Search

Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are leading neurodegenerative disorders marked by protein aggregation, with AD featuring amyloid-beta (Aβ) and tau proteins, and PD alpha-synuclein (αSyn). Dementia with Lewy bodies (DLB) often presents with a mix of these pathologies. This study explores naturally occurring autoantibodies (nAbs), including Immunoglobulin (Ig)G, IgM, and IgA, which target αSyn, Aβ and tau to maintain homeostasis and were previously found altered in AD and PD patients, among others. Main text: We extended this investigation across AD, PD and DLB patients investigating both the affinities of IgGs and levels of IgGs, IgMs and IgAs towards αSyn, Aβ and tau utilizing chemiluminescence assays. We confirmed that AD and PD patients exhibited lower levels of high-affinity anti-Aβ and anti-αSyn IgGs, respectively, than healthy controls. AD patients also showed diminished levels of high-affinity anti-αSyn IgGs, while anti-tau IgG affinities did not differ significantly across groups. However, DLB patients exhibited increased anti-αSyn IgG but decreased anti-αSyn IgM levels compared to controls and PD patients, with AD patients showing a similar pattern. Interestingly, AD patients had higher anti-Aβ IgG but lower anti-Aβ IgA levels than DLB patients. DLB patients had reduced anti-Aβ IgM levels compared to controls, and anti-tau IgG levels were lower in AD than PD patients, who had reduced anti-tau IgM levels compared to controls. AD patients uniquely showed higher anti-tau IgA levels. Significant correlations were observed between clinical measures and nAbs, with negative correlations between anti-αSyn IgG affinity and levels in DLB patients and a positive correlation with anti-αSyn IgA levels in PD patients. Disease-specific changes in nAb levels and affinity correlations were identified, highlighting altered immune responses. Conclusion: This study reveals distinctive nAb profiles in AD, DLB, and PD, pinpointing specific immune deficiencies against pathological proteins. These insights into the autoreactive immune system's role in neurodegeneration suggest nAbs as potential markers for vulnerability to protein aggregation, offering new avenues for understanding and possibly diagnosing these conditions. [ABSTRACT FROM AUTHOR]

We assessed syphilis screening data from overseas medical examinations among U.S.-bound refugees to characterize seropositive syphilis cases and treatment from January 1, 2015, to December 31, 2018. During this time period, all refugees 15 years and older were required to undergo syphilis screening prior to resettlement to the United States. Of the 160,381 refugee arrivals who had a syphilis screening performed, 697 (434 per 100,000) were diagnosed with any stage (infectious or non-infectious) of syphilis. Among the 697 persons with seropositive syphilis, a majority (63%) were from the Africa region and were male (58%), and 53 (7.6%) were diagnosed with an infectious stage of syphilis. All infectious cases were treated prior to resettlement. This information suggests a comparable risk of infection among U.S.-bound refugees compared to a report of syphilis among U.S.-bound refugees from 2009 to 2013, indicating low rates in this population for at least a decade. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate a combined effect of dietary folic acid intake, multiple genetic polymorphisms in folate metabolism, and other environmental factors on red blood cell (RBC) folate concentration in pregnancy-preparing population. Methods: 519 pregnancy-preparing subjects (260 couples) were investigated. Dietary intake was measured by 3-day dietary recalls. 13 Single Nucleotide polymorphisms (SNPs) reported in association with one-carbon metabolism including the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were genotyped. RBC folate concentration was measured using chemiluminescence assay. Hierarchical regression was applied for covariate selection. Factors showed significance(p < 0.0125) on RBC folate level was included for prediction model construction and R2 estimation. Validation cohort analysis was performed as post-hoc analysis if applicable. Results: The median RBC folate was 212.8 ng/ml. Only 10% took folic acid supplementation within three months. Based on hierarchical selection, folic acid supplementation, genetic polymorphism (especially TT genotype of MTHFR C677T), serum folate level were determinants of the variance of RBC folate concentrations, with adjusted R2 of 0.178–0.242. MTHFR A1298C polymorphism, sex difference with other socio-demographic and lifestyle factors (age, BMI, alcohol drinking, smoking, education, occupation) explained little to change in RBC folate level. Validation in another sub-cohort(n = 8105) had adjusted R2 of 0.273. Conclusion: In pregnancy-preparing subjects, folic acid supplementation, serum folate level and TT allele of MTHFR C677T polymorphism were determinants of the total variance of RBC folate level, which explained 19.8% variance in our subjects and 27.3% in the validation cohort. Food folate intake, sex and other environmental factors explained little to RBC folate level. [ABSTRACT FROM AUTHOR]

Background: Systemic sclerosis is a connective tissue disease of unknown etiology, characterized by vasculopathy, fibrosis, inflammation, and immune dysregulation that lead to widespread internal organs fibrosis, chronic ischemia, and subsequent end-stage organ failure. Our purpose was to examine the role of human epididymis protein IV as a biomarker of interstitial lung disease severity in comparison to Krebs von den Lungen-VI glycoprotein and apoprotein A2 among systemic sclerosis patients. Results: There was a highly significant elevation of serum human epididymis protein IV between systemic sclerosis patients (both with and without interstitial lung disease) and the control group (p < 0.001) with the highest value in patients having interstitial lung disease. Krebs von den Lungen-VI and apoprotein A2 also showed a significant difference in their values between the patients' and control groups (p < 0.01 and = 0.02 respectively). Conclusion: The level of human epididymis protein-IV was overexpressed in systemic sclerosis patients with interstitial lung disease in comparison to systemic sclerosis patients without interstitial lung disease indicating its high sensitivity as a potential biomarker in fibrotic activity diagnosis. [ABSTRACT FROM AUTHOR]

Backgrounds: Toxoplasmosis, a prevalent parasitic infection, is primarily caused by Toxoplasma gondii (T. gondii). This infection poses a significant threat to neonates during pregnancy and individuals with compromised immune systems. Consequently, it is imperative to develop a novel diagnostic approach that combines high sensitivity with low-risk sampling to effectively manage patients. The aim of this study is to utilize serological and molecular techniques for the diagnosis of T. gondii infection in 100 pregnant women who were under the care of a gynecologist and were candidates for amniocentesis. Methods: During the 15-19th weeks of pregnancy, a total of 100 samples each of amniotic fluid, buffy coat, plasma, and urine simultaneously were collected from pregnant women candidates for amniocentesis in Mazandaran province, northern Iran. This study involved various assessments: (1) detecting anti-T. gondii IgM and IgG in plasma through chemiluminescence assay (2) determining IgG avidity in plasma using the Enzyme-linked immunosorbent assay technique (3) identifying of T. gondii DNA in amniotic fluid, buffy coat and urine by nested PCR (nPCR) and quantitative real-time PCR (qPCR) methods targeting the REP-529 gene, as well as genotyping using GRA6 target genes, and (4) assessing the sensitivity and specificity of the nPCR and qPCR tests. Results: Out of 100 pregnant women screened, 70 were between the ages of 31 to 40 years old. Among them, 23 and 44 had one and two previous pregnancies. Additionally, 13 and 8 women had one and two history of abortions, respectively. Following serologic testing, 52% of the individuals were positive for T. gondii antibodies. Of these, 52 samples were positive for IgG antibodies, and one sample was positive for both IgG and IgM antibodies. Notably, all 52 cases with IgG positivity exhibited a high level of IgG avidity. Regarding the molecular testing of amniotic fluid samples, two pregnant women tested positive in the nPCR assay, while three tested positive in the qPCR assay. Furthermore, genotyping revealed that all positive samples belonged to type I of the T. gondii genotype. Moreover, none of the 100 buffy coat and urine samples tested positive for T. gondii using the nPCR and qPCR techniques. Conclusion: The findings of the current study suggest that serological methods alone may not be reliable in diagnosing congenital toxoplasmosis and cannot rule out the diagnosis of toxoplasmosis and must be approved by molecular tests. [ABSTRACT FROM AUTHOR]

Objectives Design Setting Animals Interventions Measurements and Main Results Conclusions (1) To compare the results of a rapid test for qualitative detection of cardiac troponin I (cTnI) values >1 ng/mL with those obtained using a reference quantitative method and (2) to perform a semiquantitative assessment of rapid test results using this point‐of‐care (POC) assay.Prospective cross‐sectional study from April 2015 to November 2020.Secondary referral hospital.Eighty dogs and 20 cats, with and without cardiovascular disease.None.Serum samples were obtained, and cTnI rapid test was conducted in parallel with chemiluminescence assay (reference standard). Positive results from the rapid test were further classified as mild and strong positives, based on subjective assessment of the color intensity of the test line. Rapid test was deemed valid in all patients. There was agreement for positive samples between the qualitative and quantitative techniques in 31 dogs and 5 cats, and for negative samples in 43 dogs and 13 cats, resulting in a strong and moderate agreement, respectively. There was a significant difference between color scale groups.The rapid test assessed provides a feasible POC option to determine concentrations of cTnI >1 ng/mL in dogs and cats and shows a moderate to strong agreement with a validated conventional quantitative assay. Furthermore, semiquantitative assessment allows estimation of the magnitude of the elevation. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation To identify biochemical changes in individuals at higher risk of developing amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) via C9orf72 hexanucleotide repeat expansion (HRE) heterozygosity.Cross‐sectional observational study of 48 asymptomatic C9orf72 HRE carriers, 39 asymptomatic non‐carrier controls, 19 people with sporadic ALS, 10 with C9orf72 ALS, 14 with sporadic FTD, and 10 with C9orf72 FTD. Relative abundance of 30 pre‐defined cerebrospinal fluid biomarkers of ALS and FTD were compared in asymptomatic C9orf72 HRE carriers and age‐matched non‐carrier controls. Differential abundance of these proteins was quantified using data independent acquisition mass spectrometry or electro chemiluminescent assay for neurofilament light chain. Unbiased analysis of the entire cerebrospinal fluid proteome was then carried out.Ubiquitin carboxyl‐hydrolase isozyme L1 levels were higher in asymptomatic C9orf72 HRE carriers compared with age‐matched non‐carriers (log2fold change 0.20, FDR‐adjusted p‐value = 0.034), whereas neurofilament light chain levels did not significantly differ. Ubiquitin carboxyl‐hydrolase isozyme L1 levels remained elevated after matching of groups by neurofilament levels (p = 0.011), and after adjusting for age, sex, and neurofilament levels. A significant difference was also observed when restricting analysis to younger participants (<37) matched by neurofilament level (p = 0.007).Elevated cerebrospinal fluid ubiquitin carboxyl‐hydrolase isozyme L1 levels in C9orf72 HRE carriers can occur in the absence of increased neurofilament levels, potentially reflecting either compensatory or pathogenic mechanisms preceding rapid neuronal loss. This brings forward the window on changes associated with the C9orf72 HRE carrier state, with potential to inform understanding of penetrance and approaches to prevention. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Architect-HIV Ag/Ab combo chemiluminescence assay is globally recognized for its sensitivity but has a notable false-positive rate. In this study, we aim to evaluate the performance of a new cost-effective screening alternative, the chemiluminescence Ag/Ab combo assay (CL-900i-HIV) from Mindray, China. We selected 195 archived samples categorized according to the INNO-LIA™ HIV I/II, the gold standard confirmatory assay. These samples included true positive (n = 38; positive by Architect-HIV & INNO-LIA-HIV), true negative (n = 101; negative by Architect-HIV & INNO-LIA-HIV), false positive (n = 20; positive by Architect-HIV & negative by INNO-LIA-HIV), and indeterminate results (n = 26). We tested all samples using the Mindray CL-900i-HIV and all positive Architect-HIV samples (n = 80) were confirmed by PCR. Compared to INNO-LIA™ HIVI/II line immunoassay confirmatory assay, Mindray CL-900i-HIV demonstrated a sensitivity of 100% (95% CI 90.7–100), specificity of 100% (95% CI 97.0–100), overall percent agreement (OPA) of 100% (95% CI 97.7–100.0), and perfect agreement with the INNO-LIA confirmatory assay (κ = 1.00). Additionally, Mindray's CL-900i-HIV exhibited a significantly lower false-positive rate (8.75%) compared to Architect-HIV's (55%). Mindray CL900i demonstrated high sensitivity and very low false-positive rate, thus, has the potential to serve as an excellent, cost-effective surrogate for HIV screening, overcoming the limitations of existing automated assays. [ABSTRACT FROM AUTHOR]

The results reported herein demonstrate for the first time that typical reducing agents in an alkaline medium initiate chemiluminescence of luminol in the presence of hemin, and the efficiency of their action is comparable to that of hydrogen peroxide and exceeds it in the case of the superoxide anion. The pertinent implications of these findings refer to new possibilities for developing chemiluminescence assays and biosensors and to precautions for determining hydrogen peroxide using luminol and hemin in samples of unknown composition, most prominently, of biological origin. [ABSTRACT FROM AUTHOR]

Antioxidant substances which can diminish the steady‐state concentration of free radicals in vivo are important in the human dietary to diminish the deleterious effects of oxidative stress. As the potential of certain substances as antioxidants is difficult to be verified in vivo, simple chemical in vitro assays which test the potential of substances as antioxidants are of great importance for the screening of new antioxidants. These assays measure the capacity of a substance to suppress free radicals. We describe here an antiradical capacity assay, based on luminol chemiluminescence, in cationic micellar medium, allowing the capacity determination of hydrophobic compounds. The antiradical capacity of antioxidants is determined using the Trolox standard by the measurement of the light emission inhibition area caused by the addition of different antiradical concentrations. The obtained results are compared to the values determined using the scavenging of stable free radicals be the substances and shown to be similar for compounds like uric acid, rutin, and quercetin. However, for vitamin E, the luminol assay results in a considerably higher antiradical capacity than the assay with a stable free radical, which is rationalized by the higher reactivity of the radical generated in the luminol assay and a specific localization of vitamin E in the micellar medium. [ABSTRACT FROM AUTHOR]

Background Growth differentiation factor 15 (GDF-15) holds promise as a novel marker for heart failure. However, current detection methods fall short of meeting essential clinical requirements. Objectives The aim of this investigation was to assess the clinical significance of serum GDF-15 detection through the chemiluminescence method and to enhance its clinical application for predicting and evaluating heart failure in patients. Methods A total of 122 patients were included in the study. Serum GDF-15 levels were assessed using the chemiluminescence method and compared with results for NT-proBNP, N-terminal pro-brain natriuretic peptide (NT-proBNP), growth stimulation expressed gene 2 (ST2), high-sensitivity C-reactive protein (hs-CRP), and left ventricular ejection fraction (LVEF). Additionally, we conducted an analysis to evaluate the correlation between these indicators and heart failure events. Results LVEF, ST2, NT-proBNP, and GDF-15 exhibited significant associations with heart failure. In the multivariate proportional hazard analysis, subsequent to adjusting for the effects of other markers, however, only LVEF and GDF-15 retained their associations with heart failure events. Notably, GDF-15 emerged as the exclusive marker suitable for diagnosing heart failure with preserved ejection fraction. Conclusion The chemiluminescence method proved efficient in the rapid and sensitive detection of GDF-15 in patients with heart failure. Additionally, GDF-15 combined with other markers created a robust multi-index model. This model is valuable for heart failure diagnosis, treatment, and monitoring, with broad clinical applicability. [ABSTRACT FROM AUTHOR]

The article discusses a study aimed at understanding the dynamics of neutralizing antibodies (NAb) and S-receptor binding protein (SRBD) antibodies in individuals receiving the BNT162b2 mRNA COVID-19 vaccine. Topics include the study's objective to examine factors influencing antibody levels after vaccination, the methods used in the study, including a cohort of 243 healthcare workers, and the importance of identifying strategies for antibody assay testing to improve clinical practices.

The issue of the qualitative and quantitative analysis of the concentration of oxidising species in aquatic environments is crucial for a wide range of biological and environmental tasks. In particular, reactive chlorine species, specifically hypochlorite (ClO−), play a significant biochemical role in the operation of the immune system. There is also the challenge of determining the presence of ClO− in purified drinking water that is supplied by water treatment systems. Traditional chemical analytical methods often lack the required selectivity and sensitivity to detect oxidising compounds, and chemiluminescence-based techniques offer an alternative solution. In this study, we propose a simple and selective approach for the chemiluminescent detection of hypochlorite in aqueous media under neutral conditions. The technique is based on measuring a chemiluminescent signal generated in the presence of hypochlorite by a combined probe comprising commercially available WS2 quantum dots and luminol. The oxidation of WS2 with hypochlorite followed by a reaction with luminol results in an intense luminescent signal that enables the selective determination of hypochlorite under neutral conditions. The greatest sensitivity with this method was achieved when combining WS2 quantum dots with L-012, a highly sensitive analogue of luminol. Additionally, the use of L-012 improved the detection limit for hypochlorite to 2 × 10−6 M. Due to its selectivity in determining hypochlorite in the presence of reactive oxygen species (hydrogen peroxide) under neutral conditions with high sensitivity and with a wide linear range, the proposed approach provides an attractive analytical tool for the analysis of water samples and biological liquids. [ABSTRACT FROM AUTHOR]

Background: Homocysteine (HCY) is a sulfur-containing amino acid that is an independent or important risk factor for the occurrence of many chronic diseases and is one of the most important indicators for determining health risks. However, existing HCY detection methods do not meet the requirements of clinical diagnosis. Therefore, there is an urgent need to establish new detection methods to meet the needs of clinical detection. Results: In this study, we used the principle of competitive method to establish a new method for the determination of HCY in human serum using a chemiluminescent enzyme immunoassay in conjunction with a chemiluminescent assay instrument that uses magnetic microparticles as the solid phase of the immunoreaction. The established method achieved satisfactory results in terms of minimum detection limit, specificity, accuracy, and clinical application. The limit of detection was 0.03 ng/mL. The intra-assay coefficient of variation (CV) was 1.94–5.05%, the inter-assay CV was 2.29–6.88%, and the recovery rate was 88.60–93.27%. Cross-reactivity with L-cysteine ranged from 0.0100 to 0.0200 μmol/L, and cross-reactivity with glutathione ranged from 0.0100 to 0.200 μmol/L, all of which were less than the limit of detection (LoD) of this method. The linear factor R of this method was greater than 0.99. Conclusions: In summary, the developed method showed a good correlation with the product from Abbott. A total of 996 clinical patients with cardiovascular diseases were evaluated using the method developed in this study. [ABSTRACT FROM AUTHOR]

Chemiluminescence is the emission of light that occurs as a result of a chemical reaction. Depending on the rate of chemiexcitation, light emission can occur as a long‐lasting, low‐intensity, glow‐type reaction or a rapid, highly intense flash‐type reaction. Assays using a flash‐type mode of action provide enhanced detection sensitivity compared to those using a glow‐type mode. Recently, our group discovered that applying spiro‐strain to 1,2‐dioxetanes significantly increases their chemiexcitation rate, thereby transforming glow‐type chemiluminescence into flash‐type chemiluminescence. However, further examination of the structure‐activity relationships revealed that the spiro‐strain severely compromises the chemical stability of the 1,2‐dioxetanes. We hypothesized that a combination of spiro‐strain, steric hindrance, and an electron‐withdrawing effect, will result in a chemically stable spiro‐strained dioxetane with an accelerated chemiexcitation rate. Indeed, spiro‐fused tetramethyl‐oxetanyl exhibited a 128‐fold faster chemiexcitation rate compared to adamantyl while maintaining similar chemical stability, with a half‐life of over 400 hours in PBS 7.4 buffer at room temperature. Turn‐on probes composed of tetramethyl‐oxetanyl spiro‐dioxetane exhibited significantly improved chemical stability in bacterial and mammalian cell media compared to previously developed dioxetane probes fused to a cyclobutyl unit. The superior chemical stability enables a tetramethyl‐oxetanyl dioxetane probe to detect β‐Galactosidase (β‐gal) activity with enhanced sensitivity in Escherichia coli (E. coli) bacterial assays and leucine aminopeptidase activity in tumoral cell lines. Overall, the development of the tetramethyl‐oxetanyl dioxetane luminophore enables us to enhance the detection sensitivity of chemiluminescent probes while maintaining high chemical stability. The results obtained in this study should assist in designing improved chemiluminescent probes and underscore the significance of strain‐release techniques in enhancing the detection sensitivity of chemiluminescence assays. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) may complicate the course of systemic autoimmune rheumatic disease (SARD) and diagnostic biomarkers are needed. Krebs von den Lungen-6 (KL-6), ferritin (FER) and interleukin 6 (IL-6) have been involved in the ILD development. Our study aimed to compare KL-6, FER, IL-6 and soluble mesothelin-related peptide (SMRP) concentrations in a cohort of idiopathic and SARD-ILD. Methods: 3169 patients were enrolled in the "UK Biomarkers in Interstitial Lung Disease (UK-BILD) Study". We selected patients affected by SARD-ILD and idiopathic ILD (usual interstitial pneumonia-idiopathic pulmonary fibrosis and fibrotic non-specific interstitial pneumonia). Serum marker concentrations were measured through chemiluminescent assays (Fujirebio Europe, Ghent, Belgium). Results: 1013 patients were selected for the study: 520 (51.3%) had idiopathic ILD and 493 (48.7%) SARD-ILD. Idiopathic ILD patients displayed higher KL-6 values than SARD-ILD (p = 0.0002). FER and SMRP, though within normal ranges, were significantly higher in idiopathic ILD (p<0.0001). Logistic regression showed good sensitivity (69.4%) and specificity (80.4%) selecting the variables FER and KL-6 concentrations, age and gender-male correlated with a diagnosis of idiopathic ILD. Conclusion: Our study showed the excellent diagnostic value of KL-6 for detecting ILD, which irrespective of the final diagnosis and extent of disease, is always elevated and is a reliable biomarker of lung fibrosis in various diseases, ranging from idiopathic to autoimmune forms. Our study proposed an ILD differentiation model including clinical background. In this context, combination of serum markers and clinical data, as seen in our cohort, may lead to a further improvement in diagnostic accuracy for ILD. [ABSTRACT FROM AUTHOR]

Introduction: Reducing cardiopulmonary bypass (CPB) induced inflammatory injury is a potentially important strategy for children undergoing multiple operations for single ventricle palliation. We sought to characterize the soluble receptor for advanced glycation end products (sRAGE), a protein involved in acute lung injury and inflammation, in pediatric patients with congenital heart disease and hypothesized that patients undergoing single ventricle palliation would have higher levels of sRAGE following bypass than those with biventricular physiologies. Methods: This was a prospective, observational study of children undergoing CPB. Plasma samples were obtained before and after bypass. sRAGE levels were measured and compared between those with biventricular and single ventricle heart disease using descriptive statistics and multivariate analysis for risk factors for lung injury. Results: sRAGE levels were measured in 40 patients: 19 with biventricular and 21 with single ventricle heart disease. Children undergoing single ventricle palliation had a higher factor and percent increase in sRAGE levels when compared to patients with biventricular circulations (4.6 vs. 2.4, p = 0.002) and (364% vs. 181%, p = 0.014). The factor increase in sRAGE inversely correlated with the patient's preoperative oxygen saturation (Pearson correlation (r) = −0.43, p = 0.005) and was positively associated with red blood cell transfusion (coefficient = 0.011; 95% CI: 0.004, 0.017; p = 0.001). Conclusions: Children with single ventricle physiology have greater increase in sRAGE following CPB as compared to children undergoing biventricular repair. Larger studies delineating the role of sRAGE in children undergoing single ventricle palliation may be beneficial in understanding how to prevent complications in this high-risk population. [ABSTRACT FROM AUTHOR]

Objective: To explore the distribution of thrombin–antithrombin complex (TAT), plasmin-α2-antiplasmin inhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) in healthy older Chinese adults, and establish the reference intervals (RIs). Methods: The Biotech Shine i2900 chemiluminescence immune assay was used to measure the plasma concentrations of TAT, PIC, TM, and t-PAIC in 1628 adults ≥ 60 years. The RIs were established using the 2.5th and 97.5th percentiles of the distribution. Results: TAT levels were lower in males than females across all ages. Differences between the ages of 60–79 and ≥ 80 in both sex groups were statistically significant, with an upward trend with age. PIC levels showed no difference between the sexes but increased with age in both groups. TM levels did not differ between the sex groups, with slight fluctuation with age. The level in females aged 60–69 was slightly higher than that in the other groups; the difference was statistically significant. T-PAIC levels were not significantly different between the sex groups, with less fluctuation with sex and age. The level in males ≥ 80 years old was slightly lower than that in the other groups; the difference was statistically significant. The RIs for all markers in healthy older Chinese adults were determined and statistically reported by age and sex. For TAT, the RIs for males aged 60–79 and ≥ 80 are 0.51–2.30 ng/mL and 0.88–3.72 ng/mL, respectively, whereas for females aged 60–79 and ≥ 80, the RIs are 0.68–2.82 ng/mL and 1.02–3.67 ng/mL, respectively. For PIC, the RIs for the age groups 60–69, 70–79, and ≥ 80 are 0.10–0.89 µg/mL, 0.12–1.00 µg/mL, and 0.21–1.04 µg/mL, respectively. The RI of TM for females aged 60–69 is 3.32–13.22 TU/mL, whereas it is 2.96–13.26 TU/mL for the other groups. The RI of t-PAIC for males aged ≥ 80 is 1.63–10.68 ng/mL, whereas it is 2.33–11.34 ng/mL for the other groups. Conclusions: Discrepancies exist in thrombus markers among different sex and age groups. The RIs of TAT, PIC, TM and t-PAIC for healthy older Chinese adults were successfully established. [ABSTRACT FROM AUTHOR]

Development of novel abrasive systems with functional activities and physicochemical properties are of great significance in the reactive oxygen species (ROS)-enhanced chemical mechanical polishing. In this work, Ce single-doped and Ce/Cu co-doped dendritic mesoporous silica nanoparticles (DMSNs), namely Ce−DMSNs and Ce/Cu−DMSNs, were produced via a simple impregnation and thermolysis procedure. The Ce and/or Cu species involved in DMSNs frameworks were characterized through X-ray diffractometry, infrared spectroscopy, scanning electron microscopy, energy dispersive spectrometry, transmission electron microscopy, X-ray photoelectron spectroscopy, and nitrogen adsorption/desorption techniques. We report the evolution of surface morphology and roughness, defects, peak-to-valley data, image surface area difference, and material removal efficiency during ROS-enhanced polishing experiments toward silica materials. All the pure, Ce single-doped, and Ce/Cu co-doped DMSNs abrasive systems offered nearly defect-free surfaces with close-to-atom scale roughness. It might be attributed to the "springlike effect" and "soft polishing/abrasion", possibly originating from the low-modulus DMSNs carriers. Among these abrasives, the Ce/Cu co-doped DMSNs systems achieved an evident improvement in removal efficiency, especially under ultraviolet irradiation-assisted polishing conditions. The coexisted Ce(Ⅲ)/Ce(Ⅳ) and Cu(Ⅰ)/Cu(Ⅱ) couples might be responsible for the effective production of ROS in photocatalysis and Fenton-like processes, thereby contributing to the Si–OH and Ce(Ⅲ)−O–Si bonding formations. The role of the developed Ce/Cu co-doped DMSNs abrasive systems in ROS-enhanced polishing processes was discussed. [ABSTRACT FROM AUTHOR]

Background: The identification of benign and malignant pulmonary nodules (BPN and MPN) can significantly reduce mortality. However, a reliable and validated diagnostic model for clinical decision-making is still lacking. Methods: Enzyme-linked immunosorbent assay and electro chemiluminescent immunoassay were utilized to determine the serum concentrations of 7AABs (p53, GAGE7, PGP9.5, CAGE, MAGEA1, SOX2, GBU4-5), and 4TTMs (CYFR21, CEA, NSE and SCC) in 260 participants (72 BPNs and 188 early-stage MPNs), respectively. The malignancy probability was calculated using Artificial intelligence pulmonary nodule auxiliary diagnosis system, or Mayo model. Along with age, sex, smoking history and nodule size, 18 variables were enrolled for model development. Baseline comparison, univariate ROC analysis, variable correlation analysis, lasso regression, univariate and stepwise logistic regression, and decision curve analysis (DCA) was used to reduce and screen variables. A nomogram and DCA were built for model construction and clinical use. Training (60%) and validation (40%) cohorts were used to for model validation. Results: Age, CYFRA21_1, AI, PGP9.5, GAGE7, and GBU4_5 was screened out from 18 variables and utilized to establish the regression model for identifying BPN and early-stage MPN, as well as nomogram and DCA for clinical practical use. The AUC of the nomogram in the training and validation cohorts were 0.884 and 0.820, respectively. Moreover, the calibration curve showed high coherence between the predicted and actual probability. Conclusion: This diagnostic model and DCA could provide evidence for upgrading or maintaining the current clinical decision based on malignancy probability stratification. It enables low and moderate risk or ambiguous patients to benefit from more precise clinical decision stratification, more timely detection of malignant nodules, and early treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Total thyroidectomy and dissection of cervical lymph node compartments, depending on serum calcitonin levels and ultrasound findings, is standard treatment for patients with medullary thyroid cancer. The aim of this study was to evaluate whether pre-operative calcitonin and CEA levels can be useful as biomarkers of the extent of lymph node metastases at diagnosis. Results indicate that pre-operative serum calcitonin and CEA levels can predict presence, number, and site of lymph node metastases and, more specifically, values of 90 pg/mL for calcitonin and 17 ng/mL for CEA accurately indicate the N1b status. Since surgery is the only curative treatment for medullary thyroid cancer and there is not a strong indication regarding the extent of lymphadenectomy, these findings may help in the choice of the extent of neck dissection. Background: In medullary thyroid cancer (MTC), lymph node metastases are often present at diagnosis and the extent of surgery is usually based upon pre-operative calcitonin and CEA levels as well as ultrasound findings. The aim of this study was to evaluate the role of pre-operative calcitonin and CEA levels as predictive markers of the burden of lymph node metastases at diagnosis. Methods: we conducted a retrospective study analyzing 87 MTC patients. Results: The median levels of calcitonin and CEA were 88.4 pg/mL and 7.0 ng/mL, respectively, in patients with no lymph nodes metastases; 108.0 pg/mL and 9.6 ng/mL, respectively, in patients with metastases to 1–5 lymph nodes; 520.5 pg/mL and 43.2 ng/mL, respectively, in patients with metastases to >5 lymph nodes. There were no significant differences in pre-operative calcitonin and CEA values between N0 and N1a patients, whereas they were significantly higher in N1b patients. Pre-operative cut-off levels distinguishing N0/N1a from N1b patients were 90 pg/mL for calcitonin (sensitivity 100%, specificity 59.3%, AUC = 0.82) and 17 ng/mL for CEA (sensitivity 100%, specificity 75%, AUC = 0.89). Conclusions: in patients with MTC, pre-operative serum calcitonin and CEA levels may drive the decision-making process to better define the extent of surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: The diagnostic value of anti-Müllerian hormone (AMH) is well established but less is known about physiological concentrations in young individuals. The aim of this study was to determine AMH levels in small animals before and around puberty and to correlate these levels with testosterone in males entering puberty. Blood samples were collected between 2 and 48 weeks after birth for AMH and testosterone measured using a chemiluminescence immune assay. AMH concentrations were higher in males than in females, with no significant differences among male individuals. However, queens had significantly higher AMH concentrations compared to bitches. A significant decreased in AMH was observed in the males beginning 24 weeks after birth, which correlated only in dogs with an increase in testosterone. In bitches, AMH remained below the detection limit until 16 weeks after birth after which it increased slightly. In queens, AMH was detectable from week 2 with a significant increase starting at week 8, even approaching the chemiluminescence immune assay's upper limit. In conclusion, queens secreted AMH much earlier and in significantly higher amounts than bitches. The decrease of AMH in male species entering puberty was observed in both dogs and tomcats, but a negative correlation with testosterone was derived only for male dogs. In recent years several studies established the diagnostic value of anti-Müllerian hormone (AMH) in companion animals. However, less is known about physiological AMH concentrations in young individuals highlighting the necessity to apply the diagnostic findings to this group. The aim of this study was to determine the AMH values of healthy male and female dogs between the age of 8 and 48 weeks, tomcats under 8 weeks and up to 48 weeks of age and queens between 2 to 12 weeks of age. In total, 96 blood samples were collected. Anti-Müllerian hormone was measured in all samples and testosterone was measured in the oldest age group of the males in both species. The hormones were analyzed using a human based chemiluminescence immune assay. Overall, AMH concentrations were higher in males than in females (p < 0.001). According to the AMH concentration there was no difference in males, but queens had significant higher AMH concentrations than bitches (p < 0.001). AMH remained high in males up to week 24 and decreased significantly thereafter (tomcats: p = 0.015; male dogs: p = 0.013), which correlated with an increase in testosterone levels for male dogs only. In bitches, AMH remained below the detection limit until the week 16 and slightly increased subsequently. In queens, AMH was detectable from the beginning with a significant increase in the older age group (p = 0.003). Half of the cats in the older age group even approached the chemiluminescence immune assay's upper limit. The results show that female cats secrete AMH much earlier than female dogs in which AMH secretion begins just shortly before the start of the puberty. In the male animals, the decrease in AMH concentration around puberty was similar in dogs and cats, but a correlation with the increase of testosterone was only observed in dogs. Further research is required to determine the origin of the high AMH concentrations in female kittens and the lack of correlation between testosterone and AMH concentrations in male kittens. [ABSTRACT FROM AUTHOR]

Background: Pauci‐immune glomerulonephritis (GN) due to antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is a common cause of crescentic GN. Despite advances in treatment, rates of mortality and progression to end‐stage kidney disease remain high. Renal involvement is diagnosed by histological examination of kidney tissue. Serum ANCAs play a significant role in AAV; however, the value of serum ANCA quantification to predict renal involvement is not well‐established. Aim: We aimed to evaluate the diagnostic accuracy of serum ANCA titres in diagnosing AAV with renal involvement. Methods: We conducted a retrospective study of consecutive native kidney biopsies reported at our centre from 2016 to 2021. We included all adults who had both a kidney biopsy and ANCA serology. ANCA serology was tested using indirect immunofluorescence with reporting of titres. Antibodies to proteinase 3 and myeloperoxidase were measured using a chemiluminescent immunoassay. Results: Eight hundred and forty‐eight native kidney biopsies were reported during the study period. Five hundred and seven cases were included. The biopsy prevalence of pauci‐immune GN in paired samples was 41/507 (8.1%). Most of the cohort had haematuria (66.6%), proteinuria (93.4%) and/or acute kidney injury (65.0%). A positive ANCA at any titre demonstrated a sensitivity of 97.6% and a specificity of 71.2% for a diagnosis of pauci‐immune GN. The area under the curve for the receiver operator characteristic was 0.93 (95% confidence interval [CI]: 0.89–0.97). A cutoff ANCA titre of 1:160 provided the optimum balance between a sensitivity of 75.6% (95% CI: 59.7%–87.6%) and a specificity of 94.0% (95% CI: 91.6%–96.0%). Conclusions: ANCA titres are highly predictive of pauci‐immune GN in the appropriate context. While serum ANCA quantitation may not replace renal biopsy, reporting will assist in the decision to start treatment early for patients with organ or life‐threatening disease. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress (OxSt) and inflammation are common in CKD and are known CV and mortality risk factors. In peritoneal dialysis (PD) OxSt and Inflammation even increase due to the use of glucose‐based solutions. Patients and Methods: This study analyzed in 15 PD patients the effect of 3 and 6 months of treatment with icodextrin‐based glucose‐free solutions on OxSt and inflammation, evaluating p22phox protein expression (Western blot), NADPH oxidase subunit, essential for OxSt activation, MYPT‐1 phosphorylation state, marker of RhoA/Rho kinase pathway (ROCK) activity, involved in the induction of OxSt (Western blot) and Malondialdehyde (MDA) production (fluorimetric assay). Interleukin (IL)‐6 blood level (chemiluminescence assay) has been measured and used as a marker of inflammation. Results: p22phox protein expression, MYPT 1 phosphorylation, and MDA were reduced after 3 months from the start of icodextrin (1.28 ± 0.18 d.u. vs. 1.50 ± 0.19, p = 0.049; 0.89 ± 0.03 vs. 0.98 ± 0.03, p = 0.004; 4.20 ± 0.18 nmol/mL vs. 4.84 ± 0.32 nmol/mL, p = 0.045, respectively). In a subgroup of 9 patients who continued the treatment up to 6 months, MYPT‐1 phosphorylation was further reduced at 6 months compared to baseline (0.84 ± 0.06 vs. 0.99 ± 0.04, p = 0.043), while p22phox protein expression was reduced only at 6 months versus baseline (1.03 ± 0.05 vs. 1.68 ± 0.22, p = 0.021). In this subgroup, MDA was reduced at 6 months versus baseline (4.03 ± 0.24 nmol/mL vs. 4.68 ± 0,32, p = 0.024) and also versus 3 months (4.03 ± 0.24 vs. 4.35 ± 0.21, p = 0.008). IL‐6 level although reduced both at 3 and 6 months, did not reach statistical significance. Conclusions: The reduction of OxSt with icodextrin‐based PD solutions, although obtained in a small patients cohort and in a limited time duration study, strongly supports the rationale of using osmo‐metabolic agents‐based fluids replacing glucose‐based fluids. Ongoing studies with these agents will provide information regarding preservation of peritoneal membrane integrity, residual renal function, and reduction of CVD risk factors such as OxSt and inflammation. [ABSTRACT FROM AUTHOR]

Background: Vitamin B12 deficiency is widely prevalent in all age groups which is of major concern. However, there is no valid Food Frequency Questionnaire (FFQ) for dietary vitamin B12 estimation. Hence, we aimed to develop and validate an FFQ for the estimation of dietary intake of Vitamin B12. Materials and Methods: Commonly consumed B12-rich food items were selected from literature and filtered using a market survey. For concordant and discriminant validation, B12 and homocysteine levels were estimated. To establish convergent validity, the Cobalamin Intake in North Indians by Food Frequency Questionnaire (COIN-FFQ) and 72-hour dietary recall (72HrDR) were both administered to the same subjects. The COIN-FFQ was readministered after initial administration for test-retest reliability. Internal consistency of the FFQ was then tested using Cronbach's alpha. Results: We enrolled 115 adults with a mean age and weight of 31.9 ± 8.7 years and 66.0 ± 11.8 kg, respectively. In total, 19.1% were vegetarian. The dietary B12 using COIN-FFQ (n = 60; mean = 4.3 ± 1.8 µg/d) was significantly correlated (r = 0.255; P = 0.049) with serum levels (mean = 120.1 ± 62.6 pmol/L) establishing concordant validity. A significant difference was noted between the dietary, serum B12, and homocysteine levels of vegetarians versus nonvegetarians establishing discriminant validity (mean diff 1.4 (0.5-2.4), P = 0.004; Z-statistic -2.182, P value 0.029, and Z-statistic -2.438; P value 0.015), respectively. FFQ was strongly correlated with 72HrDR and test--retest FFQ (n = 27; r = 0.814, P < 0.001 and r = 0.869, P < 0.001, respectively) establishing convergent validity and test--retest reliability. The internal consistency with Cronbach's alpha was in the acceptable range, 0.631 (n = 115). Conclusion: The newly developed COIN-FFQ is valid and reliable in estimating dietary B12 intake. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is a life-threatening multisystem disorder of pregnancy which has been observed in 2%–10% of pregnancies. The prevalence of Vitamin D deficiency ranges from 15% to 80%. Deficiency of Vitamin D is associated with the development of preeclampsia. This study was done to find out the prevalence of Vitamin D deficiency among preeclamptic/eclamptic and normal pregnant females, to establish Vitamin D deficiency as a causal factor of preeclampsia, and to elucidate the relation between 25 (OH) Vitamin D status and the severe preeclampsia. Materials and Methods: Blood samples were collected from 50 normotensives (controls) and 50 hypertensive pregnant females with preeclampsia/eclampsia (cases), and 25 (OH) Vitamin D level was measured by chemiluminescence Immunoassay. Results: Among the preeclamptic/eclamptic group, 32 (64%) were noted with Vitamin D deficiency and 18 (36%) with Vitamin D insufficiency. In the control group, 30 (60%) pregnant women showed Vitamin D deficiency, 19 (38%) with Vitamin D insufficiency, and a sufficient level of Vitamin D was observed in one woman (2%). Conclusion: Although it is difficult to demonstrate the correlation between Vitamin D levels and preeclampsia, there is a widespread global prevalence of Vitamin D deficiency during pregnancy. Hence, Vitamin D supplementation can be included routinely in the antenatal care program in India. [ABSTRACT FROM AUTHOR]

The safety of the mRNA and inactivated SARS-CoV-2 vaccine has been demonstrated for people living with HIV (PLHIV). However, vaccine studies in PLHIV are limited, and there is a gap in which vaccine type provides the best response in PLHIV. Thus, PLHIV may benefit from mRNA vaccine types compared to inactivated vaccines. This study aims to assess the immune responses to vaccination by measuring specific antibodies (IgG) targeting the receptor binding sites (RBDs) of the SARS-CoV-2 virus and the levels of IL-2 and IFN-γ in plasma. A total of 41 PLHIV who regularly take antiretroviral therapy (ART) over a period of six months, along with 31 individuals in a healthy control group (HC), were administered either two mRNA or inactivated vaccines. Data regarding demographics and clinical information were gathered from the medical records. An analysis was conducted on the neutralisation antibody IgG specific to RBD using the chemiluminescence microparticle assay (CMIA). The levels of IL-2 and IFN-γ were quantified using the Luminex assay method from plasma samples. Data were collected in the laboratory 28 days after each vaccination. After the first vaccination, the level of anti-SARS-CoV-2 RBD IgG was higher in PLHIV who received the mRNA vaccines than those who received inactivated vaccines (p = 0.006). The levels of mRNA in the PLHIV group showed a significant correlation with IL-2 and IFN-γ after the second vaccination (r = 0.51, p = 0.0035; r = 0.68, p = 0.002). The group of PLHIV who received the inactivated vaccine showed increased IL-2 and IFN-γ after the initial vaccination, compared to PLHIV who received the mRNA vaccine (p = 0.04; p = 0.08). Administering a two-dose vaccination is essential to increase the levels of neutralising antibodies significantly (p = 0.013) in PLHIV who have received inactivated vaccines; further study is needed to make this a recommendation. The responses observed after vaccination in PLHIV were not affected by their CD4 cell counts. PLHIV showed higher levels of SARS-CoV-2 IgG and increased IL-2 and IFN-γ levels. Our study encourages SARS-CoV-2 vaccination in PLHIV regardless of its CD4 cell counts. Furthermore, the mRNA vaccine may give robust high antibody responses in PLHIV. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency (VDD) is conventionally associated with inadequate sunlight exposure. Ironically, recent evidence suggests a rising prevalence in urban areas of tropical regions like Sri Lanka, where comprehensive data are unavailable. This study aimed to estimate the prevalence of low vitamin D status in urban adults and its impact on serum calcium. Methods: A population-based cross-sectional study was conducted among 1260 adults aged 35–74 years, living in Colombo, the most urban district in Sri Lanka. They were recruited from 63 administrative divisions, using multi-stage, probability-proportionate-to-size, cluster sampling. Non-fasting venous blood was collected without tourniquet. Low vitamin D (< 30.0 ng/mL), VDD (< 20 ng/mL) and vitamin D insufficiency (20.0–29.9 ng/mL) were determined using chemiluminescence assay method, and serum calcium using Calcium Gen2 reagent. Results: Among the population (53.3% females; mean age = 51.8 years), the prevalence of low vitamin D was 93.9% (95% CI: 92.5–95.2). This was primarily due to VDD (67.5%; 95% CI: 64.9.0–70.1%), with some insufficiency (26.4%; 95% CI: 24.0–28.9%). Most VDD cases (53.9.0%) were 'mild' (10.0- < 20.0 ng/mL) in severity, with fewer 'moderate' (12.8%) and 'severe' (0.8%) cases. Prevalence of VDD was highest in females, aged 35–44-years, living in 'highly urban' areas and of Tamil ethnicity. Further, VDD showed a decreasing trend with older age groups, while it was significantly more prevalent in females than males (72.6% vs. 61.7%; p < 0.01), across all age groups. Low serum calcium levels were observed in 9.8% of adults with low vitamin D, compared to 22.4% with normal vitamin D, implying that there could be factors other than vitamin D in maintaining serum calcium levels. Conclusions: Colombo District, representing urban settings in Sri Lanka faces a high prevalence of low vitamin D, primarily VDD, with higher rates in females, younger individuals and highly urban areas. These findings challenge assumptions about tropical regions being guaranteed of optimal vitamin D levels; and underscore the need for national vitamin D supplementation and food fortification programs, especially in high-risk urban settings in South Asian countries like Sri Lanka. [ABSTRACT FROM AUTHOR]

Background: Nitric oxide (NO) is a strong vasodilator, selectively directed on pulmonary circulation through inhaled administration. In adult intensive care units (ICU), it is mainly used for refractory hypoxemia in mechanically ventilated patients. Several medical delivery devices have been developed to deliver inhaled nitric oxide (iNO). The main purpose of those devices is to guarantee an accurate inspiratory NO concentration, whatever the ventilator used, with NO2 concentrations lower than 0.3 ppm. We hypothesized that the performances of the different available iNO delivery systems could depend on their working principle and could be influenced by the ventilator settings. The objective of this study was to assess the accuracy of seven different iNO-devices combined with different ICU ventilators' flow-by to reach inspiratory NO concentration targets and to evaluate their potential risk of toxicity. Methods: We tested seven iNO-devices on a test-lung connected to distinct ICU ventilators offering four different levels of flow-by. We measured the flow in the inspiratory limb of the patient circuit and the airway pressure. The nitric oxide/nitrogen (NO/N2) flow was measured on the administration line of the iNO-devices. NO and NO2 concentrations were measured in the test-lung using an electrochemical analyzer. Results: We identified three iNO-device generations based on the way they deliver NO flow: "Continuous", "Sequential to inspiratory phase" (I-Sequential) and "Proportional to inspiratory and expiratory ventilator flow" (Proportional). Median accuracy of iNO concentration measured in the test lung was 2% (interquartile range, IQR -19; 36), -23% (IQR -29; -17) and 0% (IQR -2; 0) with Continuous, I-Sequential and Proportional devices, respectively. Increased ventilator flow-by resulted in decreased iNO concentration in the test-lung with Continuous and I-Sequential devices, but not with Proportional ones. NO2 formation measured to assess potential risks of toxicity never exceeded the predefined safety target of 0.5 ppm. However, NO2 concentrations higher than or equal to 0.3 ppm, a concentration that can cause bronchoconstriction, were observed in 19% of the different configurations. Conclusion: We identified three different generations of iNO-devices, based on their gas administration modalities, that were associated with highly variable iNO concentrations' accuracy. Ventilator's flow by significantly impacted iNO concentration. Only the Proportional devices permitted to accurately deliver iNO whatever the conditions and the ventilators tested. [ABSTRACT FROM AUTHOR]

Introduction: Oligomeric alpha-synuclein in red blood cells (RBC-o-α-Syn) has been shown to be increased in patients with Parkinson's disease (PD). However, factors that affect RBC-o-α-Syn levels remain to be elucidated. The aim of this study is to analyze the correlations between RBC-o-α-Syn levels and the age, sex and different clinical variables of patients with PD. Methods: 167 patients with PD and 119 healthy controls (HC) were enrolled in this study. The patients with PD were diagnosed based on the MDS clinical diagnostic criteria for PD. All participants were evaluated for their clinical characteristics. Western blot analysis was used to examine the molecular sizes of RBC-o-α-Syn. A newly established chemiluminescent immunoassay was used to measure RBC-o-α-Syn levels. Results: Higher RBC-o-α-Syn levels were detected in PD patients than in HC subjects. The receiver operating characteristic (ROC) curve indicated that a cut off value of 55.29 ng/mg discriminated well between PD patients and HC subjects, with a sensitivity of 67.66% (95% CI: 60.24-74.29%), a specificity of 88.24% (95% CI: 81.22-92.86%), and an area under the curve (AUC) of 0.857. The levels of RBC-o-α-Syn were higher in female than male patients (p = 0.033). For different subtypes, the levels of RBC-o-α-Syn were higher in the MIX subtype than the tremor-dominant (TD) PD. In addition, the levels of RBC-o-α-Syn were higher in patients with than without cognitive impairment (p = 0.016), and negatively correlated with Mini-Mental State Examination (MMSE) scores (r = -0.156, p = 0.044). Conclusion: Our study demonstrates that RBC-o-α-Syn levels in patients with PD are higher than those in HC subjects and affected by the sex and the severity of cognitive impairment. [ABSTRACT FROM AUTHOR]

Background and Objectives: Thyroid disorders are one of the most common endocrine disorders affecting 4-5% of the general population. The objective of study is to evaluate the predictive value of preoperative serum TSH levels in predicting malignancy in nodular thyroid diseases. Methods: It is a longitudinal study of 28 patients with thyroid swelling admitted to surgery department in a tertiary care referral hospital, during the period of January 2011 to December 2011. Thyroid function tests were done by standard electro chemiluminescent assay and serum TSH levels, age, sex were compared with malignancy. Logistic regression analysis was used to determine which factors were predictive of malignancy. Results: 28 cases were analysed. Mean TSH levels were higher in the malignant group and in the age group of 50-65 yrs. Prevalence of malignancy was studied in the all TSH groups and it was found that the higher quartiles of serum TSH levels were found to be associated with increased risk of malignancy. Logistic regression analysis revealed that TSH levels was the only significant risk factor for malignancy. Conclusion: the serum TSH level may be useful in predicting the probability of cancer and optimizing the extent of thyroidectomy in patients with NTD. [ABSTRACT FROM AUTHOR]

Objectives Systemic sclerosis (SSc)-specific autoantibodies allow the diagnosis and predict the prognosis of SSc patients with different clinical characteristics. The aim of this study was to describe new SSc-related autoantibodies by a novel protein immunoprecipitation (IP) assay. Methods Serum samples and clinical data were collected from 307 SSc patients. Antinuclear autoantibodies were tested in all patients by indirect immunofluorescence (IIF) on HEp-2 cells. SSc-specific autoantibodies were evaluated with a commercial immunoblot and chemiluminescence immunoassay, and traditional RNA-IP. Patients negative for all these autoantibodies (n  = 51) were further tested with a non-radioactive protein IP assay. Protein bands detected on SDS–PAGE were then analysed by mass spectrometry (MS) and confirmed by western blot (WB). Additional 56 patients with nucleolar pattern by IIF were tested by protein IP-WB. Results Five patients who underwent protein IP testing showed a 110-115kDa molecular weight band on SDS–PAGE and a homogeneous nucleolar pattern by IIF. MS identified the bands as nuclear valosin-containing protein-like (NVL). An additional positive patient was detected by IP-WB. As compared with the remaining 101 negative patients, anti-NVL positive patients showed a greater prevalence of calcinosis (100% vs 18.9%, P  < 0.001), and cancer (66.7% vs 8.9%, P  = 0.002), with a particular association with synchronous cancer (OR = 16.3; P  = 0.024). Conclusion We identified NVL as a new autoantibody target by a novel protein IP assay in SSc patients with a homogeneous nucleolar IIF pattern, testing negative for all known SSc-specific autoantibodies by commercial assays and RNA IP. Anti-NVL identifies a new clinical phenotype, characterized by calcinosis and cancer. [ABSTRACT FROM AUTHOR]

Primary aldosteronism (PA) is the most common cause of endocrine arterial hypertension, and the suggested screening test for case detection is the aldosterone-to-renin ratio (ARR) or aldosterone-to-direct renin ratio (ADRR) based on radio-immunoassay (RIA) and chemiluminescence assay (CLIA), respectively. The objective of our study was to evaluate the reliability of CLIA for aldosterone and renin measurement and the diagnostic performance of ADRR. A prospective cohort of 1110 patients referred to a single laboratory medicine center underwent measurement of aldosterone and direct renin concentration (DRC) by CLIA and measurement of aldosterone and plasma renin activity (PRA) by RIA. Of 1110 patients, 640 obtained a final diagnosis of hypertension, and 90 of these patients were diagnosed with PA. Overall, between-method correlation was highly significant for aldosterone concentrations (R = 0.945, p < 0.001) and less strong but significant for DRC/PRA (R = 0.422, p < 0.001). Among hypertensive patients, in PA cases, the areas under the receiver operator characteristics (ROC) curves were 0.928 (95% confidence interval 0.904–0.954) for ADRR and 0.943 (95% confidence interval 0.920–0.966) for ARR and were comparable and not significantly different. The highest accuracy was obtained with an ADRR cut-off of 25 (ng/L)/(mIU/L), displaying a sensitivity of 91% and a specificity of 85%. The chemiluminescence assay for aldosterone and DRC is a reliable method for PA diagnosis compared to the classical RIA method. [ABSTRACT FROM AUTHOR]

Background: Due to lower operational costs, health maintenance organizations (HMOs) may prioritize Helicobacter pylori stool antigen testing (HpStAg) for the non-invasive diagnosis of H. pylori infection over 13C-urea breath tests (13C-UBTs). The aim of our study was to compare the accuracy of the diagnostic tests for H. pylori. Methods: We performed histology, rapid urease test (RUT), 13C-UBT and HpStAg on consecutive patients referred for gastroscopy. Monoclonal stool antigen test was performed using the LIAISON Meridian chemiluminescent immunoassay. Histology was examined with hematoxylin and eosin, and additional stains were performed at the pathologist's discretion. For the assessment of 13C-UBT, we compared concordant histology and RUT. HpStAg was compared to the concordant results of two of the three remaining tests. Results: 103 patients were included (36 males (35.0%), age 50.1 ± 18.4 years). The indication for gastroscopy was dyspepsia in 63 (61.2%). Agreement between RUT and histology was 95.9%. For 13C-UBT and HpStAg, respectively, H. pylori positivity was 30% (30/100) and 27.16% (22/81); sensitivity was 97% and 70%; specificity was 100% and 94.4%; accuracy was 98% and 86%; positive predictive value (PPV) was 100% and 86.4%; negative predictive value (NPV) was 93% and 86%. No demographic, clinical, or endoscopic predictors of HpStAg accuracy were identified using logistic regression. Conclusions: 13C-UBT performs better than HpStAg at our institution. When interpreting results, clinicians should consider test limitations. [ABSTRACT FROM AUTHOR]

Background: A new chemiluminescence assay, the Anti-TP-Ⅱ assay, is going to be commercially available in clinical laboratories in China and other countries. This study examined the performance of the new assay for the detection of TP infection and compared it with that of the Anti-TP assay by using large amounts of clinical samples. Methods: The precision, accuracy, anti-interference ability, and the clinical sensitivity and specificity of the Anti-TP-Ⅱ assay were evaluated. In addition, compared with those of the Anti-TP assay, the false positive and false negative rates of the Anti-TP-Ⅱ assay were evaluated for 2,436 clinical routine samples and 711 preselected Anti-TP assay reactive samples. Discrepancy of the samples was investigated with the recomLinec Treponema IgM/IgG kit or the Elecsys syphilis assay. Results: The precision, accuracy, and anti-interference ability of the Anti-TP-Ⅱ assay met the national standard of China, and there was an overall agreement of 96.75% (Kappa = 0.91) between the two assays. The sensitivity and specificity of the Anti-TP-Ⅱ assay were 100% (95% CI: 94.13% to 100%) and 99.92% (95% CI: 99.70% to 99.99%), respectively. Compared with the Anti-TP assay, the Anti-TP-Ⅱ assay significantly reduced the number of borderline samples and the false positive rate. Conclusions: Considering its excellent performance, the Anti-TP-Ⅱ assay is a good screening test for highthroughput laboratories and can replace the previous generation of reagents, the Anti-TP assay, with a superior specificity. [ABSTRACT FROM AUTHOR]

Objective: Although urinary extracellular vesicles (uEVs) have been extensively studied in various cancers, their involvement in breast cancer (BC) remains largely unexplored. The non-invasive nature of urine as a biofluid and its abundant protein content offer considerable potential for the early detection of breast cancer. Methods: This study analyzed the proteomic profiles of uEVs from BC patients and healthy controls (HC). The dysregulation of ECM1 and ANXA1 in the uEVs was validated in a larger cohort of 128 BC patients, 25 HC and 25 benign breast nodules (BBN) by chemiluminescence assay (CLIA). The expression levels of ECM1 and ANXA1 were also confirmed in the uEVs of MMTV-PyMT transgenic breast cancer mouse models. Results: LC-MS/MS analysis identified 571 dysregulated proteins in the uEVs of BC patients. ECM1 and ANXA1 were selected for validation in 128 BC patients, 25 HC and 25 BBN using CLIA, as their fold change showed a significant difference of more than 10 with p-value<0.05. Protein levels of ECM1 and ANXA1 in uEVs were significantly increased in BC patients. In addition, the protein levels of ECM1 and ANXA1 in the uEVs of MMTV-PyMT transgenic mice were observed to increase progressively with the progression of breast cancer. Conclusion: We developed a simple and purification-free assay platform to isolate uEVs and quantitatively detect ECM1 and ANXA1 in uEVs by WGA-coupled magnetic beads and CLIA. Our results suggest that ECM1 and ANXA1 in uEVs could potentially serve as diagnostic biomarkers for breast cancer. [ABSTRACT FROM AUTHOR]

Background: Congenital toxoplasmosis and congenital cytomegalovirus (cCMV) infections are noteworthy in Malaysia and can cause serious health problems in neonates. The prompt and effective detection and treatment related to both illnesses may mitigate the possibility of adverse consequences from both infections. Methods: A total of 219 neonates with suspected clinical indications of congenital toxoplasmosis and/or cCMV infections from January 2022 to December 2022 were enrolled. The first samples for IgM and IgG antibodies were screened by electrochemiluminescence immunoassay. For positive results indicative of congenital toxoplasmosis and cCMV infections, second serum samples were requested and tested within a period of 2-4 weeks after testing the first sample. Results: From the 219 first serum samples, the overall seroprevalence of congenital toxoplasmosis antibodies in suspected cases was 53%; meanwhile, the overall seroprevalence of cCMV in the suspected cases was 98.6%. The results of the paired serum sample collected for investigating congenital toxoplasmosis cases revealed that 47% of the cases presented no serological evidence of exposure while the remaining 53% of cases might have acquired passive immunity from the mother. For cCMV, the number of cases with no serological evidence of exposure was 1.4%, whereas acute infection was 1.8% and possible passive immunity from the mother represented 96.8%. Conclusion: This study found a high seroprevalence of congenital toxoplasmosis and cCMV infections, probably because they are suspected cases. This study also indicates that using paired sample analysis in the categorisation of cases can aid in accurate diagnosis and more effective treatment. [ABSTRACT FROM AUTHOR]

Objective: Betatrophin is a hepatokine that modulates hepatic glucose and lipid metabolism and contributes to non-alcoholic fatty liver disease (NAFLD) pathogenesis. Therefore, this study aimed to investigate the relationship between NAFLD and betatrophin levels in hypogonadal males. Methods: The study included 56 newly diagnosed hypogonadal males aged 18-60 and 60 eugonadal males of similar age and body mass index. All participants were assessed for anthropometric and metabolic parameters, liver function tests, and betatrophin levels. Transient elastography was used to evaluate liver steatosis [controlled attenuation parameter (CAP)] and fibrosis [liver stiffness measurement (LSM)]. Accordingly, hypogonadal and control groups were divided into NAFLD (n = 64) and non-NAFLD (n = 52). Results: Controlled attenuation parameter, LSM, waist circumference (WC), triglycerides (TG), IR index homeostasis model assessment (HOMA-IR), and betatrophin were significantly higher in the hypogonadal group than controls. Hepatic steatosis and fibrosis (67.9%-43.3%) were higher in hypogonadal males. Triglycerides, HOMA-IR, and betatrophin were higher, and total testosterone was significantly lower in the NAFLD group. Serum betatrophin was also significantly higher in patients with fibrosis than without. There was a significant positive correlation between WC, TG, HOMA-IR, betatrophin, and LSM and CAP. The predictive factors were TG (ß = 0.329, P < .001), betatrophin (ß = 0.221, P = .029), HOMA-IR (ß = 0.213, P = .019) for CAP, and betatrophin for LSM (ß = 0.466, P < .001). Conclusion: Non-alcoholic fatty liver disease is more common in hypogonadal males than in eugonadal males. Betatrophin is an independent risk factor for developing and progressing NAFLD. However, more research is needed to explain the causal relationship between betatrophin and NAFLD. [ABSTRACT FROM AUTHOR]

Objective: It was previously shown that the levels of several biomarkers increase due to acromegaly disease-related inflammation, and some markers are parallel to the disease's activity. The current study compared the possible relationship of growth differentiation factor-15 (GDF-15) with acromegaly disease activity in healthy subjects. Methods: This case-control study was conducted in a single center. It included 40 acromegaly patients (25 active/15 controlled) (47.7 ± 9.4 years, 20 female/20 male) and 24 healthy individuals (49.9 ± 10.1 years, 13 female/11 male) with age-sex-body mass index similar to the patient group. Demographic data, metabolic and hormonal parameters, and GDF-15 levels of the study population were studied. Results: The median GDF-15 levels were significantly higher in patients with acromegaly compared to healthy subjects (HS) (280.4 (Q1-Q3: 197.0-553.2) vs. 213.3 (Q1-Q3: 179.9-297.2) ng/L, P = .01). Serum GDF-15 levels of active and controlled acromegaly patients were comparable (P = .39). Interestingly, compared to HS, GDF-15 levels were significantly higher in controlled disease (P = .013), whereas GDF-15 levels tended to be higher in active disease but did not reach statistical significance (P = .06). Growth differentiation factor-15 levels were positively correlated with fasting plasma glucose (r = 0.304, P = .01) and HbA1c (r = 0.292, P = .02). When evaluated across the entire cohort, GDF-15 levels were found to be higher in diabetic patients compared to non-diabetic individuals (P = .04). Conclusion: Plasma GDF-15 levels were increased in the patients with acromegaly compared to healthy subjects. This increment may be due to accompanying diseases such as diabetes rather than a disease-specific effect. [ABSTRACT FROM AUTHOR]

Objective: Chronic hypothyroidism is associated with significant neurocognitive deficits. However, present data about the effect of acute hypothyroidism on cognitive functions are limited. This study aimed to investigate the cognitive functions of patients with differentiated thyroid carcinoma (DTC) in acute hypothyroidism caused by l-thyroxine withdrawal (THW) using auditory event-related potentials (AERPs). Methods: Twenty-three patients with DTC and fifteen healthy subjects (group 1) were involved in the study. AERPs were recorded using the standard auditory "Oddball" paradigm from the Fz, Cz, Pz, and Oz regions. P300 waves were analyzed. The first records were obtained from group 1 and DTC patients under thyroxine treatment (group 2a). In the patient group, AERP recordings of the patients were repeated approximately 1 month after the withdrawal of thyroid hormone (THW) when the patients became hypothyroid (Group 2b). Results: P300 latencies were found to be significantly longer in group 2a in the Cz (P < .01), Pz (P < .001), and Oz (P < .001) regions compared to group 1, except for Fz. Group 2b P300 latencies were also longer than group 1 Cz (P < .009), Pz (P < .001), and Oz (P < .001) regions, except Fz. When comparing group 2a and group 2b, the P300 latency of group 2b was longer in the Pz region (P < .05). Conclusion: In this study, it was shown that cognitive functions in patients with DTC had a slower cognitive function in the state of acute hypothyroidism induced by 1-month THW than in both healthy individuals and during l-thyroxine treatment. [ABSTRACT FROM AUTHOR]

Background: After the global COVID-19 crisis, understanding post-infectious immunity and vaccine efficacy remains crucial. This study aims to assess anti-SARS-CoV-2 immunity through a quantitative analysis of anti-receptor-binding domain (RBD) antibodies and rapid functional testing of the neutralizing humoral response. Methods: A retrospective analysis was conducted on samples from various cohorts, including partially vaccinated, fully vaccinated, post-COVID/no-vaccination, and post-COVID/vaccination individuals with various immune-competency statuses. The anti-RBD antibodies were measured using an automated chemiluminescence assay, while the neutralizing antibodies' (NAbs') activity was assessed through the lateral flow ichroma COVID-19 nAb test (LFT), a surrogate neutralization assay. Results: The analysis revealed various levels of anti-RBD antibodies and seroneutralization responses across cohorts, with the post-COVID/vaccination group demonstrating the most robust protection. A correlation between anti-RBD antibodies and seroneutralization was observed, albeit with varying strength depending on the subgroup analyzed. Longitudinal assessment following natural infection showed an initial surge followed by a decline in both measures. A cutoff of 3.0 log10 BAU/mL was established to predict significant seroneutralization. Conclusions: The ichroma™ COVID-19 nAb test displayed high specificity and emerged as a valuable tool for monitoring anti-SARS-CoV-2 immunity. These findings contribute to understand the antibody response dynamics and underscore the potential of rapid tests in predicting protection against SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: Perilipin 2 (PLIN2) is a protein that contributes to the formation and stability of lipid droplets. It has been associated with the development of several diseases, particularly related to glucose and lipid metabolism. In infants of diabetic mother (IDM), fetal hyperinsulinaemia leads to increased adipose tissue and macrosomia. The aim of this study was to investigate the relationship between PLIN2 levels and anthropometric measurements in the IDM and to investigate the relationship between PLIN2 levels and IGF-1, IGF-2 and leptin levels. Methods: The study group consisted of IDMs, while the control group consisted of infants born to non-diabetic mother, matched for gestational week and gender. Cord blood samples were collected from all patients to determine PLIN2, IGF-1, IGF-2 and leptin levels. Anthropometric measurements were taken for all patients at birth. Results: There were no differences between the groups in birth weight, birth length, head circumference and body mass index (BMI), but middle arm circumference, triceps, biceps, subscapular and suprailiac skinfold thickness were significantly higher in the IDM. While PLIN2, IGF-1, IGF-2 and leptin levels were similar between groups, there was a strong correlation between PLIN2 levels and IGF-2 and leptin levels. Conclusions: Even if IDMs were not macrosomic, the presence of high subcutaneous adipose tissue was not associated with PLIN2. [ABSTRACT FROM AUTHOR]

Purpose: Lung transplant recipients are at increased risk of severe disease following infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) due to high-dose immunosuppressive drugs and the lung is the main organ affected by Coronavirus disease 2019 (COVID-19). Several studies have confirmed increased SARS-CoV-2-related mortality and morbidity in patients living with lung allografts; however, detailed immunological studies of patients with SARS-CoV-2 infection in the early phase following transplantation remain scarce. Methods: We investigated patients who were infected with SARS-CoV-2 in the early phase (18–103 days) after receiving double-lung allografts (n = 4, LuTx) in comparison to immunocompetent patients who had not received solid organ transplants (n = 88, noTx). We analyzed SARS-CoV-2-specific antibody responses against the SARS-CoV-2 spike and nucleocapsid proteins using enzyme-linked immunosorbent assays (ELISA), chemiluminescence immunoassays (CLIA), and immunoblot assays. T cell responses were investigated using Elispot assays. Results: One LuTx patient suffered from persistent infection with fatal outcome 122 days post-infection despite multiple interventions including remdesivir, convalescent plasma, and the monoclonal antibody bamlanivimab. Two patients experienced clinically mild disease with prolonged viral shedding (47 and 79 days), and one patient remained asymptomatic. Antibody and T cell responses were significantly reduced or undetectable in all LuTx patients compared to noTx patients. Conclusion: Patients in the early phase following lung allograft transplantation are vulnerable to infection with SARS-CoV-2 due to impaired immune responses. This patient population should be vaccinated before LuTx, protected from infection post–LuTx, and in case of infection treated generously with currently available interventions. [ABSTRACT FROM AUTHOR]

Optical bioassays are challenged by the growing requirements of sensitivity and simplicity. Recent developments in the combination of redox cycling with different optical methods for signal amplification have proven to have tremendous potential for improving analytical performances. In this review, we summarized the advances in optical bioassays based on the signal amplification of redox cycling, including colorimetry, fluorescence, surface-enhanced Raman scattering, chemiluminescence, and electrochemiluminescence. Furthermore, this review highlighted the general principles to effectively couple redox cycling with optical bioassays, and particular attention was focused on current challenges and future opportunities. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE), is a noteworthy complication in individuals with gastric cancer, but the current diagnosis and treatment methods lack accuracy. In this study, we developed a t-PAIC chemiluminescence kit and employed chemiluminescence to detect the tissue plasminogen activator inhibitor complex (t-PAIC), thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC) and thrombomodulin (TM), combined with D-dimer and fibrin degradation products (FDP), to investigate their diagnostic potential for venous thrombosis in gastric cancer patients. The study assessed variations in six indicators among gastric cancer patients at different stages. Results: The t-PAIC reagent showed LOD is 1.2 ng/mL and a linear factor R greater than 0.99. The reagents demonstrated accurate results, with all accuracy deviations being within 5%. The intra-batch and inter-batch CVs for the t-PAIC reagent were both within 8%. The correlation coefficient R between this method and Sysmex was 0.979. Gastric cancer patients exhibited elevated levels of TAT, PIC, TM, D-D, FDP compared to the healthy population, while no significant difference was observed in t-PAIC. In the staging of gastric cancer, patients in III-IV stages exhibit higher levels of the six markers compared to those in I-II stages. The ROC curve indicates an enhancement in sensitivity and specificity of the combined diagnosis of four or six indicators. Conclusion: Our chemiluminescence assay performs comparably to Sysmex's method and at a reduced cost. The use of multiple markers, including t-PAIC, TM, TAT, PIC, D-D, and FDP, is superior to the use of single markers for diagnosing VTE in patients with malignant tumors. Gastric cancer patients should be screened for the six markers to facilitate proactive prophylaxis, determine the most appropriate treatment timing, ameliorate their prognosis, decrease the occurrence of venous thrombosis and mortality, and extend their survival. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition that affects 1.2 million children annually. Although there are several criteria for diagnosing this condition, signs are often nonspecific, and identifying sepsis is challenging. In this context, presepsin (P-SEP) seems to be a promising new biomarker since its plasma levels increase earlier than other sepsis-related proteins and its measurement is faster. We enrolled 157 minors who presented to the Pediatric Emergency Department of Agostino Gemelli Hospital with fever and suspected sepsis. Biochemical, anamnestic, and clinical data were collected. Viral agents were identified as the causative factor in 64 patients, who had an average P-SEP value of 309.04 pg/mL (SD ± 273.2), versus an average P-SEP value of 526.09 pg/mL (SD ± 657) found in 27 bacterial cases (p value: 0.0398). Four cases of overt sepsis had an average P-SEP value of 3328.5 pg/mL (SD ± 1586.6). The difference in P-SEP levels in viral versus bacterial infections was found to be statistically significant; therefore, P-SEP may have a central role in the evaluation of febrile children, helping clinicians distinguish between these two etiologies. Furthermore, amongst the cases of confirmed sepsis, P-SEP was always greater than 2000 pg/mL, while C-reactive protein and procalcitonin values appeared lower than what was considered significant. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) play an important and controversial role in carcinogenesis. Microsomal redox chains containing NADH- and NADPH-dependent oxidoreductases are among the main sites of intracellular ROS synthesis, but their role in the oxidative balance has not been fully studied. Here, we studied the activity of cytochrome b5 reductase (CYB5R) and cytochrome P450 reductase (CYPOR) in ovarian cancer tissues and cells isolated from peritoneal fluid, along with the antioxidant capacity of peritoneal fluid. We used the developed a chemiluminescence assay based on stimulation with NADH and NADPH, which reflects the activity of CYB5R and CYPOR, respectively. The activity of CYB5R and CYPOR was significantly higher in moderately and poorly differentiated ovarian adenocarcinomas compared with well-differentiated adenocarcinomas and cystadenomas. For the chemotherapy-resistant tumors, the activity of tissue CYB5R and CYPOR was lower compared to the non-resistant tumors. In the peritoneal fluid, the antioxidant capacity significantly increased in this series, benign tumors < well-differentiated < moderately and poorly differentiated adenocarcinomas, so the antioxidant excess was observed for moderately and poorly differentiated adenocarcinomas. The antioxidant capacity of peritoneal fluid and the activity of CYB5R and CYPOR of cells isolated from peritoneal fluid were characterized by a direct moderate correlation for moderately and poorly differentiated adenocarcinomas. These results indicate the significant role of NAD(P)H oxidoreductases and the antioxidant potential of peritoneal fluid in cancer biochemistry. The parameters studied are useful for diagnostics and prognostics. The developed assay can be used to analyze CYB5R and CYPOR activity in other tissues and cells. [ABSTRACT FROM AUTHOR]

Thrombus therapy is challenged by potential bleeding risk of thrombolytic agents, and external irradiation is usually needed in thrombus imaging. Herein, highly efficient theranostic platforms are designed for piezoelectric‐Fenton‐photodynamic thrombolysis and endogenous thrombus imaging in response to the elevated shear stress at the thrombus site. Piezoelectric tetragonal barium titanate (tBT) nanoparticles (NPs) are coated with Fe3+‐coordinated metal‐organic frameworks (MOFs), followed by inoculation of chlorin e6‐luminol conjugates and heparin absorption to obtain theranostic tBT@MOFCL/Hep NPs. Shear stress‐induced piezopotential on NPs accelerates Fe3+/Fe2+ transformation to deplete MOF layers, activates Fenton reaction and produces reactive oxidative species (ROS) for non‐pharmacological thrombolysis. In the meantime, the site‐specific ROS generation oxidizes luminol and the chemiluminescent resonance energy transfer with chlorin e6 generates red fluorescence for thrombus imaging without using external light irradiation. After intravenous injection into a carotid artery thrombosis model, the heparin‐mediated thrombus targeting yields 6.5‐fold higher luminescent intensity at the thrombus site. Thrombi in the carotid arteries are almost completely dissolved with integration of piezoelectric dynamic therapy, piezopotential‐enhanced Fenton reaction, and chemiluminescence‐excited photodynamic therapy, while causing no haematologic and histopathologic abnormality. This study demonstrates a concise strategy to generate shear stress‐responsive built‐in piezoelectric potentials, site‐specific non‐pharmacological thrombolysis, self‐illuminating, and stenosis degree‐adaptable thrombus imaging. [ABSTRACT FROM AUTHOR]

In the search for novel, effective inhibitors of High‐Mobility Group Box1 (HMGB1)—a protein involved in various inflammatory and autoimmune diseases as well as in cancer—we herein discovered a set of anti‐HMGB1 G‐quadruplex(G4)‐forming aptamers by using an in vitro selection procedure applied to a doped library of guanine‐rich oligonucleotides. The selected DNA sequences were then studied in a pseudo‐physiological buffer mimicking the extracellular medium, where HMGB1 exerts its pathological activity, using spectroscopic, electrophoretic, and chromatographic techniques. All the oligonucleotides proved to fold into monomeric G4s and in some cases also dimeric species, stable at physiological temperature. Remarkably, the protein preferentially recognized the sequences forming dimeric parallel G4 structures, as evidenced by a properly designed chemiluminescent binding assay which also highlighted a good selectivity of these aptamers for HMGB1. Moreover, all aptamers showed anti‐HMGB1 activity, inhibiting protein‐induced cell migration. The acquired data allowed identifying L12 as the best anti‐HMGB1 aptamer, featured by high thermal and enzymatic stability, no toxicity at least up to 5 μM concentration on healthy cells, along with potent anti‐HMGB1 activity (IC50 ca. 28 nM) and good binding affinity for the protein, thus indicating it as a very promising lead candidate for in vivo studies. [ABSTRACT FROM AUTHOR]

To evaluate the analytical characteristics of a novel high-sensitivity cardiac troponin T (hs-cTnT) test on the automatic light-initiated chemiluminescent assay (LiCA®) system, and validated its diagnostic performance for non-ST-segment elevation myocardial infarction (NSTEMI). Studies included an extensive analytical evaluation and established the 99th percentile upper reference limit (URL) from apparently healthy individuals, followed by a diagnostic performance validation for NSTEMI. Sex-specific 99th percentile URLs were 16.0 ng/L (1.7 % CV: coefficient of variation) for men (21–92 years) and 13.4 ng/L (2.0 % CV) for women (23–87 years) in serum, and 30.6 ng/L (0.9 % CV) for men (18–87 years) and 20.2 ng/L (1.4 % CV) for women (18–88 years) in heparin plasma. Detection rates in healthy individuals ranged from 98.9 to 100 %. An excellent agreement was identified between LiCA® and Elecsys® assays with a correlation coefficient of 0.993 and mean bias of −0.7 % (−1.8–0.4 %) across the full measuring range, while the correlation coefficient and overall bias were 0.967 and −1.1 % (−2.5–0.3 %) for the lower levels of cTnT (10–100 ng/L), respectively. At the specific medical decision levels (14.0 and 52.0 ng/L), assay difference was estimated to be <5.0 %. No significant difference was found between these two assays in terms of area under curve (AUC), sensitivity and specificity, negative predictive value (NPV) and positive predictive value (PPV) for the diagnosis of NSTEMI. LiCA® hs-cTnT is a reliable 3rd-generation (level 4) high-sensitivity assay for detecting cardiac troponin T. The assay is acceptable for practical use in the diagnosis of NSTEMI. [ABSTRACT FROM AUTHOR]