Mutation in beta-fibrinogen gene (C148T) is important risk factor in patients affected by thromboembolic disease.

KRAS: one actor, many potential roles in diagnosis

Association between hypovitaminosis D and systemic sclerosis: True or fake?

Abstract Background Vitamin D insufficiency/deficiency is considered a major factor triggering and enhancing several autoimmune disorders; hypovitaminosis D has been reported to be common in Systemic Sclerosis (SSc). Previous studies assessing vitamin D insufficiency/deficiency in SSc have been reviewed, and the relation with pathogenesis and clinical features has been examined. Content Eligibility criteria were: reporting measurement of Vitamin D serum levels in all participants and evaluating adult onset-SSc individuals as patients group. Results: The association between clinical features and low hormone levels is controversial. Manifold data have shown vitamin D insufficiency/deficiency …

Methionine synthase polymorphism A2756G and its association with thromboembolic disease

Heart-type fatty acid binding protein is a sensitive biomarker for early AMI detection in troponin negative patients: a pilot study

Background: Early detecting AMI in individuals presenting to the ED with chest pain continues to be a challenge. cTn is the gold standard for AMI diagnosis but early presenters (<1 hours from symptom onset) maybe cTn negative on admission. We analysed the diagnostic value of h-FABP and hs-TnI in patients presenting to ED with chest pain and no cTnI elevations. Methods: 28 AMI and 28 no-AMI individuals both presented to ED within one hour from pain onset were included. Blood donors were analysed for h-FABP cut-off identification. Among AMI patients, 55% were positive for h-FABP and 34.6% were positive for hs-TnI (p = .015), thus 21% were positive only for h-FABP. The diagnostic accuracy w…

Vitamin D and Multiple Sclerosis: An Open-Ended Story

Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease of the Central Nervous System (CNS). Genetic, epigenetic and environmental factors interact together, contributing to the complex pathogenesis of the disease. In the last decades, the role of hypovitaminosis D on MS risk was hypothesised. Several factors drive the regulation of vitamin D status, including genetics. The current review summarises the literature evidence on the association between vitamin D and MS, with a focus on the genetic polymorphisms in vitamin D-related genes. The variants of the genes codifying Vitamin D Receptor (VDR), Vitamin D Binding Protein (VDBP) and CYP enzymes have been investigated, but the f…

Cerebrospinal Fluid Analysis in Multiple Sclerosis Diagnosis: An Update

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with brain neurodegeneration. MS patients present heterogeneous clinical manifestations in which both genetic and environmental factors are involved. The diagnosis is very complex due to the high heterogeneity of the pathophysiology of the disease. The diagnostic criteria have been modified several times over the years. Basically, they include clinical symptoms, presence of typical lesions detected by magnetic resonance imaging (MRI), and laboratory findings. The analysis of cerebrospinal fluid (CSF) allows an evaluation of inflammatory processes circumscribed to the CNS and reflects chan…

Impact of Mycobacterium tuberculosis Infection on Human B Cell Compartment and Antibody Responses

Tuberculosis (TB) remains one of the most important health challenges worldwide. Control of the TB epidemic has not yet been achieved because of the lack of an effective vaccine and rapid and sensitive diagnostic approaches, as well as the emergence of drug-resistant forms of M. tuberculosis. Cellular immunity has a pivotal role against M. tuberculosis infection, but the role of humoral immunity is still controversial. We analyzed the frequency, absolute counts, and phenotypic and functional subsets of B lymphocytes in the peripheral blood of patients with active TB and subjects with latent infection compared to healthy donors. Moreover, we analyzed serum levels of total Ig and their IgA, I…

Klotho and vitamin D in multiple sclerosis: an Italian study

Introduction Low vitamin D levels have been recognised as an important risk factor for autoimmune diseases, including multiple sclerosis (MS). MS is a multifactorial disease, the pathogenesis of which contributes both to genetic and environmental factors. Polymorphisms in genes codifying molecules involved in vitamin D homeostasis have been associated with hypovitaminosis D. However, the influence of polymorphisms of Klotho, which codify a protein with a pivotal role in vitamin D metabolism, have never been investigated. The aim of this study was to evaluate the association among genetic variants of Klotho, namely rs1207568 and rs9536314, serum 25(OH)D3 levels, and multiple sclerosis (both …

APOE and longevity: study of a population of Sardinian Centenarians

Apolipoprotein E is a major determinant in lipoprotein metabolism and cardiovascular disease, it has emerged as an important molecule in several biological processes including Alzheimer's disease and cognitive function. ApoE is a polymorphic protein (ε2, ε3, ε4) with three proteic isoforms, ApoE2, ApoE3, ApoE4 (1). The aim of the study was to verify the frequencies of allelic variants a population of healthy elderly people. ApoE polymorphisms were determined by Real Time-PCR. The genotype frequencies of ApoE in our group of 71 centenarians (mean age 100.9 ±1.3) were: ε2/ε3 (12.67%); ε3/ε4 (5.63%). In the control group, consisting of 97 individuals (mean age 92.98 ±2.53), the genotype freque…

Vitamin K deficiency bleeding leading to a diagnosis of Crohn’s Disease

We report the case of a 45 year old man who came to Emergency Room of Polyclinic for sudden onset of localized ecchymosis and widespread hematomas. He was subjected to blood count and first level investigations to assess coagulation. Based on the results, second level investigations were performed. Endoscopy of the gastrointestinal tract with histological examination revealed a diagnosis of Crohn's disease. Vitamin K deficiency causes the formation of vitamin K-dependent clotting factors that cannot perform their pro-coagulant action. Consequently, patients present with hemorrhagic manifestations. Clinical and laboratory features observed in this patient show that the deficiency of vitamin …

COVID-19 and Alzheimer’s Disease

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a neurotropic virus with a high neuroinvasive potential. Indeed, more than one-third of patients develop neurological symptoms, including confusion, headache, and hypogeusia/ageusia. However, long-term neurological consequences have received little interest compared to respiratory, cardiovascular, and renal manifestations. Several mechanisms have been proposed to explain the potential SARS-CoV-2 neurological injury that could lead to the development of neurodegenerative diseases, including Alzheimer’s Disease (AD). A mutualistic relationship between AD and COVID-19 seems to exist. On the one hand, COVID-19 patients seem to …

Activity of mannose-binding lectin in centenarians

Summary We analyzed MBL2 gene variants in two cohorts of centenarians, octo-nonagenarians and nonagenarians, and in the general population, one from Sardinia Island (Italy), recruited in the frame of the AKea study, and another from Campania (southern Italy), to search for haplotypes related to longevity. We also assessed in vitro the effect of mannose-binding lectin (MBL) on various human cells at different stage of senescence. The frequency of high and null activity haplotypes was significantly lower, and the frequency of intermediate activity haplotype significantly higher in centenarians and in subjects between 80 and 99 years from both the cohorts as compared each to the general popula…

Galectin-3 in acute coronary syndrome

Acute coronary syndrome (ACS) is a very common cause of hospitalizations worldwide each year. In the past decades biomarkers have become an indispensable tool for diagnosis, risk stratification and prognosis of cardiovascular disease, including ACS. Despite Troponin is considered the gold standard in diagnosis of ACS, several molecules have been investigated to identify predictive biomarkers of prognosis. Among these, Gal-3 has emerged as a promising prognostic marker. It has a pivotal role in inflammation and fibrosis. Both experimental and clinical studies have shown Gal-3 is an independent predictor of all-cause mortality, cardiovascular death and occurrence of HF following ACS. This art…

Establishing the 99th percentile for high sensitivity cardiac troponin i in healthy blood donors from southern italy

Introduction: The knowledge of high sensitivity cardiac troponin I (hsTnI) distribution in a reference population is mandatory for its introduction in clinical practice. The aim of this study was to define the Upper Reference Limit (URL) of hsTnI measured by Single Molecule Counting technology (SMC) in an accurately selected reference population. Materials and methods: In the study 1140 blood donors were included and selected on the basis of medical history and biomarkers. High sensitivity cardiac troponin I was measured by SMC technology (Clarity, Singulex, Alamed, USA). The 99th percentile was calculated by the non-parametric method according to the Clinical and Laboratory Standard Instit…

Factor V G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase MTHFR A1298C gene polymorphism in subjects affected by thromboembolic disease

Monocyte distribution width (MDW) as a screening tool for early detecting sepsis: a systematic review and meta-analysis

Abstract Objectives Monocyte distribution has recently emerged as a promising biomarker of sepsis, especially in acute setting, such as Emergency Department and Intensive Care Unit. This study aimed to evaluate the accuracy of monocyte distribution width (MDW) for early detecting patients with sepsis by performing a systemic review and meta-analysis of published studies. Methods Relevant publications were identified by a systematic literature search on PubMed and Google Scholar from inception to September 07, 2021. Studies were divided into two groups based on the sepsis criteria applied, namely sepsis-2 or sepsis-3. Results Ten studies including 9,475 individuals, of whom 1,370 with sepsis…

Definition of the upper reference limit of glycated albumin in blood donors from Italy.

Abstract Background: Glycated Albumin (GA) has been proposed as a short-term indicator of glycemic homeostasis. The aim of this study is to describe the distribution of GA in a large sample of blood donors from Italy to evaluate whether demographic features, namely age and sex, could influence GA levels and define specific reference limits. Methods: The study included 1334 Italian blood donors. GA was measured using an enzymatic method (quantILab Glycated Albumin, IL Werfen, Germany). The upper reference limit (URL) was calculated using the non-parametric percentile method. Results: A modest, although significant, increase of GA was observed in relation to age (p<0.001), especially in ma…

The role of serum free light chain as biomarker of Myasthenia Gravis

Background and aim: Myasthenia gravis (MG) is a B lymphocyte–mediated disease affecting neuromuscular transmission. The clinical course of MG is unpredictable due to the fluctuating nature and heterogeneity of the disease. Increased levels of free light chains (FLC), which reflect B cell activation, have been detected in different autoimmune disorders. In this study, we evaluated the potential role of FLC as diagnostic and prognostic biomarkers of MG. Materials and methods: 74 MG patients and 52 healthy individuals were included in the study. Serum FLC levels were measured by turbidimetric assay (Freelite, The Binding Site Group Ltd) on the Optilite Analyser System in both groups. In MG pat…

Establishing the upper reference limit of Galectin-3 in healthy blood donors

Introduction Galectin-3 (Gal-3) is an independent predictor of poor outcomes and mortality in patients with heart failure (HF). Thus, it has been proposed as a reliable prognostic biomarker for HF. The definition of reference intervals is mandatory for interpreting the findings of experimental studies and encouraging the routine use of biomarkers in clinical practice. To date, no study assessed the reference intervals of Gal-3 and identified the biological variables that affect its concentration in a well-defined healthy population. The aim of this study was to determine the upper reference limit (URL) of Gal-3 in a highly reliable population of healthy subjects. Materials and methods We re…

Polimorfismo I/D del gene per l'enzima di conversione dell'angiotensina (ACE): gene della longevità o fattore di rischio nella patologia ipertensiva?

In recent decades, the increase in life expectancy stimulated the study of aging processes and the search for candidate genes involved in longevity. The angiotensin converting enzyme (ACE), present in all endothelial cells, plays an essential role in maintaining the homeostasis of blood flow by regulating the production of the vasoconstrictor angiotensin II and inactivating the bradykinin. Some studies reported a possible association between the polymorphism I/D of ACE gene and either hypertension and longevity. The present study was aimed to confirm these data. We studied two large cohorts of nonagenarians and centenarians. One was from Sardinia (200 subjects, 88 males, mean age: 96 years)…

Recent Updates and Advances in the Use of Glycated Albumin for the Diagnosis and Monitoring of Diabetes and Renal, Cerebro- and Cardio-Metabolic Diseases

Diabetes mellitus is a heterogeneous and dysmetabolic chronic disease in which the laboratory plays a fundamental role, from diagnosis to monitoring therapy and studying complications. Early diagnosis and good glycemic control should start as early as possible to delay and prevent metabolic and cardio-vascular complications secondary to this disease. Glycated hemoglobin is currently used as the reference parameter. The accuracy of the glycated hemoglobin dosage may be compromised in subjects suffering from chronic renal failure and terminal nephropathy, affected by the reduction in the survival of erythrocytes, with consequent decrease in the time available for glucose to attach to the hemo…

Evaluation of the EPHX1 polymorphism on serum levels of 10, 11- eposside carbamazepine

A new tool for sepsis screening in the Emergency Department

Abstract Objectives In this study, we developed and evaluated the diagnostic accuracy of the Sepsis Index for early sepsis screening in the Emergency Department (ED). Methods Sepsis Index is based on the combination of monocyte distribution width (MDW) and mean monocyte volume (MMV). Sepsis Index≥1 was selected to define sepsis. We tested its diagnostic accuracy in an ED population stratified in four groups: controls, Systemic Inflammatory Response Syndrome (SIRS), infection, and sepsis, according to Sepsis-2 criteria. Results Patients with sepsis displayed higher median Sepsis Index value than patients without sepsis. At the receiver operating characterictis (ROC) curve analysis for the pr…

Foxp3 and gata3 polymorphisms, vitamin d3 and multiple sclerosis

Background: Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D3. The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D3, and MS risk. Methods: We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs…

Time-dependent stability of monocyte distribution width (MDW)

Prostate health index (PHI) as a reliable biomarker for prostate cancer: a systematic review and meta-analysis.

Abstract Objectives Prostate cancer (PCa) represents the second most common solid cancer in men worldwide. In the last decades, the prostate health index (PHI) emerged as a reliable biomarker for detecting PCa and differentiating between non-aggressive and aggressive forms. However, before introducing it in clinical practice, more evidence is required. Thus, we performed a systematic review and meta-analysis for assessing the diagnostic performance of PHI for PCa and for detecting clinically significant PCa (csPCa). Methods Relevant publications were identified by a systematic literature search on PubMed and Web of Science from inception to January 11, 2022. Results Sixty studies, including…

The cervical fracture as first symptom of multiple myeloma: A case report

Introduction: Multiple Myeloma (MM) is a clonal disorder characterized by proliferation and accumulation of malignant plasma cells in the bone marrow. Bone disease occurs in approximately 80% of patients with newly diagnosed MM. The cervical spine is the least common site of disease involvement. Case presentation: A 60-year-old female patient was referred to the Department of Neurosurgery for bone pain. A magnetic resonance imaging (MRI) scan showed a pathological fracture of the sixth cervical vertebra (C6). The laboratory tests and the bone marrow examination led to a diagnosis of IgA χ MM (Durie Salmon stage IIIA). The patient underwent a cervical arthrodesis and started systemic Bortez…

Monocyte distribution width (MDW) as a reliable biomarker for urosepsis

Glycated albumin is correlated to insulin resistance and β-cell secretory function in subjects at risk for developing diabetes

Insulin resistance and β-cell secretory function represent two main issues in the pathogenesis of type 2 diabetes mellitus (T2DM). Conflicting results have been obtained about the association between glycated albumin (GA) and body mass index (BMI), insulin resistance and β-cell function in diabetic patients. Actually, the relationship (if any) between GA and the markers of glucose homeostasis and insulin resistance in subjects at risk of developing diabetes, has not been completely elucidated yet. Two hundred and one patients undergoing to oral glucose tolerance test (OGTT) were enrolled in the study. Routine laboratory tests, including fasting insulin, were performed at enrollment. GA was …

Prognostic Role of CSF β-amyloid 1–42/1–40 Ratio in Patients Affected by Amyotrophic Lateral Sclerosis

The involvement of β-amyloid (Aβ) in the pathogenesis of amyotrophic lateral sclerosis (ALS) has been widely discussed and its role in the disease is still a matter of debate. Aβ accumulates in the cortex and the anterior horn neurons of ALS patients and seems to affect their survival. To clarify the role of cerebrospinal fluid (CSF) Aβ 1–42 and Aβ 42/40 ratios as a potential prognostic biomarker for ALS, we performed a retrospective observational study on a cohort of ALS patients who underwent a lumbar puncture at the time of the diagnosis. CSF Aβ 1–40 and Aβ 1–42 ratios were detected by chemiluminescence immunoassay and their values were correlated with clinical features. We found a signi…

Validation of glycated albumin reference interval in healthy Caucasian pregnant women

No abstract available

Serum Vitamin D as a Biomarker in Autoimmune, Psychiatric and Neurodegenerative Diseases.

Vitamin D is a steroid hormone regulating calcium-phosphorus homeostasis, immune response and brain function. In the past thirty years, an increasing number of cohort studies, meta-analyses and randomized controlled trials (RTCs) evaluated the serum levels of 25-hydroxyvitamin D [25(OH)D], which is considered the Vitamin D status biomarker, in patients affected by neurological, psychiatric and autoimmune diseases. Although an association between low 25(OH)D serum levels and the prevalence of these diseases has been found, it is still unclear whether the serum 25(OH)D measurement can be clinically useful as a biomarker for diagnosis, prognosis and predicting treatment response in neurodegene…

Prevalenza dei polimorfismi FV Leiden, FII G20210A e iperomocisteinemia in pazienti con stroke ischemico

Genetic variants beta-fibrinogen gene, especially G-455-A polymorphism, in patients with thromboembolic disease.

Clinical Utility of Midregional Proadrenomedullin in Patients with COVID-19

Abstract Objective The aim of the study was to assess the role of midregional proadrenomedullin (MR-proADM) in patients with COVID-19. Methods We included 110 patients hospitalized for COVID-19. Biochemical biomarkers, including MR-proADM, were measured at admission. The association of plasma MR-proADM levels with COVID-19 severity, defined as a requirement for mechanical ventilation or in-hospital mortality, was evaluated. Results Patients showed increased levels of MR-proADM. In addition, MR-proADM was higher in patients who died during hospitalization than in patients who survived (median, 2.59 nmol/L; interquartile range, 2.3–2.95 vs median, 0.82 nmol/L; interquartile range, 0.57–1.03; …

Identificazionee caratterizzazione di mutazioni in regioni regolatorie del gene malattia della fibrosi cistica

Mutation epidemiology is crucial for cystic fibrosis (CF) diagnosis and counselling. ~6%-7% of alleles from CF patients do not bear mutations in the coding regions of the Cystic Fibrosis Transmembrane Regulator (CFTR) disease gene. In these patients, mutations may be present in non-coding, regulatory regions of the gene as i) intronic regions (particularly in high conserved sequences), ii) the promoter region or iii) the area at the 3’ of the gene, which is the target of microRNA regulation. We studied these regions by gene sequencing in a group of CF patients with one or both unidentified mutations after the analysis of CFTR coding regions, and in a group of CF patients with a different cl…

Fetuin-A is Associated to Serum Calcium and AHSG T256S Genotype but Not to Coronary Artery Calcification

Vascular calcification has been recently associated to an increased cardiovascular risk and mortality. In few studies, Fetuin-A showed an association to coronary artery calcification (CAC), although the physiopathological mechanism underlying this association has not been fully established yet. Seventy-four patients with one or more cardiovascular risk factor and asymptomatic for coronary vasculopathy were included in the study. CAC was evaluated by Agatston score. Serum Fetuin-A levels were determined by ELISA. Molecular analysis of AHSG T256S gene variant (rs4918) was performed by PCR-RFLP. Serum Fetuin-A was correlated to serum calcium (r = 0,321; P = 0,018), but not to serum phosphorous…

Diagnostic and prognostic value of H-FABP in acute coronary syndrome: Still evidence to bring

Abstract The assessment of chest pain patients presenting to the emergency area (EA) is still a clinical challenge, as the majority of patients are not diagnosed with acute coronary syndrome (ACS). New generation high sensitivity c-Tn (hs-cTn) assays have showed better performances compared to the standard c-Tn. However, hs-Tn still presents some limitations. Hence, novel, early biomarkers are needed in this setting. Among all, heart-type fatty acid binding protein (H-FABP) has been largely investigated. This article reviews the studies evaluating H-FABP performance in diagnosing acute myocardial infarction (AMI) and stratifying chest pain patients by risk. H-FABP optimal performances in AC…

CYP27A1, CYP24A1, and RXR-α Polymorphisms, Vitamin D, and Multiple Sclerosis: a Pilot Study.

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease resulting from a complex interaction of genetic and environmental factors. Hypovitaminosis D seems to contribute to MS susceptibility as both an environmental and a genetic risk factor. The aim of our study was to investigate the association of SNPs in CYP27A1, CYP24A1, and RXR- α genes, vitamin D status, and MS risk. We performed a nested case-control study on patients with multiple sclerosis and healthy controls. Serum 25(OH)D3 levels and genotyping of CYP27A1, CYP24A1, and RXR-α -SNPs were investigated both in MS patients and in healthy controls. Serum 25(OH)D3 levels were measured by a high-performance liquid chromatograp…

A new role of CYP2R1 in Multiple Sclerosis

C677T and A1298C polymorphism of the methylentetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis

Influence of CYP2C9 polymorphism on serum levels of phenobarbital metabolites

Longitudinal analysis of anti-SARS-CoV-2 S-RBD IgG antibodies before and after the third dose of the BNT162b2 vaccine.

AbstractImmunosurveillance by evaluating anti-spike protein receptor-binding domain (S-RBD) antibodies represents a useful tool to estimate the long immunity against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection. The aim of this study was to evaluate the kinetics of antibody response in vaccine recipients. We measured anti-S-RBD IgG levels by indirect chemiluminescence immunoassay on Maglumi 800 (SNIBE, California) in 1013 healthy individuals naïve to SARS-CoV2 infection after two and three COVID-19 vaccine doses. We found that anti-S-RBD IgG levels are higher in females than males. Antibody levels gradually decrease to a steady state after four months since the pea…

Clinical usefulness of Glycated Albumin in the diagnosis of diabetes: Results from an Italian study

Objectives: Glycated Albumin (GA) has been proposed as a screening marker for diabetes in Asian countries in the last years. Nevertheless, few studies have been conducted in Caucasian population. The aim of this study is to evaluate the clinical usefulness of GA in diabetes diagnosis in Caucasian asymptomatic subjects considered at risk of diabetes based on medical history and Fasting Plasma Glucose (FPG). Design and methods: Three hundred and thirty-four Caucasian subjects having one or more risk factor for diabetes, and/or FPG ranging from 5.6 mmol/L to 6.9 mmol/L with no symptoms for diabetes were enrolled in this study. Plasma GA was measured by an enzymatic method (quantILab Glycated A…

Deficiency of vitamin K dependent coagulation factors: first symptom of chronic inflammatory bowel disease?

Standardized measurement of circulating vitamin D [25(OH)D] and its putative role as a serum biomarker in Alzheimer's disease and Parkinson's disease

The current review provides an overview on the development of 25(OH)D measurement standardization tools over the last three decades and clarifies whether there is a role as a serum biomarker for vitamin D in neurological diseases. In the past, a lack of internationally recognized 25(OH)D reference measurement procedures and reference standard materials led to unstandardized serum total 25(OH)D results among research and clinical care laboratories. The vitamin D Standardization Program (VDSP) has been introduced in 2010 to address this problem, however, vitamin D External Quality Assessment Scheme (DEQAS) reports still show substantial sample- to- sample variability. Further, immunoassays, w…

Fetuin-A serum levels are not correlated to kidney function in long-lived subjects

Objectives: Serum Fetuin A has been identified as an inhibitor of ectopic calcification. It is reduced in subjects with chronic kidney disease (CKD) and it has been proposed as a potential link between CKD and the higher prevalence of arterial calcification observed in these patients. During ageing both the stiffening of arterial wall due to calcification and a decline in kidney function are frequent. The aim of the study is to investigate if Fetuin A serum levels are associated with ageing and with AHSG T256S polymorphism. Moreover, we aim at investigate whether serum Fetuin A is correlated to kidney function in this setting of senescence. Design and Methods: 256 health long-lived subjects…

The Role of TAR DNA Binding Protein 43 (TDP-43) as a CandiDate Biomarker of Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis

Background: TAR DNA-binding protein 43 (TDP-43) aggregation in neuronal cells is recognized as a hallmark of amyotrophic lateral sclerosis (ALS). Although the literature strongly supports the pathogenetic role of TDP-43 in ALS pathogenesis, the role of TDP-43 as a biomarker of ALS is controversial. We performed a systematic review and meta-analysis to assess the diagnostic performance of TDP-43 for ALS. Methods: Relevant publications were identified by a systematic literature search on PubMed and Web of Science from their inception to 8 April 2022. Results: Seven studies, including 472 individuals, of whom 254 had ALS according to the Revised Amyotrophic Lateral Sclerosis Functional Rating …

A singular case of multiple acquired coagulopathies with antibodies antiphospholipid

Independent Validation of Sepsis Index for Sepsis Screening in the Emergency Department

(1) Background: The early detection of sepsis is still challenging, and there is an urgent need for biomarkers that could identify patients at a high risk of developing it. We recently developed an index, namely the Sepsis Index (SI), based on the combination of two CBC parameters: monocyte distribution width (MDW) and mean monocyte volume (MMV). In this study, we sought to independently validate the performance of SI as a tool for the early detection of patients at a high risk of sepsis in the Emergency Department (ED). (2) Methods: We enrolled all consecutive patients attending the ED with a request of the CBC. MDW and MMV were measured on samples collected in K3-EDTA tubes on the UniCel …

Monocyte distribution width (MDW) as a screening tool for sepsis in the Emergency Department

Abstract Objectives The diagnosis of sepsis in the Emergency Department (ED) is challenging and a reliable biomarker is needed. The current study aimed to evaluate the diagnostic accuracy of monocyte distribution width (MDW) for the early identification of sepsis in the ED. Methods We performed a large observational study including consecutive adult patients (≥18 years of age) presenting to the ED between September and November 2019, with an order for complete blood count (CBC) evaluation. A total of 2,215 patients were enrolled and classified based on Sepsis-2 criteria as the control group (1,855), infection group (172), Systemic Inflammatory Response Syndrome (SIRS) group (100), and sepsi…

Polimorfismo del gene ACE:gene della longevità o fattore di rischio nella patologia ipertensiva

Negli ultimi decenni l’allungamento della vita media ha stimolato un particolare interesse nello studio dei processi dell’invecchiamento e nella ricerca di possibili geni coinvolti nella longevità. In particolare i centenari dimostrano di avere una prevalenza minore di malattie cardiovascolari e dei fattori di rischio ad essa correlati. L’enzima di conversione dell’angiotensina (ACE), presente in tutte le cellule endoteliali, gioca un ruolo essenziale nel mantenimento dell’omeostasi del flusso vascolare, regolando sia la produzione del vasocostrittore angiotensina II sia inattivando la bradichinina. In particolare alcuni studi hanno riportato una possibile correlazione tra il polimorfismo I…

Reference interval by the indirect approach of serum thyrotropin (TSH) in a Mediterranean adult population and the association with age and gender.

Abstract Background The serum concentration of thyrotropin (TSH) represents a first-line test in diagnostic algorithms. The estimation of TSH reference intervals (RIs) is still a matter of debate due to the high prevalence of subclinical disease making difficult the definition of truly healthy subjects. The aim of this study was to estimate TSH RIs in healthy subjects and to evaluate the effect of age and gender on TSH concentration. Methods Forty-four thousand one hundred and fifty-six TSH data were collected between July 2012 and April 2018 at the Department of Laboratory Medicine, University-Hospital, Palermo. Common and sex-specific RIs were estimated by Arzideh’s indirect method after …

Comparative analysis of biochip mosaic-based indirect immunofluorescence with enzyme-linked immunosorbent assay for diagnosing myasthenia gravis

Background: The detection of anti-acetylcholine receptor (AChR) and anti-muscle-specific tyrosine kinase (MuSK) antibodies is useful in myasthenia gravis (MG) diagnosis and management. BIOCHIP mosaic-based indirect immunofluorescence is a novel analytical method, which employs the simultaneous detection of anti-AChR and anti-MuSK antibodies in a single miniature incubation field. In this study, we compare, for the first time, the BIOCHIP MG mosaic with conventional enzyme-linked immunosorbent assay (ELISA) in the diagnosis of MG. Methods: A total of 71 patients with MG diagnosis were included in the study. Anti-AChR and anti-MuSK antibodies were measured separately by two different ELISA an…

Monocyte distribution width as a biomarker of sepsis in the intensive care unit: A pilot study.

Background Monocyte distribution width has been recently proposed as a sepsis biomarker in the emergency department. The aim of this study was to assess the role of monocyte distribution width as a diagnostic biomarker of sepsis in the intensive care unit. Methods In this prospective observational study, we included all consecutive patients admitted to the intensive care unit of the University Hospital “P. Giaccone” of Palermo. Patients were classified into three groups according to Sepsis-3 criteria: (1) patients without sepsis; (2) patients developing sepsis during their hospital stay; (3) patients admitted with sepsis. Monocyte distribution width was measured at admission (groups 1, 2, 3…

Prothrombotic variants in elderly

Association between angiotensin I - converting enzyme gene insertion/deletion polymorphism and thromboembolic disease.

The Value of a Complete Blood Count (CBC) for Sepsis Diagnosis and Prognosis.

Sepsis represents an important global health burden due to its high mortality and morbidity. The rapid detection of sepsis is crucial in order to prevent adverse outcomes and reduce mortality. However, the diagnosis of sepsis is still challenging and many efforts have been made to identify reliable biomarkers. Unfortunately, many investigated biomarkers have several limitations that do not support their introduction in clinical practice, such as moderate diagnostic and prognostic accuracy, long turn-around time, and high-costs. Complete blood count represents instead a precious test that provides a wealth of information on individual health status. It can guide clinicians to early-identify …

Short-term Changes in Gal 3 Circulating Levels After Acute Myocardial Infarction.

Background and Aims Galectin 3 (Gal 3) is a β-galactoside-binding lectin known to play a part in inflammation, adverse remodeling and fibrosis. Gal 3 seems to be linked to atherogenesis and Coronary Artery Disease (CAD), but less is known about the relationship between Gal 3 and acute myocardial infarction (AMI). The aim of the present study is to assess circulating levels of Gal 3 after AMI and to evaluate short-term changes of the biomarker within 5 days from the acute event. Methods Two hundred fifteen confirmed AMI patients (125 STEMI, M/F = 2.8; mean age: 65.4 ± 13.8 years) were enrolled in the present study; two blood samples were collected from each patient: first, within 1 h from ad…

MTHFR C677T allelic variant is not associated to plasma and cerebrospinal fluid homocysteine in amyotrophic lateral sclerosis

Effects of GLP-1 receptor agonists on myokine levels and pro-inflammatory cytokines in patients with type 2 diabetes mellitus.

Background and aims: To evaluate the change in circulating serum irisin and interleukin-6 (IL-6), in patients with type 2 diabetes mellitus (T2DM) after 6 and 12 months of GLP-1 treatment. Methods and results: Eighty-five patients with T2DM inadequately controlled with insulin or other hypoglycaemic drugs were added to dulaglutide (N° = 44) and liraglutide (N° = 41) treatment. After 6 months of GLP-1 analogues a significant decrease in BMI (p < 0.001), waist circumference (WC) (p < 0.001), fasting blood glucose (p < 0.001), HbA1c (p < 0.001), total cholesterol (p < 0.001), LDL-cholesterol (p = 0.003), triglycerides (p = 0.017), IL-6 (p = 0.045) and a significant increase in s…

Vitamin D in malaria: more hypotheses than clues

Abstract Vitamin D is a secosteroid hormone regulating calcium and phosphate metabolism, immune response and brain development. Low blood 25(OH)D levels have been reported in patients affected by infectious diseases caused by parasites, including malaria. Despite the high effectiveness of antimalarials, malaria is burdened with high morbidity and mortality, and the search for additional therapies is rapidly growing. Furthermore, available preventive measures have proved to be barely effective so far. Finding new prevention and therapy tools is a matter of urgency. Studies on animal models and humans have hypothesized some mechanisms by which the hormone can influence malaria pathogenesis, a…

Diagnostic accuracy of cerebrospinal fluid biomarkers measured by chemiluminescent enzyme immunoassay for Alzheimer disease diagnosis.

In the last decades, an important role of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD) diagnosis has emerged. The evaluation of the triad consisting of 42 aminoacid-long amyloid-beta peptide (Aβ42), total Tau (tTau) and Tau phosphorylated at threonine 181 (pTau) have been recently integrated into the research diagnostic criteria of AD. For a long time, the enzyme-linked immunosorbent assay (ELISA) has represented the most commonly used method for the measurement of CSF biomarkers levels. This study aimed to assess the diagnostic accuracy of CSF biomarkers, namely Aβ42, tTau and pTau and their ratio, measured by fully automated CLEIA assay (Lumipulse). We included 96 patie…

Separazione della beta-N-metilammino-L-alanina (BMAA) in campioni di liquor cefalorachidiano mediante HPLC con rilevazione fluorimetrica

Thromboelastography or conventional coagulation tests in polytraumatized patient: which is the best?

Additional file 1 of Circulating histones contribute to monocyte and MDW alterations as common mediators in classical and COVID-19 sepsis

Additional file 1: Table S1 Comparison of MDW characteristics between healthy subjects after 3 h of in vitro treatment and in vivo patients affected by classic and viral Sepsis. Table S2 Time-dependent MDW modifications obtained in healthy whole blood samples after in vitro treatments.

Effect of mid-region PTHrP on tumoral and immortalized human breast cells

Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer’s Disease from Other Neurological Disorders

Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aβ42/Ng and Aβ42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn…

Monocyte Distribution Width (MDW) as a biomarker of sepsis: An evidenced-based laboratory medicine approach.

Monocyte Distribution Width (MDW) is a new generation cell blood count parameter providing a measure of monocyte anisocytosis. In the last decades, it has emerged as a reliable biomarker of sepsis in the acute setting, especially emergency department, and intensive care unit. MDW has several advantages over commonly used sepsis biomarkers, including low-cost, ease and speed of measurement. The clinical usefulness of MDW has been established in several studies and some clinical laboratory medicines have already implemented it in their routine. In this article, we describe the analytical and clinical features of MDW to guide its appropriate use in clinical practice by integrating the research…

ADIPONECTIN, RESISTIN AND IL-6 PLASMA LEVELS IN SUBJECTS WITH DIABETIC FOOT AND POSSIBLE CORRELATION WITH CLINICAL VARIABLES AND CARDIOVASCULAR CO-MORBIDITY

Abstract Introduction It is very suggestive that diabetic foot is characterized by a pronounced inflammatory reaction and the pathogenic significance of this inflammation has received little attention. On this basis the aim of our study was to evaluate plasma levels of adiponectin, resistin and IL-6 in subjects with diabetic foot in comparison with subjects without foot complications. Materials and methods We recruited 34 subjects with type 2 diabetes mellitus and foot ulceration hospitalized for every condition related to diabetic disease, but not for new vascular events (group A). As controls we recruited 37 patients with type 2 diabetes mellitus without foot ulceration (group B) hospital…

C-reactive protein but not soluble CD40 ligand and homocysteine is associated to common atherosclerotic risk factors in a cohort of coronary artery disease patients.

Abstract Objectives One third to one half of the variation in vascular disease occurrence remains unexplained by traditional risk factors. Since atherosclerosis may, in part, be an inflammatory disease, circulating factors related to inflammation may be predictors of cardiovascular disease. The aim of this study was to evaluate the association between common atherosclerotic risk factors and markers of inflammation. Design and methods Serum levels of soluble CD40 (sCD40L), high-sensitive C-reactive protein (hs-CRP) and homocysteine (Hcy) were measured in 251 patients selected from a series of 438 subjects affected by previous myocardial infarction, angina or other cardiovascular diseases. Re…

The role of prothrombotic variants in acute ischemic stroke

The importance of “hot chain” in the research and characterization of cryoglobulins

Non-Skeletal Activities of Vitamin D: From Physiology to Brain Pathology.

Vitamin D is a secosteroid hormone regulating the expression of almost 900 genes, and it is involved in the regulation of calcium and phosphate metabolism, immune response, and brain development. Low blood vitamin D levels have been reported in patients affected by various diseases. Despite a large amount of literature data, there is uncertainty surrounding the role of vitamin D as a serum biomarker in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Indeed, the lack of internationally recognized 25(OH)D3 reference measurement procedures and standard materials in the past led to unstandardized serum total 25(OH)D3 results among research and clinical care laboratories. Thus…

Glycated albumin as a glycaemic marker in patients with advanced chronic kidney disease and anaemia: a preliminary report.

BACKGROUND: The association between glycated albumin (GA) and glycaemic status has not been fully described in patients with advanced chronic kidney disease (CKD) in relation to anaemia. The aim of this study was to evaluate the relationship between GA and fasting plasma glucose (FPG) and HbA1c in patients with advanced CKD and to evaluate the influence of anaemia in such relationship. MATERIALS AND METHODS: Patients with CKD stage 4 or 5 were included in the study. eGFR was calculated by the CKD-EPI creatinine equation. Plasma GA was measured by an enzymatic method. RESULTS: Eighty-one patients were included in the study, 46 (57%) were males; the mean age was 67 ± 14 years. HbA1c was corre…

FROM THE BLOOD- BRAIN BARRIER TO BEHAVIOR

Research in the field of neuropsychoimmunology has enabled the researchers to show that cytokines target the brain to organize a "sickness response," which is fever, activation of hypothalamuspituitary- adrenal axis and behavioural alterations that develop in sick individuals. perypheral cytokines do not act directly on the brain; they trigger the production of cytokines in the brain parenchima itself, with a possible relay at the interface between internal milieeu and the brain, which are endothelial cells and circumven- tricular organs. The affective and behavioural changes that develop during in- fluenza are the product of a transient brain inflammatory response induced by the same proin…

The Role of Vitamin D as a Biomarker in Alzheimer’s Disease

Vitamin D and cognition is a popular association, which led to a remarkable body of literature data in the past 50 years. The brain can synthesize, catabolize, and receive Vitamin D, which has been proved to regulate many cellular processes in neurons and microglia. Vitamin D helps synaptic plasticity and neurotransmission in dopaminergic neural circuits and exerts anti-inflammatory and neuroprotective activities within the brain by reducing the synthesis of pro-inflammatory cytokines and the oxidative stress load. Further, Vitamin D action in the brain has been related to the clearance of amyloid plaques, which represent a feature of Alzheimer Disease (AD), by the immune cell. Based on the…

Association of CYP2R1 rs10766197 with MS risk and disease progression

Background MS is a neurodegenerative autoimmune disease resulting from a complex interaction of genetic and environmental factors. Among these, vitamin D and genetic variants associated with vitamin D-metabolism gain great attention. The aim of our study was to assess five SNPs in NADSYN1 and CYP2R1 genes in relation to serum 25-OH-vitamin D3 levels in MS patients and controls. Methods 25-OH-vitamin D3 levels and genotyping of CYP2R1- and NADSYN1-SNPs were investigated both in MS patients and in healthy controls. Results The analysis revealed lower 25-OH-vitamin D3 concentrations in MS patients than in controls and an association of rs10766197 CYP2R1 SNP with MS risk. After stratifying MS p…

Effects of EPHX1 and CYP3A4 polymorphisms on carbamazepine metabolism in epileptic patients

Antonietta Caruso, Chiara Bellia, Alessia Pivetti, Luisa Agnello, Federica Bazza, Concetta Scazzone, Giulia Bivona, Bruna Lo Sasso, Marcello CiaccioDepartment of Biopathology and Medical and Forensic Biotechnologies, University of Palermo, Palermo, ItalyBackground: The aim of this study was to investigate the effect of two genetic polymorphisms in the coding regions (exon 3 and exon 4) of the EPHX1 gene, ie, 337T>C and 416A>G, respectively, on the metabolism of carbamazepine (CBZ) 10,11-epoxide (the active metabolite of CBZ) by evaluating the variation in serum CBZ 10,11-epoxide levels 4 hours after administration of the drug. Moreover, we reported the genotype frequencies of …

The effects of estradiol levels on crossmodal perception: a study on the sound induced flash illusion in healthy and menstrually related migraine individuals

Abstract Objective The sound-induced flash illusion (SIFI) is a valid paradigm to study multisensorial perception. In the “fission” SIFI, multiple flashes are perceived when observing a single flash paired with two or more beeps. SIFI is largely dependent on visual and acoustic cortex excitability; in migraine, dysfunctional cortical excitability affects SIFI perception. Since estrogen peak occurring during ovulation can increase neuronal excitability, the present study aims to verify whether cortical excitability shifts linked to the menstrual cycle could influence SIFI. Methods In a comparative prospective study, we tested the effect of estrogens on crossmodal perception using the SIFI. W…

Vitamin K Deficit leads to Chronic Inflammatory Bowel Disease Diagnosis: a case report

Effect of genetics polymorphism of carbamazepine – metabolizing enzymes in epileptic patients

Fetun-A and end stage renal disease: correlations with haemodialytic single session and genotype

Several studies showed that Fetuin-a is an extracellular calcium-regulatory protein acting as a potent inhibitor of calcium-phosphate precipitation, involved also in bone metabolism because of its high affinity for hydroxyapatite. The aim of this study is to evaluate the serum Fetuin-A levels in patients with chronic renal failure before and after a single session of dialysis and to investigate the correlation between protein serum concentrations and T256S genotype. Our results show that serum Fetuin- A levels decrease 4 hours after haemodialysis treatment and a significant correlation between 256SS homozygote and serum protein levels. Ectopic calcification and particularly intravascular ca…

Rip-1 regulation of caspase expression in PTHrP [38-94]-treated MDA-MB231 breast cancer cells

Plasminogen Activator Inhibitor-1 -675 4G/5G and Methylenetetrahydrofolate reductase gene variants in young acute myocardial infarction and juvenile ischemic stroke

Fetuin-A in elderly: effect of genotype on serum levels

Fetuin-A is a circulating inhibitor of ectopic calcification in vivo; it is decreased in patients with chronic kidney disease and correlates with glomerular filtration rate in patients with coronary artery disease. However, serum levels of Fetuin-A has not been described in elderly. Aim of the study was to evaluate Fetuin-A serum levels together with AHSG T256S genotype in a population of healthy elderly. Serum fetuin-A levels were determined by ELISA. T256S polymorphism of AHSG gene was determined by PCR-RFLP. Serum Fetuin-A was 0,38 ± 0,13 g/l in the group composed by 206 healthy centenarians. Moreover, subjects with at least one S allele had lower Fetuin-A levels (P<001). Interestingly, …

A case of Hepatitis C virus and mixed cryoglobulinemia in a patient with Kidney Disease

Hyperhomocysteinemia in patients with cognitive impairment

Cognitive impairment is common in elderly people and represents clinical feature of neurodegenerative diseases. Not all of patients with Mild Cognitive Impairment (MCI) finally develop dementia and it is interesting to investigate the role of possible markers for early diagnosis. Hyperhomocysteinemia is associated to several pathologies including cognitive impairment; aim of this study is to evaluate the correlation between cognitive performance assessment and homocysteine plasma levels. Total 74 patients and 75 healthy controls were enrolled and MCI were defined by a MMSE score lower than 26 after adjustment for years of schooling. Homocysteine plasma levels were determined. Homocysteine l…

Monocyte distribution width kinetic after surgery

Not available

Outcome predictors in SARS-CoV-2 disease (COVID-19): The prominent role of IL-6 levels and an IL-6 gene polymorphism in a western Sicilian population

Activity of mannose-binding lectin in centenarians

We analyzed MBL2 gene variants in two cohorts of centenarians, octo-nonagenarians and nonagenarians, and in the general population, one from Sardinia Island (Italy), recruited in the frame of the AKea study, and another from Campania (southern Italy), to search for haplotypes related to longevity. We also assessed in vitro the effect of mannose-binding lectin (MBL) on various human cells at different stage of senescence. The frequency of high and null activity haplotypes was significantly lower, and the frequency of intermediate activity haplotype significantly higher in centenarians and in subjects between 80 and 99 years from both the cohorts as compared each to the general population fro…

Validation of monocyte distribution width decisional cutoff for sepsis detection in the acute setting

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Mid-regional pro-adrenomedullin predicts poor outcome in non-selected patients admitted to an intensive care unit.

AbstractBackgroundMortality risk and outcome in critically ill patients can be predicted by scoring systems, such as APACHE and SAPS. The identification of prognostic biomarkers, simple to measure upon admission to an intensive care unit (ICU) is an open issue. The aim of this observational study was to assess the prognostic value of plasma mid-regional pro-adrenomedullin (MR-proADM) at ICU admission in non-selected patients in comparison to Acute Physiology and Chronic Health Evaluation II (APACHEII) and Simplified Acute Physiology Score II (SAPSII) scores.MethodsAPACHEII and SAPSII scores were calculated after 24 h from ICU admission. Plasma MR-proADM levels were measured by TRACE-Kryptor…

Midregion PTHrP regulates Rip1 and caspase expression in MDA-MB231 breast cancer cells.

It was previously reported that the midregion PTHrP domain (38-94)-amide restrains growth and invasion "in vitro", causes striking toxicity and accelerates death of some breast cancer cell lines, the most responsive being MDA-MB231 whose tumorigenesis was also attenuated "in vivo". In addition, we have demonstrated that midregion PTHrP is imported in the nucleoplasm of cultured MDA-MB231 cells, and that "in vitro" it can bind chromatin of metaphase spread preparations and also an isolated 20-mer oligonucleotide, thereby appearing endowed with a putative transcription factor-like DNA-binding ability. Here, we examined whether PTHrP (38-94)-amide was able to modulate the expression of genes e…

Reference interval of monocyte distribution width (MDW) in healthy blood donors.

Abstract Background The aim of the study was to accurately establish the reference interval (RI) of monocyte distribution width (MDW) in healthy blood donors by the direct method using different statistical approaches. Methods MDW was measured in 486 subjects. RI of MDW was calculated by the non-parametric method, the robust method and, the Harrell-Davis bootstrap method and using different tests to identify potential outliers (Dixon-Reed and Tukey). Results Lower and upper reference limits of the RI calculated by the non-parametric method were, 16.22 (90%CI 15.78–16.47) – 23.15 (90%CI 22.80–24.10) (without outlier removal), and 16.44 (90%CI 16.21–16.67) – 22.99 (90%CI 22.33–23.22) (after o…

Neurogranin as a Reliable Biomarker for Synaptic Dysfunction in Alzheimer’s Disease

(1) Background: Neurogranin is a post-synaptic protein expressed in the neurons of the hippocampus and cerebral cortex. It has been recently proposed as a promising biomarker of synaptic dysfunction, especially in Alzheimer&rsquo;s disease (AD). However, more efforts are needed before introducing it in clinical practice, including the definition of its reference interval (RI). The aim of the study was to establish the RI of cerebrospinal fluid (CSF) neurogranin levels in controls and individuals with non-neurodegenerative neurological diseases; (2) We included a total of 136 individuals that were sub-grouped as follows: AD patients (n = 33), patients with non-neurodegenerative neurological …

No effect of MTHFR C677T variant on homocysteine metabolism in Amiotrophic Lateral Sclerosis

Preliminary reference intervals of Glycated Albumin in healthy Caucasian pregnant women

Abstract Background and aims Glycated albumin (GA) could represent a useful biomarker in pregnant women for diagnosing and monitoring gestational diabetes mellitus (GDM). The establishment of reference intervals (RI) is mandatory before assessing its clinical usefulness. The RIs of GA in healthy pregnant women are not well defined. The aim of the current study was to establish the RI in a cohort consisting of Caucasian pregnant women without overt diabetes mellitus or gestational diabetes mellitus. Methods The study included 183 healthy pregnant women. GA was measured on plasma by an enzymatic method (quantILab Glycated Albumin, IL Werfen, Germany). The RI was calculated by the non-parametr…

Evaluation of Anti-SARS-Cov-2 S-RBD IgG Antibodies after COVID-19 mRNA BNT162b2 Vaccine

(1) Background: The evaluation of anti-spike protein receptor-binding domain (S-RBD) antibodies represents a useful tool to estimate the individual protection against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection

Aging and neuroinflammatory disorders: New biomarkers and therapeutic targets

: Chronic neuroinflammation is a common feature of the pathogenic mechanisms involved in various neurodegenerative age-associated disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson’s disease, and dementia. : In particular, persistent low-grade inflammation may disrupt the brain endothelial barrier and cause a significant increase of pro-inflammatory cytokines and immune cells into the cerebral tissue that, in turn, leads to microglia dysfunction and loss of neuroprotective properties. : Nowadays, growing evidence highlights a strong association between persistent peripheral inflammation, as well as metabolic alterations, and neurodegenerative disorder susceptibility. The…

Autoimmunity Features in Patients With Non-Celiac Wheat Sensitivity.

INTRODUCTION: Nonceliac wheat sensitivity (NCWS) is characterized by intestinal and extraintestinal manifestations consequent to wheat ingestion in subjects without celiac disease and wheat allergy. Few studies investigated the relationship between NCWS and autoimmunity. The aim of this study is to evaluate the frequency of autoimmune diseases (ADs) and autoantibodies in patients with NCWS. METHODS: Ninety-one patients (13 men and 78 women; mean age of 40.9 years) with NCWS, recruited in a single center, were included. Seventy-six healthy blood donors (HBD) and 55 patients with a diagnosis of irritable bowel syndrome (IBS) unrelated to NCWS served as controls. Autoantibodies levels were mea…

Utility of serum procalcitonin and C-reactive protein in severity assessment of community-acquired pneumonia in children

OBJECTIVES: Although the importance of serum Procalcitonin (PCT) levels at diagnosis is well established in adult Community-Acquired Pneumonia (CAP), its use remains controversial in pediatric CAP. The aim of our study is to investigate the role of PCT and C-Reactive Protein (CRP) in the assessment of pediatric CAP severity defined by the extent of consolidation on chest X-rays and the presence of pleural effusion. In this particular setting, no clinical severity score is available at present and chest X-ray, although important for diagnosis confirmation, is not recommended as routine test. DESIGN AND METHODS: The study involved 119 children admitted to the Department of Pediatric Infectiou…

Acute troponin i increase in absence of obstructive coronary disease: A case of takotsubo syndrome

A 66-year-old woman was admitted to the Emergency Department of Policlinico P. Giaccone, in Palermo, for non-radiating chest pain that occurred after an emotional stress. Her medical history included a positive family history for cardiovascular disease, arterial hypertension, gastro-esophageal reflux disease, and anxiety-depressive syndrome. Upon admission, the electrocardiogram showed diffuse ST-T abnormalities with an elevation of the ST segment; Troponin I was 3790 ng/L, creatine phosphokinase was 374 U/L, which became normal within 48 hours. No evidence of significant coronary artery stenosis was detected on the angiography. The echocardiogram showed apical akinesia and hyperkinesia of …

Rip-1 controlla l’espressione delle caspasi in cellule MDA-MB231 trattate con PTHrP[38-94]-amide

Evaluation of Alpha-Synuclein Cerebrospinal Fluid Levels in Several Neurological Disorders

(1) Background: Alpha-synuclein (&alpha;-syn) is a presynaptic neuronal protein that regulates several neuronal functions. In recent decades, the role of &alpha;-syn as a biomarker of neurodegenerative diseases has been explored, especially in synucleinopathies. However, only a few studies have assessed its role as biomarker in other neurological disorders. The aim of the study was to evaluate cerebrospinal fluid (CSF) &alpha;-syn levels in several neurological disorders; (2) Methods: We measured CSF &alpha;-syn levels by a commercial ELISA kit in 158 patients classified in the following group: controls, Alzheimer&rsquo;s Disease (AD), cerebrovascular diseases, inflammatory central nervous …

Vitamin D and Genetic Susceptibility to Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system (CNS), resulting from the interaction among genetic, epigenetic, and environmental factors. Vitamin D is a secosteroid, and its circulating levels are influenced by environment and genetics. In the last decades, research data on the association between MS and vitamin D status led to hypothesize a possible role for hypovitaminosis D as a risk factor for MS. Some gene variants encoding proteins involved in vitamin D metabolism, transport, and function, which are responsible for vitamin D status alterations, have been related to MS susceptibility. This review explores the current literature on the influence o…

Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis

BACKGROUND AND PURPOSE To test the hypothesis that total tau (tTau), tau phosphorylated at threonine 181 (pTau) and pTau/tTau ratio in the cerebrospinal fluid (CSF) are diagnostic and prognostic biomarkers of amyotrophic lateral sclerosis (ALS), we performed a retrospective observational study in a large cohort of ALS patients and controls. METHODS We enrolled 196 ALS patients and 91 controls, who included patients with ALS-mimicking diseases and those with non-neurodegenerative diseases. All patients underwent lumbar puncture for CSF analysis at the time of the diagnostic evaluation or to first referral. We measured tTau and pTau levels in the CSF by chemiluminescence enzyme immunoassay. R…

Role of Multiple Vitamin D-Related Polymorphisms in Multiple Sclerosis Severity: Preliminary Findings

Background: Multiple Sclerosis (MS) is a multifactorial disease whose pathogenesis is the result of interaction among genetic, epigenetic, and environmental factors. Among these, a role for vitamin D hypovitaminosis has emerged in recent decades. Vitamin D levels are influenced by both environmental and genetic factors. Single nucleotide polymorphisms (SNPs) in genes codifying for molecules involved in vitamin D metabolism have been associated with an increased risk of developing MS. However, few studies assessed the association of such SNPs with the severity of the disease. The aim of this observational study was to evaluate the potential association among vitamin D status, MS severity, an…

Therapeutic monitoring of autoantibodies Tumor Necrosis Factor α inhibitor drugs: Efficacy and benefit for patients with autoimmune diseases

Tumor necrosis factor alpha (TNFα) is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory disease, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Chron's disease and ulcerative colitis. TNFα inhibitors (anti-TNFα) are monoclonal antibodies drugs directed against TNFα (i.e. adalimumab, infliximab, etarnecept, golimumab and certolizumab). Their effect consists in reducing the inflammatory response of autoimmune diseases. Several randomized controlled trials and observational studies evaluated the therapeutic efficacy of these drugs and reported a clear benefit for patients affected by chronic inflammatory disease treated with anti-TNFα, …

Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study

Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patente…

MTHFR C677T allelic variant is not associated to plasma and cerebrospinal fluid homocysteine in amyotrophic lateral sclerosis

Amiotrophic lateral sclerosis (ALS) is a neurological disorder with a multifactorial etiopathogenesis including excitotoxicity, intracellular calcium increase and mitochondrial damage together with oxidative stress and apoptosis. Overall, the relationship between homocysteine (Hcy), motoneuron death and ALS appears to be complex and still under investigation. It has been already shown that Hcy is elevated in plasma and cerebrospinal fluid (CSF) of ALS patients, although mechanisms of hyperhomocysteinemia have not been elucidated yet. MTHFR C677T variant is the most common genetic determinant of increased homocysteinemia, but no studies regarding the effect of this polymorphism in ALS patien…

APO E allelic variants in healthy elderly people

Clinical Use of κ Free Light Chains Index as a Screening Test for Multiple Sclerosis.

Abstract Objective To assess the usefulness of the κ free light chain index (κFLCi) as a screening test to identify patients with suspected MS. Methods The study included 56 patients with a request to test for oligoclonal bands (OCBs). OCBs were detected by isoelectric focusing, followed by immunofixation. Cerebrospinal fluid (CSF) and serum κFLC were measured by a turbidimetric assay. Also, the κFLC index (κFLCi) was calculated. Results CSF κFLC levels and κFLCi were significantly higher in patients with multiple sclerosis (MS) than in patients with other neurological diseases (NDs; P &amp;lt; .001 and P &amp;lt; .001, respectively). At the cutoff value of 2.9, the κFLCi detected MS with s…

CSF homocysteine levels in Amyotrophic Lateral Sclerosis

Polimorfismo I/D del gene ACE: possibile biomarcatore genetico della patologia ipertensiva

Neurogranin as a Novel Biomarker in Alzheimer's Disease

Abstract Background In this study, we investigated the possible role of 2 novel biomarkers of synaptic damage, namely, neurogranin and α-synuclein, in Alzheimer disease (AD). Methods The study was performed in a cohort consisting of patients with AD and those without AD, including individuals with other neurological diseases. Cerebrospinal fluid (CSF) neurogranin and α-synuclein levels were measured by sensitive enzyme-linked immunosorbent assays (ELISAs). Results We found significantly increased levels of CSF neurogranin and α-synuclein in patients with AD than those without AD. Neurogranin was correlated with total tau (tTau) and phosphorylated tau (pTau), as well as with cognitive declin…

Comparison of a rapid immunochromatographic test with a chemiluminescence immunoassay for detection of anti-SARS-CoV-2 IgM and IgG

Introduction: The 2019 Coronavirus disease (COVID-19) has been characterized as a pandemic, representing a serious global public health emergency. Serological tests have been proposed as reliable tools for detecting Coronavirus SARS-CoV-2 antibodies in infected patients, especially for surveillance or epidemiological purposes. The aim of this study is to evaluate the agreement between the IgM/IgG rapid assays, based on lateral flow immunochromatographic assay, and the fully automated 2019-nCoV IgM and IgG, based on chemiluminescence immunoassay. Materials and methods: SARS-CoV-2 antibodies were measured with the BIOSYNEX COVID-19 BSS IgM/IgG test (BIOSYNEX, Illkirch-Graffenstaden, France) a…

Distribution of KIR Genes and Their HLA Ligands in Different Viral Infectious Diseases: Frequency Study in Sicilian Population

Natural killer (NK) cells play a role in defence against viral infections by killing infected cells or by producing cytokines and interacting with adaptive immune cells. Killer immunoglobulin-like receptors (KIRs) regulate the activation of NK cells through their interaction with human leucocyte antigens (HLA). Ninety-six Sicilian patients positive to Human Immunodeficiency Virus-1 (HIV) and ninety-two Sicilian patients positive to SARS-CoV-2 were genotyped for KIRs and their HLA ligands. We also included fifty-six Sicilian patients with chronic hepatitis B (CHB) already recruited in our previous study. The aim of this study was to compare the distribution of KIR–HLA genes/groups of these t…