We hypothesized that interpersonal synchrony’s known tendency to increase positive affect would have a trade-off, decreasing a person’s ability to self-regulate affect. Interpersonal synchrony predicted an increase in positive affect. Consistent with our hypothesis, it simultaneously predicted a weakening in self-regulation of affect. Intrapersonal synchrony, however, tended to oppose these effects. Our findings challenge the widespread belief that harmony with others has only beneficial effects, pointing to the need to better understand the impact of interaction dynamics on the stability and regulation of the human self.
Keywords	Medicine ; R ; Science ; Q
Subject code	150
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-CoV-2 Spike Protein 1 Activates Microvascular Endothelial Cells and Complement System Leading to Platelet Aggregation.

Perico, Luca / Morigi, Marina / Galbusera, Miriam / Pezzotta, Anna / Gastoldi, Sara / Imberti, Barbara / Perna, Annalisa / Ruggenenti, Piero / Donadelli, Roberta / Benigni, Ariela / Remuzzi, Giuseppe

Frontiers in immunology

2022 Volume 13, Page(s) 827146

Abstract: Microvascular thrombosis is associated with multiorgan failure and mortality in coronavirus disease 2019 (COVID-19). Although thrombotic complications may be ascribed to the ability of SARS-CoV-2 to infect and replicate in endothelial cells, it has been ... ...

Abstract	Microvascular thrombosis is associated with multiorgan failure and mortality in coronavirus disease 2019 (COVID-19). Although thrombotic complications may be ascribed to the ability of SARS-CoV-2 to infect and replicate in endothelial cells, it has been poorly investigated whether, in the complexity of viral infection in the human host, specific viral elements alone can induce endothelial damage. Detection of circulating spike protein in the sera of severe COVID-19 patients was evaluated by ELISA.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Angiotensin-Converting Enzyme 2 ; COVID-19 ; Complement System Proteins/metabolism ; Endothelial Cells/metabolism ; Humans ; Platelet Aggregation ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Complement System Proteins (9007-36-7) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-03-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.827146
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Article ; Online: Case Report: Effects of Anti-SARS-CoV-2 Convalescent Antibodies Obtained With Double Filtration Plasmapheresis.

Curtò, Diego / Tomatis, Federica / Gastoldi, Sara / Galbusera, Miriam / Noris, Marina / Raimondi, Federico / Lorini, Ferdinando Luca / Falanga, Anna / Marchetti, Marina / Remuzzi, Giuseppe / Ruggenenti, Piero

Frontiers in immunology

2021 Volume 12, Page(s) 711915

Abstract: Passive antibody therapy has been used to treat outbreaks of viral disease, including the ongoing pandemic of severe respiratory acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) or COVID-19. However, the real benefits of the procedure are ... ...

Abstract	Passive antibody therapy has been used to treat outbreaks of viral disease, including the ongoing pandemic of severe respiratory acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) or COVID-19. However, the real benefits of the procedure are unclear. We infused a concentrated solution of neutralizing anti-SARS-CoV-2 antibodies obtained from a convalescent donor with a single session of double filtration plasmapheresis (DFPP) into a 56-year-old woman with long history of unremitting, severe COVID-19. She was unable to establish an adequate antiviral immune response because of previous chemotherapy, including the infusion of the anti-CD20 monoclonal antibody rituximab, administered to treat a diffuse large B-cell lymphoma. The disease promptly recovered despite evidence of no endogenous anti-SARS-CoV-2 antibody production. The observation that passive antibody therapy might prove particularly effective in immunodepressed COVID-19 patients requires evaluation in prospective randomized controlled trial.
MeSH term(s)	Antibodies, Neutralizing/therapeutic use ; Antibodies, Viral/therapeutic use ; Antineoplastic Agents, Immunological/adverse effects ; Antiviral Agents/therapeutic use ; COVID-19/immunology ; COVID-19/therapy ; COVID-19/virology ; Female ; Humans ; Immunity/drug effects ; Immunization, Passive/methods ; Immunocompromised Host ; Immunoglobulin G/therapeutic use ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Middle Aged ; Plasmapheresis/methods ; RNA, Viral/genetics ; Rituximab/adverse effects ; SARS-CoV-2/genetics ; Treatment Outcome
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Antineoplastic Agents, Immunological ; Antiviral Agents ; Immunoglobulin G ; RNA, Viral ; Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2021-06-30
Publishing country	Switzerland
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.711915
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Article ; Online: C5a and C5aR1 are key drivers of microvascular platelet aggregation in clinical entities spanning from aHUS to COVID-19.

Aiello, Sistiana / Gastoldi, Sara / Galbusera, Miriam / Ruggenenti, Piero / Portalupi, Valentina / Rota, Stefano / Rubis, Nadia / Liguori, Lucia / Conti, Sara / Tironi, Matteo / Gamba, Sara / Santarsiero, Donata / Benigni, Ariela / Remuzzi, Giuseppe / Noris, Marina

Blood advances

2021 Volume 6, Issue 3, Page(s) 866–881

Abstract: Unrestrained activation of the complement system till the terminal products, C5a and C5b-9, plays a pathogenetic role in acute and chronic inflammatory diseases. In endothelial cells, complement hyperactivation may translate into cell dysfunction, ... ...

Abstract	Unrestrained activation of the complement system till the terminal products, C5a and C5b-9, plays a pathogenetic role in acute and chronic inflammatory diseases. In endothelial cells, complement hyperactivation may translate into cell dysfunction, favoring thrombus formation. The aim of this study was to investigate the role of the C5a/C5aR1 axis as opposed to C5b-9 in inducing endothelial dysfunction and loss of antithrombogenic properties. In vitro and ex vivo assays with serum from patients with atypical hemolytic uremic syndrome (aHUS), a prototype rare disease of complement-mediated microvascular thrombosis due to genetically determined alternative pathway dysregulation, and cultured microvascular endothelial cells, demonstrated that the C5a/C5aR1 axis is a key player in endothelial thromboresistance loss. C5a added to normal human serum fully recapitulated the prothrombotic effects of aHUS serum. Mechanistic studies showed that C5a caused RalA-mediated exocytosis of von Willebrand factor (vWF) and P-selectin from Weibel-Palade bodies, which favored further vWF binding on the endothelium and platelet adhesion and aggregation. In patients with severe COVID-19 who suffered from acute activation of complement triggered by severe acute respiratory syndrome coronavirus 2 infection, we found the same C5a-dependent pathogenic mechanisms. These results highlight C5a/C5aR1 as a common prothrombogenic effector spanning from genetic rare diseases to viral infections, and it may have clinical implications. Selective C5a/C5aR1 blockade could have advantages over C5 inhibition because the former preserves the formation of C5b-9, which is critical for controlling bacterial infections that often develop as comorbidities in severely ill patients. The ACCESS trial registered at www.clinicaltrials.gov as #NCT02464891 accounts for the results related to aHUS patients treated with CCX168.
MeSH term(s)	Atypical Hemolytic Uremic Syndrome ; COVID-19 ; Endothelial Cells ; Humans ; Platelet Aggregation ; SARS-CoV-2
Language	English
Publishing date	2021-11-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021005246
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