Synthesis, characterization, interactions with the DNA duplex dodecamer d(5'-CGCGAATTCGCG-3') and cytotoxicity of binuclear η-arene-Ru(II) complexes.

The novel binuclear η-arene-Ru(II) complexes with the general formula {[(η-cym)Ru(L)](μ-BL)}(PF), and their corresponding water soluble {[(η-cym)Ru(L)](μ-BL)}Cl, where cym = -cymene, L = 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen), BL = 4,4'-bipyridine (BL-1), 1,2-bis(4-pyridyl)ethane (BL-2) and 1,3-bis(4-pyridyl)propane (BL-3), were synthesized and characterized. The structure of {[(η-cym)Ru(phen)](μ-BL-1)}(PF) was determined by X-ray single crystal methods. The interaction of {[(η-cym)Ru(phen)](μ-BL-)}Cl ( = 1, 2, 3; (4), (5) and (6) correspondingly) with the DNA duplex d(5'-CGCGAATTCGCG-3') was studied by means of NMR techniques and fluorescence titrations.

Retrospective identification of new psychoactive substances in patient samples submitted for clinical drug analysis.

New psychoactive substances (NPS) are life threatening through unpredictable toxicity and limited analytical options for clinicians. We present the retrospective identification of NPS in raw data from a liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based multidrug panel analysis on 14 367 clinical oral fluid samples requested during 2019 mainly by psychiatric and addiction care clinics. Retrospectively analysed NPS included 48 notified originally in 2019 by the European Union Early Warning System (EU EWS) and 28 frequently reported in Sweden.

Association between Vitamin D Serum Levels and Immune Response to the BNT162b2 Vaccine for SARS-CoV-2.

The use of micronutrients such as vitamin D could improve the response to viral vaccines, particularly in immunosuppressed and immunosenescent subjects. Here, we analysed the association between serum 25-hydroxyvitamin D (25OHD) levels and the immune response elicited by the BNT162b2 vaccine in a cohort of 101 healthcare workers naïve for SARS-CoV-2 infection. We observed no significant differences in anti-spike (S) IgG and T-cell responses according to the 25OHD status at baseline.

Alterations in glycosaminoglycan biosynthesis associated with the Ehlers-Danlos syndromes.

Proteoglycans consist of a core protein substituted with one or more glycosaminoglycan (GAG) chains and execute versatile functions during many physiological and pathological processes. The biosynthesis of GAG chains is a complex process that depends on the concerted action of a variety of enzymes. Central to the biosynthesis of heparan sulfate (HS) and chondroitin sulfate/dermatan sulfate (CS/DS) GAG chains is the formation of a tetrasaccharide linker region followed by biosynthesis of HS or CS/DS-specific repeating disaccharide units, which then undergo modifications and epimerization.

A + T ± status across MCI and dementia due to AD: a clinic-based, retrospective study.

Background: This study aimed at comparing, within the 2018 NIA-AA amyloidosis/tauopathy/neurodegeneration (ATN) framework, the distribution of T ± profiles across A + patients with MCI and dementia in a retrospective, single-center, clinic-based cohort.

Methods: We retrospectively collected data on N = 168 A + patients with either MCI due to AD (N = 50) or probable AD dementia (ADD; N = 118). ATN status was assigned, according to the 2018 NIA-AA framework, based on cerebrospinal fluid (CSF) biomarker concentrations.

Profiling of lipid mediators in atherosclerotic carotid plaques from type 2 diabetic and non-diabetic patients.

Background And Aims: Diabetes is associated with an accelerated development of atherosclerosis. Specific mechanisms related to diabetes and hyperglycemia may play a role in this process. In particular, alterations of arachidonic acid (AA) metabolism have been reported.

Quantitative Analysis of Vertical Transmission of Maternal SARS-CoV-2 Antibodies to Neonates and Young Infants Following Immunization During Pregnancy.

Serum antibody levels to SARS-CoV-2 in infants born to mothers who had received 2 doses of the BNT2b2 vaccine during pregnancy correlated positively with increasing gestational age at vaccination (P < .01) and negatively with increasing time from vaccination (P < .01), with a significant drop in infants aged >60 days (P = .

Progressive, Qualitative, and Quantitative Alterations in HDL Lipidome from Healthy Subjects to Patients with Prediabetes and Type 2 Diabetes.

Prediabetes is a clinically silent, insulin-resistant state with increased risk for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD). Since glucose homeostasis and lipid metabolism are highly intersected and interrelated, an in-depth characterization of qualitative and quantitative abnormalities in lipoproteins could unravel the metabolic pathways underlying the progression of prediabetes to T2D and also the proneness of these patients to developing premature atherosclerosis. We investigated the HDL lipidome in 40 patients with prediabetes and compared it to that of 40 normoglycemic individuals and 40 patients with established T2D using Nuclear Magnetic Resonance (NMR) spectroscopy.

Association of per- and polyfluoroalkyl substances with thyroid homeostasis during pregnancy in the SELMA study.

Objectives: To investigate the association of exposure to per- and polyfluoroalkyl substances (PFAS) during early pregnancy with markers of the maternal thyroid system.

Methods: Serum concentrations of seven PFAS as well as thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4), free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. Outcomes were concentrations of TSH and thyroid hormones, FT4/FT3 or TT4/TT3 ratios, TSH/FT4 ratio as a marker of the negative feedback loop, TT4/FT4 or TT3/FT3 ratios as markers of the binding of thyroid hormones to binding proteins.

TSH and FT4 Reference Intervals in Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis.

Context: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology.

Objective: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts.

Methods: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021.

Long-term Transplant Function After Thrombolytic Treatment Ex Vivo of Donated Kidneys Retrieved 4 to 5 H After Circulatory Death.

Background: Using a novel thrombolytic technique, we present long-term transplant function, measured by creatinine and iohexol clearance, after utilizing kidneys from porcine donors with uncontrolled donation after circulatory deaths, with 4.5-5 h of warm ischemia.

Methods: Pigs in the study group were subjected to simulated circulatory death.

Clinical prediction models for mortality in patients with covid-19: external validation and individual participant data meta-analysis.

Objective: To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19.

Design: Two stage individual participant data meta-analysis.

Setting: Secondary and tertiary care.

Distant free air is not a contraindication for definitive laparoscopic treatment of acute perforated diverticulitis: a multi-center experience.

The paradigm of emergency laparotomy with sigmoid resection and protective stoma has been challenged for perforated diverticular disease (PDD) with free extraluminal air. Early clinical stabilization could lead to interval laparoscopic resection without stoma within 2 weeks from perforation. Patients admitted for acute diverticulitis underwent abdominal computed tomography (CT) scan.

Distribution of the Clinical Manifestations of Alpha 1 Antitrypsin Deficiency in Respiratory Outpatients from an Area of Northern Italy.

Background: Alpha 1 antitrypsin deficiency (AATD) is an autosomal codominant genetic condition that affects Caucasians of the European population due to the presence of a deficient allele of the SERPINA1 gene. A frequency of about 1/5,000 individuals has been estimated in Italy.

Objectives: The aim of the study was to evaluate the distribution of the clinical manifestations of severe and intermediate genetic AATD in the geographic area around Parma in Northern Italy.

Serum neurofilament light chain levels in Covid-19 patients without major neurological manifestations.

Background: Increased serum levels of neurofilament light chain (sNFL), a biomarker of neuroaxonal damage, have been reported in patients with Covid-19. We aimed at investigating whether sNFL is increased in Covid-19 patients without major neurological manifestations, is associated with disease severity, respiratory and routine blood parameters, and changes longitudinally in the short term.

Methods: sNFL levels were measured with single molecule array (Simoa) technology in 57 hospitalized Covid-19 patients without major neurological manifestations and in 30 neurologically healthy controls.

Reactive vaccination as control strategy for an outbreak of invasive meningococcal disease caused by C:P1.5-1,10-8:F3-6:ST-11(cc11), Bergamo province, Italy, December 2019 to January 2020.

In Italy, serogroup C meningococci of the clonal complex cc11 (MenC/cc11) have caused several outbreaks of invasive meningococcal disease (IMD) during the past 20 years. Between December 2019 and January 2020, an outbreak of six cases of IMD infected with MenC/cc11 was identified in a limited area in the northern part of Italy. All cases presented a severe clinical picture, and two of them were fatal.

Tools for Efficient Genome Editing; ZFN, TALEN, and CRISPR.

The last two decades have marked significant advancement in the genome editing field. Three generations of programmable nucleases (ZFNs, TALENs, and CRISPR-Cas system) have been adopted to introduce targeted DNA double-strand breaks (DSBs) in eukaryotic cells. DNA repair machinery of the cells has been exploited to introduce insertion and deletions (indels) at the targeted DSBs to study function of any gene-of-interest.

Evaluation of antibody titer kinetics and SARS-CoV-2 infections in a large cohort of healthcare professionals ten months after administration of the BNT162b2 vaccine.

Background: Real-world population studies have shown waning immunity, over time, after receiving the two doses of the BNT162b2 COVID-19 vaccine. Studies reporting the long-term humoral response are important to drive future vaccination strategies like the introduction of the booster dose. Yet, available literature on long follow-up periods is scarce.

Impact of add-back FSH on human and mouse prostate following gonadotropin ablation by GnRH antagonist treatment.

Objective: During androgen ablation in prostate cancer by the standard gonadotropin-releasing hormone (GnRH) agonist treatment, only luteinizing hormone (LH) is permanently suppressed while circulating follicle-stimulating hormone (FSH) rebounds. We explored direct prostatic effects of add-back FSH, after androgen ablation with GnRH antagonist, permanently suppressing both gonadotropins.

Methods: The effects of recombinant human (rFSH) were examined in mice treated with vehicle (controls), GnRH antagonist degarelix (dgx), dgx + rFSH, dgx + flutamide, or dgx + rFSH + flutamide for 4 weeks.

Concordance between indirect fibrosis and steatosis indices and their predictors in subjects with overweight/obesity.

Background: The non-invasive assessment of steatosis/fibrosis tried to overcome some of peri-procedural risk of liver biopsy; for this, several indices of steatosis and fibrosis in liver have been proposed.

Aim: To evaluate concordance of non-invasive fibrosis and steatosis indices in a large population of adult subjects at risk of NAFLD, and how obesity and its physio-pathological features may interact with steatosis/fibrosis indexes and related biomarkers of cardio-metabolic risk.

Methods: Indices of steatosis (fatty liver index-FLI), NAFLD liver fat score-NLFS)) and fibrosis (Fibrosis 4 (FIB-4), BARD, BAAT and FORN) were calculated in 1145 outpatients with overweight or obesity at risk for T2D and NAFLD.

The Critical Role of the Branched Chain Amino Acids (BCAAs) Catabolism-Regulating Enzymes, Branched-Chain Aminotransferase (BCAT) and Branched-Chain α-Keto Acid Dehydrogenase (BCKD), in Human Pathophysiology.

Branched chain amino acids (BCAAs), leucine, isoleucine and valine, are essential amino acids widely studied for their crucial role in the regulation of protein synthesis mainly through the activation of the mTOR signaling pathway and their emerging recognition as players in the regulation of various physiological and metabolic processes, such as glucose homeostasis. BCAA supplementation is primarily used as a beneficial nutritional intervention in chronic liver and kidney disease as well as in muscle wasting disorders. However, downregulated/upregulated plasma BCAAs and their defective catabolism in various tissues, mainly due to altered enzymatic activity of the first two enzymes in their catabolic pathway, BCAA aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKD), have been investigated in many nutritional and disease states.

Glycoproteomic and Phenotypic Elucidation of Expression Variants in the SID Histo-Blood Group System.

The Sda histo-blood group antigen (GalNAcβ1-4(NeuAcα2-3)Galβ-R) is implicated in various infections and constitutes a potential biomarker for colon cancer. Sd(a−) individuals (2−4% of Europeans) may produce anti-Sda, which can lead to incompatible blood transfusions, especially if donors with the high-expressing Sd(a++)/Cad phenotype are involved. We previously reported the association of B4GALNT2 mutations with Sd(a−), which established the SID blood-group system.