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University of Manchester
1.
Harrison, Elizabeth.
A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND
NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS.
Degree: 2016, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300347
► Background: Malnutrition and gastrointestinal (GI) involvement are common in patients with systemic sclerosis (SSc). Despite malnutrition being common, little is known about its associations and…
(more)
▼ Background: Malnutrition and gastrointestinal (GI)
involvement are common in patients with
systemic sclerosis (SSc).
Despite malnutrition being common, little is known about its
associations and predictors. Although patients are frequently
screened and assessed for malnutrition, different clinically
applicable assessment modalities in SSc have not been compared. An
understanding of the relationship between dietary intake and energy
expenditure is important for nutritional assessment and management.
However, studies have not compared these. For many years, home
parenteral nutrition (HPN) has been used in patients with
intestinal failure, but little outcome data exists to support its
role in SSc. GI involvement results in dysmotility, the underlying
mechanism for the development of which is unknown. However,
autonomic dysfunction has been proposed.Aims: To explore aspects of
the nutritional assessment and management of patients with SSc. To
seek associations and predictors of nutritional decline. To
investigate for a link between GI dysmotility and autonomic
dysfunction.Methods: Study 1: A retrospective review of the
survival and outcome data of patients commenced on HPN over 22
years. Study 2: An assessment of 168 patients recruited over 12
months and restudied after approximately 1 year. Assessment
included demographics, clinical data, GI and functional
questionnaires, nutrition screening tool, oral aperture, mid-upper
arm and 4-site anthropometry, bioelectrical impedance and
biochemical testing. Re-study included weight change. Study 3: A 3
day assessment of dietary intake and energy expenditure using food
record charts and SenseWear® Armband involving 36 patients
recruited to Study 2. Study 4: Patients and matched controls
completed GI and autonomic questionnaires, an autonomic battery, a
gastric emptying study and postprandial cardiovascular measures and
GI sensations and symptoms scores.Results: Study 1: The cumulative
probabilities of surviving on HPN at 2, 5 and 10 years were 75%,
37% and 23%. HPN-associated complication rates were low. Study 2:
Nutritional screening failed to identify all patients who lost
weight. Mid-arm circumference correlated with body mass index (BMI)
and weight change. Four-site anthropometry correlated with BMI more
strongly (r=0.65 vs. r=0.49) than bioelectrical impedance analysis.
Small intestinal, but not oesophageal, involvement correlated with
baseline nutritional status. No clear predictors of nutritional
decline were identified. Study 3: Predicted energy intakes
correlated with measured expenditures, but absolute values
differed. Energy intakes did not correlate with expenditures. Study
4: Autonomic measures did not correlate with gastric emptying.
However, autonomic results were hindered by patient-related and
technical limitations.Conclusion: Nutritional screening tools
cannot be relied upon to detect all at risk patients. MAC and
4-site anthropometry may have a role in nutritional assessment.
When an accurate appreciation of energy requirements is needed,
kinematic monitors…
Advisors/Committee Members: HERRICK, ARIANE AL, LAL, SIMON S, Herrick, Ariane, Mclaughlin, John, Lal, Simon.
Subjects/Keywords: systemic sclerosis; gastrointestinal; nutrition
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Harrison, E. (2016). A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND
NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300347
Chicago Manual of Style (16th Edition):
Harrison, Elizabeth. “A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND
NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS.” 2016. Doctoral Dissertation, University of Manchester. Accessed January 23, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300347.
MLA Handbook (7th Edition):
Harrison, Elizabeth. “A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND
NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS.” 2016. Web. 23 Jan 2021.
Vancouver:
Harrison E. A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND
NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Jan 23].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300347.
Council of Science Editors:
Harrison E. A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND
NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300347

Boston University
2.
Creed, Mitchell Peterson.
Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation.
Degree: MA, Biochemistry, 2013, Boston University
URL: http://hdl.handle.net/2144/21141
► Systemic sclerosis (SSc) is a clinically heterogenous chronic fibrotic disease which affects skin and internal organs. While the pathogenesis of SSc remains unknown, the hallmark…
(more)
▼ Systemic sclerosis (SSc) is a clinically heterogenous chronic fibrotic disease which affects skin and internal organs. While the pathogenesis of SSc remains unknown, the hallmark of both localized and diffuse SSc in the skin is the replacement of normal dermal architecture with excessive deposition of collagen and other connective tissue macromolecules. Progressive replacement of tissue architecture by collagen-rich extracellular matrix (ECM) results in functional impairment of affected organs. Fibrotic damage to these affected organs accounts for much of the morbidity and mortality concomitant with SSc, particularly in the lungs.
Myofibroblasts are the primary ECM-secreting cells during wound healing and fibrosis. Myocardin-related transcription factor A (MRTF-A), is an important regulator of myofibroblast differentiation, depending on serum response factor (SRF) for smooth muscle actin (SMA) and Sp1 in the regulation of collagen gene expression. MRTF-A continually shuttles between the nucleus and cytoplasm in unstimulated cells. Signals of stress, mechanical force, and migration control MRTF-A movement by a mechanism in which Rho-activated cytoskeletal actin polymerization induces its relocation from the cytoplasm to the nucleus. The major hypothesis in this thesis is that MRTF-A is dysregulated (impairment of a physiological regulatory mechanisms) and/or activated in SSc patients in part through transforming growth factor beta (TGF-β). To test this hypothesis, immunohistochemistry using MRTF-A antibodies was performed on SSc patient skin lesions and healthy control skin. Staining was observed in the epidermis, epidermal structures, vasculature and dermis of SSc and healthy control skin. In the epidermal layer of patients with SSc, there was significantly more nuclear localization of MRTF-A then in normal controls. Prominent staining is also present in endothelial, perivascular and some perivascular inflammatory cells of SSc patients. Perivascular staining was not seen in healthy controls. Interestingly, there was some accumulation of nuclear MRTF-A in areas typical of myofibroblasts in SSc skin, but this staining is not as striking as vascular staining.
TGF-β activates MRTF-A in a cell-specific manner. As SSc typically begins within the skin, human dermal fibroblasts (HDF) were grown in culture. HDFs synthesize and secrete collagen to a greater extent when compared to human lung fibroblasts (IMR90 cells). Treatment with TGF-β enhances cytoplasmic localization of MRTF-A at 4-8 hours in HDFs and prolongs nuclear localization.
Transgenic mouse lung cells were isolated from an MRTF-A loss-of-function mouse carrying the 3.6 kb proximal promoter of the rat COL1A1 gene driving topaz green fluorescent protein (GFP) (pOB3.6COLGFPtpz). Since angiotensin II (ANG II) may enhance TGF-β response or collagen transcription directly, wild type (WT) and MRTF-A knockout (KO) cells were treated with ANG II and TGF-β. Quantification of collagen transcription by GFP fluorescence and protein synthesis by Western and secretion…
Subjects/Keywords: Medicine; Biochemistry; Systemic sclerosis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Creed, M. P. (2013). Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/21141
Chicago Manual of Style (16th Edition):
Creed, Mitchell Peterson. “Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation.” 2013. Masters Thesis, Boston University. Accessed January 23, 2021.
http://hdl.handle.net/2144/21141.
MLA Handbook (7th Edition):
Creed, Mitchell Peterson. “Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation.” 2013. Web. 23 Jan 2021.
Vancouver:
Creed MP. Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation. [Internet] [Masters thesis]. Boston University; 2013. [cited 2021 Jan 23].
Available from: http://hdl.handle.net/2144/21141.
Council of Science Editors:
Creed MP. Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation. [Masters Thesis]. Boston University; 2013. Available from: http://hdl.handle.net/2144/21141

University of Manchester
3.
Harrison, Elizabeth.
A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis.
Degree: PhD, 2016, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/a-prospective-assessment-of-gastrointestinal-disease-and-nutritional-status-in-patients-with-systemic-sclerosis(683a2e56-8b59-4202-882f-5f22a98f46e0).html
;
http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686800
► Background: Malnutrition and gastrointestinal (GI) involvement are common in patients with systemic sclerosis (SSc). Despite malnutrition being common, little is known about its associations and…
(more)
▼ Background: Malnutrition and gastrointestinal (GI) involvement are common in patients with systemic sclerosis (SSc). Despite malnutrition being common, little is known about its associations and predictors. Although patients are frequently screened and assessed for malnutrition, different clinically applicable assessment modalities in SSc have not been compared. An understanding of the relationship between dietary intake and energy expenditure is important for nutritional assessment and management. However, studies have not compared these. For many years, home parenteral nutrition (HPN) has been used in patients with intestinal failure, but little outcome data exists to support its role in SSc. GI involvement results in dysmotility, the underlying mechanism for the development of which is unknown. However, autonomic dysfunction has been proposed. Aims: To explore aspects of the nutritional assessment and management of patients with SSc. To seek associations and predictors of nutritional decline. To investigate for a link between GI dysmotility and autonomic dysfunction. Methods: Study 1: A retrospective review of the survival and outcome data of patients commenced on HPN over 22 years. Study 2: An assessment of 168 patients recruited over 12 months and restudied after approximately 1 year. Assessment included demographics, clinical data, GI and functional questionnaires, nutrition screening tool, oral aperture, mid-upper arm and 4-site anthropometry, bioelectrical impedance and biochemical testing. Re-study included weight change. Study 3: A 3 day assessment of dietary intake and energy expenditure using food record charts and SenseWear® Armband involving 36 patients recruited to Study 2. Study 4: Patients and matched controls completed GI and autonomic questionnaires, an autonomic battery, a gastric emptying study and postprandial cardiovascular measures and GI sensations and symptoms scores. Results: Study 1: The cumulative probabilities of surviving on HPN at 2, 5 and 10 years were 75%, 37% and 23%. HPN-associated complication rates were low. Study 2: Nutritional screening failed to identify all patients who lost weight. Mid-arm circumference correlated with body mass index (BMI) and weight change. Four-site anthropometry correlated with BMI more strongly (r=0.65 vs. r=0.49) than bioelectrical impedance analysis. Small intestinal, but not oesophageal, involvement correlated with baseline nutritional status. No clear predictors of nutritional decline were identified. Study 3: Predicted energy intakes correlated with measured expenditures, but absolute values differed. Energy intakes did not correlate with expenditures. Study 4: Autonomic measures did not correlate with gastric emptying. However, autonomic results were hindered by patient-related and technical limitations. Conclusion: Nutritional screening tools cannot be relied upon to detect all at risk patients. MAC and 4-site anthropometry may have a role in nutritional assessment. When an accurate appreciation of energy requirements is needed, kinematic…
Subjects/Keywords: 616.7; systemic sclerosis; gastrointestinal; nutrition
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Harrison, E. (2016). A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/a-prospective-assessment-of-gastrointestinal-disease-and-nutritional-status-in-patients-with-systemic-sclerosis(683a2e56-8b59-4202-882f-5f22a98f46e0).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686800
Chicago Manual of Style (16th Edition):
Harrison, Elizabeth. “A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis.” 2016. Doctoral Dissertation, University of Manchester. Accessed January 23, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/a-prospective-assessment-of-gastrointestinal-disease-and-nutritional-status-in-patients-with-systemic-sclerosis(683a2e56-8b59-4202-882f-5f22a98f46e0).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686800.
MLA Handbook (7th Edition):
Harrison, Elizabeth. “A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis.” 2016. Web. 23 Jan 2021.
Vancouver:
Harrison E. A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Jan 23].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/a-prospective-assessment-of-gastrointestinal-disease-and-nutritional-status-in-patients-with-systemic-sclerosis(683a2e56-8b59-4202-882f-5f22a98f46e0).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686800.
Council of Science Editors:
Harrison E. A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis. [Doctoral Dissertation]. University of Manchester; 2016. Available from: https://www.research.manchester.ac.uk/portal/en/theses/a-prospective-assessment-of-gastrointestinal-disease-and-nutritional-status-in-patients-with-systemic-sclerosis(683a2e56-8b59-4202-882f-5f22a98f46e0).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686800

Temple University
4.
Zacharakis, Nikolaos.
Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells.
Degree: PhD, 2014, Temple University
URL: http://digital.library.temple.edu/u?/p245801coll10,249827
► Microbiology and Immunology
Systemic sclerosis (SSc) is a chronic autoimmune disease of the connective tissue. Immune system dysregulation, excessive deposition of collagen and microvascular damage…
(more)
▼ Microbiology and Immunology
Systemic sclerosis (SSc) is a chronic autoimmune disease of the connective tissue. Immune system dysregulation, excessive deposition of collagen and microvascular damage in the skin and multiple internal organs are the main pathologic characteristics of the disease. Little is known about the mechanisms that are responsible for the pathogenesis of SSc. However, evidence has been accumulated demonstrating that T cells play a key role in the initiation and propagation of the disease. Previous studies in our laboratory have identified the presence of high proportions of identical β–chains TCR transcripts, demonstrating the presence of clonal expansion of T cells in skin biopsies from patients with SSc of recent onset. These T cells have undergone proliferation and clonal expansion in response to as yet unidentified antigen(s). The hypothesis that has been tested in this study is whether clonally expanded T cells in skin biopsies of patients with SSc of recent onset recognize self or non–self (possibly viral) putative SSc antigens, including DNA topoisomerase I, cytomegalovirus (CMV) and parvovirus. With the objective to identify the antigens recognized by clonally expanded T cells in skin biopsies of patients with SSc, we examined the presence of α– and β–chain TCR transcripts. Amplification of α–chain TCR transcripts by the non–palindromic adaptor PCR (NPA–PCR)/Vα specific PCR followed by cloning and sequencing revealed the presence of several clonally expanded α–chain TCR transcripts in skin biopsies from four patients with SSc and peripheral blood from one of these patients. Additionally, several clonally expanded β–chain TCR transcripts were identified in skin biopsies from all three of these patients with SSc examined, after NPA–PCR/Vβ specific amplification followed by cloning and sequencing. To identify the antigens recognized by these in vivo clonally expanded α– and β–chain TCR clones, full length α– and β– chain TCR transcripts containing the identified CDR3 regions from the clonally expanded TCR clones from the patients SSc–21 and SSc–22 were constructed. Pairs of clonally expanded, full length α– and β–chain TCR transcripts and appropriate controls were expressed in mutant TCR negative cells of the Jurkat T cell line (J.RT3–T3.5) by using a retroviral gene transfer and expression system. Each clonally expanded α–chain TCR transcript was combined with each clonally expanded β–chain TCR transcript from the same patient, generating T cells lines containing all pairing combinations of the clonally expanded TCR transcripts for each SSc patient. A total of 52 T cell lines were generated, including 10 control T cell lines. The surface expression of the TCR complex on these T cell lines was verified by flow cytometric analysis using antibodies against the α/β TCR…
Advisors/Committee Members: Platsoucas, Chris D., Tsygankov, Alexander;, Oleszak, Emilia, Soprano, Kenneth J., Skorski, Tomasz, Henderson, Earl E., Monos, Dimitrios;.
Subjects/Keywords: Immunology;
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zacharakis, N. (2014). Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,249827
Chicago Manual of Style (16th Edition):
Zacharakis, Nikolaos. “Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells.” 2014. Doctoral Dissertation, Temple University. Accessed January 23, 2021.
http://digital.library.temple.edu/u?/p245801coll10,249827.
MLA Handbook (7th Edition):
Zacharakis, Nikolaos. “Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells.” 2014. Web. 23 Jan 2021.
Vancouver:
Zacharakis N. Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells. [Internet] [Doctoral dissertation]. Temple University; 2014. [cited 2021 Jan 23].
Available from: http://digital.library.temple.edu/u?/p245801coll10,249827.
Council of Science Editors:
Zacharakis N. Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells. [Doctoral Dissertation]. Temple University; 2014. Available from: http://digital.library.temple.edu/u?/p245801coll10,249827

University of Dundee
5.
McSwiggan, Stephen John.
Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression).
Degree: PhD, 2014, University of Dundee
URL: https://discovery.dundee.ac.uk/en/studentTheses/163dc6e5-b5dd-4945-9756-8dae629cff48
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620768
► Background: Systemic sclerosis (SSc) is an autoimmune disease associated with significant mortality and morbidity. Cardiovascular causes are the single largest contributor to premature death. To…
(more)
▼ Background: Systemic sclerosis (SSc) is an autoimmune disease associated with significant mortality and morbidity. Cardiovascular causes are the single largest contributor to premature death. To date, much of the focus on managing the care of SSc patients has concentrated on traditional risk factors related to fibrotic and microvascular dysfunction. There is, however, evidence of a strong cardiovascular component to the disease and points to macrovascular dysfunction as being a key contributor to the premature mortality associated with SSc. This thesis reports on the conduct of a multi-centre, randomised, placebo-controlled clinical trial (the SSTEP Study). The aim of the study was to assess whether oral Iloprost was more effective than placebo in reducing cardiovascular events and disease progression in SSc. Methods: Two hundred and sixteen patients with systemic sclerosis were recruited, between February 2002 and February 2005, at nine centres in the UK and Ireland. After one month placebo run-in, participants were randomised to either oral Iloprost (50-200mcg daily) or matched placebo. Baseline demographics, disease characteristics and organ screening data were collected, and participants were reviewed annually for endpoint measurements; CV events, SSc disease progression and mortality, with regular safety reviews between these annual visits. Participants were followed up for a period of 4 to 7 years. Results: Data analysis of the combination of the two measures (survival free from death or a cardiovascular event) demonstrated a trend towards favouring Iloprost over placebo but the difference was not statistically significant (Logrank test: Chi square=0.75, p=0.39). When time to a confirmed cardiovascular endpoint alone was examined there was a suggestion of a benefit from Iloprost, but the difference was again not statistically significant (Logrank test, Chi square =0.82, p=0.37). There was no statistically significant change in the rate at which organ screening endpoints occurred throughout follow-up, and for each endpoint there was no statistically significant difference between results in patients randomised to Iloprost compared to those randomised to placebo. Withdrawal from the treatment to which the patient was randomised was frequent with 97 (45%) of the total participants discontinuing study medication. ‘On treatment’ analysis, undertaken using the endpoint of death or confirmed cardiovascular endpoint, just failed to show statistical significance at the 5% level (p=0.054). Conclusion: The results of the SSTEP study showed that there was a trend towards favouring oral Iloprost over placebo in systemic sclerosis, though there was no statistically significant evidence to recommend its use to prevent disease progression. The high rate of withdrawal from both Iloprost and placebo hindered the possibility of demonstrating that Iloprost was effective in this study. It cannot be concluded that it is a useful therapy that may prevent premature mortality or progression to cardiovascular disease in this patient…
Subjects/Keywords: 610; Systemic sclerosis; Iloprost; Cardiovascular disease
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
McSwiggan, S. J. (2014). Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression). (Doctoral Dissertation). University of Dundee. Retrieved from https://discovery.dundee.ac.uk/en/studentTheses/163dc6e5-b5dd-4945-9756-8dae629cff48 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620768
Chicago Manual of Style (16th Edition):
McSwiggan, Stephen John. “Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression).” 2014. Doctoral Dissertation, University of Dundee. Accessed January 23, 2021.
https://discovery.dundee.ac.uk/en/studentTheses/163dc6e5-b5dd-4945-9756-8dae629cff48 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620768.
MLA Handbook (7th Edition):
McSwiggan, Stephen John. “Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression).” 2014. Web. 23 Jan 2021.
Vancouver:
McSwiggan SJ. Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression). [Internet] [Doctoral dissertation]. University of Dundee; 2014. [cited 2021 Jan 23].
Available from: https://discovery.dundee.ac.uk/en/studentTheses/163dc6e5-b5dd-4945-9756-8dae629cff48 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620768.
Council of Science Editors:
McSwiggan SJ. Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression). [Doctoral Dissertation]. University of Dundee; 2014. Available from: https://discovery.dundee.ac.uk/en/studentTheses/163dc6e5-b5dd-4945-9756-8dae629cff48 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620768

University of Melbourne
6.
Ferdowsi, Nava.
Development of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis.
Degree: 2018, University of Melbourne
URL: http://hdl.handle.net/11343/213954
► Objective: Systemic Sclerosis (SSc) is a multi-organ connective tissue disease resulting in fibrosis of the skin and internal organs. We sought to develop the first…
(more)
▼ Objective: Systemic Sclerosis (SSc) is a multi-organ connective tissue disease resulting in fibrosis of the skin and internal organs. We sought to develop the first damage index (DI) in systemic sclerosis (SSc).
Methods: Following systematic review of the literature focusing on methodology used to develop damage indices in other rheumatological conditions, the following methods were used to develop the SCTC-DI. The conceptual definition of organ damage in SSc was determined through consensus by a working group of the Scleroderma Clinical Trials Consortium (SCTC). Systematic review of the literature and consultation with three experienced patient partners and 7 non-rheumatologist experts produced a list of potential items for inclusion in the DI. The following steps were used to reduce the items; (1) Expert members of the SCTC (n=331) were invited by email to rate the appropriateness of each item for inclusion in the DI using a web-based survey. Items with >60% consensus were retained; (2) Using a prospectively acquired Australian cohort data set of 1,568 patients followed for a mean of 4.8 years, the univariable relationships between the remaining items and the end points of mortality and morbidity (physical component summary score of the Short Form 36) were analysed, and items with p value < 0.10 were retained; (3) using multivariable regression analysis against the above endpoints, coefficients were used to determine a weighted score for each item; (4) internal and external retrospective validation was performed to demonstrate construct and criterion validity.
Results: Ninety-three (28.1%) complete survey responses were analysed; 58 of 83 items were retained. The univariable relationships with death and/or morbidity endpoints were statistically significant for 22 items. One further item was forced into the multivariable model by experts, due to clinical importance, to create a 23-item weighted SCTC Damage Index (SCTC-DI).
Conclusions: Through the combined use of consensus and data driven methods, a 23-item SCTC-DI was developed. Future prospective validation is planned.
Subjects/Keywords: systemic Sclerosis; outcome measure; organ damage
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ferdowsi, N. (2018). Development of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis. (Masters Thesis). University of Melbourne. Retrieved from http://hdl.handle.net/11343/213954
Chicago Manual of Style (16th Edition):
Ferdowsi, Nava. “Development of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis.” 2018. Masters Thesis, University of Melbourne. Accessed January 23, 2021.
http://hdl.handle.net/11343/213954.
MLA Handbook (7th Edition):
Ferdowsi, Nava. “Development of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis.” 2018. Web. 23 Jan 2021.
Vancouver:
Ferdowsi N. Development of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis. [Internet] [Masters thesis]. University of Melbourne; 2018. [cited 2021 Jan 23].
Available from: http://hdl.handle.net/11343/213954.
Council of Science Editors:
Ferdowsi N. Development of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis. [Masters Thesis]. University of Melbourne; 2018. Available from: http://hdl.handle.net/11343/213954

Universidade do Rio Grande do Sul
7.
Pavan, Thais Rohde.
Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica.
Degree: 2015, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/150716
► Introdução: A capilaroscopia periungueal (CPU) tem sido relacionada ao dano a órgãos-alvo na esclerose sistêmica (ES). No entanto, estudos relativos à gravidade das alterações da…
(more)
▼ Introdução: A capilaroscopia periungueal (CPU) tem sido relacionada ao dano a órgãos-alvo na esclerose sistêmica (ES). No entanto, estudos relativos à gravidade das alterações da CPU com a mortalidade evidenciam resultados discrepantes. Este estudo tem como objetivo verificar associação da gravidade da microangiopatia periférica na CPU com o risco de morte na ES. Pacientes e métodos: Cento e setenta pacientes com ES foram prospectivamente avaliados e acompanhados em média de 9,3 anos. Além da avaliação clínica, os pacientes foram submetidos à sorologia, testes de função pulmonar, ecocardiograma e tomografia computadorizada pulmonar de alta resolução (TCAR). A perda capilar na CPU foi avaliada pelo escore avascular (EA), que varia de 0 a 3. O número médio de ectasias, megacapillaries e hemorragias por dedo também foi registrado. O modelo de Cox proporcional Uni e Multivariado foi utilizado para analisar a associação do escore avascular com o risco de morte através da associação Hazard ratio (HR). Resultados: Por análise de Cox univariada, o escore avascular associado à mortalidade foi estatisticamente significativo (HR = IC 1.54, 95%: 1.13-2.09, p = 0.006), mas outras variáveis capilaroscópicas (número de ectasias, megacapillaries e hemorragias por dedo) não foram (p> 0,40 para todos os testes). Após o ajuste para escore de pele, idade, sexo, origem étnica, e sinais de isquemia digital, a associação entre o escore avascular perdeu significância estatística (HR = 1.23, IC: 0.84-1.81, p = 0.276). Também não houve associação significativa do escore avascular quando ajustado para uma combinação de resultados de exames complementares. Conclusões: A gravidade da desvascularização na CPU está relacionada a um maior risco de mortalidade na ES; No entanto, a associação não é estatisticamente significativa após ajuste para outras variáveis clínicas e laboratoriais. Apesar do fato de não mostrar uma associação independente do EA com a mortalidade, consideramos que é útil na avaliação de pacientes com diagnóstico de esclerose sistêmica, uma vez que pode dar uma visão geral e confiável da gravidade da doença.
Introduction: The nailfold capillaroscopy (NCF) has been related to end-organ damage in Systemic sclerosis (SSc). However, studies relating the severity of NCF alterations with mortality have rendered mixed results. This study aims to verify the association of the severity of peripheral microangiopathy in the NFC with the risk of death in SSc. Patients and methods: One hundred and seventy SSc patients were prospectively evaluated and followed a mean of 9.3 years. Besides clinical evaluation, patients underwent serology, pulmonary function tests, Doppler echocardiography, and pulmonary high resolution computed tomography (HRCT). Capillary loss on NCF was evaluated using the avascular score (AS), ranging from 0 to 3. The mean number of ectasias, megacapillaries and hemorrhages per finger was also recorded; univariate and multivariate Cox proportional models were used to analyze the association of the AS with the risk of…
Advisors/Committee Members: Xavier, Ricardo Machado, Chakr, Rafael Mendonça da Silva.
Subjects/Keywords: Systemic sclerosis; Escleroderma sistêmico; Mortalidade; Capillaroscopy; Angioscopia microscópica; Mortality; Cohort studies
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Pavan, T. R. (2015). Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/150716
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Pavan, Thais Rohde. “Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica.” 2015. Thesis, Universidade do Rio Grande do Sul. Accessed January 23, 2021.
http://hdl.handle.net/10183/150716.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Pavan, Thais Rohde. “Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica.” 2015. Web. 23 Jan 2021.
Vancouver:
Pavan TR. Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2015. [cited 2021 Jan 23].
Available from: http://hdl.handle.net/10183/150716.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Pavan TR. Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica. [Thesis]. Universidade do Rio Grande do Sul; 2015. Available from: http://hdl.handle.net/10183/150716
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
8.
Huang, Hongtai.
On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer.
Degree: 2015, Johns Hopkins University
URL: http://jhir.library.jhu.edu/handle/1774.2/37905
► This work seeks to develop reliable biomarkers of disease activity, progression and outcomes through the identification of significant associations between high-throughput flow cytometry data and…
(more)
▼ This work seeks to develop reliable biomarkers of disease activity, progression and outcomes through the identification of significant associations between high-throughput flow cytometry data and a scleroderma clinical phenotype – initially, interstitial lung disease (ILD) - which is the leading cause of morbidity and mortality in
Systemic Sclerosis (SSc). A specific aim of the work involves developing a clinically useful screening tool (hereafter a filter). Such a filter could yield accurate assessments of disease state such as the risk or presence of SSc-ILD, the activity of lung involvement and the possibility to respond to therapeutic intervention. Ultimately this instrument should facilitate a refined stratification of SSc patients into clinically relevant subsets at the time of diagnosis and subsequently during the course of the disease, preventing bad outcomes from disease progression or unnecessary treatment side effects. This role could involve a scenario in
which an SSc patient passes the presumptive (FVCstpp) test for ILD, but the filter indicates that their flow cytometry (FC) profile is consistent with ILD. In such a case, a physician might: 1) increase frequency of testing to detect early development of ILD; 2) implement more sophisticated diagnostic procedures (e.g., high resolution chest CT scan - HRCT) to confirm the presence of ILD; and 3) consider prophylactic disease modifying treatments. Note that the intention of this research is not to develop screening tools that merely aim at predictive accuracy, but to produce methods that also contribute to the understanding of disease mechanisms. Having used ILD as phenotype, subsequent analyses in this thesis used different phenotypes: antiTopoisomerase (ATA), antiCentromere Anti Nuclear Antibodies (these antibodies are most strongly associated with diffuse and limited
systemic sclerosis respectively) and cancer. This research was based on clinical and peripheral blood flow cytometry
data (Immune Response In Scleroderma, IRIS) from consented patients followed at the Johns Hopkins Scleroderma Center. Methods. The methods utilized in the work involve: (1) data mining (Conditional Random Forests - CRF) to identify subsets of FC variables that are highly effective in classifying ILD patients; (2) Gene Set Enrichment Analysis (GSEA) to further refine FC subsets; (3) stochastic simulation and Classification and Regression Trees (CART) to design, test and validate ILD filters; and (4) Stepwise Generalized Linear Model (GLM) regression and Drop-in-Deviance testing to identify minimal size, best performing models for predicting ILD status from both FC and selected clinical variables. Results. IRIS flow cytometry data provides useful information in assessing the ILD status of SSc patients. Our hybrid analysis approach proved successful in predicting SSc patient ILD status with a high degree of success (out-of-sample > 82%; training data set 79 patients, validation data
set 40 patients). Pre-partitioning patients into groups using CART significantly increased…
Advisors/Committee Members: Burke, Thomas A (advisor).
Subjects/Keywords: Data Analysis;
Flow Cytometry;
Systemic Sclerosis;
Autoimmune disorders
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Huang, H. (2015). On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/37905
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Huang, Hongtai. “On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer.” 2015. Thesis, Johns Hopkins University. Accessed January 23, 2021.
http://jhir.library.jhu.edu/handle/1774.2/37905.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Huang, Hongtai. “On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer.” 2015. Web. 23 Jan 2021.
Vancouver:
Huang H. On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer. [Internet] [Thesis]. Johns Hopkins University; 2015. [cited 2021 Jan 23].
Available from: http://jhir.library.jhu.edu/handle/1774.2/37905.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Huang H. On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer. [Thesis]. Johns Hopkins University; 2015. Available from: http://jhir.library.jhu.edu/handle/1774.2/37905
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manchester
9.
Arthur, Donna Louise.
Doppler Optical Coherence Tomography for Microcirculation
Studies.
Degree: 2014, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:216264
► This thesis forms part of an ongoing long-term project to investigate the suitability of Doppler optical coherence tomography (OCT) as a measurement tool to investigate…
(more)
▼ This thesis forms part of an ongoing long-term
project to investigate the suitability of Doppler optical coherence
tomography (OCT) as a measurement tool to investigate skin
thickness and blood flow in patients with
systemic sclerosis.There
is a discussion of the characterisation of an electro-optic phase
modulator for use in a Doppler OCT imaging system which is being
built for the purpose of clinical studies. In addition to this the
development of software for the same system is described. The work
includes a comparison of two methods of obtaining Doppler
information that were tested with the system; a phase resolved
method and a correlation mapping method. Initial structural and
Doppler images obtained using the system are presented.In addition
to this the development of semi-automated software to measure skin
thickness from both OCT and high frequency ultrasound images is
discussed. The results of a study, for which this software was
developed, into skin thickness measurements using both techniques
in both patients with
systemic sclerosis and healthy controls are
presented. Both OCT and high frequency ultrasound were able to
measure a statistically significant difference in epidermal
thickness at multiple locations on the body.Finally, the
modification of a freely available Monte Carlo simulation for light
propagation in multi-layered tissue (MCML) to enable the simulation
of structural and Doppler OCT images is covered. The simulation was
able to extract the magnitude of the simulated flow accurately to
within an order of magnitude, and after a simple filter was applied
to eliminate fluctuations in the data the structure of the Doppler
image closely matched what was modelled.
Advisors/Committee Members: HERRICK, ARIANE AL, MURRAY, ANDREA AK, Dickinson, Mark, Herrick, Ariane, Murray, Andrea.
Subjects/Keywords: OCT; Optical Coherence Tomography; Imaging; Doppler; Systemic sclerosis; Microcirculation
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Arthur, D. L. (2014). Doppler Optical Coherence Tomography for Microcirculation
Studies. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:216264
Chicago Manual of Style (16th Edition):
Arthur, Donna Louise. “Doppler Optical Coherence Tomography for Microcirculation
Studies.” 2014. Doctoral Dissertation, University of Manchester. Accessed January 23, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:216264.
MLA Handbook (7th Edition):
Arthur, Donna Louise. “Doppler Optical Coherence Tomography for Microcirculation
Studies.” 2014. Web. 23 Jan 2021.
Vancouver:
Arthur DL. Doppler Optical Coherence Tomography for Microcirculation
Studies. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2021 Jan 23].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:216264.
Council of Science Editors:
Arthur DL. Doppler Optical Coherence Tomography for Microcirculation
Studies. [Doctoral Dissertation]. University of Manchester; 2014. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:216264

Boston University
10.
Rice, Lisa.
Biomarkers in systemic scelrosis.
Degree: PhD, Molecular and Translational Medicine, 2016, Boston University
URL: http://hdl.handle.net/2144/16736
► Systemic sclerosis (SSc; scleroderma) is a chronic multisystem autoimmune disease that includes prominent skin involvement in all patients and is characterized by fibrosis, inflammation, and…
(more)
▼ Systemic sclerosis (SSc; scleroderma) is a chronic multisystem autoimmune disease that includes prominent skin involvement in all patients and is characterized by fibrosis, inflammation, and microvascular injury of the skin and internal organs. Clinical trial design for patients with systemic sclerosis (SSc) has been confounded by the heterogeneity of disease progression and lack of objective outcome measures. This has hampered identification of therapies for patients who have frequently fatal fibrotic complications. Direct pulmonary complications are the leading cause of death in SSc. For clinical trials in patients with diffuse cutaneous SSc, identification of a pharmacodynamic biomarker associated with clinical improvement would allow for alternative approaches to trial design. Furthermore, identification of a diagnostic biomarker for SSc complicated by pulmonary arterial hypertension (SSc-PAH) would provide a reliable non-invasive method for diagnosis of pulmonary arterial hypertension.
Through the combination of high throughput technologies and clinical information we have identified three preliminary biomarkers for SSc: i) Two pharmacodynamic biomarkers for diffuse skin disease (dcSSc), one in using mRNA from skin biopsies and one using proteomic profiles from sera; ii) a serum based proteomic classifier for the screening and diagnostic evaluation of pulmonary arterial hypertension in systemic sclerosis.
We show these biomarkers can be applied to assess changes in skin disease in dSSc patients over time and with further development could be used to supplement or replace the physical examination assessment (Modified Rodnan Skin Score, MRSS) as an outcome measure in clinical trials for dcSSc patients. Routine use of these biomarkers in SSc clinical trial design could expand treatment options for a patient population that currently has few if any treatment options that slow progression of disease.
Furthermore we identified a serum biomarker for the major SSc pulmonary complication, SSc-PAH. This diagnostic SSc-PAH biomarker has the potential to be used as a screening tool in order to reduce the need for unnecessary invasive diagnostic procedures. This non-invasive screening method could lead to early diagnosis thus improving patient survival and aid in clinical management of a complication for which there are several treatments but which is still frequently fatal.
Subjects/Keywords: Medicine; Biomarkers; mRNA; Proteins; Systemic sclerosis; Pulmonary arterial hypertension
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Rice, L. (2016). Biomarkers in systemic scelrosis. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/16736
Chicago Manual of Style (16th Edition):
Rice, Lisa. “Biomarkers in systemic scelrosis.” 2016. Doctoral Dissertation, Boston University. Accessed January 23, 2021.
http://hdl.handle.net/2144/16736.
MLA Handbook (7th Edition):
Rice, Lisa. “Biomarkers in systemic scelrosis.” 2016. Web. 23 Jan 2021.
Vancouver:
Rice L. Biomarkers in systemic scelrosis. [Internet] [Doctoral dissertation]. Boston University; 2016. [cited 2021 Jan 23].
Available from: http://hdl.handle.net/2144/16736.
Council of Science Editors:
Rice L. Biomarkers in systemic scelrosis. [Doctoral Dissertation]. Boston University; 2016. Available from: http://hdl.handle.net/2144/16736
11.
P.A. Lonati.
LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE.
Degree: 2013, Università degli Studi di Milano
URL: http://hdl.handle.net/2434/215886
► IL-17 cytokine family has recently emerged as critical players in immunity and inflammatory diseases, both involved in initiating or maintaining the fibrosis process. Indeed, an…
(more)
▼ IL-17 cytokine family has recently emerged as critical players in immunity and inflammatory diseases, both involved in initiating or maintaining the fibrosis process.
Indeed, an inflammatory infiltrate is characteristic of the early phases of fibrosis development and inflammatory cells may profoundly affect the ECM production by releasing soluble products or by direct cell-to-cell interactions that modify fibroblast metabolism.
Fibrosis is characteristic of many diseases, as
systemic sclerosis (SSc), morphea, acrodermatitis chronica atrophicans, Shulman fasciitis and the cutaneous form of graft versus host disease (GVHD).
In particular has been shown that IL-17A is present not only in the biological fluids but also in the skin of individuals affected by SSc.
The aims of this study are to understand if the IL-17 isoforms are expressed in the skin of individuals affected by these diseases and which are the cells responsible for the production of IL-17A. Moreover we are interested in understanding if the treatment with Iloprost or NAC can modify the expression of the IL-17 isoforms in the skin of SSc patients and if also the cells responsible for the production of IL-17A are modified by these drugs.
Bioptic material was obtained from the involved individuals affected by different fibrotic diseases and from healthy donors (HD) undergoing plastic surgery. We adopted an immunohistochemistry and immunofluorescence approach to identify and quantify in vivo the presence of cells positive for the IL-17 isoforms, the IL-17 receptors, IL-4, IL-22, INF-γ, CD3 and Tryptase.
All the IL-17 isoforms are expressed in all the bioptic samples analyzed, without significant differences between the HD and the pathologic groups. IL-17A is produced by both CD3 and mast cells, and are significantly more numerous in the HD than in the SSc skin (p=0,0485).
The expression of the IL-17 isoforms in the skin of SSc patients treated with Iloprost changes unevenly in all the patients. The same happens for the expression of IL-17C in the skin of SSc individuals treated with NAC, while these patients show a marked (but not significant) increase number of IL-17A and IL-17F positive cells and a decreased number of IL-17E positive cells.
The treatment with Iloprost induces also the decrease in the number of both CD3 and mast cells producing IL-17A, while NAC induces the increase in the number of CD3 IL-17A producing cells. The number of mast cells producing IL-17A in patients treated with NAC changes unevenly.
The number of CD3 and mast cells that produce IL-17A does not reflect the total number of IL-17A positive cells localized in the analyzed samples. This could mean that other cell types are responsible for IL-17A production.
Given the role of the IL-17 isoforms in the immunity and inflammatory pathway, the presence of these cytokines in the skin of patients affected by fibrotic diseases can mean that they can be involved in the fibrotic process. This is confirmed by the modification of the expression of the IL-17 isoforms in the skin of…
Advisors/Committee Members: tutor: C. Chizzolini, P. Meroni, M.O. Borghi, coordinatore: A. Gianni, MERONI, PIERLUIGI, GIANNI, ALESSANDRO.
Subjects/Keywords: interleukin 17; fibrosis; systemic sclerosis; Iloprost; Settore MED/16 - Reumatologia
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lonati, P. (2013). LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215886
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lonati, P.A.. “LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE.” 2013. Thesis, Università degli Studi di Milano. Accessed January 23, 2021.
http://hdl.handle.net/2434/215886.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lonati, P.A.. “LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE.” 2013. Web. 23 Jan 2021.
Vancouver:
Lonati P. LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 23].
Available from: http://hdl.handle.net/2434/215886.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lonati P. LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215886
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University
12.
Marden, Grace.
Investigating the defects of postnatal global Fli1 deletion in a mouse model.
Degree: MS, Pathology, 2020, Boston University
URL: http://hdl.handle.net/2144/41292
► Scleroderma (SSc) is an autoimmune disease characterized by dysfunctional immunity, vasculopathy, and fibrosis of the skin and internal organs. There is a poor prognosis for…
(more)
▼ Scleroderma (SSc) is an autoimmune disease characterized by dysfunctional immunity, vasculopathy, and fibrosis of the skin and internal organs. There is a poor prognosis for SSc patients and effective therapeutics have not yet been developed. Many mouse models have been developed, but most fail to recapitulate all of the symptoms seen in SSc patients. In this study we characterize a Fli1flox/flox mouse with CAG Cre under the beta-actin promoter. Based on what has been previously described in mice with deletion of Fli1 in specific cell types, we predicted that global postnatal deletion of Fli1 will result in
systemic fibrosis, vasculopathy, and inflammation in these mice. The penetrance of a phenotype was highly variable; however, mice that developed a phenotype displayed disorganized vascular networks, fibrosis and proinflammatory cytokines and chemokines in the skin and lungs after 4 and 8 weeks of Fli1 deficiency. Increased macrophage and dendritic cell populations were observed in the lungs after 8 weeks. Fli1flox/flox CAG Cre mice exhibited hair loss after 5 months of Fli1 deletion. Since our experiments focus mainly on the lungs and skin, more experiments are required to characterize these mice to determine if they can be used as a novel animal model of SSc.
Advisors/Committee Members: Trojanowska, Maria (advisor), Kim, Jiyoun (advisor).
Subjects/Keywords: Pathology; CAG Cre; Fibrosis; Fli1; Mice; Systemic sclerosis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Marden, G. (2020). Investigating the defects of postnatal global Fli1 deletion in a mouse model. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/41292
Chicago Manual of Style (16th Edition):
Marden, Grace. “Investigating the defects of postnatal global Fli1 deletion in a mouse model.” 2020. Masters Thesis, Boston University. Accessed January 23, 2021.
http://hdl.handle.net/2144/41292.
MLA Handbook (7th Edition):
Marden, Grace. “Investigating the defects of postnatal global Fli1 deletion in a mouse model.” 2020. Web. 23 Jan 2021.
Vancouver:
Marden G. Investigating the defects of postnatal global Fli1 deletion in a mouse model. [Internet] [Masters thesis]. Boston University; 2020. [cited 2021 Jan 23].
Available from: http://hdl.handle.net/2144/41292.
Council of Science Editors:
Marden G. Investigating the defects of postnatal global Fli1 deletion in a mouse model. [Masters Thesis]. Boston University; 2020. Available from: http://hdl.handle.net/2144/41292

University of Manchester
13.
Hughes, Michael.
Digital ulcers in systemic sclerosis: investigating the
outcome measures of treatment efficacy, pathophysiology, and the
development of local treatments.
Degree: 2016, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305671
► Introduction: Digital ulcers (DUs) are responsible for much of the pain and disability associated with systemic sclerosis (SSc), and are a biomarker of internal organ…
(more)
▼ Introduction: Digital ulcers (DUs) are responsible
for much of the pain and disability associated with systemic
sclerosis (SSc), and are a biomarker of internal organ involvement
and poor prognosis. DUs are often used as the primary end-point in
SSc clinical trials, although the reliability of rheumatologists in
grading DUs is poor to moderate at best. Fingertip DUs are believed
to be ischaemic in aetiology, whereas, extensor DUs are thought to
occur due to mechanical factors and recurrent microtrauma.
Treatments for DUs are often poorly tolerated due to systemic
vasodilation. The overarching aim was to investigate the definition
and objective measurement of SSc-related DUs, their
pathophysiology, and a new light treatment.Method: Five studies
were undertaken. (1) A web-based study in which photographs of
digital lesions were graded, all either with or without clinical
context. (2) A pilot study to assess the feasibility and
tolerability of high-frequency ultrasound (HFUS) imaging to measure
DUs. (3) A retrospective study examining whether thermographic
abnormalities are associated with DUs. (4) A double-blind,
randomised, crossover, controlled study of glyceryl trinitrate
(GTN) to explore the pathophysiology of DUs in SSc. (5). A
feasibility study of a novel light (red, infrared and blue) device
to treat SSc-related DUs.Results: (1) 51 rheumatologists graded
≥4500 images. The clinical context (without vs with, weighted kappa
statistic) did not significantly improve the intra- (0.32,0.36) or
inter-rater (0.64,0.71) reliability. (2) HFUS was performed on 15
DUs and was well tolerated and feasible in the majority. DU
measurement was possible in most (n=13) DUs, the mean DU depth and
width were 0.99mm and 5.74mm, respectively. (3) Patients (n=138)
with abnormal (compared to normal) thermography were more likely
(adjusted odds ratio = 2.84) to develop future DUs, including
multiple episodes. (4) 16 DUs were studied; the microvessels of the
DU centre were responsive to GTN, with an increase in perfusion,
with a similar effect in both fingertip and extensor DUs. There was
less of a clear signal in the DU periphery. (5) Light treatment was
safe, feasible and well tolerated (46 light treatments administered
in 8 patients, one studied on three separate occasions). There was
a significant improvement (change in visual analogue score per
visit) in DUs as assessed by both patient (-7.1, P=<0.001) and
clinician opinion (-5.2, P=<0.001). DU perfusion (measured by
LDI) significantly increased post-treatment.Conclusion: The
reliability of DU grading did not improve with clinical context.
HFUS was feasible and well tolerated, and measurement was possible
in most DUs. Our data suggests that many DUs might have an
ischaemic drive, including extensor DUs. A novel light treatment
was safe, feasible and well tolerated, with a tentative suggestion
of treatment efficacy.
None
None
Advisors/Committee Members: ROBERTS, CHRISTOPHER CT, MURRAY, ANDREA AK, Roberts, Christopher, Herrick, Ariane, Murray, Andrea.
Subjects/Keywords: Systemic sclerosis; Scleroderma; Digital ulcers; Outcome measures; Pathophysiology
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hughes, M. (2016). Digital ulcers in systemic sclerosis: investigating the
outcome measures of treatment efficacy, pathophysiology, and the
development of local treatments. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305671
Chicago Manual of Style (16th Edition):
Hughes, Michael. “Digital ulcers in systemic sclerosis: investigating the
outcome measures of treatment efficacy, pathophysiology, and the
development of local treatments.” 2016. Doctoral Dissertation, University of Manchester. Accessed January 23, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305671.
MLA Handbook (7th Edition):
Hughes, Michael. “Digital ulcers in systemic sclerosis: investigating the
outcome measures of treatment efficacy, pathophysiology, and the
development of local treatments.” 2016. Web. 23 Jan 2021.
Vancouver:
Hughes M. Digital ulcers in systemic sclerosis: investigating the
outcome measures of treatment efficacy, pathophysiology, and the
development of local treatments. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Jan 23].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305671.
Council of Science Editors:
Hughes M. Digital ulcers in systemic sclerosis: investigating the
outcome measures of treatment efficacy, pathophysiology, and the
development of local treatments. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305671

Vrije Universiteit Amsterdam
14.
Overbeek, M.J.
Pulmonary arterial hypertension in systemic sclerosis
.
Degree: 2010, Vrije Universiteit Amsterdam
URL: http://hdl.handle.net/1871/16052
Subjects/Keywords: systemic sclerosis;
pulmonary arterial hypertension
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Overbeek, M. J. (2010). Pulmonary arterial hypertension in systemic sclerosis
. (Doctoral Dissertation). Vrije Universiteit Amsterdam. Retrieved from http://hdl.handle.net/1871/16052
Chicago Manual of Style (16th Edition):
Overbeek, M J. “Pulmonary arterial hypertension in systemic sclerosis
.” 2010. Doctoral Dissertation, Vrije Universiteit Amsterdam. Accessed January 23, 2021.
http://hdl.handle.net/1871/16052.
MLA Handbook (7th Edition):
Overbeek, M J. “Pulmonary arterial hypertension in systemic sclerosis
.” 2010. Web. 23 Jan 2021.
Vancouver:
Overbeek MJ. Pulmonary arterial hypertension in systemic sclerosis
. [Internet] [Doctoral dissertation]. Vrije Universiteit Amsterdam; 2010. [cited 2021 Jan 23].
Available from: http://hdl.handle.net/1871/16052.
Council of Science Editors:
Overbeek MJ. Pulmonary arterial hypertension in systemic sclerosis
. [Doctoral Dissertation]. Vrije Universiteit Amsterdam; 2010. Available from: http://hdl.handle.net/1871/16052

Univerzitet u Beogradu
15.
Zlatanović, Maja B., 1976-.
Uticaj sistemske skleroze na građu i funkciju srca i
perifernu mikrocirkulaciju.
Degree: Medicinski fakultet, 2018, Univerzitet u Beogradu
URL: https://fedorabg.bg.ac.rs/fedora/get/o:18999/bdef:Content/get
► Medicina - Interna medicina - reumatologija / Medicine - Internal medicine – rheumatology
Sistemska skleroza je kompleksno autoimuno oboljenje koje karakteriše sistemska fibroza i vaskularno…
(more)
▼ Medicina - Interna medicina - reumatologija /
Medicine - Internal medicine – rheumatology
Sistemska skleroza je kompleksno autoimuno
oboljenje koje karakteriše sistemska fibroza i vaskularno
oštećenje. Kardiološke i pulmološke manifestacije bolesti su glavni
uzroci morbiditeta i mortaliteta. Fibroza dovodi do strukturnog,
funkcionalnog i mehaniĉkog remodelovanja leve i desne komore, što
dalje moţe izazvati poremećaje sprovoĊenja i aritmije. Nove
ehokardiografske tehnike pruţaju uvid u srĉanu funkciju i mehaniku
uporedivu sa onim kod magnetne rezonance srca, "zlatnog standarda"
meĊu metodama vizuelizacije srca. Varijabilnost srĉane frekvencije
je vrlo pouzdana neinvazivna tehnika koja ispituje autonomni nervni
sistem, simpatiĉku i parasimpatiĉku aktivnost, dobijenu iz
24-ĉasovnog EKG zapisa. MeĊutim, još uvek je nedovoljno ispitan
odnos izmeĊu parametara mehanike srca i neravnoteţe autonomne
funkcije kod bolesnika sa sistemskom sklerozom, a koji moţe imati
znaĉajne kliniĉke implikacije u predviĊanju nepovoljnog ishoda kod
ovih bolesnika. Cilj: Ovo istraţivanje je imalo za cilj da ispita
strukturu, funkciju i mehaniku srca, i proceni autonomnu funkciju
kod bolesnika sa sistemskom sklerozom. TakoĊe, imalo je za cilj da
ispita meĊusobni odnos izmeĊu novih ehokardiografski parametara i
parametara autonomne funkcije srca, kao i njihov odnos sa
pokazateljima periferne mikroangiopatije kod ovih bolesnika.
Metodologija: Istraţivanje je obuhvatilo 45 bolesnika sa sistemskom
sklerozom, bez kardiovaskularnih simptoma, koji se leĉe u Institutu
za reumatologiju u Beogradu i 30 zdravih dobrovoljaca uparenih
prema uzrastu i polu. Kod svih bolesnika ukljuĉenih u istraţivanje
obavljen je kliniĉki pregled, modifikovani Rodnanov skin skor,
serološki testovi, testovi plućne funkcije, kapilaroskopija, indeks
aktivnosti bolesti, 24-ĉasovni Holter EKG putem koga je analizirana
varijabilnost srĉane frekvencije u vremenskom i frekventnom domenu,
i kompletna dvodimenzionalna ehokardiografija, ukljuĉujući analizu
straina putem speckle tracking metode. Rezultati: Parametri
strukture leve komore (debljina meĊukomorskog septuma, relativna
debljina zida leve komore, indeks mase leve komore, indeks volumena
leve pretkomore, p<0.01) i desne ventrikularne strukture
(debljina zida desne komore, p<0.01) znaĉajno su bili veći kod
bolesnika sa sistemskom sklerozom...
Advisors/Committee Members: Damjanov, Nemanja, 1955-.
Subjects/Keywords: systemic sclerosis; heart; echocardiography; mechanics;
heart rate variability; microangiopathy;
capillaroscopy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zlatanović, Maja B., 1. (2018). Uticaj sistemske skleroze na građu i funkciju srca i
perifernu mikrocirkulaciju. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:18999/bdef:Content/get
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zlatanović, Maja B., 1976-. “Uticaj sistemske skleroze na građu i funkciju srca i
perifernu mikrocirkulaciju.” 2018. Thesis, Univerzitet u Beogradu. Accessed January 23, 2021.
https://fedorabg.bg.ac.rs/fedora/get/o:18999/bdef:Content/get.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zlatanović, Maja B., 1976-. “Uticaj sistemske skleroze na građu i funkciju srca i
perifernu mikrocirkulaciju.” 2018. Web. 23 Jan 2021.
Vancouver:
Zlatanović, Maja B. 1. Uticaj sistemske skleroze na građu i funkciju srca i
perifernu mikrocirkulaciju. [Internet] [Thesis]. Univerzitet u Beogradu; 2018. [cited 2021 Jan 23].
Available from: https://fedorabg.bg.ac.rs/fedora/get/o:18999/bdef:Content/get.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zlatanović, Maja B. 1. Uticaj sistemske skleroze na građu i funkciju srca i
perifernu mikrocirkulaciju. [Thesis]. Univerzitet u Beogradu; 2018. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:18999/bdef:Content/get
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manchester
16.
Arthur, Donna Louise.
Doppler optical coherence tomography for microcirculation studies.
Degree: PhD, 2014, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/doppler-optical-coherence-tomography-for-microcirculation-studies(a18d59c3-6cfb-4266-98b1-188040bc120f).html
;
http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603145
► This thesis forms part of an ongoing long-term project to investigate the suitability of Doppler optical coherence tomography (OCT) as a measurement tool to investigate…
(more)
▼ This thesis forms part of an ongoing long-term project to investigate the suitability of Doppler optical coherence tomography (OCT) as a measurement tool to investigate skin thickness and blood flow in patients with systemic sclerosis. There is a discussion of the characterisation of an electro-optic phase modulator for use in a Doppler OCT imaging system which is being built for the purpose of clinical studies. In addition to this the development of software for the same system is described. The work includes a comparison of two methods of obtaining Doppler information that were tested with the system; a phase resolved method and a correlation mapping method. Initial structural and Doppler images obtained using the system are presented. In addition to this the development of semi-automated software to measure skin thickness from both OCT and high frequency ultrasound images is discussed. The results of a study, for which this software was developed, into skin thickness measurements using both techniques in both patients with systemic sclerosis and healthy controls are presented. Both OCT and high frequency ultrasound were able to measure a statistically significant difference in epidermal thickness at multiple locations on the body. Finally, the modification of a freely available Monte Carlo simulation for light propagation in multi-layered tissue (MCML) to enable the simulation of structural and Doppler OCT images is covered. The simulation was able to extract the magnitude of the simulated flow accurately to within an order of magnitude, and after a simple filter was applied to eliminate fluctuations in the data the structure of the Doppler image closely matched what was modelled.
Subjects/Keywords: 616.07; OCT; Optical Coherence Tomography; Imaging; Doppler; Systemic sclerosis; Microcirculation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Arthur, D. L. (2014). Doppler optical coherence tomography for microcirculation studies. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/doppler-optical-coherence-tomography-for-microcirculation-studies(a18d59c3-6cfb-4266-98b1-188040bc120f).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603145
Chicago Manual of Style (16th Edition):
Arthur, Donna Louise. “Doppler optical coherence tomography for microcirculation studies.” 2014. Doctoral Dissertation, University of Manchester. Accessed January 23, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/doppler-optical-coherence-tomography-for-microcirculation-studies(a18d59c3-6cfb-4266-98b1-188040bc120f).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603145.
MLA Handbook (7th Edition):
Arthur, Donna Louise. “Doppler optical coherence tomography for microcirculation studies.” 2014. Web. 23 Jan 2021.
Vancouver:
Arthur DL. Doppler optical coherence tomography for microcirculation studies. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2021 Jan 23].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/doppler-optical-coherence-tomography-for-microcirculation-studies(a18d59c3-6cfb-4266-98b1-188040bc120f).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603145.
Council of Science Editors:
Arthur DL. Doppler optical coherence tomography for microcirculation studies. [Doctoral Dissertation]. University of Manchester; 2014. Available from: https://www.research.manchester.ac.uk/portal/en/theses/doppler-optical-coherence-tomography-for-microcirculation-studies(a18d59c3-6cfb-4266-98b1-188040bc120f).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603145

University of Manchester
17.
Hughes, Michael.
Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments.
Degree: PhD, 2016, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/digital-ulcers-in-systemic-sclerosis-investigating-the-outcome-measures-of-treatment-efficacy-pathophysiology-and-the-development-of-local-treatments(a2d6fb1e-f347-4abf-9d8f-5319d2d0aeed).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764427
► Introduction: Digital ulcers (DUs) are responsible for much of the pain and disability associated with systemic sclerosis (SSc), and are a biomarker of internal organ…
(more)
▼ Introduction: Digital ulcers (DUs) are responsible for much of the pain and disability associated with systemic sclerosis (SSc), and are a biomarker of internal organ involvement and poor prognosis. DUs are often used as the primary end-point in SSc clinical trials, although the reliability of rheumatologists in grading DUs is poor to moderate at best. Fingertip DUs are believed to be ischaemic in aetiology, whereas, extensor DUs are thought to occur due to mechanical factors and recurrent microtrauma. Treatments for DUs are often poorly tolerated due to systemic vasodilation. The overarching aim was to investigate the definition and objective measurement of SSc-related DUs, their pathophysiology, and a new light treatment. Method: Five studies were undertaken. (1) A web-based study in which photographs of digital lesions were graded, all either with or without clinical context. (2) A pilot study to assess the feasibility and tolerability of high-frequency ultrasound (HFUS) imaging to measure DUs. (3) A retrospective study examining whether thermographic abnormalities are associated with DUs. (4) A double-blind, randomised, crossover, controlled study of glyceryl trinitrate (GTN) to explore the pathophysiology of DUs in SSc. (5). A feasibility study of a novel light (red, infrared and blue) device to treat SSc-related DUs. Results: (1) 51 rheumatologists graded ≥ 4500 images. The clinical context (without vs with, weighted kappa statistic) did not significantly improve the intra- (0.32,0.36) or inter-rater (0.64,0.71) reliability. (2) HFUS was performed on 15 DUs and was well tolerated and feasible in the majority. DU measurement was possible in most (n=13) DUs, the mean DU depth and width were 0.99mm and 5.74mm, respectively. (3) Patients (n=138) with abnormal (compared to normal) thermography were more likely (adjusted odds ratio = 2.84) to develop future DUs, including multiple episodes. (4) 16 DUs were studied; the microvessels of the DU centre were responsive to GTN, with an increase in perfusion, with a similar effect in both fingertip and extensor DUs. There was less of a clear signal in the DU periphery. (5) Light treatment was safe, feasible and well tolerated (46 light treatments administered in 8 patients, one studied on three separate occasions). There was a significant improvement (change in visual analogue score per visit) in DUs as assessed by both patient (-7.1, P = < 0.001) and clinician opinion (-5.2, P = < 0.001). DU perfusion (measured by LDI) significantly increased post-treatment. Conclusion: The reliability of DU grading did not improve with clinical context. HFUS was feasible and well tolerated, and measurement was possible in most DUs. Our data suggests that many DUs might have an ischaemic drive, including extensor DUs. A novel light treatment was safe, feasible and well tolerated, with a tentative suggestion of treatment efficacy.
Subjects/Keywords: Outcome measures; Systemic sclerosis; Scleroderma; Digital ulcers; Pathophysiology
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hughes, M. (2016). Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/digital-ulcers-in-systemic-sclerosis-investigating-the-outcome-measures-of-treatment-efficacy-pathophysiology-and-the-development-of-local-treatments(a2d6fb1e-f347-4abf-9d8f-5319d2d0aeed).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764427
Chicago Manual of Style (16th Edition):
Hughes, Michael. “Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments.” 2016. Doctoral Dissertation, University of Manchester. Accessed January 23, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/digital-ulcers-in-systemic-sclerosis-investigating-the-outcome-measures-of-treatment-efficacy-pathophysiology-and-the-development-of-local-treatments(a2d6fb1e-f347-4abf-9d8f-5319d2d0aeed).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764427.
MLA Handbook (7th Edition):
Hughes, Michael. “Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments.” 2016. Web. 23 Jan 2021.
Vancouver:
Hughes M. Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Jan 23].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/digital-ulcers-in-systemic-sclerosis-investigating-the-outcome-measures-of-treatment-efficacy-pathophysiology-and-the-development-of-local-treatments(a2d6fb1e-f347-4abf-9d8f-5319d2d0aeed).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764427.
Council of Science Editors:
Hughes M. Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments. [Doctoral Dissertation]. University of Manchester; 2016. Available from: https://www.research.manchester.ac.uk/portal/en/theses/digital-ulcers-in-systemic-sclerosis-investigating-the-outcome-measures-of-treatment-efficacy-pathophysiology-and-the-development-of-local-treatments(a2d6fb1e-f347-4abf-9d8f-5319d2d0aeed).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764427

University of Lund
18.
Andréasson, Kristofer.
Systemic sclerosis. Novel molecular and epidemiological
features of disease.
Degree: 2013, University of Lund
URL: https://lup.lub.lu.se/record/4175733
;
https://portal.research.lu.se/ws/files/3716319/4175734.pdf
► Systemic sclerosis (SSc) is a systemic rheumatic disease with significant mortality and morbidity. Different estimations of disease prevalence and incidence have been presented from various…
(more)
▼ Systemic sclerosis (SSc) is a systemic rheumatic
disease with significant mortality and morbidity. Different
estimations of disease prevalence and incidence have been presented
from various parts of the world. While lung involvement is a common
cause of SSc-related death, a majority of SSc patients suffer from
symptoms originating in the gastrointestinal (GI) tract. By
combining data from a population based register with individual
case ascertainment, we investigated the epidemiology of SSc in a
defined region in southern Sweden comprising one million adult
inhabitants. The investigation was performed by using
classification criteria presented in 1980 and in 2013 respectively.
SSc prevalence was estimated to 305 per million and the annual
incidence 19 per million and year by application of the 2013
classification criteria. We show that the novel criteria identify
SSc subjects who were overlooked by the previous criteria. Usage of
either criteria set resulted in prevalence estimates that are
higher than previous reports from northern Europe, but similar to
reports from southern Europe. Cartilage oligomeric matrix protein
(COMP) is a promising biomarker of skin fibrosis in SSc. We have
investigated the potential for S-COMP to serve as a biomarker for
SSc associated lung fibrosis and as a predictor of SSc survival.
S-COMP showed only minimal associations with the development or
presence of pulmonary fibrosis. SSc patients with pathological
S-COMP in early SSc were at an increased risk of death. To further
explore the mechanisms behind COMP and fibrosis, we investigated
skin fibrosis in mice deficient in COMP. These mice were not
resistant to skin fibrosis. GI disease is a common visceral
manifestation of SSc. The inflammatory protein complex S100A8/A9,
also known as calprotectin, has been associated with several
rheumatic diseases. Faecal calprotectin (FC) is a validated
biomarker in inflammatory bowel disease. We have explored the
biomarker potential of FC in SSc. FC correlated with SSc
manifestations in the GI tract. FCs showed little variation upon
repeated testing. FC was higher in SSc compared to other rheumatic
diseases. The development of inflammation and fibrosis was
investigated in reference to S100A8/A9 in an experimental mouse
model. S100A8 and S100A9 were found to localise to inflamed and
fibrotic skin tissue. Using the same model, we could not identify
any significant reduction of inflammation or fibrosis in S100A9
deficient mice. I suggest that FC, a feasible biomarker already
available in routine clinical care, could be a valid biomarker of
GI disease in SSc. Further studies are warranted to elucidate the
mechanisms behind pathological FC testing in SSc.
Subjects/Keywords: Rheumatology and Autoimmunity; Systemic sclerosis; fibrosis; COMP; calprotectin; biomarker; gastrointestinal
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Andréasson, K. (2013). Systemic sclerosis. Novel molecular and epidemiological
features of disease. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/4175733 ; https://portal.research.lu.se/ws/files/3716319/4175734.pdf
Chicago Manual of Style (16th Edition):
Andréasson, Kristofer. “Systemic sclerosis. Novel molecular and epidemiological
features of disease.” 2013. Doctoral Dissertation, University of Lund. Accessed January 23, 2021.
https://lup.lub.lu.se/record/4175733 ; https://portal.research.lu.se/ws/files/3716319/4175734.pdf.
MLA Handbook (7th Edition):
Andréasson, Kristofer. “Systemic sclerosis. Novel molecular and epidemiological
features of disease.” 2013. Web. 23 Jan 2021.
Vancouver:
Andréasson K. Systemic sclerosis. Novel molecular and epidemiological
features of disease. [Internet] [Doctoral dissertation]. University of Lund; 2013. [cited 2021 Jan 23].
Available from: https://lup.lub.lu.se/record/4175733 ; https://portal.research.lu.se/ws/files/3716319/4175734.pdf.
Council of Science Editors:
Andréasson K. Systemic sclerosis. Novel molecular and epidemiological
features of disease. [Doctoral Dissertation]. University of Lund; 2013. Available from: https://lup.lub.lu.se/record/4175733 ; https://portal.research.lu.se/ws/files/3716319/4175734.pdf

Boston University
19.
Barron, Alexander Michael Shuford.
Perivascular fibroblast activation states in human skin diseases.
Degree: PhD, Microbiology, 2020, Boston University
URL: http://hdl.handle.net/2144/39384
► The perivascular adventitia (PA) senses and responds to injuries in blood vessels and the tissues they feed. Cells in the PA form the outermost vascular…
(more)
▼ The perivascular adventitia (PA) senses and responds to injuries in blood vessels and the tissues they feed. Cells in the PA form the outermost vascular layer, joining the circulatory system to other organs. Housing hematopoietic, mesenchymal and neuronal cells allows flexible adventitial responses to diverse perturbations. However, the PA response can also be pathogenic. Thickening of the adventitia may drive ischemia and hypertension. It can also be a niche for local lymphocyte priming in diseases such as idiopathic pulmonary arterial hypertension. Despite their importance, PA contributions to skin diseases were understudied.
The hypothesis that contrasting two cutaneous diseases, scleroderma and discoid lupus erythematosus (DLE), would illuminate discrete PA alterations was explored. Vascular changes are prominent, but distinct, in both diseases. Studying perivascular adventitial changes in these diseases may yield insights into both dermal and vascular pathologies. PA fibroblasts in healthy human skin were phenotypically distinct from the surrounding dermal fibroblasts. In both scleroderma and DLE, PA fibroblasts expanded and expressed surface markers not observed in healthy skin including vascular cell adhesion molecule 1 (VCAM1), podoplanin (PDPN) and the p75 low affinity nerve growth factor receptor (NGFR). Elaborated networks of PA fibroblasts in DLE expressed VCAM1 and enmeshed dense, T cell-rich infiltrates. Transcriptional analyses indicated positive correlations between VCAM1, T cell chemoattractants and interleukin (IL)-15, which promotes their survival. Activated PA fibroblasts in DLE likely create a supportive niche for T cells infiltrating the skin.
In contrast, enlarged PA fibroblast networks in scleroderma expressed NGFR in the absence of leukocyte infiltrates. This PA fibroblast phenotype was shared among reparative and pathologic scarring, and four dermal tumors. NGFR is a mesenchymal stem cell (MSC) marker, and expanded NGFR+ mesenchymal cells were immediately adjacent to cluster of differentiation (CD)34+ and CD73+ PA MSC. Expression of NGFR by PA fibroblasts is likely associated with reparative responses. Different stimuli induced VCAM1 and NGFR on cultured human dermal fibroblasts, supporting these as discrete activation states. In conclusion, these studies demonstrated the responsive and plastic nature of human dermal PA mesenchymal cells, and pointed to connections with vascular alterations in skin diseases.
Advisors/Committee Members: Browning, Jeffrey L. (advisor), Viglianti, Gregory A. (advisor).
Subjects/Keywords: Immunology; Adventitia; Fibroblasts; Lupus; Skin; Systemic sclerosis; T cells
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Barron, A. M. S. (2020). Perivascular fibroblast activation states in human skin diseases. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/39384
Chicago Manual of Style (16th Edition):
Barron, Alexander Michael Shuford. “Perivascular fibroblast activation states in human skin diseases.” 2020. Doctoral Dissertation, Boston University. Accessed January 23, 2021.
http://hdl.handle.net/2144/39384.
MLA Handbook (7th Edition):
Barron, Alexander Michael Shuford. “Perivascular fibroblast activation states in human skin diseases.” 2020. Web. 23 Jan 2021.
Vancouver:
Barron AMS. Perivascular fibroblast activation states in human skin diseases. [Internet] [Doctoral dissertation]. Boston University; 2020. [cited 2021 Jan 23].
Available from: http://hdl.handle.net/2144/39384.
Council of Science Editors:
Barron AMS. Perivascular fibroblast activation states in human skin diseases. [Doctoral Dissertation]. Boston University; 2020. Available from: http://hdl.handle.net/2144/39384

University of Southern California
20.
Chen, Chider.
From mesenchymal stem cell therapy to discovery of drug
therapy for systemic sclerosis.
Degree: PhD, Cranio-Facial Biology, 2014, University of Southern California
URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/370638/rec/2918
► Bone marrow mesenchymal stem cells (BMMSCs) are non‐hematopoietic multipotent stem cells capable of differentiating into both mesenchymal and non‐mesenchymal cell types. In addition to generate…
(more)
▼ Bone marrow mesenchymal stem cells (BMMSCs) are
non‐hematopoietic multipotent stem cells capable of differentiating
into both mesenchymal and non‐mesenchymal cell types. In addition
to generate bone structure to replace damaged and diseased tissues,
preclinical and clinical studies have shown that BMMSCs display
profound immunomodulatory functions via inhibiting the
proliferation and function of several major immune cells such as T
lymphocytes, B lymphocytes, natural killer (NK), and dendritic
cells. Thus,
systemic infusion of BMMSCs has been used to treat a
variety of diseases, including acute graft-versus-host-disease
(GVHD), ameliorating HSC engraftment,
systemic lupus erythematosus
(SLE), intestinal and bowel disease (IBD), and sepsis. However, the
detailed mechanism in which BMMSCs regulate immune function is not
fully understood. ❧ In the first part of Chapter 2 of this study,
we show that
systemic infusion of BMMSCs induces a transient T cell
apoptosis via the Fas Ligand (FasL)‐mediated Fas pathway and
ameliorates diseased phenotypes in fibrillin-1 (FBN1) mutated
systemic sclerosis (SSc) and dextran sulfate sodium‐induced
experimental colitis mice. The therapeutic mechanism of BMMSC
infusion is associated with phagocytosis of apoptotic T cell
debris, leading to a high level of macrophage‐mediated transforming
growth factor beta (TGFβ) production and a subsequent immune
tolerance. Importantly, we provided clinical evidence to show that
MSC infusion in SSc patients resulted in a T cell apoptosis and
up‐regulation of Tregs. Additionally, we revealed that Fas null
BMMSCs, with normal FasL function, failed to induce T cell
apoptosis and offer therapeutic effect for SS and colitis mice.
Mechanistic study showed that Fas governed monocyte chemotactic
protein 1 (MCP-1) secretion in BMMSCs, which plays a crucial role
in the recruitment of T cells to BMMSCs for FasL‐mediated
apoptosis. In summary, BMMSCs use Fas to control MCP-1 secretion
for the recruitment of T cells and subsequently use FasL to induce
activated T cell apoptosis. Macrophages take debris of apoptotic T
cells to release a high level of TGFβ, leading to up‐regulation of
regulatory T cells (Tregs) and, ultimately, immune tolerance for
immunotherapies. ❧ This study uncovers the role of Fas and FasL in
BMMSC‐based immune therapies, which may serve as a basis to develop
novel strategies for improving cell‐based therapies. The
significance of this study is to identify a novel mechanism of
BMMSC‐associated immunomodulation and immune therapy. Also, Fas and
FasL collaboratively induce immune tolerance suggests a potential
new mechanism that receptor/ligand coupled to execute therapeutic
effect in cell‐based treatment. This study covered experimental
evidences for stem cell biology, molecular mechanism of BMMSC
associated immunomodulation, and stem cell-based immunotherapies. ❧
In second part of Chapter 2 of this study, we showed for the first
time that telomerase activity is required for maintaining the
immunomodulatory properties of MSCs. Telomerase deficient…
Advisors/Committee Members: Shi, Songtao (Committee Chair), Chai, Yang (Committee Member), Chuong, Cheng-Ming (Committee Member), Ying, Qi-Long (Committee Member), Paine, Michael L. (Committee Member), Le, Anh (Committee Member).
Subjects/Keywords: immunomodulation; mesenchymal stem cell; osteopenia; rapamycin; systemic sclerosis; telomerase
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chen, C. (2014). From mesenchymal stem cell therapy to discovery of drug
therapy for systemic sclerosis. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/370638/rec/2918
Chicago Manual of Style (16th Edition):
Chen, Chider. “From mesenchymal stem cell therapy to discovery of drug
therapy for systemic sclerosis.” 2014. Doctoral Dissertation, University of Southern California. Accessed January 23, 2021.
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/370638/rec/2918.
MLA Handbook (7th Edition):
Chen, Chider. “From mesenchymal stem cell therapy to discovery of drug
therapy for systemic sclerosis.” 2014. Web. 23 Jan 2021.
Vancouver:
Chen C. From mesenchymal stem cell therapy to discovery of drug
therapy for systemic sclerosis. [Internet] [Doctoral dissertation]. University of Southern California; 2014. [cited 2021 Jan 23].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/370638/rec/2918.
Council of Science Editors:
Chen C. From mesenchymal stem cell therapy to discovery of drug
therapy for systemic sclerosis. [Doctoral Dissertation]. University of Southern California; 2014. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/370638/rec/2918
21.
Sobanski, Vincent.
Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity.
Degree: Docteur es, Sciences de la vie et de la santé, 2017, Université Lille II – Droit et Santé
URL: http://www.theses.fr/2017LIL2S027
► La sclérodermie systémique (ScS) est une connectivite associant atteinte vasculaire, auto-immunité et fibrose. Cette pathologie est associée à une morbi-mortalité importante, et les ressources thérapeutiques…
(more)
▼ La sclérodermie systémique (ScS) est une connectivite associant atteinte vasculaire, auto-immunité et fibrose. Cette pathologie est associée à une morbi-mortalité importante, et les ressources thérapeutiques sont limitées. La physiopathologie de la ScS n’est que partiellement connue, mais il apparait que les liens entre le système immunitaire et la fibrose sont étroits. Ainsi, la ScS peut être considérée comme un modèle prototypique d’étude des liens immunité-fibrose. Il s’agit d’une maladie hétérogène, c’est-à-dire que les phénotypes cliniques présentés par les patients sont variables, rendant complexe l’établissement d’une classification des patients en groupes homogènes. Mieux comprendre cette hétérogénéité est un préalable indispensable à la constitution d’endotypes, permettant l’étude des mécanismes physiopathologiques propres à chacun d’entre eux.L’objectif de cette Thèse a été de mieux appréhender cette hétérogénéité clinique et d’étudier la place des marqueurs immunologiques, en particulier les auto-anticorps, en tant que biomarqueurs de cette hétérogénéité.Le premier travail a été une classification sans a priori des patients de la cohorte européenne EUSTAR (European Scleroderma Trials and Research Group) par une analyse en cluster sur 24 variables sélectionnées (atteintes cliniques, auto-anticorps). Deux puis 6 groupes de patients homogènes ont été obtenus, dont la survie était significativement différente. Ce travail a suggéré qu’il existait des groupes homogènes de patients au-delà de la dichotomie historique forme cutanée diffuse vs. limitée. La présence d’atteintes viscérales et le statut des auto-anticorps apparaissent comme des éléments importants dans la constitution des groupes.Le deuxième travail s’est intéressé au dosage des chaines légères libres sériques (serum free light chain : SFLC) dans la ScS. Le taux de SFLC est plus élevé chez les patients ScS que chez les contrôles et est associé à des paramètres de gravité de la maladie tels que le score de Rodnan, les scores d’activité, les pressions pulmonaires et la DLCO. Cette étude apporte des arguments supplémentaires pour évoquer la participation active des lymphocytes B à la physiopathologie de la ScS.Nous avons ensuite réalisé une estimation de la prévalence des anticorps anti-ARN polymérase de type III dans notre cohorte de patients avec ScS avant d’inclure ces données dans une revue systématique avec méta-analyse. Ce travail a montré que la prévalence de ces anticorps était hétérogène entre les centres. Les facteurs potentiels pouvant expliquer une partie de cette hétérogénéité sont des facteurs géographiques, suggérant l’implication de facteurs génétiques et/ou environnementaux.Le dernier travail a été dédié à l’hypertension artérielle pulmonaire (HTAP) des connectivites, en particulier de la ScS. A partir d’une cohorte de patients provenant du centre de référence de l’HTAP du Royaume-Uni, les anticorps anti-U1RNP ont été analysés en tant que marqueur pronostique. Ces anticorps sont associés de façon significative à une meilleure survie des…
Advisors/Committee Members: Dubucquoi, Sylvain (thesis director).
Subjects/Keywords: Hétérogénéité; Endotypes; Sclérodermie systémique; Auto-anticorps; Auto-antibodies; Systemic sclerosis; Heterogeneity
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sobanski, V. (2017). Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity. (Doctoral Dissertation). Université Lille II – Droit et Santé. Retrieved from http://www.theses.fr/2017LIL2S027
Chicago Manual of Style (16th Edition):
Sobanski, Vincent. “Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity.” 2017. Doctoral Dissertation, Université Lille II – Droit et Santé. Accessed January 23, 2021.
http://www.theses.fr/2017LIL2S027.
MLA Handbook (7th Edition):
Sobanski, Vincent. “Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity.” 2017. Web. 23 Jan 2021.
Vancouver:
Sobanski V. Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity. [Internet] [Doctoral dissertation]. Université Lille II – Droit et Santé 2017. [cited 2021 Jan 23].
Available from: http://www.theses.fr/2017LIL2S027.
Council of Science Editors:
Sobanski V. Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity. [Doctoral Dissertation]. Université Lille II – Droit et Santé 2017. Available from: http://www.theses.fr/2017LIL2S027
22.
Marut, Wioleta.
ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique.
Degree: Docteur es, Immunologie, 2012, Université Paris Descartes – Paris V
URL: http://www.theses.fr/2012PA05T079
► Plusieurs rapports ont suggéré que les formes réactives de l'oxygène (FRO) et d'azote sont impliquées dans la pathogénèse de la ScS. Les fibroblastes ScS de…
(more)
▼ Plusieurs rapports ont suggéré que les formes réactives de l'oxygène (FRO) et d'azote sont impliquées dans la pathogénèse de la ScS. Les fibroblastes ScS de la peau et des organes internes surproduisent des FRO qui déclenchent la prolifération des fibroblastes et la synthèse de collagène de type I, conduisant à l'initiation et à la progression de la ScS. Le laboratoire a mis au point un modèle de souris ScS, induite par injections itératives de HOCl. Comme dans la ScS humaine, les fibroblastes de la peau de souris ScS produisent de manière constitutive de grandes quantités de FRO. Nous avons utilisé cette propriété pour induire sélectivement l'apoptose de fibroblastes de souris ScS. Le catalyseur organotelluride-(PHTE) 2NQ et le composé naturel Dipropyltertrasulfide (DPTTS) sont capables d'augmenter specifiquement la production de FRO par les fibroblastes et d’induire un stress oxydatif létal dans les fibroblastes sclérodermiques. Ce phénomène n'a aucun impact sur les fibroblastes normaux qui présentent des taux de FRO basaux faible et un statut oxydant / antioxydant normal. De nombreuses études ont également prouvé l’importance des espèces azotées dans la l’induction de la ScS. Chez les patients atteints de SSc, le taux sérique de l'oxyde nitrique est considérablement accru. De plus, le NO peut se combiner avec d'autres radicaux libres comme l'anion superoxyde (O•-2) pour former le peroxynitrite (ONOO-) qui est hautement cytotoxique et contribue à l'inflammation, la fibrose et l'apoptose des cellules endothéliales. La production de NO par les cellules endothéliales ou les fibroblastes peut être stimulée par l'angiotensine II, principal peptide de la voie rénine-angiotensine (RAS). Comme chez les patients atteints de sclérodermie, les souris HOCl/ScS présentent des taux sériques d'angiotensine II élevés, ce qui est favorable à la prolifération des fibroblastes, à la fibrose, et à l'inflammation. Ces observations nous ont conduites à tester les effets de l'Irbésartan, un antagoniste des récepteurs de l’angiotensine II de type I (AT1 RA) dans le ScS modèle murin. Un nouveau modèle animal basé sur l'exposition chronique à des ROS et présentant de nombreuses similitudes avec la maladie humaine, m'a permis d'étudier de nouveaux traitements de la ScS. Ces nouvelles approches sont basées sur l'action cytotoxique de composés pro-oxydants - (PHTE) 2NQ et DPTTS - et sur les effets anti-nitrosatifs de molécules comme l'Irbésartan. Ces stratégies thérapeutiques originales ouvrent des perspectives intéressantes dans le traitement de la ScS, où l'arsenal thérapeutique est actuellement encore limité.
Several reports have suggested that reactive oxygen and nitrogen species are involved in SSc pathogenesis. SSc fibroblast from skin and internal organs overproduce ROS that trigger the proliferation of fibroblasts and the synthesis of type I collagen leading to the initiation and progresion of SSc. As in human SSc, skin fibroblasts from SSc mice constitutively produce large amounts of ROS. We have used this property to selectively…
Advisors/Committee Members: Batteux, Frédéric (thesis director).
Subjects/Keywords: Traitement de la sclérodermie systémique; Systemic sclerosis treatment; 610
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Marut, W. (2012). ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique. (Doctoral Dissertation). Université Paris Descartes – Paris V. Retrieved from http://www.theses.fr/2012PA05T079
Chicago Manual of Style (16th Edition):
Marut, Wioleta. “ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique.” 2012. Doctoral Dissertation, Université Paris Descartes – Paris V. Accessed January 23, 2021.
http://www.theses.fr/2012PA05T079.
MLA Handbook (7th Edition):
Marut, Wioleta. “ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique.” 2012. Web. 23 Jan 2021.
Vancouver:
Marut W. ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique. [Internet] [Doctoral dissertation]. Université Paris Descartes – Paris V; 2012. [cited 2021 Jan 23].
Available from: http://www.theses.fr/2012PA05T079.
Council of Science Editors:
Marut W. ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique. [Doctoral Dissertation]. Université Paris Descartes – Paris V; 2012. Available from: http://www.theses.fr/2012PA05T079
23.
Bournia, Vasiliki - Kalliopi.
Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα.
Degree: 2019, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
URL: http://hdl.handle.net/10442/hedi/46131
► Systemic Sclerosis (SSc) is a rare, systemic, autoimmune disorder characterized by vasculopathy, dysregulation of the immune system and fibrosis of skin and internal organs. The…
(more)
▼ Systemic Sclerosis (SSc) is a rare, systemic, autoimmune disorder characterized by vasculopathy, dysregulation of the immune system and fibrosis of skin and internal organs. The severity and significant variability of clinical manifestations of SSc and the need for targeted treatment, renders the search for reliable prognostic markers imperative. The present study of prognostic factors in SSc is divided in two sections. In the first section we comparatively assessed the performance of different nailfold video-capillaroscopic (NVC) parameters in identifying SSc among patients with RP. In addition we compared consistency of various clinical correlations of NVC between two different timepoints and evaluated the prognostic capacity of NVC in SSc patients. Patients and Methods: At baseline we clinically and capillaroscopically evaluated 242 consecutive patients referred to our department for NVC (138 with SSc, 12 withvery early diagnosis of SSc, 36 with primary Raynaud phenomenon και 56 with non-SSc related secondary Raynaud phenomenon); 173 were reevaluated after 3.38±1.47years. Sixty-two healthy volunteers served as controls. Capillaroscopy pattern( normal/early/active/late) was qualitatively defined. Capillary loss, dilated, giant or ramified capillaries and micro-hemorrhages were scored semi-quantitatively. Results: Capillary loss score had the highest diagnostic accuracy at discriminating patients with an SSc-spectrum disorder from patients with RP of different etiology and controls, as defined by ROC curve analysis [AUC (95% CI)=0.905 (0.869-0.942)], followed by dilatation score [0.863 (0.818-0.907)] and giant score [0.835(0.787-0.884)]. By contrast, micro-hemorrhages [0.720 (0.662-0.779)] and ramifications scores [0.604 (0.539-0.670)] performed worse. Comparison of clinical correlations of NVC between two sequential time points in 85 SSc patients, showed low levels of consistency over time. Multivariate analysis in 94 SSc patients indicated that active (OR=3.305, p=0.043) and late (OR=6.900, p=0.023) baseline capillaroscopy pattern predicted occurrence of a combined adverse disease outcome [forced vital capacity (FVC) deterioration>10% and/or DLCO deterioration>15%and/or mRSS deterioration>3.5 and/or first occurrence of digital ulcers and/or death) ] at 3 year follow-up. Conclusions: Dilatation score performs best of all semi-quantitative NVC parameters in diagnosing SSc and although clinical correlations of capillaroscopic findings change over time, our study confirms earlier reports that worse capillaroscopy pattern at baseline correlates with higher likelihood for adverse prognosis. In the second section of our study we tried to examine whether plasma levels of CXCL4-L1, the non-allelic variant of CXCL4, a chemokine which has already been implicated in the pathogenesis of SSc and has an established predictive role in this disease, differ between SSc patients and healthy controls. Patients and Methods: CXCL4 plasma levels were measured by ELISA in 94 SSc patients, 5 VEDOSS patients and 74 healthy controls.…
Subjects/Keywords: Συστηματικό σκληρόδερμα; Τριχοειδοσκόπηση; Βιοδείκτες; Systemic sclerosis; Capillaroscopy; Biomarkers
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bournia, V. -. K. (2019). Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/46131
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Bournia, Vasiliki - Kalliopi. “Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα.” 2019. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed January 23, 2021.
http://hdl.handle.net/10442/hedi/46131.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Bournia, Vasiliki - Kalliopi. “Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα.” 2019. Web. 23 Jan 2021.
Vancouver:
Bournia V-K. Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2019. [cited 2021 Jan 23].
Available from: http://hdl.handle.net/10442/hedi/46131.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Bournia V-K. Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2019. Available from: http://hdl.handle.net/10442/hedi/46131
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidad del Rosario
24.
Rojas Quintana, Manuel Eduardo.
The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study.
Degree: 2019, Universidad del Rosario
URL: http://repository.urosario.edu.co/handle/10336/19850
► BACKGROUND: Resilience is considered the capability to positively respond to adverse events. Since this capacity in considered a “continuum” process, long-term stressors and psychosocial factors…
(more)
▼ BACKGROUND: Resilience is considered the capability to positively respond to adverse events. Since this capacity in considered a “continuum” process, long-term stressors and psychosocial factors are thought to be crucial for resilience development, especially in those patients with chronic inflammatory systemic diseases. However, the role of clinical, biological and socioeconomic characteristics in autoimmune rheumatic diseases (ARDs) is still unknown. OBJECTIVE To evaluate the association between resilience and socioeconomic, biological and clinical factors in four autoimmune rheumatic diseases (ARDs) namely: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SS) and systemic sclerosis (SSc). METHODS: A cross-sectional study in 188 women with SLE (n= 70), RA (n= 51), SS (n= 32), and SSc (n= 35) was done. Resilience was evaluated by the “Brief Resilience Scale”, whereas independent factors including age, age at onset, duration of disease, socioeconomic status, excersice, severity of symptoms and polyautoimmunity (PolyA) were evaluated by surveys and chart reviews. A panel of 15 serum cytokines and 14 autoantibodies were evaluated simultaneously. Bivariate, classification and regression trees (CART), and multiple linear regressions were used to analyze data. RESULTS: CART analysis showed that patients younger than 48 years with SLE, RA, and SSc who had low socioeconomic status showed the lowest resilience scores, whereas those patients between 48 and 66 years exhibited the highest resilience levels despite socioeconomic status. Interestingly, regular physical activity was associated with highest resilience in SSc. In addition, Interleukin-6 (IL-6) was associated low resilience scores (β= -0.581120, p=0.02) and with severity of symptoms (β=1.8395, p=0.04) in SSc. Neither PolyA nor severity of symptoms influenced resilience in the four ARDs studied. Cytokine levels did not significantly differ between groups based on regular physical activity. CONCLUSIONS: Resilience is a continuum trait associated to socioeconomic status and age. In addition, IL-6 and exercise are key factors for resilience in SSc. These results highlight the relevance of biological and socioeconomic factors in the development of resilience in autoimmunity.
Centro de Estudio de Enfermedades Autoinmunes (CREA)
Universidad del Rosario (ABN011)
Colciencias (Grant No 122254531722/Grant No0425-2013)
Advisors/Committee Members: Acosta-Ampudia, Yeny, Molano-González, Nicolas, Anaya, Juan Manuel, Monsalve, Diana M., Pacheco, Yovana, Ramirez-Santana, Carolina, Rodríguez-Jimenez, Monica, Rodríguez, Yhojan, Mantilla, Ruben Dario.
Subjects/Keywords: Resilience; Rheumatoid arthritis; Systemic lupus erythematosus; Systemic sclerosis; Sjögren’s síndrome; 616; Artritis reumatoide; Lupus eritematoso sistémico; Esclerodermia Sistémica; Síndrome de Sjögren
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Rojas Quintana, M. E. (2019). The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study. (Thesis). Universidad del Rosario. Retrieved from http://repository.urosario.edu.co/handle/10336/19850
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rojas Quintana, Manuel Eduardo. “The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study.” 2019. Thesis, Universidad del Rosario. Accessed January 23, 2021.
http://repository.urosario.edu.co/handle/10336/19850.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rojas Quintana, Manuel Eduardo. “The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study.” 2019. Web. 23 Jan 2021.
Vancouver:
Rojas Quintana ME. The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study. [Internet] [Thesis]. Universidad del Rosario; 2019. [cited 2021 Jan 23].
Available from: http://repository.urosario.edu.co/handle/10336/19850.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rojas Quintana ME. The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study. [Thesis]. Universidad del Rosario; 2019. Available from: http://repository.urosario.edu.co/handle/10336/19850
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
25.
Cossu, Marta.
Molecular and cellular profiling of systemic sclerosis and its preclinical stages.
Degree: 2017, University Utrecht
URL: http://dspace.library.uu.nl/handle/1874/353102
;
URN:NBN:NL:UI:10-1874-353102
;
urn:isbn:978-90-393-68039
;
URN:NBN:NL:UI:10-1874-353102
;
http://dspace.library.uu.nl/handle/1874/353102
► The development of unrestrained fibrosis in the skin and internal organs is the hallmark of systemic sclerosis (SSc). Nevertheless, it is known that fibrosis is…
(more)
▼ The development of unrestrained fibrosis in the skin and internal organs is the hallmark of
systemic sclerosis (SSc). Nevertheless, it is known that fibrosis is preceded by vascular and immune modifications. On the basis of SSc-specific autoantibodies and nailfold capillary lesions it is possible to identify individuals with Raynaud’s phenomenon considered at increased risk to develop SSc when compared with the general population. Furthermore, some characteristic SSc features are not fibrotic, they can precede fibrosis and still be sufficient to meet the EUropean League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SSc. In my PhD thesis I aimed to characterize how patients with early SSc and SSc without any sign of fibrosis differ from fibrotic SSc patients (limited and diffuse cutaneous SSc; lcSSc and dcSSc), by that contributing to increase the knowledge about the events which lead to the onset of fibrosis and provide new ground to prevent it. To do so, we first investigated how different factors involved in vascular and immune activation “behave” in the circulation of early SSc individuals, in patients with SSc without fibrotic features, comparing with fibrotic SSc patients. We then investigated in the different groups natural killer (NK) and NKT-like cells, important in infections control, tumor development and immuneregulation. We found that: - the Interferon (IFN) signature described in SSc patients with fibrosis, is already present since the early SSc stage and in the non-fibrotic SSc group to an even higher extent then in fibrotic SSc patients: - markers of vascular damage (angiopoietin-2, CXCL16, E-selectin, ICAM-1) are already elevated in the circulation of early SSc patients and in a gradually increasing fashion in patients with SSc without fibrotic features and to the highest degree in fibrotic SSc patients, mirroring the same deteriorating trend in clinical parameters (inflammation indicators, lung involvement) from early SSc to non-fibrotic SSc and finally to the lcSSc and dcSSc subsets; - CXCL10, CXCL11, TNFR2 and CHI3L1 can clearly distinguish patients with early SSc and even more the ones with SSc without fibrotic features from healthy controls (HC). Furthermore, within each patient group, the patients who faster evolved (early SSc developing full-blown SSc and non-fibrotic SSc developing fibrotic features) were the ones with the highest circulating levels of CXCL10 and TNFR2; - NK and NKT-like cells from early SSc and non-fibrotic SSc patients produce higher levels of pro-inflammatory/pro-fibrotic molecules (TNF-α, IL-6) than HC in response to different activating triggers; - in the circulation of patients with the most extensive skin fibrosis, dcSSc - but not in early SSc nor in patients with SSc without fibrosis -, a reduction of NK cells expressing the activating receptor NKp46 and of NKT-like cells expressing Killer-Immunoglobulin-like (KIR) receptors are observed. These patterns suggest that in dcSSc patients both NK and NKT-like cells could be…
Advisors/Committee Members: Radstake, Timothy, Dolstra, H., Vonk, M.C..
Subjects/Keywords: systemic sclerosis; arly systemic sclerosis; NK cells; NKT-like cells
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cossu, M. (2017). Molecular and cellular profiling of systemic sclerosis and its preclinical stages. (Doctoral Dissertation). University Utrecht. Retrieved from http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102
Chicago Manual of Style (16th Edition):
Cossu, Marta. “Molecular and cellular profiling of systemic sclerosis and its preclinical stages.” 2017. Doctoral Dissertation, University Utrecht. Accessed January 23, 2021.
http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102.
MLA Handbook (7th Edition):
Cossu, Marta. “Molecular and cellular profiling of systemic sclerosis and its preclinical stages.” 2017. Web. 23 Jan 2021.
Vancouver:
Cossu M. Molecular and cellular profiling of systemic sclerosis and its preclinical stages. [Internet] [Doctoral dissertation]. University Utrecht; 2017. [cited 2021 Jan 23].
Available from: http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102.
Council of Science Editors:
Cossu M. Molecular and cellular profiling of systemic sclerosis and its preclinical stages. [Doctoral Dissertation]. University Utrecht; 2017. Available from: http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102
26.
Cossu, Marta.
Molecular and cellular profiling of systemic sclerosis and its preclinical stages.
Degree: 2017, University Utrecht
URL: https://dspace.library.uu.nl/handle/1874/353102
;
URN:NBN:NL:UI:10-1874-353102
;
urn:isbn:978-90-393-68039
;
URN:NBN:NL:UI:10-1874-353102
;
https://dspace.library.uu.nl/handle/1874/353102
► The development of unrestrained fibrosis in the skin and internal organs is the hallmark of systemic sclerosis (SSc). Nevertheless, it is known that fibrosis is…
(more)
▼ The development of unrestrained fibrosis in the skin and internal organs is the hallmark of
systemic sclerosis (SSc). Nevertheless, it is known that fibrosis is preceded by vascular and immune modifications. On the basis of SSc-specific autoantibodies and nailfold capillary lesions it is possible to identify individuals with Raynaud’s phenomenon considered at increased risk to develop SSc when compared with the general population. Furthermore, some characteristic SSc features are not fibrotic, they can precede fibrosis and still be sufficient to meet the EUropean League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SSc. In my PhD thesis I aimed to characterize how patients with early SSc and SSc without any sign of fibrosis differ from fibrotic SSc patients (limited and diffuse cutaneous SSc; lcSSc and dcSSc), by that contributing to increase the knowledge about the events which lead to the onset of fibrosis and provide new ground to prevent it. To do so, we first investigated how different factors involved in vascular and immune activation “behave” in the circulation of early SSc individuals, in patients with SSc without fibrotic features, comparing with fibrotic SSc patients. We then investigated in the different groups natural killer (NK) and NKT-like cells, important in infections control, tumor development and immuneregulation. We found that: - the Interferon (IFN) signature described in SSc patients with fibrosis, is already present since the early SSc stage and in the non-fibrotic SSc group to an even higher extent then in fibrotic SSc patients: - markers of vascular damage (angiopoietin-2, CXCL16, E-selectin, ICAM-1) are already elevated in the circulation of early SSc patients and in a gradually increasing fashion in patients with SSc without fibrotic features and to the highest degree in fibrotic SSc patients, mirroring the same deteriorating trend in clinical parameters (inflammation indicators, lung involvement) from early SSc to non-fibrotic SSc and finally to the lcSSc and dcSSc subsets; - CXCL10, CXCL11, TNFR2 and CHI3L1 can clearly distinguish patients with early SSc and even more the ones with SSc without fibrotic features from healthy controls (HC). Furthermore, within each patient group, the patients who faster evolved (early SSc developing full-blown SSc and non-fibrotic SSc developing fibrotic features) were the ones with the highest circulating levels of CXCL10 and TNFR2; - NK and NKT-like cells from early SSc and non-fibrotic SSc patients produce higher levels of pro-inflammatory/pro-fibrotic molecules (TNF-α, IL-6) than HC in response to different activating triggers; - in the circulation of patients with the most extensive skin fibrosis, dcSSc - but not in early SSc nor in patients with SSc without fibrosis -, a reduction of NK cells expressing the activating receptor NKp46 and of NKT-like cells expressing Killer-Immunoglobulin-like (KIR) receptors are observed. These patterns suggest that in dcSSc patients both NK and NKT-like cells could be…
Advisors/Committee Members: Radstake, Timothy, Dolstra, H., Vonk, M.C..
Subjects/Keywords: systemic sclerosis; arly systemic sclerosis; NK cells; NKT-like cells
Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cossu, M. (2017). Molecular and cellular profiling of systemic sclerosis and its preclinical stages. (Doctoral Dissertation). University Utrecht. Retrieved from https://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; https://dspace.library.uu.nl/handle/1874/353102
Chicago Manual of Style (16th Edition):
Cossu, Marta. “Molecular and cellular profiling of systemic sclerosis and its preclinical stages.” 2017. Doctoral Dissertation, University Utrecht. Accessed January 23, 2021.
https://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; https://dspace.library.uu.nl/handle/1874/353102.
MLA Handbook (7th Edition):
Cossu, Marta. “Molecular and cellular profiling of systemic sclerosis and its preclinical stages.” 2017. Web. 23 Jan 2021.
Vancouver:
Cossu M. Molecular and cellular profiling of systemic sclerosis and its preclinical stages. [Internet] [Doctoral dissertation]. University Utrecht; 2017. [cited 2021 Jan 23].
Available from: https://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; https://dspace.library.uu.nl/handle/1874/353102.
Council of Science Editors:
Cossu M. Molecular and cellular profiling of systemic sclerosis and its preclinical stages. [Doctoral Dissertation]. University Utrecht; 2017. Available from: https://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; https://dspace.library.uu.nl/handle/1874/353102
27.
Ntelis, Konstantinos.
Μελέτη της επίδρασης χορήγησης κλοπιδογρέλης σε ασθενείς με συστηματική σκλήρυνση στην παραγωγή σεροτονίνης και τις κλινικές εκδηλώσεις της νόσου.
Degree: 2017, University of Patras; Πανεπιστήμιο Πατρών
URL: http://hdl.handle.net/10442/hedi/41758
► Objectives: Activated platelets release serotonin that binds 5-HT2B receptor on fibroblasts leading to fibroblast activation. Clopidogrel, an inhibitor of ADP-dependent platelet activation prevents fibrosis in…
(more)
▼ Objectives: Activated platelets release serotonin that binds 5-HT2B receptor on fibroblasts leading to fibroblast activation. Clopidogrel, an inhibitor of ADP-dependent platelet activation prevents fibrosis in animal models of systemic sclerosis (SSc). We aimed at assessing whether i) ADP-dependent platelet activation is increased in patients with SSc compared to healthy subjects and patients with rheumatoid arthritis (RA) and ii) whether clopidogrel can effectively suppress ADP-dependent activation, reduce circulating serotonin levels and hence, favorably affect fibrosis or vasculopathy in patients with systemic sclerosis.Methods: Thirteen patients with SSc were recruited. Platelet activation was assessed by aggregometry prior to and following 14 days of clopidogrel treatment. At the same time points serotonin, soluble vascular cell adhesion molecule 1 (s-VCAM1) and soluble intercellular cell adhesion molecule 1 (s-ICAM1), two markers of endothelial dysfunction, were measured. Results: ADP-dependent platelet activation was similar between patients with SSc (n=13), patients with RA (n=28) and healthy subjects (n=22) (mean ± SEM AU*min: 392.1 ± 58.4, 535.5 ± 61.33 and 570.9 ± 42.9 in patients with SSc, patients with RA and healthy subjects respectively, p=0.14). Clopidogrel treatment significantly reduced platelet activation in patients with SSc (mean ± SEM AU*min: 392.1 ± 58.4 vs 163.8 ± 51.7, p=0.014). Clopidogrel treatment did not affect serotonin levels but led to a significant increase in s-VCAM 1 (p=0.03). Three patients developed new digital ulcers during the study. The potential association of the study drug with the development of new digital ulcers led to early termination of the study.Conclusion: Clopidogrel may worsen markers of endothelial function and associate with development of new digital ulcers in patients with SSc.
Σκοπός: Τα ενεργοποιημένα αιμοπετάλια απελευθερώνουν σεροτονίνη που συνδέεται με τον υποδοχέα 5-HT2B στους ινοβλάστες οδηγώντας στην ενεργοποίησή τους. Η κλοπιδογρέλη, ένας αναστολέας της επαγόμενης από ADP διέγερσης των αιμοπεταλίων, αναστέλλει την ίνωση σε ζωικά μοντέλα συστηματικής σκλήρυνσης (ΣΣ). Στοχεύσαμε να εκτιμήσουμε i) εάν η ADP-επαγόμενη ενεργοποίηση των αιμοπεταλίων είναι αυξημένη στους ασθενείς με Σ.Σ. σε σχέση με τους υγιείς μάρτυρες και τους ασθενείς με ρευματοειδή αρθρίτιδα (ΡΑ), ii) εάν η κλοπιδογρέλη μπορεί να αναστείλλει αποτελεσματικά την ADP-επαγόμενη ενεργοποίηση των αιμοπεταλίων, να μειώσει τα επίπεδα της κυκλοφορούσας στον ορό σεροτονίνης και επομένως να επηρεάσει θετικά την αγγειοπάθεια και την ίνωση στους ασθενείς με ΣΣ. Μέθοδοι: 13 ασθενείς με ΣΣ στρατολογήθηκαν. Η διέγερση των αιμοπεταλίων αξιολογήθηκε πριν και 14 ημέρες μετά τη χορήγηση κλοπιδογρέλης. Στα ίδια χρονικά σημεία μετρήθηκαν στο περιφερικό αίμα τα επίπεδα της σεροτονίνης και 2 δεικτών ενδοθηλιακής δυσλειτουργίας (s-VCAM1 και s-ICAM1).Αποτελέσματα: Η επαγόμενη με ADP διέγερση των αιμοπεταλίων ήταν παρόμοια μεταξύ των ασθενών με ΣΣ (n=13), των ασθενών με ΡΑ (n=28) και των υγιών…
Subjects/Keywords: Σκληρόδερμα; Συστηματική σκλήρυνση; Δακτυλικά έλκη; Κλοπιδογρέλη; Scleroderma; Systemic sclerosis; Digital ulcers; Clopidogrel
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ntelis, K. (2017). Μελέτη της επίδρασης χορήγησης κλοπιδογρέλης σε ασθενείς με συστηματική σκλήρυνση στην παραγωγή σεροτονίνης και τις κλινικές εκδηλώσεις της νόσου. (Thesis). University of Patras; Πανεπιστήμιο Πατρών. Retrieved from http://hdl.handle.net/10442/hedi/41758
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ntelis, Konstantinos. “Μελέτη της επίδρασης χορήγησης κλοπιδογρέλης σε ασθενείς με συστηματική σκλήρυνση στην παραγωγή σεροτονίνης και τις κλινικές εκδηλώσεις της νόσου.” 2017. Thesis, University of Patras; Πανεπιστήμιο Πατρών. Accessed January 23, 2021.
http://hdl.handle.net/10442/hedi/41758.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ntelis, Konstantinos. “Μελέτη της επίδρασης χορήγησης κλοπιδογρέλης σε ασθενείς με συστηματική σκλήρυνση στην παραγωγή σεροτονίνης και τις κλινικές εκδηλώσεις της νόσου.” 2017. Web. 23 Jan 2021.
Vancouver:
Ntelis K. Μελέτη της επίδρασης χορήγησης κλοπιδογρέλης σε ασθενείς με συστηματική σκλήρυνση στην παραγωγή σεροτονίνης και τις κλινικές εκδηλώσεις της νόσου. [Internet] [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2017. [cited 2021 Jan 23].
Available from: http://hdl.handle.net/10442/hedi/41758.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ntelis K. Μελέτη της επίδρασης χορήγησης κλοπιδογρέλης σε ασθενείς με συστηματική σκλήρυνση στην παραγωγή σεροτονίνης και τις κλινικές εκδηλώσεις της νόσου. [Thesis]. University of Patras; Πανεπιστήμιο Πατρών; 2017. Available from: http://hdl.handle.net/10442/hedi/41758
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade Estadual de Campinas
28.
Bombini, Mariana Freschi, 1984-.
Alteração olfatória na esclerose sistêmica : frequência e fatores associados: Olfactory abnormalities in systemic sclerosis : frequency and associated factors.
Degree: 2018, Universidade Estadual de Campinas
URL: http://repositorio.unicamp.br/jspui/handle/REPOSIP/331095
► Abstract: The olfactory system mediated an interaction among the central nervous system (CNS), mood, cognition and inflammatory changes. Olfactory abnormalities are frequent in autoimmune diseases,…
(more)
▼ Abstract: The olfactory system mediated an interaction among the central nervous system (CNS), mood, cognition and inflammatory changes. Olfactory abnormalities are frequent in autoimmune diseases, but in patients with
systemic sclerosis (SSc) it is little explored. SSc is a complex disease characterized by chronic inflammation, vasculopathy and fibrosis of the skin and internal organs. Thirty-five consecutives patients with SSc following for one years and 40 age and sex matched controls were assessed olfactory function using the three stages of the Sniffin 'Sticks test (SST), which include odor threshold (TH), odor discrimination (DIS), and odor identification (ID). The TDI is the sum of them, and it was calculate separately for gender and age groups. All these scores were analysed according with Beck's Depression (BDI) and Beck's Anxiety Inventories (BAI), cognitive capacity by the Montreal Cognitive Assessment (MOCA), activity and severity disease and the hippocampus and amygdala volumes with magnetic resonance (RM). All analyzes were performed twice, first at the study entry and second one years later. At all SST stages we observed that the olfactory capacity worsen with age (p?0.05). Olfactory abnormalities was significantly associated with age, disease duration, disease activity, and hippocampal and amygdala volumes. The linear regression showed that the scores obtained from the of the second analysis were correlate with the variables of the first analysis. The BAI score (95%CI=0.042-0.430, p=0.019), right hippocampus volume (95%CI= 0.007-0.025, p=0.001), left hippocampus volume (95%CI= (-0.021)-(-0.004), p=0.006) and right amygdala volume (95%CI= -0.030-0.000, p=0.050), R2=0.588. The DIS score was correlated with right hippocampus (95%CI= 0.004-0.013, p=0.001) and left hippocampus volume (95%CI= (-0.009)-(-0.001), p=0.019), R2=0.471. The ID score was correlated with right hippocampi (95%CI= 0.000-0.006, p=0.05) and left hippocampus volume (95%CI= -0.006-0.000, p=0.05), R2=0.457. The TH score was correlated with MOCA score (95%CI= (-0.574)-(-0.030), p=0.031), BAI score (95%CI= 0.020-0.271, p=0.024), BDI score (95%CI= 0.004-0.013, p=0.001) and left amygdala volume (95%CI= (-0.020)-0.000), p=0.046), R2=0.492. The olfactory analyses can provide information about CNS, specific clinical involvement being useful for monitoring disease progression and TH would be an early marker of olfactory abnormality in SSc
Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS (CRUESP), Appenzeller, Simone, 1974- (advisor), Universidade Estadual de Campinas. Faculdade de Ciências Médicas (institution), Programa de Pós-Graduação em Fisiopatologia Médica (nameofprogram), Souza, Alexandre Wagner Silva de (committee member), Sachetto, Zoraida (committee member), Reis, Fabiano (committee member), Trevisani, Virginia Fernandes Moça (committee member).
Subjects/Keywords: Escleroderma sistêmico; Olfato; Sistema nervoso central; Systemic sclerosis; Smell; Central nervous system
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bombini, Mariana Freschi, 1. (2018). Alteração olfatória na esclerose sistêmica : frequência e fatores associados: Olfactory abnormalities in systemic sclerosis : frequency and associated factors. (Thesis). Universidade Estadual de Campinas. Retrieved from http://repositorio.unicamp.br/jspui/handle/REPOSIP/331095
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Bombini, Mariana Freschi, 1984-. “Alteração olfatória na esclerose sistêmica : frequência e fatores associados: Olfactory abnormalities in systemic sclerosis : frequency and associated factors.” 2018. Thesis, Universidade Estadual de Campinas. Accessed January 23, 2021.
http://repositorio.unicamp.br/jspui/handle/REPOSIP/331095.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Bombini, Mariana Freschi, 1984-. “Alteração olfatória na esclerose sistêmica : frequência e fatores associados: Olfactory abnormalities in systemic sclerosis : frequency and associated factors.” 2018. Web. 23 Jan 2021.
Vancouver:
Bombini, Mariana Freschi 1. Alteração olfatória na esclerose sistêmica : frequência e fatores associados: Olfactory abnormalities in systemic sclerosis : frequency and associated factors. [Internet] [Thesis]. Universidade Estadual de Campinas; 2018. [cited 2021 Jan 23].
Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/331095.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Bombini, Mariana Freschi 1. Alteração olfatória na esclerose sistêmica : frequência e fatores associados: Olfactory abnormalities in systemic sclerosis : frequency and associated factors. [Thesis]. Universidade Estadual de Campinas; 2018. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/331095
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
29.
上原, 顕仁; ウエハラ, アキヒト.
Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis : 強皮症の皮膚線維化におけるノルエピネフリンの役割.
Degree: 博士(医学), 2016, Gunma University / 群馬大学
URL: http://hdl.handle.net/10087/10391
学位記番号:医博甲1596号
Subjects/Keywords: systemic sclerosis; norepinephrine; skin fibrosis
…overexpression in systemic sclerosis. Ann Rheum Dis 71,
1235–1242 (2012).
19. Sato, S… …skin thickness score in
patients with systemic sclerosis. J Der Sci 27, 140–146 (2001… …with systemic sclerosis trigger collagen production
in fibroblasts. Arthritis Rheum 65, 481… …in inflammation, vasculopathy, and
fibrosis in systemic sclerosis. Int J Rheumatol 2011… …721608 (2011).
24. Shima, Y. et al. The skin of patients with systemic sclerosis…
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
上原, 顕仁; ウエハラ, . (2016). Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis : 強皮症の皮膚線維化におけるノルエピネフリンの役割. (Thesis). Gunma University / 群馬大学. Retrieved from http://hdl.handle.net/10087/10391
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
上原, 顕仁; ウエハラ, アキヒト. “Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis : 強皮症の皮膚線維化におけるノルエピネフリンの役割.” 2016. Thesis, Gunma University / 群馬大学. Accessed January 23, 2021.
http://hdl.handle.net/10087/10391.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
上原, 顕仁; ウエハラ, アキヒト. “Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis : 強皮症の皮膚線維化におけるノルエピネフリンの役割.” 2016. Web. 23 Jan 2021.
Vancouver:
上原, 顕仁; ウエハラ . Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis : 強皮症の皮膚線維化におけるノルエピネフリンの役割. [Internet] [Thesis]. Gunma University / 群馬大学; 2016. [cited 2021 Jan 23].
Available from: http://hdl.handle.net/10087/10391.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
上原, 顕仁; ウエハラ . Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis : 強皮症の皮膚線維化におけるノルエピネフリンの役割. [Thesis]. Gunma University / 群馬大学; 2016. Available from: http://hdl.handle.net/10087/10391
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Freie Universität Berlin
30.
Makowka, Alexander.
Relation between nutritional state and physical functionality in systemic
sclerosis in consideration of clinical parameters.
Degree: 2017, Freie Universität Berlin
URL: http://dx.doi.org/10.17169/refubium-8583
► Introduction: Patients with Systemic sclerosis (SSc) often show a reduced nutritional status due to disease-specific mechanisms. It affects the course of the disease and survival.…
(more)
▼ Introduction: Patients with
Systemic sclerosis (SSc) often show a reduced
nutritional status due to disease-specific mechanisms. It affects the course
of the disease and survival. The relation between nutritional status and
functional parameters, known from other populations, was investigated in SSc
in this study. Methods: Residential, semi-residential and ambulatory patients
with SSc according to ACR/EULAR-classification criteria were recruited at
rheumatological department, Charité Berlin. Clinical and disease-specific data
was collected according to standardised protocols. Nutritional status was
assessed by: body mass index (BMI), Malnutrition Universal Screening Tool
(MUST) and bioelectrical impedance analysis (BIA) respectively its raw
parameter phase angle α (PhA). Physical function was assessed by: maximum grip
strength, maximum knee extension strength and peak expiratory flow (PEF),
International Physical Activity Questionnaire (IPAQ) and ABILHAND
questionnaire. Results: 130 patients were included with 90.8 % women, median
age of 60.0 (50.8 – 72.0) years. Median modified Rodnan Skin Score (mRSS) was
6.0 (2.5 – 10.5), median Scleroderma Health Assessment Questionnaire (SHAQ) –
score 0.97 (0.44 – 1.56). High prevalence of inflammation (28.0 % elevated
CRP), heart failure (54.8 % elevated NT-proBNP) and anemia (31.1 %) was found.
8.5 % of the participants were underweight according to BMI-class, 26.2 %
showed high risk of malnutrition according to MUST-score and 37.5 % showed
PhA-values below the fifth reference percentile. Median grip strength was 16.0
(10.0 – 21.0) kgF with 52.9 % definedly weak results. Median knee extension
strength was 16.5 (11.0 – 25.0) kgF. Median PEF was 320.0 (270.0 – 400.0)
l/min with 48.8 % definedly low results. According to IPAQ 20.8 % of
participants exhibited low physical activity. Median ABILHAND-logit-value was
1.70 (0.31 – 2.94), whereas 24.6 % of participants could not perform all
requested activities. PhA correlated with all parameters of physical function.
Groups formed according to BMI-class and MUST-score displayed significant
differences for grip strength, knee extension strength, total physical
activity and ABILHAND-logit-value. Classification of PhA according to
reference percentiles only displayed differences for grip strength and total
physical activity. Of clinical parameters especially SHAQ-score, NT-proBNP and
number of drugs taken correlated significantly with nutritional status and
physical function. An independent influence of PhA and/or MUST-score on
functional parameters was shown. Conclusion: Reduced nutritional status and
reduced physical activity are common in patients with SSc. Groups formed
according to BMI, MUST and BIA were suitable to display differences for grip
strength, knee extension strength, total physical activity and hand function,
whereas patients with further reduced nutritional status reached lower values
of physical function.
Advisors/Committee Members: [email protected] (contact), m (gender), N.N. (firstReferee), N.N. (furtherReferee).
Subjects/Keywords: nutritional state; physical functionality; systemic sclerosis; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
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APA (6th Edition):
Makowka, A. (2017). Relation between nutritional state and physical functionality in systemic
sclerosis in consideration of clinical parameters. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-8583
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Makowka, Alexander. “Relation between nutritional state and physical functionality in systemic
sclerosis in consideration of clinical parameters.” 2017. Thesis, Freie Universität Berlin. Accessed January 23, 2021.
http://dx.doi.org/10.17169/refubium-8583.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Makowka, Alexander. “Relation between nutritional state and physical functionality in systemic
sclerosis in consideration of clinical parameters.” 2017. Web. 23 Jan 2021.
Vancouver:
Makowka A. Relation between nutritional state and physical functionality in systemic
sclerosis in consideration of clinical parameters. [Internet] [Thesis]. Freie Universität Berlin; 2017. [cited 2021 Jan 23].
Available from: http://dx.doi.org/10.17169/refubium-8583.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Makowka A. Relation between nutritional state and physical functionality in systemic
sclerosis in consideration of clinical parameters. [Thesis]. Freie Universität Berlin; 2017. Available from: http://dx.doi.org/10.17169/refubium-8583
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
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