scholarly journals TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 209
Author(s):  
Miguel A. Rubio ◽  
Mireia Herrando-Grabulosa ◽  
Roser Velasco ◽  
Israel Blasco ◽  
Monica Povedano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cellular Localization ◽  
Clinical Symptoms ◽  
Healthy Controls ◽  
Cytoplasmic Localization ◽  
Potential Biomarker ◽  
Skin Biopsies ◽  
Dermal Cells ◽  
Als Patients ◽  
Motoneuron Degeneration

Diagnosis of ALS is based on clinical symptoms when motoneuron degeneration is significant. Therefore, new approaches for early diagnosis are needed. We aimed to assess if alterations in appearance and cellular localization of cutaneous TDP-43 may represent a biomarker for ALS. Skin biopsies from 64 subjects were analyzed: 44 ALS patients, 10 healthy controls (HC) and 10 neurological controls (NC) (Parkinson’s disease and multiple sclerosis). TDP-43 immunoreactivity in epidermis and dermis was analyzed, as well as the percentage of cells with TDP-43 cytoplasmic localization. We detected a higher amount of TDP-43 in epidermis (p < 0.001) and in both layers of dermis (p < 0.001), as well as a higher percentage of TDP-43 cytoplasmic positive cells (p < 0.001) in the ALS group compared to HC and NC groups. Dermal cells containing TDP-43 were fibroblasts as identified by co-labeling against vimentin. ROC analyses (AUC 0.867, p < 0.001; CI 95% 0.800–0.935) showed that detection of 24.1% cells with cytoplasmic TDP-43 positivity in the dermis had 85% sensitivity and 80% specificity for detecting ALS. We have identified significantly increased TDP-43 levels in epidermis and in the cytoplasm of dermal cells of ALS patients. Our findings provide support for the use of TDP-43 in skin biopsies as a potential biomarker.

HLA-G Expression in the Skin of Patients with Systemic Sclerosis

2009 ◽  
Vol 36 (6) ◽  
pp. 1230-1234 ◽  
Author(s):  
ISABELA J. WASTOWSKI ◽  
PERCIVAL D. SAMPAIO-BARROS ◽  
ELIANE M.I. AMSTALDEN ◽  
GUSTAVO MARTELLI PALOMINO ◽  
JOÃO FRANCISCO MARQUES-NETO ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Control Sample ◽  
Healthy Controls ◽  
Skin Disorders ◽  
Disease Prognosis ◽  
Laboratory Variables ◽  
Skin Biopsies ◽  
Dermal Cells

Objective.To determine HLA-G expression in skin biopsies from patients with systemic sclerosis (SSc), and its association with epidemiological, clinical, and laboratory variables and survival.Methods.Paraffin-embedded skin biopsies obtained from 21 SSc patients (14 limited SSc, 7 diffuse SSc) and from 28 healthy controls were studied. HLA-G expression was evaluated by immunohistochemistry.Results.HLA-G molecules were detected in 57% of skin biopsies from patients with SSc (9 from limited SSc, 3 from diffuse SSc), whereas no control sample expressed HLA-G (p = 0.000004). In patients, HLA-G molecules were consistently observed within epidermal and some dermal cells. HLA-G expression was associated with a lower frequency of vascular cutaneous ulcers (p = 0.0004), telangiectasias (p = 0.008), and inflammatory polyarthralgia (p = 0.02). After a 15-year followup, SSc patients who exhibited HLA-G survived longer than patients who did not.Conclusion.HLA-G is expressed in skin biopsies from patients with SSc, and this is associated with a better disease prognosis. This suggests a modulatory role of HLA-G in SSc, as observed in other skin disorders.

scholarly journals Cortical thickness and surface area relate to specific symptoms in early relapsing–remitting multiple sclerosis

2014 ◽  
Vol 21 (4) ◽  
pp. 402-414 ◽  
Author(s):  
Gro O Nygaard ◽  
Kristine B Walhovd ◽  
Piotr Sowa ◽  
Joy-Loi Chepkoech ◽  
Atle Bjørnerud ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Surface Area ◽  
Cortical Thickness ◽  
Clinical Symptoms ◽  
Cortical Surface ◽  
Healthy Controls ◽  
Neurological Disability ◽  
Cortical Surface Area ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Background: Cortical atrophy is common in early relapsing–remitting multiple sclerosis (RRMS). Whether this atrophy is caused by changes in cortical thickness or cortical surface area is not known, nor is their separate contributions to clinical symptoms. Objectives: To investigate the difference in cortical surface area, thickness and volume between early RRMS patients and healthy controls; and the relationship between these measures and neurological disability, cognitive decline, fatigue and depression. Methods: RRMS patients ( n = 61) underwent magnetic resonance imaging (MRI), neurological and neuropsychological examinations. We estimated cortical surface area, thickness and volume and compared them with matched healthy controls ( n = 61). We estimated the correlations between clinical symptoms and cortical measures within the patient group. Results: We found no differences in cortical surface area, but widespread differences in cortical thickness and volume between the groups. Neurological disability was related to regionally smaller cortical thickness and volume. Better verbal memory was related to regionally larger surface area; and better visuo-spatial memory, to regionally larger cortical volume. Higher depression scores and fatigue were associated with regionally smaller cortical surface area and volume. Conclusions: We found that cortical thickness, but not cortical surface area, is affected in early RRMS. We identified specific structural correlates to the main clinical symptoms in early RRMS.

scholarly journals Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile

2017 ◽  
Vol 75 (5) ◽  
pp. 272-276 ◽  
Author(s):  
Marcelo Chaves ◽  
Mariela Bettini ◽  
Maria Cecilia Fernandez ◽  
Maria Jose Garcia Basalo ◽  
Juan Ignacio Rojas ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Cognitive Profile ◽  
Healthy Controls ◽  
Potential Biomarker ◽  
Preliminary Study ◽  
Als Patients ◽  
Lateral Sclerosis

ABSTRACT The objective of this preliminary study was to correlate diffusion tensor imaging (DTI) alterations with the cognitive profile of patients with amyotrophic lateral sclerosis (ALS). Methods This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA) was analyzed in the white matter using the tract based spatial statistics program. Results Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3) and 13 healthy controls (four females, average age 66.9 + - 2) were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001). Discussion In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.

Uric acid: a potential biomarker of multiple sclerosis and of its disability

2015 ◽  
Vol 53 (5) ◽  
Author(s):  
Marcello Moccia ◽  
Roberta Lanzillo ◽  
Raffaele Palladino ◽  
Cinzia Russo ◽  
Antonio Carotenuto ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Uric Acid ◽  
Longitudinal Design ◽  
Therapeutic Strategies ◽  
Healthy Controls ◽  
Nitrogen Species ◽  
Lower Serum ◽  
Secondary Progressive ◽  
Potential Biomarker ◽  
Relapsing Remitting

AbstractUric acid (UA) is a strong natural scavenger of reactive oxygen and nitrogen species, with evidence of possible use in the treatment of animal models of multiple sclerosis (MS). Consequently, serum UA has gained much attention as a possible biomarker of MS. We aim to investigate differences in serum UA levels between MS subjects and controls and evaluate possible relationships of UA with MS clinical features.We recruited relapsing-remitting and secondary progressive MS subjects and healthy controls and measured their serum UA levels. We excluded subjects presenting concomitant conditions affecting UA levels.MS subjects (n=362) and controls (n=181) were recruited by propensity score matching (PSM). Statistical analyses were corrected for age, gender, and renal function. MS subjects presented significantly lower serum UA levels than controls (analysis of variance, p=0.014, adjusted rOur findings support the importance of serum UA as a biomarker of MS disability and progression. Further studies with longitudinal design should be specifically designed to evaluate the importance of UA in the different stages of MS and in relation to distinct therapeutic strategies.

scholarly journals Optimal Utility of H-Reflex RDD as a Biomarker of Spinal Disinhibition in Painful and Painless Diabetic Neuropathy

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1247
Author(s):  
Anne Worthington ◽  
Alise Kalteniece ◽  
Maryam Ferdousi ◽  
Luca Donofrio ◽  
Shaishav Dhage ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Initial Response ◽  
Healthy Controls ◽  
Painful Diabetic Neuropathy ◽  
Stimulus Response ◽  
Rate Dependent ◽  
Potential Biomarker ◽  
Spinal Inhibition

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2–4 and 2–5 at 1 Hz, AUC = 0.84 (95%CI 0.76–0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.

scholarly journals Bio-artificial pleura using autologous dermal fibroblast sheets to mitigate air leaks during thoracoscopic lung resection

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Masato Kanzaki ◽  
Ryo Takagi ◽  
Kaoru Washio ◽  
Mami Kokubo ◽  
Shota Mitsuboshi ◽  
...  
Keyword(s):  
Dermal Fibroblast ◽  
Lung Resection ◽  
Fibroblast Cell ◽  
Patient Specific ◽  
Cell Content ◽  
Cell Monolayers ◽  
Air Leaks ◽  
Skin Biopsies ◽  
Dermal Cells ◽  
Lung Resections

AbstractLung air leaks (LALs) due to visceral pleura injury during surgery are a difficult-to-avoid complication in thoracic surgery (TS). Reliable LAL closure is an important patient management issue after TS. We demonstrated both safeties of transplantation of a cultured human autologous dermal fibroblast sheet (DFS) to LALs. From May 2016 to March 2018, five patients who underwent thoracoscopic lung resection met all the inclusion criteria. Skin biopsies were acquired from each patient to source autologous dermal cells for DFS fabrication. During the primary culture, fibroblasts migrated from the dermal tissue pieces and proliferated to form cell monolayers. These fibroblasts were subcultured to confluence. Transplantable DFSs were fabricated from these subcultured fibroblasts that were trypsinized and seeded onto temperature-responsive culture dishes. After 10 days of fabrication culture, intact patient-specific DFS were harvested. DFSs were analyzed for fibroblast cell content and tissue contaminants prior to application. For closing intraoperative LAL, mean number of transplanted autologous DFS per patient was 6 ± 2 sheets. Mean chest drainage duration was 5.0 ± 4.8 days. The two patients with major LAL had a drainage duration of more than 7 days. All patients currently have no LAL recurrence after discharge. DFSs effectively maintain LAL closure via remodeling of the deposited extracellular matrix. The use of autologous DFSs to permanently close air leaks using a patient-derived source is expected to reduce surgical complications during high-risk lung resections.

scholarly journals The acute phase response protein SERPINA3 is increased in tear fluid from the unaffected eyes of patients with unilateral acute anterior uveitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jon Roger Eidet ◽  
Maja Akopian ◽  
Ole K. Olstad ◽  
Øystein Kalsnes Jørstad ◽  
Morten C. Moe ◽  
...  
Keyword(s):  
Acute Phase ◽  
Anterior Uveitis ◽  
Acute Phase Response ◽  
Phase Response ◽  
Tear Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Bacterial Keratitis ◽  
Acute Anterior Uveitis ◽  
Potential Biomarker

Abstract Background To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls. Methods Thirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay. Results Relative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population. Conclusions The acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.

Upper Extremity Motor Fatigability as an Early Indicator in Pediatric Onset Multiple Sclerosis

2021 ◽  
pp. 088307382199988
Author(s):  
Giuseppina Pilloni ◽  
Martin Malik ◽  
Raghav Malik ◽  
Lauren Krupp ◽  
Leigh Charvet
Keyword(s):  
Multiple Sclerosis ◽  
Grip Strength ◽  
Upper Extremity ◽  
Static Fatigue ◽  
Healthy Controls ◽  
Fatigue Index ◽  
Left Hand ◽  
Right Hand ◽  
Computer Based ◽  
Pediatric Onset

Aim: To adopt a computer-based protocol to assess grip fatigability in patients with pediatric-onset multiple sclerosis to provide detection of subtle motor involvement identifying those patients most at risk for future decline. Method: Pediatric-onset multiple sclerosis patients were recruited during routine outpatient visits to complete a grip assessment and compared to a group of healthy age- and sex-matched controls. All participants completed a computer-based measurement of standard maximal grip strength and repetitive and sustained grip performance measured by dynamic and static fatigue indices. Results: A total of 38 patients with pediatric-onset multiple sclerosis and 24 healthy controls completed the grip protocol (right-hand dominant). There were no significant group differences in maximal grip strength bilaterally (right: 21.8 vs 19.9 kg, P = .25; left: 20.4 vs 18.7 kg, P = .33), although males with pediatric-onset multiple sclerosis were significantly less strong than healthy controls (right: 26.53 vs 21.23 kg, P = .009; left; 25.13 vs 19.63 kg, P = .003). Both dynamic and static fatigue indices were significantly higher bilaterally in pediatric-onset multiple sclerosis compared with healthy control participants (left-hand dynamic fatigue index: 18.6% vs 26.7%, P = .003; right-hand static fatigue index: 28.3% vs 41.3%, P < .001; left-hand static fatigue index: 31.9% vs 42.6%, P < .001). Conclusion: Brief repeatable grip assessment including measures of dynamic and sustained static output can be a sensitive indicator of upper extremity motor involvement in pediatric-onset multiple sclerosis, potentially identifying those in need of intervention to prevent future disability.

scholarly journals Decision making under ambiguity and risk in adolescent-onset schizophrenia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dandan Li ◽  
Fengyan Zhang ◽  
Lu Wang ◽  
Yifan Zhang ◽  
Tingting Yang ◽  
...  
Keyword(s):  
Decision Making ◽  
Executive Function ◽  
Iowa Gambling Task ◽  
Clinical Symptoms ◽  
Healthy Controls ◽  
Syndrome Scale ◽  
Significant Difference ◽  
Abnormal Pattern ◽  
Negative Syndrome ◽  
The Relationship

Abstract Objective Numerous studies have identified impaired decision making (DM) under both ambiguity and risk in adult patients with schizophrenia. However, the assessment of DM in patients with adolescent-onset schizophrenia (AOS) has been challenging as a result of the instability and heterogeneity of manifestations. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT), which are frequently used to evaluate DM respectively under ambiguity and risk, are sensitive to adolescents and neuropsychiatric patients. Our research intended to examine the performance of DM in a relatively large sample of patients with AOS using the above-mentioned two tasks. We also aimed to take a closer look at the relationship between DM and symptom severity of schizophrenia. Methods We compared the performance of DM in 71 patients with AOS and 53 well-matched healthy controls using IGT for DM under ambiguity and GDT for DM under risk through net scores, total scores and feedback ration. Neuropsychological tests were conducted in all participants. Clinical symptoms were evaluated by using Positive and Negative Syndrome Scale (PANSS) in 71 patients with AOS. Pearson’s correlation revealed the relationship among total score of DM and clinical and neuropsychological data. Results Compared to healthy controls, patients with AOS failed to show learning effect and had a significant difference on the 5th block in IGT and conducted more disadvantageous choices as well as exhibited worse negative feedback rate in GDT. Apart from DM impairment under risk, diminished DM abilities under ambiguity were found related to poor executive function in AOS in the present study. Conclusions Our findings unveiled the abnormal pattern of DM in AOS, mainly reflected under the risky condition, extending the knowledge on the performance of DM under ambiguity and risk in AOS. Inefficient DM under risk may account for the lagging impulse control and the combined effects of developmental disease. In addition, our study demonstrated that the performance on IGT was related to executive function in AOS.

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