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 Adrenomedullin Is a Diagnostic and Prognostic Biomarker for Acute Intracerebral Hemorrhage

2021 ◽  
Vol 43 (1) ◽  
pp. 324-334
Author(s):  
Francisco J. Julián-Villaverde ◽  
Laura Ochoa-Callejero ◽  
Eva Siles ◽  
Esther Martínez-Lara ◽  
Alfredo Martínez
Keyword(s):  
Hemorrhagic Stroke ◽  
Prognostic Biomarker ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Nitroso Compounds ◽  
Healthy Controls ◽  
Stroke Patients ◽  
Important Health ◽  
Acute Intracerebral Hemorrhage ◽  
Changes Over Time

Hemorrhagic stroke remains an important health challenge. Adrenomedullin (AM) is a vasoactive peptide with an important role in cardiovascular diseases, including stroke. Serum AM and nitrate–nitrite and S-nitroso compounds (NOx) levels were measured and compared between healthy volunteers (n = 50) and acute hemorrhagic stroke patients (n = 64). Blood samples were taken at admission (d0), 24 h later (d1), and after 7 days or at the time of hospital discharge (d7). Neurological severity (NIHSS) and functional prognosis (mRankin) were measured as clinical outcomes. AM levels were higher in stroke patients at all times when compared with healthy controls (p < 0.0001). A receiving operating characteristic curve analysis identified that AM levels at admission > 69.0 pg/mL had a great value as a diagnostic biomarker (area under the curve = 0.89, sensitivity = 80.0%, specificity = 100%). Furthermore, patients with a favorable outcome (NIHSS ≤ 3; mRankin ≤ 2) experienced an increase in AM levels from d0 to d1, and a decrease from d1 to d7, whereas patients with unfavorable outcome had no significant changes over time. NOx levels were lower in patients at d0 (p = 0.04) and d1 (p < 0.001) than in healthy controls. In conclusion, AM levels may constitute a new diagnostic and prognostic biomarker for this disease, and identify AM as a positive mediator for hemorrhagic stroke resolution.

Proteomic Profile of Urinary Extracellular Vesicles Identifies AGP1 as a Potential Biomarker of Primary Aldosteronism

Endocrinology ◽  
2021 ◽  
Vol 162 (4) ◽  
Author(s):  
Eric R Barros ◽  
Juan Pablo Rigalli ◽  
Alejandra Tapia-Castillo ◽  
Andrea Vecchiola ◽  
Morag J Young ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Primary Aldosteronism ◽  
Proteomic Analysis ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Extracellular Vesicle ◽  
Parent Cell ◽  
Spot Urine ◽  
Potential Biomarker ◽  
Aldosterone To Renin Ratio

Abstract Context Primary aldosteronism (PA) represents 6% to 10% of all essential hypertension patients and is diagnosed using the aldosterone-to-renin ratio (ARR) and confirmatory studies. The complexity of PA diagnosis encourages the identification of novel PA biomarkers. Urinary extracellular vesicles (uEVs) are a potential source of biomarkers, considering that their cargo reflects the content of the parent cell. Objective We aimed to evaluate the proteome of uEVs from PA patients and identify potential biomarker candidates for PA. Methods Second morning spot urine was collected from healthy controls (n = 8) and PA patients (n = 7). The uEVs were isolated by ultracentrifugation and characterized. Proteomic analysis on uEVs was performed using LC-MS Orbitrap. Results Isolated uEVs carried extracellular vesicle markers, showed a round shape and sizes between 50 and 150 nm. The concentration of uEVs showed a direct correlation with urinary creatinine (r = 0.6357; P = 0.0128). The uEV size mean (167 ± 6 vs 183 ± 4nm) and mode (137 ± 7 vs 171 ± 11nm) was significantly smaller in PA patients than in control subjects, but similar in concentration. Proteomic analysis of uEVs from PA patients identified an upregulation of alpha-1-acid glycoprotein 1 (AGP1) in PA uEVs, which was confirmed using immunoblot. A receiver operating characteristic curve analysis showed an area under the curve of 0.92 (0.82 to 1; P = 0.0055). Conclusion Proteomic and further immunoblot analyses of uEVs highlights AGP1 as potential biomarker for PA.

scholarly journals D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256744
Author(s):  
Ayusha Poudel ◽  
Yashasa Poudel ◽  
Anurag Adhikari ◽  
Barun Babu Aryal ◽  
Debika Dangol ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Respiratory Illness ◽  
Immunofluorescence Assay ◽  
Cox Proportional Hazards ◽  
Optimal Cutoff ◽  
Cutoff Value ◽  
Potential Biomarker ◽  
D Dimer

Introduction Coronavirus Disease 2019 is a primarily respiratory illness that can cause thrombotic disorders. Elevation of D-dimer is a potential biomarker for poor prognosis in COVID-19, though optimal cutoff value for D-dimer to predict mortality has not yet been established. This study aims to assess the accuracy of admission D-dimer in the prognosis of COVID-19 and to establish the optimal cutoff D-dimer value to predict hospital mortality. Methods Clinical and laboratory parameters and outcomes of confirmed COVID-19 cases admitted to four hospitals in Kathmandu were retrospectively analyzed. Admitted COVID-19 cases with recorded D-dimer and definitive outcomes were included consecutively. D-dimer was measured using immunofluorescence assay and reported in Fibrinogen Equivalent Unit (μg/ml). The receiver operating characteristic curve was used to determine the accuracy of D-dimer in predicting mortality, and to calculate the optimal cutoff value, based on which patients were divided into two groups and predictive value of D-dimer for mortality was measured. Results 182 patients were included in the study out of which 34(18.7%) died during the hospital stay. The mean admission D-dimer among surviving patients was 1.067 μg/ml (±1.705 μg/ml), whereas that among patients who died was 3.208 μg/ml (±2.613 μg/ml). ROC curve for D-dimer and mortality gave an area under the curve of 0.807 (95% CI 0.728–0.886, p<0.001). Optimal cutoff value for D-dimer was 1.5 μg/ml (sensitivity 70.6%, specificity 78.4%). On Cox proportional hazards regression analysis, the unadjusted hazard ratio for high D-dimer was 6.809 (95% CI 3.249–14.268, p<0.001), and 5.862 (95% CI 2.751–12.489, p<0.001) when adjusted for age. Conclusion D-dimer value on admission is an accurate biomarker for predicting mortality in patients with COVID-19. 1.5 μg/ml is the optimal cutoff value of admission D-dimer for predicting mortality in COVID-19 patients.

MiR-221-3p as a Potential Biomarker for Patients with Psoriasis and Its Role in Inflammatory Responses in Keratinocytes

2021 ◽  
pp. 1-7
Author(s):  
Zhichao Meng ◽  
Jianwei Qiu ◽  
Hong Zhang
Keyword(s):  
Cell Proliferation ◽  
Inflammatory Responses ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Therapeutic Interventions ◽  
Cell Counting ◽  
Inflammatory Factors ◽  
Hacat Cells ◽  
Potential Biomarker ◽  
Factor Α

<b><i>Introduction:</i></b> This study investigated serum miR-221-3p levels in psoriatic patients and the characterization of serum miR-221-3p in keratinocyte inflammatory responses was further assessed. <b><i>Methods:</i></b> qRT-PCR was used to detect the expression level of miR-221-3p in the serum of 46 patients with psoriasis and 42 healthy controls. The receiver operating characteristic curve evaluated the diagnostic ability of miR-221-3p in psoriasis. The effect of miR-221-3p on HaCaT cell proliferation was detected by using a cell counting Kit-8 and Transwell. ELISA was used to detect serum and keratinocyte pro-inflammatory factors. <b><i>Results:</i></b> miR-221-3p was significantly increased in the serum of patients with psoriasis. The area under the curve was 0.861, the sensitivity was 80.4%, and the specificity was 85.7%. Serum miR-221-3p was positively correlated with the expression levels of tumor necrosis factor-α, interleukin (IL)-17A, and IL-22. Cell experiments showed that reducing the expression of miR-221-3p could significantly inhibit cell proliferation. Additionally, miR-221-3p downregulation also inhibited the release of some inflammatory factors in the HaCaT cells. <b><i>Discussion/Conclusion:</i></b> MiR-221-3p is a latent biomarker of psoriasis patients. Lower expression of miR-221-3p inhibits the cell proliferation and inflammatory responses of HaCaT cells, which offers a possible target for the therapeutic interventions of psoriasis.

scholarly journals Alterations of Erythrocytic Phosphorylated Alpha-Synuclein in Different Subtypes and Stages of Parkinson's Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Xu-Ying Li ◽  
Wei Li ◽  
Xin Li ◽  
Xu-Ran Li ◽  
Linjuan Sun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Duration ◽  
Late Onset ◽  
Area Under The Curve ◽  
Alpha Synuclein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Olfactory Loss ◽  
Potential Biomarker

Serine 129-phosphorylated alpha-synuclein (pS-α-syn) is a major form of α-syn relevant to the pathogenesis of Parkinson's disease (PD), which has been recently detected in red blood cells (RBCs). However, alterations of RBC-derived pS-α-syn (pS-α-syn-RBC) in different subtypes and stages of PD remains to be investigated. In the present study, by using enzyme-linked immunosorbent assay (ELISA) to measure pS-α-syn-RBC, we demonstrated significantly higher levels of pS-α-syn-RBC in PD patients than in healthy controls. pS-α-syn-RBC separated the patients well from the controls, with a sensitivity of 93.39% (95% CI: 90.17–95.81%), a specificity of 93.11% (95% CI: 89.85–95.58%), and an area under the curve (AUC) of 0.96. Considering motor subtypes, the levels of pS-α-syn-RBC were significantly higher in late-onset than young-onset PD (p = 0.013) and in those with postural instability and gait difficulty than with tremor-dominant (TD) phenotype (p = 0.029). In addition, the levels of pS-α-syn-RBC were also different in non-motor subtypes, which were significantly lower in patients with cognitive impairment (p = 0.012) and olfactory loss (p = 0.004) than in those without such symptoms. Moreover, the levels of pS-α-syn-RBC in PD patients were positively correlated with disease duration and Hoehn &amp; Yahr stages (H&amp;Y) (p for trend =0.02 and &lt;0.001) as well as UPDRS III (R2 = 0.031, p = 0.0042) and MoCA scores (R2 = 0.048, p = 0.0004). The results obtained suggest that pS-α-syn-RBC can be used as a potential biomarker for not only separating PD patients from healthy controls but also predicting the subtypes and stages of PD.

scholarly journals Pharmacological Modulation of Rate-Dependent Depression of the Spinal H-Reflex Predicts Therapeutic Efficacy against Painful Diabetic Neuropathy

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 283
Author(s):  
Corinne A. Lee-Kubli ◽  
XiaJun Zhou ◽  
Corinne G. Jolivalt ◽  
Nigel A. Calcutt
Keyword(s):  
Neuropathic Pain ◽  
Diabetic Neuropathy ◽  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Diabetic Rats ◽  
H Reflex ◽  
Painful Diabetic Neuropathy ◽  
Painful Neuropathy ◽  
Inhibitory Function ◽  
Rate Dependent

Impaired rate-dependent depression (RDD) of the spinal H-reflex occurs in diabetic rodents and a sub-set of patients with painful diabetic neuropathy. RDD is unaffected in animal models of painful neuropathy associated with peripheral pain mechanisms and diabetic patients with painless neuropathy, suggesting RDD could serve as a biomarker for individuals in whom spinal disinhibition contributes to painful neuropathy and help identify therapies that target impaired spinal inhibitory function. The spinal pharmacology of RDD was investigated in normal rats and rats after 4 and 8 weeks of streptozotocin-induced diabetes. In normal rats, dependence of RDD on spinal GABAergic inhibitory function encompassed both GABAA and GABAB receptor sub-types. The time-dependent emergence of impaired RDD in diabetic rats was preceded by depletion of potassium-chloride co-transporter 2 (KCC2) protein in the dorsal, but not ventral, spinal cord and by dysfunction of GABAA receptor-mediated inhibition. GABAB receptor-mediated spinal inhibition remained functional and initially compensated for loss of GABAA receptor-mediated inhibition. Administration of the GABAB receptor agonist baclofen restored RDD and alleviated indices of neuropathic pain in diabetic rats, as did spinal delivery of the carbonic anhydrase inhibitor acetazolamide. Pharmacological manipulation of RDD can be used to identify potential therapies that act against neuropathic pain arising from spinal disinhibition.

scholarly journals Salivary IL-6 Concentration Is Associated with Frailty Syndrome in Older Individuals

Diagnostics ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 117
Author(s):  
Pablo Gómez-Rubio ◽  
Isabel Trapero ◽  
Omar Cauli ◽  
Cristina Buigues
Keyword(s):  
Characteristic Curve ◽  
Area Under The Curve ◽  
Activity Level ◽  
Frailty Syndrome ◽  
Older Individuals ◽  
Cross Sectional ◽  
Potential Biomarker ◽  
Syndrome Individual ◽  
The Relationship ◽  
Frailty Criteria

Background: One of the physiological changes that is most closely associated with frailty is the increase in pro-inflammatory cytokines, and IL-6 in particular. Most studies have demonstrated this association using blood samples. We analyzed the relationship between frailty syndrome, individual frailty criteria, and IL-6 levels obtained by saliva tests. Methods: A cross-sectional pilot study was performed among women institutionalized in nursing homes. Frailty was defined as having three or more of the following components: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those components. Results: There was a significant and positive correlation between the frailty score and salivary IL-6 concentration. Regarding the associations between IL-6 and individual dichotomized frailty criteria, there were significant differences in salivary IL-6 concentration in two frailty criteria: weight loss (p = 0.002) and low physical activity (p = 0.007). Receiver operating characteristic curve analysis showed that IL-6 concentration significantly (p < 0.05) (although moderately) discriminated patients that progressed in the frailty syndrome (the area under the curve value was 0.697 with 95% CI 0.566–0.827). Conclusions: Salivary IL-6 concentration can be used as potential biomarker of frailty syndrome and as a tool to monitor the effects of interventions in frail individuals.

scholarly journals Association between Plasma HMGB-1 and Silicosis: A Case-Control Study

2018 ◽  
Vol 19 (12) ◽  
pp. 4043 ◽  
Author(s):  
Jixuan Ma ◽  
Yun Zhou ◽  
Wei Li ◽  
Lili Xiao ◽  
Meng Yang ◽  
...  
Keyword(s):  
Case Control Study ◽  
Nonlinear Models ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
High Mobility ◽  
Case Control ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Natural Cubic Spline ◽  
Control Study

High-mobility group box-1 (HMGB-1) has been associated with fibrotic diseases. However, the role of HMGB-1 in silicosis is still uncertain. In this study, we conducted a case-control study involving 74 patients with silicosis and 107 age/gender-matched healthy controls in China. An Enzyme-linked immunosorbent assay (ELISA) was used to examine the concentrations of plasma HMGB-1 among all subjects. A logistic regression model and receiver operating characteristic curve (ROC) analysis were performed to assess the relationships between HMGB-1 and silicosis. We observed that plasma HMGB-1 concentrations were significantly increased in silicosis patients when compared with healthy controls (p < 0.05). Each 1 ng/mL increase in plasma HMGB-1 was positively associated with increased odds of silicosis, and the odds ratio (OR) (95% confidence interval) was 1.86 (1.52, 2.27). Additionally, compared with subjects with lower HMGB-1 concentrations, increased odds of silicosis were observed in those with higher HMGB-1 concentrations, and the OR was 15.33 (6.70, 35.10). Nonlinear models including a natural cubic spline function of continuous HMGB-1 yielded similar results. In ROC analyses, we found that plasma HMGB-1 >7.419 ng/mL had 81.6% sensitivity and 80.4% specificity for silicosis, and the area under the curve (AUC) was 0.84. Our results demonstrated that elevated plasma HMGB-1 was positivity associated with increased OR of silicosis.

scholarly journals Circulating miR-185-5p as a Potential Biomarker for Arrhythmogenic Right Ventricular Cardiomyopathy

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2578
Author(s):  
Claudia Sacchetto ◽  
Zenab Mohseni ◽  
Robin M. W. Colpaert ◽  
Libero Vitiello ◽  
Marzia De Bortoli ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Disease Onset ◽  
Area Under The Curve ◽  
P Value ◽  
Healthy Controls ◽  
Ventricular Cardiomyopathy ◽  
Characteristic Analysis ◽  
Potential Biomarker ◽  
Fatty Replacement

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease characterized by progressive myocardial fibro-fatty replacement, arrhythmias and risk of sudden death. Its diagnosis is challenging and often it is achieved after disease onset or postmortem. In this study, we sought to identify circulating microRNAs (miRNAs) differentially expressed in ARVC patients compared to healthy controls. In the pilot study, we screened the expression of 754 miRNAs from 21 ARVC patients and 20 healthy controls. After filtering the miRNAs considering a log fold-change cut-off of ±1, p-value < 0.05, we selected five candidate miRNAs for a subsequent validation study in which we used TaqMan-based real-time PCR to analyse samples from 37 ARVC patients and 30 healthy controls. We found miR-185-5p significantly upregulated in ARVC patients. Receiver operating characteristic analysis indicated an area under the curve of 0.854, corroborating the link of this miRNA and ARVC pathophysiology.

scholarly journals A Novel Peripheral Whole Blood hsa_circ_0005430 is a Potential Biomarker for Lung Adenocarcinoma

2021 ◽  
Author(s):  
YINYU Mu ◽  
Fuyi Xie ◽  
Chunxia Ye ◽  
Dongdong Yang
Keyword(s):  
Lung Adenocarcinoma ◽  
Whole Blood ◽  
Area Under The Curve ◽  
Circular Rna ◽  
Diagnostic Value ◽  
Carbohydrate Antigen ◽  
Youden Index ◽  
Healthy Controls ◽  
Potential Biomarker ◽  
Significant Difference

Abstract Background: This study was aimed to determine the circular RNA 5430(hsa_circ_0005430) in peripheral whole blood（PWB）from lung adenocarcinoma (LA) patients is a novel biomarker for screening LA.Methods: The expression levels of hsa_circ_0005430 in PWB from 20 LA patients and 10 healthy controls were performed using real-time quantitative reverse transcription-polymerase chain reaction(RT-qPCR). Serum CEA, CA199 and CA50 were detected by chemiluminescent immunoassay. Spearman’ correlation test was used to evaluate the correlation of hsa_circ_0005430 and clinical variables. The receiver operating characteristic (ROC) curve was established to evaluate its diagnostic value. Results: PWB hsa_circ_0005430 was significantly elevated in LA patients, comparing with healthy controls. There was no significant difference in hsa_circ_0005430 level among different pathological factors of LA. In these LA patients, we found a significant correlation between PWB hsa_circ_0005430 and disease activity, including carcinoembryonic antigen(CEA), carbohydrate antigen 199(CA199) and carbohydrate antigen 50 (CA50). ROC analysis showed that PWB hsa_circ_0005430 had an area under the curve(AUC) of 0.75 (95% CI 0.567-0.928, P< 0.001) to discriminate LA patients from controls with sensitivity of 0.900 and specificity of 0.65. The highest Youden index was 0.55 and the corresponding optimal cut-off value was 0.14. Conclusions: This study revealed that PWB hsa_circ_0005430 in LA may serve as a potential biomarker for LA patients diagnosis.

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