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Background: Thrombocytopenia, common in preterm newborns, may increase bleeding risk and is often treated with transfusions. Recent studies reveal that transfusing platelets at a high threshold worsens outcomes, possibly due to a "developmental mismatch" between adult‐derived platelets and neonatal hemostatic system. Cord blood‐derived platelet concentrates (CBPCs) could be an alternative for newborns. Our study aims to produce and evaluate the quality parameters of CBPCs during storage. Study Design and Methods: Cord blood was collected from placentas after near‐term and full‐term pregnancies. Several production methods were attempted to obtain CBPCs, varying centrifugation settings, filtration, and dilution procedures. Adult‐derived platelet concentrates (PCs) processed with the same methods, and standard PCs from five buffy‐coats were used as controls. Storage tests were performed on days 2, 4–5, 7 from the collection. Results: CBPCs parameters were compared with adult‐derived PCs, and no significant differences were found for mean platelet volume (MPV), swirling, morphology, glucose, lactate, pCO2, and pO2. pH and bicarbonate were lower in CBPCs. Some significant differences between methods in CD62P expression and JC‐1 ratio were observed. Compared with standard PCs, CBPCs showed lower platelet concentration, pH, and JC‐1. Additionally, both in CBPCs as well as in control PCs, the apoptosis marker phosphatidylserine was elevated. Discussion: CBPCs were of comparable quality to control PCs during storage. However, apoptosis markers in both groups were elevated, suggesting processing and storage of low volumes of PCs require further optimization. Also, filtration of low volumes leads to significant platelet loss, an issue that requires remedy. [ABSTRACT FROM AUTHOR]

Three series of new ionic liquids (ILs), namely imidazolium‐, pyrazolium‐, and bis‐benzimidazolium‐containing ILs, were prepared from low‐cost, unprotected carbohydrates. Information on anion‐cation interactions and solvation shell were obtained via diffusion NMR and heteronuclear Overhauser correlation maps (HOESY), respectively. [ABSTRACT FROM AUTHOR]

Background: Phlebotomy is among the main determinants of anemia of prematurity. Blood sparing policies endorsed umbilical cord blood (here called placental) as an alternative source for laboratory testing. Little is known on the suitability of placental blood to evaluate neonatal hemostasis of newborn infants. We aimed to compare the hemostatic profile of paired placental and infant venous blood, by means of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, protein C, thromboelastography (TEG) and thrombin generation assay (TGA).Study Design: This was an observational single-center study.Methods: We collected at birth venous citrated blood from both placental and infant venous source and performed PT, APTT, fibrinogen, antithrombin, protein C, TEG (reaction time-R; kinetics-K alpha angle-α, maximum amplitude-MA and lysis at 30 minutes-LY30), and TGA (endogenous thrombin potential-ETP).Results: We enrolled 60 neonates with a median gestational age (range) of 37 weeks (28+1 -41) and birth-weight 2417 g (950-4170). Based on TEG and TGA, placental blood showed a procoagulant imbalance as indicated by lower median R (4.0 vs. 6.1 min; p < 0.001) and K (1.3 vs. 2.2 min; p < 0.001); higher α-angle (69.7 vs. 57.4°; p < 0.001) and ETP (1260 vs. 1078; p = 0.002) than those observed for infant venous blood. PT and APTT did not differ significantly between the two groups.Conclusions: While placental and neonatal blood samples are equally suitable to measure the standard coagulation tests PT and APTT, placental blood leads to a procoagulant imbalance when testing is performed with TEG or TGA. These effects should be considered when interpreting results stemming from investigation of neonatal hemostasis. [ABSTRACT FROM AUTHOR]

Objective: To determine variations in cord blood gas (CBG) parameters after 3-minute delayed cord clamping (DCC) in vaginal deliveries (VDs) and caesarean deliveries (CDs) at term without fetal distress.Design: Prospective observational study.Setting: University hospital.Sample: CBG from 97 VDs and 124 CDs without fetal distress.Methods: Comparison of paired arterial-venous CBG parameters drawn at birth from the unclamped cord and after 3-minutes DCC for VDs and CDs.Main Outcome Measures: Base excess, bicarbonate, haematocrit and haemoglobin from both arterial and venous cord blood, lactate, neonatal outcomes, partial pressure of oxygen (pO2 ), partial pressure of carbon dioxide (pCO2 ), pH, and postpartum haemorrhage.Results: Arterial cord blood pH, bicarbonate ( HCO3- , mmol/l), and base excess (BE, mmol/l) decreased significantly after 3-minute DCC both in VDs (pH = 7.23 versus 7.27; P < 0.001; HCO3-  = 23.3 versus 24.3; P = 0.004; BE = -5.1 versus -2.9; P < 0.001) and CDs (pH = 7.28 versus 7.34; P < 0.001; HCO3-  = 26.2 versus 27.2; P < 0.001; BE = -1.5 versus 0.7; P < 0.001). After 3-minute DCC, pCO2 increased in CDs only (57 versus 51; P < 0.001), whereas lactate increased more in CDs compared with VDs (lactate, +1.1 [0.9, 1.45] versus +0.5 [-0.65, 2.35]; P = 0.01). Postpartum maternal haemorrhage, neonatal maximum bilirubin concentration, and need for phototherapy were similar between the two groups. Newborns born by CD more frequently required postnatal clinical monitoring or admission to a neonatal intensive care unit.Conclusions: After 3-minute DCC, the acid-base status shifted towards mixed acidosis in CDs and prevalent metabolic acidosis in VDs. CDs were associated with a more pronounced increase in arterial lactate, compared with VDs.Tweetable Abstract: By 3-minute DCC, acid-base status shifts towards mixed and metabolic acidosis in caesarean and vaginal delivery, respectively. [ABSTRACT FROM AUTHOR]

BACKGROUND Silverskin is a by‐product obtained from coffee roasting. It is characterized by a high content of dietary fibre, phenolic compounds and caffeine. The aim of this study was to assess the silverskin obtained from two species of Coffea (Arabica and Robusta) at three percentages (2%, 4%, or 6%) into cow whole‐milk yogurt to raise the nutraceutical value of the products and to verify the bioaccessibility of bioactive compounds during the shelf‐life of 3 weeks. RESULTS: The amount and origin of silverskin significantly influenced all the physicochemical parameters. Concerning the bioactive compounds, the highest levels were observed in yogurt supplemented with 6% of silverskin. Between the coffee species, Arabica yielded the highest 5‐caffeoylquinic acid content and the strongest antioxidant activity, whereas Robusta gave the highest caffeine content. The digestion increased antioxidant activity in the yogurt, possibly because of greater accessibility of compounds. CONCLUSION: The results obtained highlighted that silverskin can be used in yogurt production to increase the nutraceutical value of the products and that the bioactive compounds are bioaccessible during the digestion process. The characteristics and bioaccessibility of the resulting yogurt were strongly correlated with the coffee species and with the percentage added. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

A series of glycomimetics of UDP-GlcNAc, in which the b-phosphate has been replaced by either an alkyl chain or a triazolyl ring and the sugar moiety has been replaced by a pyrrolidine ring, has been synthesized by the application of different click-chemistry procedures. Their affinities for human O-GlcNAc transferase (hOGT) have been evaluated and studied both spectroscopically and computationally. The binding epitopes of the best ligands have been determined in solution by means of saturation transfer difference (STD) NMR spectroscopy. Experimental, spectroscopic, and computational results are in agreement, pointing out the essential role of the binding of b-phosphate. We have found that the loss of interactions from the b-phosphate can be counterbalanced by the presence of hydrophobic groups at a pyrroline ring acting as a surrogate of the carbohydrate unit. Two of the prepared glycomimetics show inhibition at a micromolar level. [ABSTRACT FROM AUTHOR]

Representative derivatives of uridine-conjugated amino acids that have been suitably protected for Fmoc solid-phase chemistry have been prepared through efficient procedures that use "click" reactions as key steps, including thiol+ene radical reactions and copper-catalyzed azide alkyne cycloaddition (CuAAC) reactions. Several linkers between the amino acid and nucleoside units, including alkyl chains and a triazole ring, have been successfully employed. Alkyl chains offer retention of flexibility, to allow the bisubstrate analogues to adopt an appropriate orientation, whilst the triazole ring can promote additional interactions at the active sites of target enzymes. Furthermore, a neutral surrogate of the pyrophosphate unit has been prepared by using a Staudinger-Vilarrasa reaction as a key step. Neutral analogues are promising surrogates for avoiding difficulties owing to cell-membrane permeability. [ABSTRACT FROM AUTHOR]

Glycosyltransferases (GTs) are enzymes that transfer carbohydrates to a range of substrates and they play a fundamental role in the recognition processes associated with several diseases. The design of glycomimetics of nucleoside diphosphate (NDP) sugars-the natural substrates that act as inhibitors or modulators of GTs-is not only necessary for the development of glycan-based therapeutic drugs, but is also a crucial tool for understanding their mechanisms of action. Whilst a large number of inhibitors that consist of modifications of the carbohydrate unit and the pyrophosphate linkage have been designed, less attention has been paid to modifications at the ribose moiety and the nucleobase. However, in recent years, promising results have been obtained through such variations, which were prompted by the initial interest in the photolabeling of enzymes to study their structure. In this Focus Review, we survey recent progress in the synthesis of NDP-sugar analogues that are modified at the ribose moiety or at the heterocyclic base. [ABSTRACT FROM AUTHOR]

The Leloir donors are nucleotide sugars essential for a variety of glycosyltransferases (GTs) involved in the transfer of a carbohydrate to an acceptor substrate, typically a protein or an oligosaccharide. A series of less-polar nucleotide sugar analogues derived from uridine have been prepared by replacing one phosphate unit with an alkyl chain. The methodology is based on the radical hydrophosphonylation of alkenes, which allows coupling of allyl glycosyl compounds with a phosphate unit suitable for conjugation to uridine. Two of these compounds, the GalNAc and galactose derivatives, were further tested on a model GT, such as GalNAc-T2 (an important GT widely distributed in human tissues), to probe that both compounds bound in the medium-high micromolar range. The crystal structure of GalNAc-T2 with the galactose derivative traps the enzyme in an inactive form; this suggests that compounds only containing the β-phosphate could be efficient ligands for the enzyme. Computational studies with GalNAc-T2 corroborate these findings and provide further insights into the mechanism of the catalytic cycle of this family of enzymes. [ABSTRACT FROM AUTHOR]

BACKGROUND Hazelnut skin is the perisperm of the hazelnut kernel. It is separated from the kernel during the roasting process and is normally discarded. Recent studies have reported that hazelnut skin is a rich source of dietary fibre as well as of natural antioxidants owing to the presence of phenolic compounds. The aim of this study was to assess the use of hazelnut skins obtained from different cultivars for enhancing the nutritional value of fresh egg pasta. RESULTS Skins obtained from roasted hazelnuts of four different varieties were used at three concentrations as a flour replacement in fresh egg pasta. Hazelnut skin concentration significantly influenced all evaluated physicochemical parameters as well as consumers' appreciation for the pasta, but significant differences were also observed between the four varieties. Although pasta produced with 10 and 15% hazelnut skin displayed the highest content of polyphenolic compounds and antioxidant activity in vitro, pasta containing 5% Tombul hazelnut skin showed maximum consumer preference. CONCLUSION The results obtained in the present study highlighted that it is possible to use hazelnut skin in fresh pasta production to obtain a fortified food with high fibre content and antioxidant activity. The characteristics of the resulting pasta were strictly correlated with the hazelnut variety used for skin production and, of course, with the percentage of skin that was added. © 2014 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

ABSTRACT Alkene and alkyne functional polyester-based dendrimers of generation 1 to 4 have been prepared and reacted under free-radical conditions with 2-acetamido-2-deoxy-1-thio-β- D-glucose (GlcNAc-SH). As the alkene-dendrimers underwent the addition of one thiyl radical per ene group whereas each yne group of alkyne-dendrimers was saturated by two thiyl radicals, a collection of glycodendrimers with glycan density ranging from six to ninety-six GlcNAc per dendrimer was obtained. The recognition properties of the prepared glycodendrimers toward the wheat germ agglutinin (WGA) were evaluated by enzyme-linked lectin assay (ELLA). The eight glycodendrimers were excellent ligands showing IC50 values in the nanomolar range and relative potencies per sugar unit up to 2.27 e6 when compared to monosaccharidic GlcNAc used as monovalent reference. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2422-2433 [ABSTRACT FROM AUTHOR]

Polyphenol composition of the shell, pulp, and roasted and unroasted kernels of the argan fruit was qualitatively and quantitatively determined by HPLC coupled with electrospray negative ionization ion trap MS (HPLC-ESI-MS). Eleven phenolic compounds were identified. Unroasted kernels and shell contained various polyphenols but the pulp was characterized by a very high amount of total polyphenols (75.78 mg of gallic acid equivalent/g). The radical scavenging (DPPH . method) and antioxidant activity (ABTS method) of each fruit part was also determined. Argan fruit pulp showed the highest radical scavenging activity (0.17 ± 0.005 µM Trolox equivalent (TE)/mg) and antioxidant activity (0.375 ± 0.07 µM TE/mg). Therefore, argan fruit polyphenols are good candidates to be exploited as health supplements and nutraceuticals. [ABSTRACT FROM AUTHOR]

The article presents questions and answers related to blood donation including improved blood safety measures, irradiation guidelines for neonatal transfusion and recommendations for any pathogen-inactivated types of blood components.

Systemic autoimmune diseases are characterized by the presence in patient sera of high titers of autoantibodies directed against self-antigens. The characterization of specific autoantigen–autoantibody system is very important for research as well as for diagnostic tools and several techniques can be employed in such immunological studies. In this review an overview of the different biochemical methods of antigen preparation and the specific methodological applications is given, also describing potential critical aspects and benefits of the different protocols. [ABSTRACT FROM AUTHOR]

Autoantibodies to double-stranded DNA (dsDNA) are, by definition, serological markers of systemic lupus erythematosus. However, the clinical value of anti-dsDNA antibodies largely depends on the assay principle and analytical variables of the methods used to quantitate and immunologically characterize them. In the present article, an overview of current methods for anti-dsDNA antibody detection is presented, together with a look at the future trends in technologies newly employed in this field. [ABSTRACT FROM AUTHOR]

Anti-prothrombin (anti-PT) antibodies are recently identified antibodies directed toward a phospholipid-binding protein (prothrombin), which deserve attention for the reported clinical and pathogenic relevance in antiphospholipid syndrome and systemic lupus erythematosus (SLE). We have recently carried out a longitudinal study on the predictive value of anti-PT antibodies in SLE showing that they have a higher diagnostic accuracy for thrombosis than anti-β2-GPI and anticardiolipin antibodies, and, along with LAC activity, are the best predictors of thromboembolic events in SLE patients. [ABSTRACT FROM AUTHOR]

Objectives Autoimmune targeting of hypothalamic-neurohypophyseal structures in children and young adults with posterior pituitary and anterior pituitary dysfunction, as well as pituitary stalk involvement, are not yet completely understood. Design We aimed to (1) evaluate the presence of circulating vasopressin-cell autoantibodies (AVPc-Abs) in young patients with central diabetes insipidus (CDI), (2) detect organ-specific autoantibodies as markers of autoimmunity, and (3) define the relationship between immune markers and neuroimaging findings. Patients Twenty patients were evaluated at a median age of 16·3 years. Twelve patients had idiopathic CDI, six had Langerhans cell histiocytosis (LCH) and two had germinoma. AVPc-Abs were evaluated in 40 healthy children. Magnetic resonance imaging (MRI) of the hypothalamic-pituitary region was performed longitudinally in all subjects. Measurements Circulating arginine vasopressin (AVP), protein tyrosine phosphatase (IA2), glutamic acid decarboxylase (GAD), 21-hydroxylase (21-OH), endomysium antibodies (EMA), parietal cell (PCA), thyroid peroxidase (TPO), thyroglobulin (TG) and TSH-receptor (TSHr) autoantibodies were evaluated. Results Circulating AVPc-Abs were found in 15 patients (75%), nine with idiopathic CDI, four with LCH and two with germinoma; the pituitary stalk was involved in most of them. Five patients with idiopathic CDI showed a persistence of AVPc-Abs during follow-up and one became positive subsequently. Serum IA2 autoantibodies were demonstrated in 14 patients (70%) and 21-OH autoantibodies in three of them. Conclusion In idiopathic CDI, circulating AVPc-Abs suggest an autoimmune involvement of the neurohypophyseal system. The identification of AVPc-Abs in subjects who could have either idiopathic CDI or LCH or germinoma, however, indicates that AVPc-Abs cannot be considered a completely reliable marker of autoimmune CDI. Thus, close clinical and MRI follow-up are needed because AVPc-Abs may mask germinoma or LCH. [ABSTRACT FROM AUTHOR]

Cells respond to conditions that impair homeostasis through ex novo synthesis of stress proteins, which differ in subcellular localization and biological function and whose differential expression depends on the type of the stressing stimulus and on the involvement of the specific stress-response signaling cascade. The biological significance of such an event is the increased resistance against further perturbations of cell homeostasis, and thus, enhanced survival. We will review briefly the available evidence concerning stress response of skeletal muscle cells, including recent results indicating the involvement of endoplasmic reticulum stress response and proteins in skeletal muscle cell differentiation and in progression of muscle diseases. [ABSTRACT FROM AUTHOR]

Successful pregnancy depends on an adaptation of the maternal immune system that becomes tolerant to fetal antigens of paternal origin. The altered immune regulation induced by pregnancy occurs predominantly at the maternal–fetal interface, but it has also been observed in the maternal circulation. Th1/Th2 shift is one of the most important immunologic changes during gestation. It is due to the progressive increase of estrogens, which reach peak level in the third trimester of pregnancy. At these high levels, estrogens suppress the Th1-mediated responses and stimulate Th2-mediated immunologic responses. For this reason Th1-mediated diseases, such as rheumatoid arthritis, tend to improve, while Th2-mediated diseases, such as systemic lupus erythematosus (SLE) tend to worsen during pregnancy. However, in some recent studies SLE flare-ups were less frequently observed in the third trimester of gestation in comparison to the second trimester and postpartum period. These data are apparently in contrast to the Th2 immune-response polarization expected during pregnancy due to the progressive increase of estrogens. Some further data suggest that in SLE patients estradiol serum levels are surprisingly lower than expected during the third trimester of pregnancy, probably due to a placental compromise. This occurrence could lead to a lower-than-expected increase of IL-6, accounting for the low humoral immune response and the low disease activity observed in the third trimester of pregnancy in such patients. [ABSTRACT FROM AUTHOR]

Over the past number of years numerous data have been published regarding increased atherosclerosis in patients with systemic lupus erythematosus (SLE), and it has been shown that premature or accelerated atherosclerosis is an important cause of morbidity and mortality in these patients. Besides the traditional risk factors for cardiovascular disease, the association between SLE and atherosclerosis can be attributed to additional risk factors closely related to inflammation and autoimmunity. In particular, several autoantibodies and their respective autoantigens have been identified as possible factors in the development and progression of the atherosclerotic process in SLE. The understanding of SLE-related risk factors for enhanced atherosclerosis could shed more light on disease mechanisms, leading to new therapeutic strategies for the treatment of cardiovascular diseases in SLE patients. In the present paper, the biological characteristics and possible pathogenetic role of the oxidized low-density lipoprotein (oxLDL) and anti-oxLDL, β2-glycoprotein I (β2GPI) and anti-β2GPI, and heat-shock protein 60/65 (HSP60/65) and anti- HSP60/65 autoantibody systems are summarized. [ABSTRACT FROM AUTHOR]

In the last few years, several reports have shown that chromatin (nucleosome) represents the main autoantigen-immunogen in systemic lupus erythematosus (SLE) and that specific antibodies are an important marker of the disease. To verify the clinical sensitivity and specificity of antinucleosome autoantibodies (ANuAs), we evaluated three ELISA immunoassay methods using different autoantigen preparations: Quanta Lite Chromatin, Medizym Anti-nucleo, and Nucleosome IgG Elisa. We compared the results with those obtained using two ELISA assays for determining anti-native DNA (antinDNA) antibodies: Axis-Shield and EliA dsDNA. We tested sera from 321 patients: 101 with SLE and 220 controls—48 with infectious diseases; 73 with autoimmune rheumatic disease (20 with rheumatoid arthritis, 30 with systemic sclerosis, and 23 with primary Sjögren's syndrome), and 99 healthy subjects. Using the manufacturer-recommended cutoff, the sensitivity for the three kits was 69%, 78%, and 74%, and specificity was 100%, 94.6%, and 95.0%, respectively. Using the cutoff corresponding to 95% specificity, the sensitivity of the methods for the ANuA assay was 86%, 77%, and 74%—higher than obtained with the two ELISA methods for anti-nDNA (65% and 64%). This study demonstrates that (1) the commercial reagents employed in clinical laboratories for ANuA detection show good sensitivity and high specificity; (2) ANuAs are more sensitive than anti-nDNA antibodies for diagnosing SLE; and (3) different solid-phase antigen preparations and methods used to define cutoff levels may affect a test's clinical performance. [ABSTRACT FROM AUTHOR]

Glycopeptides derived from the glycoprotein mucin‐1 (MUC1) have shown potential as tumor‐associated antigens for cancer vaccine development. However, their low immunogenicity and non‐selective conjugation to carriers present significant challenges for the clinical efficacy of MUC1‐based vaccines. Here, we introduce a novel vaccine candidate based on a structure‐guided design of an artificial antigen derived from MUC1 glycopeptide. This engineered antigen contains two non‐natural amino acids and has an α‐S‐glycosidic bond, where sulfur replaces the conventional oxygen atom linking the peptide backbone to the sugar N‐acetylgalactosamine. The glycopeptide is then specifically conjugated to the immunogenic protein carrier CRM197 (Cross‐Reactive Material 197), a protein approved for human use. Conjugation involves selective reduction and re‐bridging of a disulfide in CRM197, allowing the attachment of a single copy of MUC1. This strategy results in a chemically defined vaccine while maintaining both the structural integrity and immunogenicity of the protein carrier. The vaccine elicits a robust Th1‐like immune response in mice and generates antibodies capable of recognizing human cancer cells expressing tumor‐associated MUC1. When tested in mouse models of colon adenocarcinoma and pancreatic cancer, the vaccine is effective both as a prophylactic and therapeutic use, significantly delaying tumor growth. In therapeutic applications, improved outcomes were observed when the vaccine was combined with an anti‐programmed cell death protein 1 (anti‐PD‐1) checkpoint inhibitor. Our strategy reduces batch‐to‐batch variability and enhances both immunogenicity and therapeutic potential. This site‐specific approach disputes a prevailing dogma where glycoconjugate vaccines require multivalent display of antigens. [ABSTRACT FROM AUTHOR]

A correction to the article "Idiopathic central diabetes insipidus in children and young adults is commonly associated with vasopressin-cell antibodies and markers of autoimmunity" that was published in the 2006 issue of the journal is presented.

Review: 88 refs. [ABSTRACT FROM AUTHOR]