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Aim: Associations between serum biomarkers S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) in neonates with hypoxic-ischaemic encephalopathy (HIE) offer contradicting data in regard to neurocognitive outcome. The aim of our study was to provide another dataset to answer this question if S100B or NSE correlates to outcome in neonatal HIE. In addition, we investigate whether amplitude-integrated EEG (aEEG) or magnetic resonance imaging (MRI) also has predictive value., Methods: In neonates with HIE born in Vorarlberg, Austria, (n = 34) from 2012to 2020, NSE and S100B serum levels were measured on day one. aEEG was installed at admission and MRI performed within 7 days. Surviving children (n = 27) were categorised as good or poor outcome by using an age-appropriate neurocognitive test and a standardised neurological follow-up. Positive and negative predictive values and receiver operating characteristic curves were calculated to evaluate the prognostic value., Results: S100B showed best positive and negative predictive value, 72.7% and 90.5%, respectively, and a significant area under the curve of 0.820. NSE showed a positive and a negative predictive value of 43.8% and 81.3% and an area under the curve of 0.757. Severely abnormal aEEG and abnormal MRI significantly correlated with outcome (p = 0.024 and 0.001 respectively)., Conclusion: S100B and NSE on day one, severely abnormal aEEG and abnormal MRI show a significant correlation and good predictive value for neurocognitive outcome., (© 2024 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

To explore the effect of acute hypervolemic hemodilution (AHH) with bicarbonated Ringer's solution (BRS) on perioperative serum S100β protein (S100β) and neuron-specific enolase (NSE) in elderly patients undergoing spine surgery. Ninety patients with lumbar spondylolisthesis and fracture surgery admitted to our hospital from January 2022 to August 2022 were selected as the study subjects, and they were randomly and equally divided into group H1 (AHH with BRS), group H2 (AHH with lactated Ringer's solution) and group C (no hemodilution). The serum contents of S100β and NSE of the three groups at different times were evaluated. There were significant differences in the incidence of postoperative cognitive dysfunction (POCD) among the three groups at T1 and T2 ( P  < 0.05). There were obvious differences in the contents of S100β and NSE among the three groups at T1 and T2 ( P  < 0.001), with no overt difference in the incidence of perioperative complications among the three groups ( P  > 0.05). The use of AHH with BRS can effectively reduce the effect on cognitive function in the elderly with spine surgery, which greatly reduces the nervous system injury, and has certain application value in clinic.

Objectives: To investigate the repair effects of He's qiangtong method of acupuncture (involved bloodletting technique with strong action of unblocking) on the neurovascular unit of the patients with acute ischemic stroke (AIS) in terms of serological indicators so as to provide new ideas for the treatment of AIS., Methods: Seventy subjects with AIS were randomly divided into an observation group (35 cases, 1 case dropped out) and a control group (35 cases , 4 cases dropped out). Patients in the control group were treated with conventional regimen. In the observation group, the bloodletting was operated, combined with the conventional treatment. Bloodletting was performed at Baihui (GV20), Sishencong (EX-HN1) and bilateral Erjian (EX-HN6), using He's qiangtong method of acupuncture, 3 times a week and for 2 weeks. Before and after treatment, the scores of the national institute of health stroke scale (NIHSS), the modified Rankin scale (MRS), and the Barthel index were evaluated；and the serological levels of the serum brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and blood-brain barrier permeability-associated protein (S100β protein) were detected in the two groups., Results: After treatment, NIHSS score and MRS score were decreased ( P <0.01), and Barthel score was increased ( P <0.01) in both groups. NIHSS score of the observation group was lower than that of the control group ( P <0.01). Compared with those before treatment, the content of BDNF in both groups increased ( P <0.05), and VEGF content was elevated in the observation group ( P <0.05) after treatment. The total effective rate was 100% (34/34) in the observation group, higher than that (67.74%, 21/31) in the control group ( P <0.01)., Conclusions: He's qiangtong method of acupuncture can promote the recovery of neurological deficits in AIS patients and effectively improve their motor function and the activity of daily living, which may be related to the reconstruction of neurovascular unit in the brain of AIS patients by increasing the levels of serological repair factors.

The use of nanozymes has become a promising auxiliary approach to "turn on" surface-enhanced Raman scattering (SERS) signals for the label-free detection of disease markers. Nevertheless, there are still major challenges to develop bifunctional nanomaterials with both excellent enzyme-like activity and high SERS performance. To this end, a novel Z-scheme MoO 3- x /CuS heterojunction was first constructed as a powerful "two-in-one" substrate, which can not only catalyze leucomalachite green (LMG) to SERS-active malachite green (MG) but also serve as an efficient substrate to amplify the SERS signal of catalysate. Due to the strong interfacial coupling effect between the MoO 3- x and CuS nanomaterial, which promoted the separation and transport of carriers in the heterojunction, the MoO 3- x /CuS heterojunction showed higher peroxidase-like activity compared to individual components and the previously reported heterojunction nanozymes. Inspired by these results, a sandwich-type SERS immunoassay for the detection of the cerebral infarction biomarker S100 calcium-binding protein (S100B) was proposed based on the output signal of MG at 1620 cm -1 . Furthermore, introducing the antifouling material chitosan on the surface of the MoO 3- x /CuS heterojunction can effectively resist nonspecific protein adsorption and significantly improve the detection accuracy of the immunoassay. Therefore, the SERS immunoassay based on the MoO 3- x /CuS heterojunction realized highly sensitive and selective detection of S100B in the concentration range of 0.001 to 100 ng/mL, with a low limit of detection of 0.47 pg/mL. The developed method has been successfully used for the accurate detection of S100B in clinical serum. The results showed that the level of S100B in the serum of cerebral infarction patients can be distinguished from those of healthy individuals and intracranial tumor patient controls. In addition, the acquired values of S100B in the serum of cerebral infarction patients based this strategy were well consistent with the results of electrochemiluminescence (ECL) detection with a relative error of less than ±7.3. It is expected that this work may open up a paradigm for improving detection sensitivity and accuracy for the early diagnosis and treatment monitoring of cerebral infarction in the clinic.

Background: Recent advancements in animal studies have demonstrated the potential of normobaric hyperoxia (NBO) as a promising intervention for preserving the integrity of the blood-brain barrier (BBB). However, there is still limited understanding of the effects of NBO on BBB function in patients with clinical stroke. Therefore, the objective of this study was to investigate the efficacy of NBO therapy in attenuating BBB damage and reducing brain injury in individuals undergoing endovascular treatment (EVT) for acute stroke., Methods and Results: This study enrolled patients from the OPENS-1 (Normobaric Hyperoxia Combined With Reperfusion for Acute Ischemic Stroke) study, with 43 patients receiving NBO combined with EVT and 43 patients receiving EVT alone. The main outcome measures included serum levels of occludin, MMP-9 (matrix metalloproteinase-9), NSE (neuron-specific enolase), and S100b at 24 hours and 7 days, as well as the intracranial extravasation rate at 24 hours. Serum markers were assessed using ELISA, and intracranial contrast extravasation was visualized using dual-energy computed tomography scan. We analyzed a total of 86 patients and found that the 24-hour serum markers levels of BBB damage and brain injury were significantly lower in the group receiving NBO therapy combined with EVT compared with the group receiving EVT alone. Similarly, at 7 days, the levels of occludin, MMP-9, and NSE were lower in the NBO+EVT group. We also found that the 24-hour serum levels of occludin and MMP-9 were correlated with intracranial contrast extravasation. Additionally, the incidence of intracranial contrast extravasation was lower in the NBO+EVT group compared with the EVT group (35.9% versus 60.5%, P =0.031)., Conclusions: This study offers valuable insights into the positive impact of NBO on maintaining BBB integrity and reducing brain injury in patients with acute stroke undergoing EVT.

Despite numerous studies conducted by various research teams, predicting long-term outcomes (known as Post-COVID-19 Syndrome, PCS) that may result from Coronavirus Disease 2019 (COVID-19) remains challenging. PCS affects over a million people, primarily those with comorbid conditions. Therefore, it is crucial to undertake research aimed at developing a predictive model for early diagnosis of PCS, which in turn would enable faster preventive actions. The aim of this study was to assess the value of measuring and attempt a quantitative evaluation using Enzyme-Linked Immunosorbent Assay (ELISA) tests of three non-serum proteins, whose presence in the blood during COVID-19 was associated with severe disease progression: neutrophil elastase (NE), calcium-binding protein S100B, and neuron-specific enolase (NSE). The concentrations of these proteins were measured in blood serum samples collected before the COVID-19 pandemic from (1) patients with type 2 diabetes (T2DM); (2) advanced stage diabetic nephropathy (NfT2DM); (3) a healthy group; and in blood serum samples collected two years after recovering from COVID-19 from patients with (4) T2DM and (5) NfT2DM. It was found that elevated levels of NE and NSE were significantly more common ( p < 0.05) in patients with NfT2DM after recovering from COVID-19 compared to the other groups, while elevated levels of S100B were significantly more frequently observed in patients with T2DM after recovering from COVID-19 ( p < 0.05). Demonstrating differences in the prevalence of NE, NSE, and S100B in individuals who recovered from COVID-19 with T2DM and NfT2DM makes these proteins important components of the developing predictive model for early detection of PCS. To our knowledge, this is the first study showing the significance of NE, NSE, and S100B in PCS in the context of T2DM and NfT2DM.

Background: There is a significant lack of therapeutic options for mild cognitive impairment (MCI), which is rapidly becoming a global epidemic due to aging. Transcranial photobiomodulation (t-PBM) involves delivering near-infrared light (NIR) to the scalp, targeting cortical areas of the brain. NIR t-PBM has recently emerged as a potential therapy for various neurodegenerative conditions, including memory issues., Aims: This study aimed to evaluate cognition scores (primary outcome), depression, anxiety, resilience scores, neuroplasticity, and neurodegeneration biomarkers (secondary outcomes) in individuals with MCI undergoing t-PBM therapy or receiving a placebo., Materials and Methods: A total of 93 older adult individuals with MCI were randomly assigned to either a t-PBM (n = 47) or Placebo (n = 46) group. Clinical assessments were conducted at baseline, 60 days post-treatment, and a 150-day follow-up. We also measured serum levels of brain-derived neurotrophic factor (BDNF), a neuroplasticity biomarker, as well as neuron-specific enolase (NSE) and calcium-binding protein B (S100B), which are neurodegeneration biomarkers. Intervention effects were analyzed using repeated measures (RM) two-way ANOVA followed by Tukey post hoc test. Fischer's exact test and Generalized Estimating Equations (GEE) were also applied., Results: Of the 93 older adults individuals invited to participate, 76 (t-PBM: 40, placebo: 36) completed the study. The t-PBM significantly improved cognition as measured by the Montreal Cognitive Assessment (MoCA) compared to placebo (p = 0.0301). The delta values for MoCA scores were 3.20 in the t-PBM group and 1.97 in the placebo group. This effect persisted until the three-month follow-up, accompanied by increased BDNF levels in the t-PBM group but not in the placebo group (p = 0.0046). The delta values for BDNF were 821.94 in the t-PBM group and 359.41 in the placebo group. t-PBM did not alter depression, anxiety, resilience scores, nor the levels of NSE and S100B in individuals with MCI., Conclusion: The t-PBM increases cognitive function and BDNF levels in adults with MCI. Its application as an adjunctive treatment may play a crucial role in preventing neurodegenerative diseases., Competing Interests: Declaration of competing interest Dr. Cassano consulted for Janssen Research and Development and for Niraxx Inc.; he was funded by PhotoThera Inc., LiteCure LLC. and Cerebral Sciences Inc. to conduct studies on transcranial photobiomodulation; is a shareholder of Niraxx Inc.; and has filed several patents related to the use of near infrared light in psychiatry. All other authors declare that they do not have any known competing financial interests or personal relationships that could influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Study Objective: The effect of volatile anesthetics on postoperative recovery in older adults is still not entirely clear. Thus, we evaluated the effect of desflurane versus sevoflurane anesthesia on speed of postoperative recovery in older adults eligible for same-day discharge. We further evaluated the incidence of postoperative nausea and vomiting (PONV), bispectral index (BIS) values, and S100B concentrations., Design: Single-center, prospective, observer-blinded, randomized clinical trial., Setting: Operating room., Patients: 190 patients ≥65 years of age and scheduled for minor- to moderate-risk noncardiac surgeries., Interventions: Goal-directed administration of desflurane versus sevoflurane for maintenance of anesthesia with an intraoperative goal of BIS 50 ± 5., Measurements: The primary outcome was the time to anesthesia recovery, which was defined as the time between arrival at the post-anesthesia care unit (PACU) and reaching criteria for discharge from PACU, based on modified Aldrete score ≥ 12 points. Modified Aldrete scores were assessed at PACU arrival and thereafter in five-minute intervals. PONV was evaluated during PACU stay and the first three postoperative days, BIS values were recorded during PACU stay, and S100B values were measured before and after surgery, and on the second postoperative day., Main Results: 95 patients were randomized to receive desflurane, and 95 patients to receive sevoflurane. We did not observe a significant difference in median duration of postoperative recovery between the groups (desflurane: 0 min [0;0]; sevoflurane: 0 min [0;0]; p = 0.245). 77 patients (81.1%) in the desflurane group and 84 patients (88.4%) in the sevoflurane group already had Aldrete scores ≥12 points upon arrival at PACU (p = 0.277). There was also no significant difference in the incidences of PONV (p = 0.606), postoperative BIS values (p = 0.197), and postoperative maximum S100B concentrations (p = 0.821) between the groups., Conclusions: Despite previous reports, we did not observe significant faster recovery times after desflurane anesthesia. Both volatile anesthetics may be appropriate for same-day discharge in older adults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Cranial computed tomography (CT) scan is the most widely used tool to rule out intracranial lesions after pediatric traumatic brain injury (TBI). However, in pediatric population, the radiation exposure can lead to an increased risk of hematological and brain neoplasm. Defined in 2019 National Institute for Health and Care Excellence (NICE) guidelines as "troponins for the brain", serum biomarkers measurements, particularly S100B, have progressively emerged as a supplementary tool in the management of TBI thanks to their capacity to predict intracranial post-traumatic lesions., Methods: This systematic review was conducted following the PRISMA protocol (preferred reporting items for systematic reviews and meta-analyses). No chronological limits of study publications were included. Studies reporting data from children with TBI undergoing serum S100B measurement and computed tomography (CT) scans were included., Results: Of 380 articles screened, 10 studies met the inclusion criteria. Patients admitted with mild-TBI in the Emergency Department (ED) were 1325 (80.25%). The overall pooled sensitivity and specificity were 98% (95% CI, 92-99%) and 45% (95% CI, 29-63%), respectively. The meta-analysis revealed a high negative predictive value (NVP) (99%; 95% CI, 94-100%) and a low positive predictive value (PPV) (41%; 95% CI, 16-79%). Area under the curve (AUC) was 76% (95% CI, 65-85%). The overall pooled negative predictive value (NPV) was 99% (95% CI, 99-100%)., Conclusions: The measurement of serum S100B in the diagnostic workflow of mTBI could help informed decision-making in the ED setting, potentially safely reducing the use of CT scan in the pediatric population. The high sensitivity and excellent negative predictive values look promising and seem to be close to the values found in adults. Despite this, it must be pointed out the high heterogeneity (> 90%) found among studies. In order for S100B to be regularly introduced in the pediatric workflow for TBI, it is important to conduct further studies to obtain cut-off levels based on pediatric reference intervals., (© 2024. The Author(s).)

Cardiac arrest (CA) is a serious health concern that often results in mortality or severe neurological dysfunction in the case of survival. Our aim was to explore the neurological prognostic factors in patients with CA. This retrospective observational study included adult patients with CA. We investigated serum neuron-specific enolase (NSE), S100 calcium-binding protein β (S100β), and indices and parameters at 1, 3, 5, 7 and intensive care unit (ICU) discharge days after CA. The primary study endpoint was the Cerebral Performance Category (CPC) scale score at ICU discharge, which was dichotomized as good neurological outcome (CPC 1-2: full recovery or moderate disability) and poor neurological outcome (CPC 3-5: severe disability, vegetative state, or death). Of the 191 adult patients with CA, 42 (22%) had good neurological outcomes, and 149 (78%) had poor neurological outcomes. NSE at 1,3,5,7 and ICU discharge days showed excellent predictive accuracy for neurological outcomes (area under the curve [AUC]: 0.666, 0.716, 0.870, 0.739, and 0.901, respectively). However, S100β exhibited general predictive power (AUC: 0.666, 0.573, 0.607, 0.594, 0.727). Finally, the early warning model, which combined day 1 NSE, day 1 S100β, cardiac arrest time, SOFA scores, APACHE II scores, and age, was used to screen CA patients with poor neurological prognosis at early stages and had an AUC of 0.792. Serum concentrations of NSE and S100β were significantly elevated in CA patients and could be prognostic biomarkers to predict neurological outcomes. Day 1 NSE and S100β combined with multiple indicators could be a decent early warning model for poor neurological prognosis in patients with CA., (© 2024. The Author(s).)

Background: Postoperative cognitive dysfunction (POCD) is one of the major complications after surgery, with devastating clinical outcomes. Although POCD is a condition with a multifactorial pathophysiology, blood-brain barrier (BBB) dysfunction and neuronal injury have been shown to play a critical role, especially in the elderly. Previous studies have demonstrated that the choice of anesthetics affect BBB permeability and neuroinflammation. However, most studies are carried out on animals, with limited research undertaken on humans. Therefore, we will compare the effect of intravenous anesthetics and inhaled anesthetics on BBB dysfunction and the change of inflammatory markers after surgery., Methods: One hundred and fifty-four patients who are 60 years of age or older undergoing major surgery for more than 2 h will be randomly allocated to two anesthetics groups (intravenous, inhaled) in a 1:1 ratio. In the intravenous anesthetics group (group P), propofol will be infused with a target-controlled infusion (TCI) system throughout the entire surgery. In the inhaled anesthetics group (group G), bolus injection of propofol will be administered for loss of consciousness, and simultaneously sevoflurane will be initiated for the maintenance of anesthesia. The primary outcome is the change in serum S100 calcium binding protein β (S100β) at four time points: before induction of anesthesia, at the end of surgery, 4 h after surgery, postoperative day 1. Secondary outcomes include changes in the inflammatory markers, serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and C-reactive protein; the incidence of delirium; and the change in the cognitive function between groups. In patients pre-scheduled for postoperative intensive care unit admission, the cerebrospinal fluid/serum albumin quotient (Qalb) between the two groups will be compared before and after surgery, and change in inflammatory markers in serum and CSF will be analyzed in relation to the Qalb., Discussion: The current study will compare the effect of intravenous versus inhaled anesthetics on blood-brain barrier permeability and, as a result, the difference in neuroinflammation in elderly patients. Also, the study results will provide additional information to develop intraoperative anesthetic strategies to reduce POCD., Trial Registration: The trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024., (© 2024. The Author(s).)

Background: S100β is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100β and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear., Methods: Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100β levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome., Results: A total of 1072 patients were included in the analysis. The highest S100β levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100β level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: β 36.853, 95% confidence interval (CI) 22.659-51.048, P < 0.001; non-dominant: β 23.645, 95% CI 10.774-36.516, P = 0.007). However, serum S100β levels at 24 h were more strongly associated with NIHSS scores at 24 h and 3-month unfavorable outcome in patients with dominant hemisphere stroke (NIHSS: β 3.470, 95% CI 2.392-4.548, P < 0.001; 3-month outcome: odds ratio (OR) 5.436, 95% CI 2.936-10.064, P < 0.001) than in those with non-dominant hemisphere stroke (NIHSS: β 0.326, 95% CI  - 0.735-1.387, P = 0.547; 3-month outcome: OR 0.882, 95% CI 0.538-1.445, P = 0.619). The association of S100β levels and HT was not significant in either stroke lateralization group., Conclusions: Serum S100β levels 24 h after IVT were independently associated with HT, infarct volume, and prognosis in patients with IVT, which suggests the application value of serum S100β in judging the degree of disease and predicting prognosis., (© 2024. The Author(s).)

Background: Melanoma is the most aggressive skin cancer with ability to recur also after early-stage tumor surgery. The aim was to identify early-stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma., Methods: Eighty patients were enrolled in the study. BRAF V600E mutation was determined in FFPE tissue and plasma samples using ultrasensitive ddPCR with pre-amplification. The level of S100B was determined in plasma by immunoassay chemiluminescent method., Results: The best prediction of melanoma recurrence after surgery was observed in patients with combined high level of S100B (S100B high ) and ctDNA BRAFV600E (BRAF mut ) in preoperative (57.1% vs. 12.5%, p = 0.025) as well as postoperative blood samples (83.3% vs. 14.3%, resp., p = 0.001) in comparison with low S100B and BRAF wild-type. Similarly, patients with preoperative and postoperative S100B high and BRAF mut experienced worse prognosis (DFI p = 0.05, OS p = 0.131 and DFI p = 0.001, OS = 0.001, resp.)., Conclusion: We observed the benefit of the estimation of combination of S100B and ctDNA BRAF mut in peripheral blood for identification of patients at high risk of recurrence and unfavorable prognosis., Significance: There is still no general consensus on molecular markers for deciding the appropriateness of adjuvant treatment of early-stage melanoma. We have shown for the first time that the combined determination of the ctDNA BRAF mut oncogene (liquid biopsy) and the high level of tumor marker S100B in pre- and postoperative plasma samples can identify patients with the worst prognosis and the highest risk of tumor recurrence. Therefore, modern adjuvant therapy would be appropriate for these patients with resectable melanoma, regardless of disease stage., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

The pathophysiology behind neurological and cognitive sequelae of COVID-19 may be related to dysfunction of the blood-brain barrier (BBB) and previous research indicate transient neuronal injury and glial activation. The aim of this study was to investigate if COVID-19 is related to increased BBB permeability by analyzing leakage of biomarkers such as astrocyte-derived extracellular vesicles (EVs) and S100B. We also investigated whether levels of these biomarkers correlated with self-reported symptoms that persisted > 2 months. The samples in this 1-year follow-up study came from an ongoing longitudinal study of unvaccinated patients hospitalized for COVID-19 at Danderyd University Hospital, Stockholm, Sweden, between April and June 2020. Blood samples were collected at baseline and 4, 8, and 12 months after hospitalization. Information on self-reported clinical symptoms was collected at follow-up visits. A total of 102 patients were enrolled, and 47 completed all follow-up measurements. Peak levels of both biomarkers were observed at 4 months in the subset of 55 patients who were measured at this timepoint. At 12 months, the biomarkers had returned to baseline levels. The biomarkers were not correlated with any of the long-term self-reported symptoms. COVID-19 is associated with transient increased BBB permeability, shown by elevated levels of astrocyte biomarkers in plasma. However, these levels return to baseline 12 months post-infection and do not correlate with long-term symptoms. Further research is needed to unravel the underlying mechanisms causing long-term symptoms in COVID-19 patients., (© 2024. The Author(s).)

Permanent inflammatory demyelinating and neurodegenerative processes lead to neurological disability in patients with multiple sclerosis (MS). The anti-inflammatory properties of vitamin D 3 (VitD) are well established, but its role in neurodegeneration is still uncertain. The usefulness of the serum concentration of VitD as a potential biomarker in evaluating brain injury in terms of recently known smoldering MS was under consideration. Methods: We assessed the concentrations of the parameters of brain injury (NF-H, GPAF, S100B, UCHL1) in the cerebrospinal fluid (CSF) of relapsing-remitting (RRMS, n = 123) and progressive MS (PMS, n = 88) patients in the group with normal levels of VitD (VitDn) and in the VitD deficiency group (VitDd). The levels of NF-H and UCHL1 were higher in the group of VitDd compared to VitDn. The higher serum levels of VitD were correlated with lower concentrations of GFAP, NF-H and S100B in the CSF of the whole group of MS patients and in women with MS as opposed to the levels of UCHL1. In men, there were noted negative correlations between the levels of serum VitD and GFAP and NF-H in CSF but not between VitD and S100B and UCHL1. The negative correlations were observed between VitD and the selected parameters of brain injury in MS patients, in women as well as in men. The concentrations of serum VitD together with selected parameters of brain injury in CSF seem to be promising biomarkers of neurodegeneration processes in smoldering MS.

Background: Bipolar disorders (BD) are chronic, debilitating disorders. The blood-brain barrier (BBB) has been increasingly investigated in BD. This systematic review aimed to assess the available evidence on the relationship between BD and markers of BBB dysfunction., Methods: A systematic search in PubMed, Embase, PsycINFO, CINAHL and Web of Science was run where the primary outcomes were BBB markers such as S100B, albumin ratio, matrix metalloproteinase (MMP), cell adhesion molecule (CAM), and tight junction proteins. Techniques included blood, cerebrospinal fluid (CSF), post-mortem, genetic and imaging methods in BD compared to healthy controls., Results: 55 studies were identified, 38 of which found an association between BD and markers of BBB dysfunction. 16/29 studies found increased blood/CSF albumin ratio, S100B, CAMs or MMP levels in BD participants compared to controls. 5/19 post-mortem studies found increased levels of chondroitin sulphate proteoglycans, intercellular CAM, neurexin or claudin-5 mRNA in distinct locations throughout the brain in BD compared to controls. One imaging study identified extensive BBB leakage in 30 % of BD participants, compared to 0 % in controls., Limitations: The diversity in methodologies used in the included studies makes direct comparison of results challenging. Furthermore, imaging methods are the gold standard, but only one study used them. Other markers are only indicative of BBB permeability., Conclusions: This review suggests an association between BD and BBB dysfunction. Further research is needed to provide definite answers considering the existing literature's limitations, and to clarify whether this association provides a pathogenic mechanism, or is an epiphenomenon of BD., Competing Interests: Declaration of competing interest TP has received a speaking honorarium from Janssen for an educational lecture on an unrelated topic. TP was supported by a NIHR Clinical Lectureship. PRAS reports non-financial support from Janssen Research and Development LLC, personal fees and non-financial support from Frontiers in Psychiatry, personal fees from Allergan, funding from National Institute for Health and Care Research (NIHR) UK, and grant from H Lundbeck, outside the submitted work. No other declarations of interest exist. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Head injury is a potentially lethal and frequently occurring condition in the emergency department (ED). Reliable and fast diagnosis is important both for patients and flow in the ED. Circulating S100B is used to rule out the need for head computer tomography in low-risk patients with mild head injury. The flow of these patients through the ED would benefit from shorter turn-around time. Standard serum clotting tubes require 30-60 min clotting time, followed by an analysis time of 45 min. Here, we evaluated the performance of two alternative blood collection tubes; a rapid serum tube (RST) with a recommend clotting time of 5 min and a hirudin tube (HIR) for instant anticoagulation. S100B measurement was performed on paired blood samples from 221 subjects using a Roche Cobas 602 analyser. The performances of the alternative tubes were evaluated by method comparison to the standard serum clotting tube, repeatability and agreement of results obtained from alternative tubes compared with the standard clotting tube. Both alternative tubes had a minor positive bias (RST = 0.011 µg/L, HIR = 0.008 µg/L). The repeatability was 2% for RST and 10% for HIR, while being 4% for the standard clotting tube. In the agreement analysis, the positive and negative predictive values for RST were 62% and 100% while being 73% and 99% for HIR respectively. Our study suggests that RST is a feasible alternative to reduce laboratory turn-around time in S100b analysis.

Increasing evidence implicates that inflammatory factors do play a crucial role in the pathophysiology of schizophrenia. However, the association between inflammatory markers and different symptom dimensions and cognitive function of schizophrenia remains unclear. A total of 140 drug-naïve patients with schizophrenia and 69 healthy controls matched for age and gender were enrolled. Peripheral blood plasma concentrations of S-100 calcium-binding protein B (S100B), neutrophil gelatinase-associated lipocalin (NGAL), and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay (ELISA). Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), and cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Compared with healthy controls, patients with schizophrenia had significantly worse cognitive function and lower levels of NGAL and IFN-γ (P < 0.001). In schizophrenia, plasma NGAL and IFN-γ levels negatively correlated with positive symptom scores (all P < 0.05). There was a positive correlation between plasma levels of NGAL and IFN-γ with visual learning, neurocognition, and MCCB total score (all P < 0.05). We found that NGAL levels (β = 0.352, t = 5.553, 95% CI 0.228-0.477, P < 0.001) and negative symptoms subscale scores (β = - 0.321, OR = 0.725, 95% CI 648-0.811, P < 0.001) were independently associated with the MCCB total score. Further, binary logistic regression analysis indicated that the concentrations of NGAL (β = - 0.246, OR = 0.782, 95% CI 0.651-0.939, P = 0.008) were independently associated with the diagnosis of schizophrenia. There was a positive correlation between NGAL and IFN-γ levels and MCCB total score in schizophrenia. NGAL level was an independent protective factor for cognitive function and an independent risk factor for the diagnosis of schizophrenia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = - 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI.Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28-30, 2024, in Estoril, Lisbon, Portugal., (© 2024. The Author(s).)

S100 calcium-binding protein B (S100B) is a protein primarily known as a biomarker for central nervous system (CNS) injuries, reflecting blood-brain barrier (BBB) permeability and dysfunction. Recently, S100B has also been implicated in cardiovascular diseases, including heart failure (HF). Thus, we investigated serum levels of S100B in 146 chronic HF patients from the Cognition.Matters-HF study and their association with cardiac and cognitive dysfunction. The median S100B level was 33 pg/mL (IQR: 22-47 pg/mL). Higher S100B levels were linked to longer HF duration ( p = 0.014) and increased left atrial volume index ( p = 0.041), but also with a higher prevalence of mild cognitive impairment ( p = 0.023) and lower visual/verbal memory scores ( p = 0.006). In a multivariable model, NT-proBNP levels independently predicted S100B (T-value = 2.27, p = 0.026). S100B did not impact mortality (univariable HR (95% CI) 1.00 (0.99-1.01); p = 0.517; multivariable HR (95% CI) 1.01 (1.00-1.03); p = 0.142), likely due to its reflection of acute injury rather than long-term outcomes and the mild HF phenotype in our cohort. These findings underscore S100B's value in comprehensive disease assessment, reflecting both cardiac dysfunction and potentially related BBB disruption.

Background and Objectives: Neuroinflammation, particularly early astrocyte reactivity, is a significant driver of Alzheimer disease (AD) pathogenesis. It is unclear how the levels of astrocyte biomarkers change in patients across the AD continuum and which best reflect AD-related change. We performed a systematic review and meta-analysis of 3 blood astrocyte biomarkers (glial fibrillary acidic protein [GFAP], chitinase-3-like protein 1 [YKL-40], and S100B) in patients clinically diagnosed with AD., Methods: MEDLINE and Web of Science were searched on March 23, 2023, without restrictions on language, time, or study design, for studies reporting blood levels of the astrocyte biomarkers GFAP, YKL-40, or S100B in patients on the AD continuum (including those with mild cognitive impairment [MCI] and dementia) and a cognitively unimpaired (CU) control population. AD diagnosis was based on established diagnostic criteria and/or comprehensive multidisciplinary clinical consensus. Studies reporting indirect biomarker measures (e.g., levels of biomarker autoantibodies) were excluded. Risk of bias assessment was performed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. Pooled effect sizes were determined using the Hedge g method with a random-effects model. The review was prospectively registered on PROSPERO (registration number CRD42023458305)., Results: The search identified 1,186 studies; 36 met inclusion criteria (AD continuum n = 3,366, CU n = 4,115). No study was assessed to have a high risk of bias. Compared with CU individuals, patients on the AD continuum had higher GFAP and YKL-40 levels (GFAP effect size 1.15, 95% CI 0.94-1.36, p < 0.0001; YKL-40 effect size 0.38, 95% CI 0.28-0.49, p < 0.0001). Both biomarkers were elevated in more advanced clinical stages of the disease (i.e., in AD dementia compared with MCI due to AD: GFAP effect size 0.48, 95% CI 0.19-0.76, p = 0.0009; YKL-40 effect size 0.34, 95% CI 0.10-0.57, p = 0.0048). No significant differences in blood S100B levels were identified., Discussion: We demonstrated significant elevations in blood GFAP and YKL-40 levels in patients on the AD continuum compared with CU individuals. Furthermore, within the AD clinical spectrum, significant elevation correlated with more advanced disease stage. Our findings suggest that both biomarkers reflect AD-related pathology. Our findings are limited by the lack of cultural and linguistic diversity in the study populations meta-analyzed. Future meta-analyses using a biomarker-defined AD population are warranted.

Experimental and clinical studies have indicated a potential role of the protein S100β in the pathogenesis and phenotype of neurodegenerative diseases. However, its impact on spinocerebellar ataxia type 2 (SCA2) remains to be elucidated. The objective of the study is to determine the serum levels of S100β in SCA2 and its relationship with molecular, clinical, cognitive, and peripheral inflammatory markers of the disease. Serum concentrations of S100β were measured by enzyme-linked immunosorbent assay in 39 SCA2 subjects and 36 age- and gender-matched controls. Clinical scores of ataxia, non-ataxia symptoms, cognitive dysfunction, and some blood cell count-derived inflammatory indices were assessed. The SCA2 individuals manifested S100β levels similar to the control group, at low nanomolar concentrations. However, the S100β levels were directly associated with a better performance of cognitive evaluation within the SCA2 cohort. Moreover, the S100β levels were inversely correlated with most peripheral inflammatory indices. Indeed, the neutrophil-to-lymphocyte ratio significantly mediated the effect of serum S100β on cognitive performance, even after controlling for the ataxia severity in the causal mediation analysis. Our findings suggested that, within physiologic concentrations, the protein S100β exerts a neuroprotective role against cognitive dysfunction in SCA2, likely via the suppression of pro-inflammatory mechanisms., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: A number of biomarkers are used to evaluate the duration of the epileptic seizure and the interictal period following neuronal injury. Invasive diagnostic methods are increasingly being replaced by peripheral or minimally invasive biomarkers that give results faster and are more secure., Purpose: We aimed to evaluate serum glial fibrillary acidic protein (GFAP), S100B, and ubiquitin C-terminal hydrolase (UCHL-1) levels in children with epilepsy., Methods: Our study included 3 groups: a nonrefractory epilepsy group, a refractory epilepsy group, and a control group. The GFAP, S100B, and UCHL-1 levels in serum samples collected 2-24 hours after the last seizure were analyzed using enzyme-linked immunosorbent assays., Results: A total of 69 children participated in the study, with 35 participants in the refractory epilepsy group, 18 in the nonrefractory epilepsy group, and 16 in the control group. The GFAP values in the refractory (25.4 ng/mL) and nonrefractory (26.1 ng/mL) epilepsy groups were found to be statistically significantly higher than those in the control group (17.9 ng/mL; P  = .001). The S100B values were found to be significantly higher in the refractory epilepsy group (34.13 pg/mL) than in both the control group and the nonrefractory epilepsy group (28.05 pg/mL; P  = .028). No significant differences were observed in the UCHL-1 levels between the 3 groups., Conclusions: We conclude that the observed differences may be due to the increased expression of S100B and GFAP caused by increased and repetitive neuronal damage in refractory epilepsies compared with nonrefractory epilepsies., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Despite the use of validated guidelines in the management of mild traumatic brain injury (mTBI), processes to limit unnecessary brain scans are still not sufficient and need to be improved. The use of blood biomarkers represents a relevant adjunct to identify patients at risk for intracranial injury requiring computed tomography (CT) scan., Content: Biomarkers currently recommended in the management of mTBI in adults and children are discussed in this review. Protein S100 beta (S100B) is the best-documented blood biomarker due to its validation in large observational and interventional studies. Glial fibrillary acidic protein (GFAP) and ubiquitin carboxyterminal hydrolase L-1 (UCH-L1) have also recently demonstrated their usefulness in patients with mTBI. Preanalytical, analytical, and postanalytical performance are presented to aid in their interpretation in clinical practice. Finally, new perspectives on biomarkers and mTBI are discussed., Summary: In adults, the inclusion of S100B in Scandinavian and French guidelines has reduced the need for CT scans by at least 30%. S100B has significant potential as a diagnostic biomarker, but limitations include its rapid half-life, which requires blood collection within 3 h of trauma, and its lack of neurospecificity. In 2018, the FDA approved the use of combined determination of GFAP and UCH-L1 to aid in the assessment of mTBI. Since 2022, new French guidelines also recommend the determination of GFAP and UCH-L1 in order to target a larger number of patients (sampling within 12 h post-injury) and optimize the reduction of CT scans. In the future, new cut-offs related to age and promising new biomarkers are expected for both diagnostic and prognostic applications., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Especially in the era of successful systemic therapy, there is an urgent need to detect early disease recurrence in stage III melanoma patients. This study investigates if serum S100 calcium-binding protein B (S100B) can detect disease recurrence in stage III melanoma patients., Methods: A retrospective cohort study was conducted at the University Medical Center Groningen (UMCG). Adult AJCC 8th stage III melanoma patients in whom serum S100B was measured as part of follow-up from January 2010 until April 2023 were included. The association between serum S100B and disease recurrence was evaluated using standard definitions for sensitivity and positive predictive value (PPV)., Results: Overall, 147 patients were included (mean age was 60.4 years, 53.1 % were female). Most patients were classified as stage IIIB (39, 26.5 %) and IIIC (73, 49.7 %). During median follow-up of 56 months, 69 (46.9 %) patients experienced disease recurrence. Seventeen out of 18 patients with elevated serum S100B (≥0.15 μg/L) experienced disease recurrence (PPV of 94.4 %). However, 52 out of 69 patients with disease recurrence had normal serum S100B (sensitivity of 24.6 %). Eight out of 17 (47.1 %) patients were asymptomatic (P = 0.608), twelve (70.6 %) patients had at least four distant metastases (P < 0.001)., Conclusion: The clinical value of serum S100B to detect disease recurrence in stage III melanoma patients is negligible since only one out of four patients with disease recurrence have elevated serum S100B. Furthermore, half of stage III melanoma patients with elevated S100B experienced symptoms, and most patients already have multiple distant metastases., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: Disturbed autonomic nervous system (ANS) may promote inflammatory, immune, and oxidative stress responses, which may increase the risk of acute coronary events. S100β has been proposed as a biomarker of neuronal injury that would provide an insightful understanding of the crosstalk between the ANS, immune-inflammatory cells, and plaques that drive atherosclerosis. This study investigates the correlation between S100β, and functional coronary stenosis as determined by quantitative flow ratio (QFR)., Methods: Patients with unstable angina pectoris (UAP) scheduled for coronary angiography and QFR were retrospectively enrolled. Serum S100β levels were determined by enzyme-linked immunosorbent assay. The Gensini score was used to estimate the extent of atherosclerotic lesions and the cumulative sum of three-vessel QFR (3V-QFR) was calculated to estimate the total atherosclerotic burden., Results: Two hundred thirty-three patients were included in this study. Receiver operator characteristic (ROC) curve indicated that S100β>33.28 pg/mL predicted functional ischemia in patients with UAP. Multivariate logistic analyses showed that a higher level of S100β was independently correlated with a functional ischemia-driven target vessel (QFR ≤0.8). This was also closely correlated with the severity of coronary lesions, as measured by the Gensini score (OR = 5.058, 95% CI: 2.912-8.793, p <0.001). According to 3V-QFR, S100β is inversely associated with total atherosclerosis burden (B = -0.002, p <0.001)., Conclusions: S100β was elevated in the functional ischemia stages of UAP. It was independently associated with coronary lesion severity as assessed by Gensini score and total atherosclerosis burden as estimated by 3V-QFR in patients with UAP., (Copyright © 2024. Published by Elsevier Inc.)

Major depressive disorder (MDD) is a debilitating illness that includes depressive mood. Repetitive Transcranial Magnetic Stimulation (rTMS) is a therapy method used in the treatment of MDD. The purpose of this study was to assess neurotrophic factors, and oxidative stress levels in MDD patients and evaluate the changes in these parameters as a result of rTMS therapy. Twenty-five patients with MDD and twenty-six healthy volunteers with the same demographic characteristics were included in the study. Brain-derived neurotrophic factors were measured photometrically with commercial kits. Oxidative stress parameters were measured by the photometric method. Oxidative stress index (OSI) and disulfide (DIS) levels were calculated with mathematical formulas. In this study, total antioxidant status (TAS), total thiol (TT), and native thiol (NT) antioxidant parameters and brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and allopregnanolone (ALLO) levels were reduced in pre-rTMS with regard to the healthy control group; TOS, OSI, DIS, and S100 calcium-binding protein B (S100B) levels were increased statistically significantly (p < 0.01). Moreover, owing to TMS treatment; TAS, TT, NT, BDNF, GDNF, and ALLO levels were increased compared to pre-rTMS, while DIS, TOS, OSI, and S100B levels were decreased significantly (p < 0.01). The rTMS treatment reduces oxidative stress and restores thiol-disulfide balance in MDD patients. Additionally, rTMS modulates neurotrophic factors and neuroactive steroids, suggesting its potential as an antidepressant therapy. The changes in the biomarkers evaluated may help determine a more specific approach to treating MDD with rTMS therapy., (© 2024. The Author(s).)

Background: Low concentrations of S100B have neurotrophic effects and can promote nerve growth and repair, which plays an essential role in the pathophysiological and histopathological alterations of major depressive disorder (MDD) during disease development. Studies have shown that plasma S100B levels are altered in patients with MDD. In this study, we investigated whether the plasma S100B levels in MDD differ between genders., Methods: We studied 235 healthy controls (HCs) (90 males and 145 females) and 185 MDD patients (65 males and 120 females). Plasma S100B levels were detected via multifactor assay. The Mahalanobis distance method was used to detect the outliers of plasma S100B levels in the HC and MDD groups. The Kolmogorov-Smirnov test was used to test the normality of six groups of S100B samples. The Mann-Whitney test and Scheirer-Ray-Hare test were used for the comparison of S100B between diagnoses and genders, and the presence of a relationship between plasma S100B levels and demographic details or clinical traits was assessed using Spearman correlation analysis., Results: All individuals in the HC group had plasma S100B levels that were significantly greater than those in the MDD group. In the MDD group, males presented significantly higher plasma S100B levels than females. In the male group, the plasma S100B levels in the HC group were significantly higher than those in the MDD group, while in the female group, no significant difference was found between the HC and MDD groups. In the male MDD subgroup, there was a positive correlation between plasma S100B levels and years of education. In the female MDD subgroup, there were negative correlations between plasma S100B levels and age and suicidal ideation., Conclusions: In summary, plasma S100B levels vary with gender and are decreased in MDD patients, which may be related to pathological alterations in glial cells., (© 2024. The Author(s).)

Introduction: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in both adult civilian and military populations. Currently, diagnostic and prognostic methods are limited to imaging and clinical findings. Biomarker measurements offer a potential method to assess head injuries and help predict outcomes, which has a potential benefit to the military, particularly in the deployed setting where imaging modalities are limited. We determine how biomarkers such as ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), S100B, neurofilament light chain (NFL), and tau proteins can offer important information to guide the diagnosis, acute management, and prognosis of TBI, specifically in military personnel., Materials and Methods: We performed a narrative review of peer-reviewed literature using online databases of Google Scholar and PubMed. We included articles published between 1988 and 2022., Results: We screened a total of 73 sources finding a total of 39 original research studies that met inclusion for this review. We found five studies that focused on GFAP, four studies that focused on UCH-L1, eight studies that focused on tau proteins, six studies that focused on NFL, and eight studies that focused on S100B. The remainder of the studies included more than one of the biomarkers of interest., Conclusions: TBI occurs frequently in the military and civilian settings with limited methods to diagnose and prognosticate outcomes. We highlighted several promising biomarkers for these purposes including S100B, UCH-L1, NFL, GFAP, and tau proteins. S100B and UCH-L1 appear to have the strongest data to date, but further research is necessary. The robust data that explain the optimal timing and, more importantly, trending of these biomarker measurements are necessary before widespread application., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Traumatic brain injury (TBI) is a sudden brain injury due to an external force that causes a large number of deaths and permanent disabilities every year. S100B has been recognized as a potential objective quantitative biomarker for screening the prognosis of TBI and severe head injury. In this article, an anti-S100B monoclonal antibody was immobilized on cysteamine (Cy) functionalized gold nanoparticles (AuNPs) by EDC-NHS chemistry, which enabled S100B resonance Rayleigh scattering (RRS) detection based on antibody-labeled gold nanoparticles. The prepared conjugates were characterized by ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Based on the specific binding of the antibody and antigen, the RRS intensities at 381 nm and 541 nm wavelengths were significantly enhanced, and thus a dual wavelength overlapping resonance Rayleigh scattering (DWO-RRS) method was established. The scattering intensity of the two overlapping peaks was proportional to the concentration of S100B in the range of 0.05-4.5 ng mL -1 with a detection limit of 0.002 ng mL -1 . The proposed DWO-RRS method is time-saving, simple, sensitive, and can be used to determine the concentration of S100B in human serum with satisfactory results, which has a promising application in the early diagnosis of TBI.

Background: This work aimed to analyze serum S100B levels and brain-derived neurotrophic factor (BDNF) in patients with lumbar disc prolapse to test their predictive values concerning the therapeutic efficacy of pulsed radiofrequency., Methods: This prospective interventional study was carried out on 50 patients candidates for radiofrequency for treating symptomatic lumbar disc prolapse. Pain severity and functional disability were assessed using the Numeric Rating Scale (NRS) and Functional rating index (FRI) before as well as two weeks, 1, 3, and 6 months after the radiofrequency. Quantitative assessment of serum S100B level and BDNF was done for all the included patients one day before radiofrequency., Results: The scores of NRS and FRI were significantly improved at two weeks, 1, 3, and 6 months following radiofrequency (P-value < 0.001 in all comparisons). Statistically significant positive correlations were found between duration of pain, NRS, and S100B serum level before radiofrequency, and both NRS (P-value = 0.001, 0.035, < 0.001 respectively) and FRI (P-value = < 0.001, 0.009, 0.001 respectively) 6 months following radiofrequency. Whereas there were statistically significant negative correlations between BDNF serum level before radiofrequency and both NRS and FRI 6 months following radiofrequency (P-value = 0.022, 0.041 respectively). NRS and S100B serum levels before radiofrequency were found to be independent predictors of NRS 6 months following radiofrequency (P-value = 0.040. <0.001, respectively)., Conclusion: Serum level of S100B is a promising biomarker that can predict functional outcomes after pulsed radiofrequency in patients with lumbar disc prolapse., (© 2024. The Author(s).)

Background: Juvenile idiopathic arthritis (JIA) is the most prevalent rheumatic disease in children, and the inflammatory process is widely studied, primarily characterized by its impact on joint health. Emerging evidence suggests that JIA may also affect the central nervous system (CNS). This study investigates the potential CNS involvement in JIA by analyzing the presence of astrocyte-derived extracellular vesicles (EVs) and the S100B protein in plasma, both of which are indicative of astrocyte activity and blood-brain barrier (BBB) integrity., Methods: EDTA plasma from 90 children diagnosed with JIA and 10 healthy controls, matched by age and gender, was analyzed for extracellular vesicles by flow cytometric measurement. Astrocyte-derived EVs were identified using flow cytometry with markers for aquaporin 4 (AQP-4) and glial fibrillary acidic protein (GFAP). Levels of the S100B protein were measured using a commercial ELISA. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score (JADAS27, 0-57), and pain levels were measured using a visual analogue scale (VAS, 0-10 cm)., Results: Our analyses revealed a significantly higher concentration of astrocyte-derived EVs in the plasma of children with JIA compared with healthy controls. Furthermore, children with JADAS27 scores of 1 or higher exhibited notably higher levels of these EVs. The S100B protein was detectable exclusively in the JIA group., Conclusion: The elevated levels of astrocyte-derived EVs and the presence of S100B in children with JIA provide evidence of BBB disruption and CNS involvement, particularly in those with higher disease activity. These findings underscore the importance of considering CNS health in the comprehensive management of JIA. Further research is required to elucidate the mechanisms behind CNS engagement in JIA and to develop treatments that address both joint and CNS manifestations of the disease., (© 2024. The Author(s).)

Objectives: To evaluate some confounding factors that influence the concentrations of S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl-terminal hydrolase L-1 (UCH-L1) in older individuals. Indeed, recent guidelines have proposed the combined use of S100B and the "GFAP-UCH-L1" mTBI test to rule out mild traumatic brain injuries (mTBI). As older adults are the most at risk of mTBI, it is particularly important to understand the confounding factors of those mTBI rule-out biomarkers in aging population., Methods: The protein S100B and the "GFAP and UCH-L1" mTBI test were measured using Liaison XL (Diasorin) and Alinity I (Abbott), respectively, in 330 and 341 individuals with non-suspected mTBI from the SarcoPhAge cohort., Results: S100B, GFAP and UCH-L1 were all significantly correlated with renal function whereas alcohol consumption, Geriatric Depression Score (GDS), smoking habits and anticoagulant intake were not associated with any of these three biomarkers. Body mass index (BMI) and age were associated with GFAP and UCH-L1 expression while sex and mini-mental state examination (MMSE) were only associated with GFAP. According to the manufacturer's cut-offs for mTBI rule-out, only 5.5 % of participants were positive for S100B whereas 66.9 % were positive for the "GFAP-UCH-L1" mTBI test. All positive "GFAP-UCH-L1" mTBI tests were GFAP+/UCH-L1-. Among individuals with cystatin C>1.55 mg/L, 25 % were positive for S100B while 90 % were positive for the mTBI test., Conclusions: Our data show that confounding factors have different impacts on the positivity rate of the "GFAP-UCH-L1" mTBI test compared to S100B., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: To dynamically observe the changes in hypoxia-inducible factor 1α (HIF-1α) and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in children with traumatic brain injury (TBI) and evaluate their clinical value in predicting the severity and prognosis of pediatric TBI., Methods: A prospective study included 47 children with moderate to severe TBI from January 2021 to July 2023, categorized into moderate (scores 9-12) and severe (scores 3-8) subgroups based on the Glasgow Coma Scale. A control group consisted of 30 children diagnosed and treated for inguinal hernia during the same period, with no underlying diseases. The levels of HIF-1α, BNIP3, autophagy-related protein Beclin-1, and S100B were compared among groups. The predictive value of HIF-1α, BNIP3, Beclin-1, and S100B for the severity and prognosis of TBI was assessed using receiver operating characteristic (ROC) curves., Results: Serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in the TBI group were higher than those in the control group ( P <0.05). Among the TBI patients, the severe subgroup had higher levels of HIF-1α, BNIP3, Beclin-1, and S100B than the moderate subgroup ( P <0.05). Correlation analysis showed that the serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were negatively correlated with the Glasgow Coma Scale scores ( P <0.05). After 7 days of treatment, serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in both non-surgical and surgical TBI patients decreased compared to before treatment ( P <0.05). ROC curve analysis indicated that the areas under the curve for predicting severe TBI based on serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were 0.782, 0.835, 0.872, and 0.880, respectively ( P <0.05), and for predicting poor prognosis of TBI were 0.749, 0.775, 0.814, and 0.751, respectively ( P <0.05)., Conclusions: Serum levels of HIF-1α, BNIP3, and Beclin-1 are significantly elevated in children with TBI, and their measurement can aid in the clinical assessment of the severity and prognosis of pediatric TBI.

Aclinical and immunological examination of men with occupational pathology, including vibration disease (VD), occupational sensorineural hearing loss (SHL), and chronic mercury intoxication (CMI), was carried out. The comparison group consisted of men comparable in age and total work experience. Serum concentrations of neurotrophins (S100β, MBP, BDNF) and antibodies (ABs) to S100β and MBP proteins were determined by enzyme-linked immunosorbent assay. An increase in the level of the S100β protein was shown in CMI, VD, and a tendency for its increase was found in SHL. In parallel, an increase in AB to the S100β protein in VD and SHL and a decrease in AB in CMI were noted. A comparative assessment of MBP levels indicated a pronounced increase in its serum concentrations in patients with CMI and VD versus the comparison group. At the same time, an increase in the level of serum ABs to MBP in individuals with VD and SHL, and a decrease in patients with CMI were noted. In patients with CMI, a significant decrease in the BDNF concentration was found, while in SHL and VD, no statistically significant differences were found in comparison with the comparison group. The results obtained confirm importance of assessing serum concentrations of neurotrophic proteins and ABs to them in the case of occupational damage to the nervous system caused by exposure to physical and chemical factors.

Objective: To observe the levels of serum 3-nitrotyrosine (3-NT), neuronal PAS domain protein 4 (NPASDP-4), and S100β protein in patients diagnosed with cerebral infarction and analyze their correlation with cognitive dysfunction in these patients., Methods: The study included a cohort of 158 patients suffering from cerebral infarction who were admitted to the Liwan District Hospital of Traditional Chinese Medicine between January 2021 and December 2022. After stabilizing vital signs, all patients underwent the Montreal Cognitive Assessment (MoCA) to assess their cognitive function. Based on the assessment results, they were divided into two groups: the cognitive dysfunction group (121 cases) and the normal cognitive function group (37 cases). The baseline characteristics and serum levels of 3-NT, neuronal PAS domain protein 4 (NPASDP-4), and S100β protein were compared in the patient cohorts. Furthermore, the correlation between these three indicators and cognitive function in patients suffering from cerebral infarction was analyzed. A logistic regression model was constructed to analyze how serum levels of 3-NT, NPASDP-4, and S100β protein levels affected cognitive function in patients suffering from cerebral infarction. ROC curve analysis was conducted to assess the predictive value of serum 3-NT, NPASDP-4, and S100β protein levels for cognitive function in patients suffering from cerebral infarction., Results: Among the 158 patients with cerebral infarction, 121 (76.58%) had cognitive dysfunction, while 37 (23.42%) had normal cognitive function. The levels of 3-NT, NPASDP-4, and S100β protein were found to be significantly higher in the cognitive dysfunction group compared to the normal cognitive function group (t = 5.788, 7.774, 6.460; P = .000, .000, .000). The point-biserial correlation analysis results showed a positive correlation between serum levels of 3-NT, NPASDP-4, and S100β protein and the occurrence of cognitive dysfunction in patients suffering from cerebral infarction (r=0.420, 0.529, 0.424; P = .000, .000, .000). The logistic regression model demonstrated that serum levels of 3-NT(95%CI: 1.299-2.603), NPASDP-4(95%CI: 1.487-3.386), and S100β protein(95%CI: 1.153-8.746) were risk factors for cognitive dysfunction in patients suffering from cerebral infarction (OR=1.839, 2.244, 1.429; P = .001, .000, .240). ROC curve analysis demonstrated that serum 3-NT, NPASDP-4, and S100β protein levels exhibited a certain predictive value for cognitive function in patients with cerebral infarction (AUC = 0.789, 0.881, 0.820)., Conclusion: Serum levels of 3-NT, NPASDP-4, and S100β protein are closely related to the cognitive function of patients with cerebral infarction, and abnormal changes in these levels may exacerbate cognitive dysfunction in these patients.

Purpose: Neurotoxicity concerns have been raised over general anesthesia and sedation medication use in children. Such concerns are largely based on animal studies, historical anesthetic agents, and assessment tools, thus warranting further investigations. Blood biomarkers in detecting neuronal inflammation and apoptosis are novel methods for detecting neuronal damage. Therefore, the aim of this feasibility study was to assess the usefulness of the levels of four plasma biomarkers in dental general anesthesia (DGA) as surrogate markers of neurotoxicity in children. The secondary aim was to compare changes in motor manipulative skills pre- and post-anesthetic exposure., Methods: This single-center prospective observational study included 22 healthy children aged between 3 and 6 years old who underwent DGA. Subclinical neurotoxicity was measured with a panel of four plasma biomarkers: Caspase-3, neuron-specific enolase (NSE), neurofilament light chain, and S100B at three time points (1; at start, 2; end and 3; on recovery from DGA). The Skillings-Mack test was used to identify the difference in the biomarker levels at three time points. Motor manipulative score assessment, prior and two weeks after DGA was also performed., Results: A total of 22 study participants (mean age = 5 ± 1 years) were included with a median DGA duration of 106 ± 28 min. A reduction in Caspase-3 levels was recorded, with pairwise comparison over three time points, reporting a statistical significance between time point 2 vs. 1 and time point 3 vs. 1. Although fluctuations in NSE levels were recorded, no significant changes were found following pairwise comparison analysis. Among other biomarkers, no significant changes over the three periods were recorded. Furthermore, no significant changes in manipulative motor scores were reported., Conclusion: Caspase-3 reduced significantly in the short time frames during day-care DGA; this might be due to the relatively short anesthesia duration associated with dental treatment as compared with more extensive medical-related treatments. Therefore, further studies on Caspase-3 as a potential biomarker in pediatric DGA neurotoxicity are required to further ascertain results of this study., (© 2024. The Author(s).)

Objectives: Data in literature indicate that in patients suffering a minor head injury (MHI), biomarkers serum levels could be effective to predict the absence of intracranial injury (ICI) on head CT scan. Use of these biomarkers in case of patients taking oral anticoagulants who experience MHI is very limited. We investigated biomarkers as predictors of ICI in anticoagulated patients managed in an ED., Methods: We conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The outcome was delayed ICI (dICI), defined as ICI on the second CT scan after a first negative CT scan. We assessed the sensitivity (SE), specificity (SP), negative predictive value (NNV) and positive predictive value (PPV) of the biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in order to identify dICI., Results: Our study population was of 234 patients with a negative first CT scan who underwent a second CT scan. The rate of dICI was 4.7 %. The NPV for the detection of dICI were respectively (IC 95 %): S100B 92.7 % (86.0-96.8 %,); ubiquitin C-terminal hydrolase-L1 (UCH-L1) 91.8 % (83.8-96.6 %); glial fibrillary protein (GFP) 100 % (83.2-100 %); TBI 100 % (66.4-100 %). The AUC for the detection of dICI was 0.407 for S100B, 0.563 for neuron-specific enolase (NSE), 0.510 for UCH-L1 and 0.720 for glial fibrillary acidic protein (GFAP), respectively., Conclusions: The NPV of the analyzed biomarkers were high and they potentially could limit the number of head CT scan for detecting dICI in anticoagulated patients suffering MHI. GFAP and Alinity TBI seem to be effective to rule out a dCI, but future trials are needed., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: To study the relationship of serum markers of glial and neuronal degeneration with neuropsychological tests reflecting various cognitive domains of executive functions in patients with alcohol use disorders (AUDs)., Material and Methods: A total of 74 men participated in the study, including 30 healthy volunteers and 44 patients with AUDs. The study of executive functioning was carried out using Go/No-Go, Corsi and Color Stroop tests. Concentrations of calcium-binding protein (S100B), myelin basic protein (MBP) and glial fibrillar acid protein (GFAP) «Sandwich» were determined in the blood serum of patients and control groups by solid-phase enzyme immunoassay., Results: The levels of S100B and MBP in patients with AUDs were significantly higher than the control values ( U =194.5; p =0.002 and U =198.5; p =0.003), whereas the content of GFAP in patients did not significantly exceed the control values ( U =287; p =0.181). Patients with AUDs performed worse on the Go/No-Go task ( U =133; p =0.002), the Corsi test ( U =133.5; p =0.003) and the Color Stroop test ( U =60; p <0.001) compared to controls. Significant Spearman's correlations were found between the concentration of S100B and the number of errors in the Go/No-Go task (R=0.537; p =0.004), as well as the duration of alcohol dependence (R=0.321; p =0.021). The MBP content in blood serum was directly correlated with the number of errors in the Go/No-Go task (R=0.654; p <0.001) and inversely with spatial working memory in the Corsi test (R=-0.588; p <0.001)., Conclusion: The serum levels of S100B and MBP correlate with various domains of executive functions (inhibitory control and spatial working memory) in patients with AUDs. It is assumed that these biomarkers can potentially be used as markers of progression, tracking subtle cognitive changes among patients with AUDs.

Introduction: Sepsis-associated brain dysfunction is a common organ dysfunction in sepsis. The main goal of this study was to verify whether the combined assessment of central nervous system injury markers (i.e. S100B, NSE, GFAP) and disease severity as per the Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) classification systems, would increase the accuracy of death prediction in septic shock., Material and Methods: Markers of neuronal damage were determined in 55 patients diagnosed with septic shock with no previous neurological disease. Clinical data was collected and the scores on the APACHE II, SAPS II and SOFA prognostic scales were calculated. Death before discharge from the Intensive Care Unit (ICU) was established as the endpoint., Results: Nineteen patients (35%) died before ICU discharge. Patients who died had significantly higher S100B and NSE values, and APACHE II, SAPS II and SOFA scores (P< 0.05 for all). At the time of septic shock diagnosis, NSE levels more accurately predicted the risk of death before ICU discharge than S100B. However, NSE had no better predictive value for short-term mortality than APACHE II, SAPS II and SOFA. Adding C-reactive protein (CRP) and S100B concentrations to the APACHE II score created a predictive model with 95% mortality accuracy (AUC = 0.95; 95%CI 0.85-0.99; P = 0.03)., Conclusions: The assessment of acute neuronal injury plays an important role in prognostication in patients with septic shock. The concentration of S100B protein in combination with APACHE II score and concentration of CRP more accurately predicts mortality than the APACHE II alone.

Objectives: Preeclampsia is one of the most feared complications of pregnancy, which can progress rapidly to serious complications such as death of both mother and fetus. To present, the leading cause of preeclampsia is still debated. The purpose of this article was to explore the clinical significance of S100B protein, a kind of Ca2+ -sensor protein, in the early-onset severe preeclampsia., Material and Methods: Nine pregnant women with early-onset severe preeclampsia (the study group) and 13 healthy pregnant women (the control group) were included in this study. The level of S100B in the amniotic fluid, maternal blood, and umbilical cord blood were detected by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance imaging (SPRi) methods. Diagnostic values of S100B for early-onset severe preeclampsia were assessed by Receiver Operating Characteristic (ROC) curve analysis., Results: The levels of S100B in maternal blood and amniotic fluid in the study group were higher than those in the control group (p < 0.05). ROC curve analysis showed that S100B detected by SPRi method (SPRi-S100B) showed a cut-off level of 181 ng/mL with sensitivity of 100%, a specificity of 84.6%, and a Youden index of 0.846 in the maternal blood, which had better clinical significance and diagnostic value (at than that detected by ELISA (ELISA-S100B)., Conclusions: The levels of S100B detected by SPRi in maternal blood can indicate early-onset severe preeclampsia and perinatal brain injury.

Aim: Antenatal corticosteroids (ACS) are recommended for women at risk of preterm birth before 34 weeks' gestation. However, adverse effects of ACS on the fetal brain have also been reported. The time interval from ACS administration to delivery (ACS-to-delivery interval) might alter the effect of ACS on the fetal brain. This study aimed to evaluate the effect of ACS-to-delivery interval on cord blood S100 calcium-binding protein B (S100B) levels as a biomarker of brain damage., Methods: Women who delivered between 2012 and 2020 at a tertiary medical center were divided into three groups according to ACS use and ACS-to-delivery interval, retrospectively: non-ACS, ACS ≤7 days, and ACS >7 days. Patients who did not complete the ACS regimen were excluded. The primary outcome was cord blood S100B levels., Results: Cord blood S100B levels were significantly lower in the ACS ≤7 days group than in the non-ACS and ACS >7 days groups. In the multiple regression analysis, birth ≤7 days after ACS showed a significant negative association with S100B level (p < 0.001)., Conclusions: Reduced S100B levels were observed in infants born ≤7 days after ACS but not in infants born >7 days after ACS. These findings suggest the importance of ACS timing to optimize its effects on the fetal brain, although further studies are required to identify these mechanisms., (© 2023 Japan Society of Obstetrics and Gynecology.)

Abstract: Background : COVID-19 disease severity markers include mostly molecules related to not only tissue perfusion, inflammation, and thrombosis, but also biomarkers of neural injury. Clinical and basic research has demonstrated that SARS-COV-2 affects the central nervous system. The aims of the present study were to investigate the role of neural injury biomarkers and to compare them with inflammatory markers in their predictive ability of mortality. Methods : We conducted a prospective observational study in critically ill patients with COVID-19 and in a cohort of patients with moderate/severe disease. S100b, neuron-specific enolase (NSE), and inflammatory markers, including soluble urokinase plasminogen activator receptor (suPAR), were measured on intensive care unit or ward admission, respectively. Statistical comparisons between patient groups were performed for all biomarkers under investigation. Correlations between different biomarkers were tested with Spearman correlation coefficient. Receiver operating characteristic curves were plotted using mortality as the classification variable and the biomarker levels on admission as the prognostic variables. Results : A total of 70 patients with COVID-19 were included in the final analysis. Of all studied biomarkers, s100b had the best predictive ability for death in the intensive care unit, with an area under the curve of 0.73 (0.61-0.83), P = 0.0003. S100b levels correlated with NSE, interleukin (IL)-8, and IL-10 (0.27 < rs < 0.37, P < 0.05), and tended to correlate with suPAR ( rs = 0.26, P = 0.05), but not with the vasopressor dose ( P = 0.62). Conclusion : Among the investigated biomarkers, s100b demonstrated the best predictive ability for death in COVID-19 patients. The overall biomarker profile of the patients implies direct involvement of the nervous system by the novel coronavirus., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Objective: S100B is a glial cell protein with bimodal function. In low concentrations, it exerts neurotrophic effects, but higher levels reflect neuronal distress. Recent research suggests that this molecule may be a biomarker of response to electroconvulsive therapy (ECT). We examined the effect of ECT on serum S100B and its utility as 1) a biomarker of a depressive state and 2) a predictor of ECT response. We also wanted to ensure that ECT does not cause a marked serum S100B elevation, indicating neural distress., Methods: We measured serum S100B in 22 in-patients treated with ECT due to depression. Depression severity was assessed using 17-item Hamilton Rating Scale for Depression (HAMD-17). The data were collected before an ECT series, within 1 week after the series (post-ECT), and at a 6-month follow-up. Changes in serum S100B and clinical outcomes were tested using a linear mixed model. A relationship between serum S100B and the clinical outcomes was examined using Spearman's and partial correlation., Results: Serum S100B did not change significantly immediately after an ECT series or 6 months later. The post-ECT serum S100B change was not associated with the clinical effect (rho = 0.14, n = 22, p = 0.54). The baseline serum S100B did not predict the clinical effect when controlling for age ( r = 0.02, n = 22, df = 19, p = 0.92)., Conclusion: The study neither supports serum S100B as a state marker of depression nor a predictor of ECT response. No evidence for ECT-related neural distress was found.

Background: Vitiligo is a depigmented skin disease. S100B is a damage-associated molecular pattern protein proposed as a marker of melanocyte cytotoxicity., Aim: To detect the sensitivity of serum levels of S100B as a disease activity marker in vitiligo patients., Methods: Four patient groups of both sexes: twenty segmental vitiligo, twenty non-segmental active vitiligo patients, twenty non-segmental stable vitiligo patients and thirty healthy controls age and sex-matched, patients were subjected to vitiligo disease activity score (VIDA score) and Vitiligo Extent Tensity Index (VETI) score., Results: An increased level of S100B was observed in patients with vitiligo compared to control, there was statistically significant increase in its level in non- segmental-active than non-segmental stable and segmental-stable. Roc analysis for S100B to predict cases vs control was confirmed by getting cut off point 80.2   pg/ml, with high sensitivity 96.67 and high specificity 96.67. Roc analysis for S100B to predict non-segmental-active versus segmental and non-segmental was also confirmed by getting cut off point 118.3 pg/ml, with sensitivity 80.0 and specificity 77.50., Conclusion: S100B can be used as indicators for disease activity with high sensitivity and specificity in Egyptian vitiligo patients.

Background: Rapid disease progression in neuroemergencies is associated with blood-brain barrier (BBB) disruption. We investigated a less invasive strategy for assessing BBB status by evaluating S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) at early stages of the hypoxic-ischemic brain injury (HIBI) cascade., Methods: This retrospective study used prospectively collected data from patients with out-of-hospital cardiac arrest (August 2019-July 2021). Albumin specimens obtained from serum and cerebrospinal fluid via arterial catheter and lumbar puncture were used to measure the albumin quotient (Qa), which is widely accepted as the gold standard method for detecting BBB disruption. Serum S100B and NSE levels were measured simultaneously following the return of spontaneous circulation. We conducted linear regression to evaluate the relationship between S100B and Qa and the predictive performance of S100B for abnormal Qa. The primary study outcome was abnormal Qa (>0.007)., Results: Forty-one patients were enrolled; 30 showed an abnormal Qa suggestive of BBB disruption. S100B levels were significantly higher than in those with a normal Qa (0.244 μg/L [interquartile range [IQR], 0.146-0.823 vs 0.754 μg/L [IQR, 0.317-2.228], P = .03). We report a positive correlation between serum S100B and Qa (R2 = 0.110; P = .04). The area under the receiver operating characteristics curve (AUROC) evaluating the predictive performance of S100B with respect to abnormal Qa was 0.718 (95% confidence interval, 0.556-0.847). The cutoff value for S100B (with respect to BBB disruption) in the total cohort was 0.283 μg/L (sensitivity, 80.0%; specificity, 72.7%). Subgroup analyses in patients with serum neuron-specific enolase (NSE) levels of <40.8 ng/mL (excluding those with established neuronal cell injury) showed an improved correlation coefficient (R2 = 0.382; P < .01) and predictive performance (AUROC, 0.836 [95% confidence interval, 0.629-0.954]) compared with the total cohort., Conclusions: Serum S100B obtained at an early stage of the HIBI cascade is associated with abnormal Qa, suggesting BBB disruption. The predictive performance of S100B and the correlation between serum S100B and Qa can be improved using a complementary strategy (i.e., evaluations of S100B and NSE levels) that combines considerations of cell damage in astrocytes and neurons., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ineffective stress-coping in Africans is associated with cardiac ischemia during acute mental stress. Ischemic conditions may be worsened by stress-induced release of glial-derived S100‑calcium-binding-protein β (S100B), which is pro-apoptotic for cardiomyocytes. Whether estradiol as coping regulator and cardio-protective factor will protect against pro-apoptotic effects, remains unclear. Therefore, we aimed to investigate stress-induced associations between cardiac troponin T/cTnT (cardiac ischemic marker), S100B and estradiol in a bi-ethnic cohort of defensive copers of both sexes. The target population study included African and Caucasian teachers of both sexes (n = 344; aged 20-65 years). The Stroop-color-word-conflict-test was administrated for 1 min to induce acute mental stress in the participants. A chronic stress risk phenotype score was obtained. The Coping Strategy Indicator determined habitual defensive/avoidance/seeking social support coping scores. Fasting blood samples were obtained prior to and 10 min post-Stroop-stress to assess cTnT, S100B and estradiol levels. An interaction between ethnicity, sex and defensive coping (p < 0.05) was found for acute stress-induced percentage changes in estradiol. In defensive coping African men, the Stroop-color-word-conflict-test elicited decreases in S100B and increases in estradiol. Again, in this group, S100B decreases were related to unchanged cTnT, a chronic stress risk phenotype and acute estradiol increases (p < 0.05). No associations among main markers were apparent in the African women or the Caucasian defensive copers of both sexes. In the defensive coping African men, the markers studied may play a relevant role in the brain-cardiovascular system interaction during stress exposure. Further research is needed to elaborate on potential mechanisms and to establish clinical relevance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ischemic stroke is the main cause of permanent disability in adult patients. No commonly accepted method were discovered to predict stroke before the first symptoms. Activation of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMP) and S100B protein may be observe in patients with symptomatic carotid artery stenosis. Hemorrhagic transformation of ischemic stroke may be associated with changes in MMP, TIMP and S100B., Aim: The aim of this study was to determine if MMP-9, TIMP-1 and S-100B protein may markers of forthcoming ischemic stroke in patients undergoing carotid endarterectomy., Materials and Methods: Blood samples were taken and an analysis of circulating proteins (MMP-9, TIMP-1, S100B) 73 subsequent patients with carotid artery stenosis ≥70% (33 asymptomatic and 40 symptomatic), who were referred for potential revascularization., Results: A statistically significant difference was found between MMP- 9 levels in patients with ischemic stroke compared to patients with asymptomatic carotid stenosis after endarterectomy. Also, average TIMP-1 levels in patients with ischemic stroke and stenosis ≥70% were statistically significantly higher than the average levels in patients after endarterectomy. In terms of S-100B, a higher mean value was observed in patients with stroke than in endarterectomy group. No statistical differences were found in the levels of that proteins in the hemorrhagic transformation of ischemic stroke., Conclusions: Increased levels of MMP-9, TIMP-1 and S-100B in patients with ischemic stroke compared to patients with asymptomatic carotid stenosis after endarterectomy showed that abovementioned proteins may be a good predictive factor of ischemic stroke in patients undergoing carotid endarterectomy., (© 2022 MEDPRESS.)

The pathophysiological changes underlying stress-related mental disorders remain unclear. However, research suggests that alterations in astrocytes and neurons may be involved. This study examined potential peripheral markers of such alterations, including S100B and neurofilament light chain (NF-L). We compared plasma levels of S100B and NF-L in patients with chronic stress-induced exhaustion disorder (SED), patients with major depressive disorder (MDD), and healthy controls. We also investigated whether levels of S100B and NF-L correlated with levels of astrocyte-derived extracellular vesicles (EVs that indicate astrocyte activation or apoptosis) and with symptom severity. Only women had measurable levels of S100B. Women with SED had higher plasma levels of S100B than women with MDD (P < 0.001) and healthy controls (P < 0.001). Self-rated symptoms of cognitive failures were positively correlated with levels of S100B (r s  = 0.434, P = 0.005) as were depressive symptoms (r s  = 0.319, P < 0.001). Plasma levels of astrocyte-derived EVs were correlated with levels of S100B (r s  = 0.464, P < 0.001). Plasma levels of NF-L did not differ between the groups and were not correlated with symptom severity or EV levels. Thus, long-term stress without sufficient recovery and SED may be associated with raised plasma levels of S100B, which may be evidence of pathophysiological changes in astrocytes. The findings also support the hypothesis that plasma levels of S100B are associated with cognitive dysfunction., (© 2022. The Author(s).)