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

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.

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Adrenomedullin Is a Diagnostic and Prognostic Biomarker for Acute Intracerebral Hemorrhage

Current Issues in Molecular Biology ◽

10.3390/cimb43010027 ◽

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.

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

Endocrinology ◽

10.1210/endocr/bqab032 ◽

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.

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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 ◽

10.1371/journal.pone.0256744 ◽

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.

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

Skin Pharmacology and Physiology ◽

10.1159/000515114 ◽

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

Introduction: 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. Methods: 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. Results: 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. Discussion/Conclusion: 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.

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

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.623977 ◽

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 & Yahr stages (H&Y) (p for trend =0.02 and <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.

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

Diagnostics ◽

10.3390/diagnostics11020283 ◽

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.

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

Diagnostics ◽

10.3390/diagnostics12010117 ◽

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms19124043 ◽

2018 ◽

Vol 19 (12) ◽

pp. 4043 ◽

Cited By ~ 1

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.

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Soluble Triggering Receptor Expressed on Myeloid Cells 2 From Cerebrospinal Fluid in Sleep Disorders Related to Parkinson’s Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.753210 ◽

2021 ◽

Vol 13 ◽

Author(s):

Mingshu Mo ◽

Yuting Tang ◽

Lijian Wei ◽

Jiewen Qiu ◽

Guoyou Peng ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Sleep Disorders ◽

Characteristic Curve ◽

Myeloid Cells ◽

Diagnostic Value ◽

Healthy Controls ◽

Potential Biomarker ◽

The Central Nervous System ◽

The Relationship

Background: Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor exclusively expressed in the central nervous system (CNS). It contributes to abnormal protein aggregation in neurodegenerative disorders, but its role in Parkinson’s disease (PD) is still unclear.Methods: In this case-control study, we measured the concentration of the soluble fragment of TREM2 (sTREM2) in PD patients, evaluated their sleep conditions by the PD sleep scale (PDSS), and analyzed the relationship between sTREM2 and PD symptoms.Results: We recruited 80 sporadic PD patients and 65 healthy controls without disease-related variants in TREM2. The concentration of sTREM2 in the CSF was significantly higher in PD patients than in healthy controls (p < 0.01). In the PD group, the concentration of sTREM2 had a positive correlation with α-syn in the CSF (Pearson r = 0.248, p = 0.027). Receiver operating characteristic curve (ROC) analyses showed that sTREM2 in the CSF had a significant diagnostic value for PD (AUC, 0.791; 95% CI, 0.711–0.871, p < 0.05). The subgroup analysis showed that PD patients with sleep disorders had a significantly higher concentration of sTREM2 in their CSF (p < 0.01). The concentration of sTREM2 in the CSF had a negative correlation with the PDSS score in PD patients (Pearson r = −0.555, p < 0.01). The ROC analyses showed that sTREM2 in the CSF had a significant diagnostic value for sleep disorders in PD (AUC, 0.733; 95% CI, 0.619–0.846, p < 0.05).Conclusion: Our findings suggest that CSF sTREM2 may be a potential biomarker for PD and it could help predict sleep disorders in PD patients, but multicenter prospective studies with more participants are still needed to confirm its diagnostic value in future.

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Magnetic resonance T1-mapping evaluates the degree of thyroid destruction in patients with autoimmune thyroiditis

Endocrine Connections ◽

10.1530/ec-18-0175 ◽

2018 ◽

Vol 7 (12) ◽

pp. 1315-1321 ◽

Cited By ~ 1

Author(s):

Jia Liu ◽

Min Liu ◽

Zhe Chen ◽

Yumei Jia ◽

Guang Wang

Keyword(s):

Autoimmune Thyroiditis ◽

Thyroid Dysfunction ◽

T1 Mapping ◽

Interstitial Fibrosis ◽

Characteristic Curve ◽

Area Under The Curve ◽

Diagnostic Value ◽

Healthy Controls ◽

Autoimmune Thyroid ◽

A New Technique

Objective Autoimmune thyroiditis (AIT) is the most common autoimmune thyroid disease. Longitudinal relaxation time mapping (T1-mapping) measured by MRI is a new technique for assessing interstitial fibrosis of some organs, such as heart and liver. This study aimed to evaluate the relationship between T1-mapping value and thyroid function and determine the usefulness of T1-mapping in identifying thyroid destruction in AIT patients. Methods This case–control study recruited 57 drug-naïve AIT patients and 17 healthy controls. All participants were given thyroid MRI, and T1-mapping values were measured using a modified look-locker inversion-recovery sequence. Results AIT patients had significantly higher thyroid T1-mapping values than the healthy controls (1.077 ± 177 vs 778 ± 82.9 ms; P < 0.01). A significant increase in thyroid T1-mapping values was presented along with the increased severity of thyroid dysfunction (P < 0.01). Correlation analyses showed that increased thyroid T1-mapping values were associated with higher TSH and lower FT3 and FT4 levels (TSH: r = 0.75; FT3: r = −0.47; FT4: r = −0.72; all P < 0.01). Receiver-operating characteristic curve analysis revealed a high diagnostic value of T1-mapping values for the degree of thyroid destruction (area under the curve was 0.95, 95% CI: 0.90–0.99, P < 0.01). Conclusions AIT patients have higher thyroid T1-mapping values than the healthy controls, and the T1-mapping values increased with the progression of thyroid dysfunction. Thyroid T1-mapping value might be a new index to quantitatively evaluate the degree of thyroid destruction in AIT patients.

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