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Newborns admitted to neonatal intensive care units (NICU) are at increased risk of health care-associated infections. Serratia marcescens represent the third most common pathogen in NICU outbreaks. Here we present an outbreak investigation performed using Whole Genome Sequencing (WGS) analyses and the control measures implemented to limit the spread of S. marcescens in the NICU of an Italian hospital. In February 2023 S. marcescens was isolated from six newborns, when in 2022 this pathogen was isolated only from two samples in the same ward. Measures for infection prevention were adopted. Routinary surveillance screening, performed with rectal swabs collected at admission and weekly thereafter, was implemented to search for S. marcescens presence. Environmental samples were collected. All the isolates, obtained from the conjunctival swab of six newborns, from rectal swab of two newborns who did not develop infections, as well as from the aerators of two faucets, were sequenced. WGS analyses showed no correlation between the isolates from newborns and environmental isolates. The implementation of the measures for infection prevention and control had enabled us to successfully control the outbreak within a short period. WGS analyses proved to be crucial in outbreak investigation to limit the spreading of the pathogens. [ABSTRACT FROM AUTHOR]

Introduction: Glypican-3 (GPC3) is an oncofetal protein involved in cellular signaling, strongly expressed in the placenta, absent or diminished in postnatal life, but often increased in human malignancies. Germline loss-of-function variants of GPC3 gene are associated with Simpson-Golabi-Behmel syndrome type 1 (SGBS1), a rare recessive X-linked overgrowth disease characterized by typical facial features, congenital abnormalities, and an increased risk of developing childhood cancers.Methods: A clinical suspicion of SGBS1 was postulated for a newborn with prenatal history of overgrowth and polyhydramnios, presenting with neonatal weight and length >99th percentile, coarse facies, iris and retinal coloboma, supernumerary nipples, and splenomegaly. While waiting for whole-genome sequencing (WGS) results, we investigated placental GPC3 immunohistochemical expression in the proband, in three additional cases of SGBS1, and disorders commonly associated with fetal macrosomia and/or placentomegaly.Results: WGS in the proband identified a likely pathogenic maternally inherited missense variant in GPC3: c.1645A > G, (p.Ile549Val), and GPC3 immunohistochemistry demonstrated full-thickness loss of stain of the placental parenchyma. The same pattern ("null") was also present in the placentas of three additional cases of SGBS1, but not in those of unaffected controls.Discussion: Immunohistochemical expression of GPC3 in the placenta is highly reproducible. Our findings showed that a "null pattern" of staining is predictive of SGBS1 and represents a valuable aid in the differential diagnosis of fetal macrosomias, allowing targeted genetic testing and earlier diagnosis. [ABSTRACT FROM AUTHOR]

Background and Aims: Despite the potential benefits of thromboelastography (TEG) for bedside hemostatic assessment in critical care settings, its accuracy remains to be determined, especially in critically ill neonates. We determined the intra-assay reproducibility of TEG parameters: Reaction time (R), clot kinetics (K) and Maximum Amplitude (MA) in a cohort of very low birth weight (VLBW) infants.Study Design: Observational study.Subjects: One hundred VLBW newborns.Outcome Measures: We performed TEG duplicate measurements for blood samples from VLBW newborns. To assess for correlation, we calculated the coefficients of correlation by plotting the values of the first vs the second measurement. Paired samples were compared with t-test and the coefficient of variation (CV) on paired results was also calculated as a measure of variability. To evaluate the agreement between duplicates, Bland-Altman (BA) analysis was performed.Results: We evaluated 228 TEG pairs. Both the coefficient of correlation and the BA analysis showed an acceptable level of agreement between duplicates. TEG variability (CV, mean ± SD) was highest for K (10.4%, ±12.9), lowest for MA (3.6%, ±8.0) and moderate for R (7.9%, ±9.0). The results from ANOVA one-way analysis describe different variability trends: K-CV increased at higher values, while MA-CV and R-CV increased at lower values.Conclusions: In VLBW newborns, the agreement between TEG duplicate measurements for R and MA parameters is adequate for clinical purposes. TEG is a promising tool to quickly assess hemostasis ensuring a significant blood sparing in critically ill neonates. [ABSTRACT FROM AUTHOR]

Abstract Background Advances in cardiorespiratory monitoring have made the extracorporeal membrane oxygenation (ECMO) technique safer for the patient. Noninvasive, continuous tools are available, although data on their applications in the neonatal ECMO setting are lacking. Objective We retrospectively described the neonatal clinical application of this continuous, noninvasive ECMO monitor and compared the analyzed parameters from those derived from blood gas analysis. Materials and methods We performed 897 h of cardiorespiratory monitoring during neonatal venoarterial-ECMO (VA-ECMO) for four patients affected by (cardio-) respiratory failure, to compare the reliability of a noninvasive, continuous monitoring Spectrum M4® (M4) (Spectrum Medical, Gloucester, England) to an invasive, intermittent co-monitoring with blood gas analyzer (Radiometer Medical ApS, Brønshøj, Denmark). Results A range of 117 pairs (time-matched BGA-derived vs. M4-derived parameters) was retrospectively analyzed. T -test, linear regression and Bland–Altman analysis for hemoglobin, hematocrit, venous oxygen saturation, oxygen delivery, oxygen consumption, oxygen extraction ratio, oxygen partial pressure, and carbon dioxide partial pressure showed a strong relationship between the two monitors for all parameters analyzed (p < 0.0001). Conclusions Continuous, noninvasive cardiorespiratory monitoring appears to be feasible and reliable, although its accuracy needs to be verified in a more extensive cohort. [ABSTRACT FROM AUTHOR]

The functionalization of glycosides with ionic compounds such as ionic liquids provides enhanced polarity for the labelled glycans thanks to the presence of a permanent positive charge. The chemical derivatisation of glycans with ionic liquids constitutes an emerging strategy to boost the detection sensitivity in MS applications. This allows the straightforward monitoring and detection of the presence of labelled glycans in complex matrices and in those cases where very limited amounts of material were available such as in biological samples and chemoenzymatic reactions. The use of ionic liquid based derivatisation agents can be further exploited for the labelling of live cells via metabolic oligosaccharide engineering for the detection of cancer biomarkers and for the tuning of live cells-surface properties with implications in cancer prognosis and progression. In this mini-review we summarise the latest development of the ionic liquid based derivatisation agents in glycoscience focussing on their use for sensitive MS applications. [Display omitted] • Ionic liquids (ILs) are a highly sensitive probe for glycomics and mass spectrometry applications. • IL-functionalysed glycans provide a sensitive analytical tool for the monitoring of chemoenzymatic reactions in complex media. • Metabolic oligosaccharide engineering applications using IL-based probes impacts the glycoproteomic profile of live cells. [ABSTRACT FROM AUTHOR]

The effect of five different storage conditions on the total phenolic content (TPC), the antioxidant capacity (AC), the phenolic compound profile, the total amount of quantified phenolics, the hexanal content, and the sensory characteristics of hazelnuts of two cultivars (Tonda Gentile Trilobata or TGT and Delisava—harvest 2010 and 2011) were investigated for two consecutive years. The storage variables were time (0, 4, 8 and 12 months), temperature (ambient temperature, refrigeration at 5 °C, or frozen at −25 °C) and O 2 availability (ambient air, vacuum or modified atmosphere). Comparing the cultivars, Delisava exhibited the highest levels of TCP and AC for both harvests and all storage conditions; however, it was characterized by the highest hexanal content (more than sixfold higher than TGT). At the end of the storage, the TPC and AC decreased with respect to day 0 in both cultivars, with AC losses ranging between 12% and 35% and TPC losses of approximately 15%. However, these parameters were not able to distinguish the storage conditions. The hazelnut phenolic compound profiles did not seem to be affected by storage techniques in either cultivar; additionally, the sensory analysis panellists were not able to discriminate between the storage conditions. Hexanal was confirmed to be a good marker of lipid oxidation, and its content generally increased during storage in both cultivars; nevertheless, changes were well-controlled by storage conditions where low temperature and reduced oxygen worked synergistically. The absence of oxygen seemed to be more relevant with respect to low temperature, and a good preservation of raw hazelnut kernels was achieved by storage under vacuum with or without preliminary nitrogen flushing. [ABSTRACT FROM AUTHOR]

Shoulder dystocia is a rare but severe obstetric complication associated with an increased risk of brachial plexus palsies, fractures of the clavicle and humerus, hypoxic-ischemic encephalopathy and, rarely, neonatal death. Here we describe a fatal case of shoulder dystocia in a term newborn, although labor was uneventful, fetal heart rate tracing was normal until the delivery of the head and the head-to-body delivery interval (HBDI) occurred within 5 min. Full resuscitation was performed for 35 min without success. Hemoglobin concentration evaluated on the umbilical cord still attached to the placenta was within normal range, while neonatal venous hemoglobin concentration blood gases at 9 min of life showed severe metabolic acidosis and anemia. As previously described by others, our case supports the hypothesis of a hypovolemic shock as the cause of neonatal death, probably due to acute placental retention of fetal blood. The death of the newborn following shoulder dystocia is an event that still presents numerous gaps in knowledge. Further research should focus on. [ABSTRACT FROM AUTHOR]

Abstract: Wet spent coffee grounds (SCGs) from espresso capsules, a post-consumer organic solid residue produced worldwide, were analysed to determine their chemical and microbiological stability during storage. In particular, the changes in the total phenolic content and antioxidant capacity (based on two free radical scavenging assays and one oxygen radical absorbance assay) were determined on espresso SCG stored in capsules for up to one month at room temperature in a container open to the air. Phenolic compounds were also identified and quantified using high performance liquid chromatography coupled with diode array and mass detectors. Microbiological analysis was performed in parallel on the same stored SCG to determine the total counts and quantify the main microbial groups present during the storage. The total phenolic content, antioxidant capacity and the most important bioactive compounds, such as the total caffeoylquinic acids, were significantly stable during storage for up to one month, while overall microbial stability was observed for up to two weeks of storage. Overall, the recovery of espresso coffee capsules within 15days could guarantee the maintenance of microbiological stability as well as the content of valuable antioxidant compounds. [Copyright &y& Elsevier]

Objective: To determine the evolution of congenital hypothyroidism in preterms and the clinical features of permanent forms. Study design: We retrospectively evaluated 24 preterm children detected by newborn screening for congenital hypothyroidism: first screening with blood-thyroid stimulating hormone cutoff ≥10 mU/L and second screening with blood-thyroid stimulating hormone cutoff ≥5 mU/L. After the age of 2 years, patients with eutopic thyroid had diagnostic reevaluations, including thyroid function testing and thyroid ultrasonography after L-thyroxine therapy withdrawal. Results: The first screening identified 21.7% of patients with thyroid stimulating hormone elevation, and the second screening identified 73.9% of patients. One patient (4.4%) was identified with a third screening test; 21 patients had an eutopic thyroid and 3 patients a thyroid dysgenesis. At reevaluation, 5 patients (23.8%) showed permanent hypothyroidism (serum-thyroid stimulating hormone [s-TSH] >10 mU/L) resulting in the need to reintroduce therapy, 5 patients (23.8%) showed persistent hyperthyrotropinemia (s-TSH 5-10 mU/L), and 11 infants (52.4%) transient hypothyroidism (s-TSH <5 mU/L). The main clinical features of patients affected by permanent hypothyroidism were 1 case of assisted reproduction, 2 twins, 2 small for gestational age, 1 maternal thyroiditis, and 2 patients with malformations/syndromes. Conclusions: Premature birth is a significant risk for congenital hypothyroidism with eutopic thyroid. In preterm infants, the evolution of congenital hypothyroidism remains difficult to predict. Our data emphasizes the high incidence of transient hypothyroidism in preterm infants, and the importance of diagnostic reevaluation to determine the definitive diagnosis. [Copyright &y& Elsevier]

Abstract: 40% of the subduction margins of the Earth are intra-oceanic. They show significant variability in terms of extension and shortening. We investigated numerically the physical controls of these processes using a 2D petrological-thermo-mechanical intra-oceanic subduction model with spontaneous volcanic arc growth and deformation. We varied the fluid- and melt-related weakening, the ages of both the subduction slab and the overriding plate, the subducting plate velocities, and the cohesive strength of rocks. Three main geodynamic regimes were identified: retreating subduction with opening of a backarc basin, stable subduction, and advancing, compressive subduction. The main difference between these regimes is the degree of rheological coupling between plates, which is governed by the intensity of rheological weakening induced by fluids and melts. Retreating subduction regimes require plate decoupling, which results from strong weakening due to both fluids and melts. Spreading centers nucleate either in forearc or in intraarc regions. Episodic trench migration is often due to variations of plate coupling with time, which is caused by (fore) arc deformation. Stable subduction regime with little variation in the trench position forms at an intermediate plate coupling and shows a transient behavior from the retreating to advancing modes. The advancing subduction regime results from strong plate coupling. At the mature stage, this subduction mode is associated with both partial fragmentation and subduction of the previously serpentinized forearc region. Forearc subduction is typically associated with a magmatic pulse, which is caused by dehydration of subducted serpentinized forearc fragments. Our models demonstrate distinct differences in thermal and lithological structure of subduction zones formed in these different geodynamic regimes. Results compare well with variations observed in natural intra-oceanic arcs. [Copyright &y& Elsevier]

A spatially-explicit version of the recent multimedia fate model SoilPlus was developed and applied to predict the runoff of three pesticides in a small agricultural watershed in northeastern Italy. In order to evaluate model response to increasing spatial resolution, a tiered simulation approach was adopted, also using a dynamic model for surface water (DynA model), to predict the fate of pesticides in runoff water and sediment, and concentrations in river water. Simulation outputs were compared to water concentrations measured in the basin. Results showed that a high spatial resolution and scenario complexity improved model predictions of metolachlor and terbuthylazine in runoff to an acceptable performance (R 2 = 0.64–0.70). The importance was also shown of a field-based database of properties (i.e. soil texture and organic carbon, rainfall and water flow, pesticides half-life in soil) in reducing the distance between predicted and measured surface water concentrations and its relevance for risk assessment. [Copyright &y& Elsevier]

Abstract: This study evaluated the effect of different storage conditions currently used by the industry, on the chemical, physical and sensory characteristics of ‘Tonda Gentile delle Langhe’ hazelnuts, during one year of storage. The traditional method of in-shell preservation in a storage room at ambient temperature was compared with refrigerated storage of shelled nuts at 4°C and 55% relative humidity, with or without modified atmosphere (1% oxygen, 99% nitrogen). The following parameters were measured: moisture content, lipid content, total phenolic content, and antioxidant capacity of the kernel; acidity and peroxide value of the oil. The kernel resistance to breakage was evaluated by texture analysis using a compression test. The hazelnuts were also evaluated by sensory analysis. The results showed that the acidity and the peroxide value were the most discriminating parameters. After one year of storage, the acidity of hazelnuts stored at ambient temperature (0.47% oleic acid) was higher than the value considered the acceptable limit after storage (0.40% oleic acid), while refrigerated storage maintained a low level of acidity and lipid oxidation, with the best performance in modified atmosphere (0.13% oleic acid; 0.057 O2 mmolkg−1). Sensory analysis after 12 months also showed differences among the three storage treatments. In-shell storage of hazelnuts at ambient temperature was able to preserve the kernels below threshold limits of acidity and oxidative degradation for up to 8 months, but refrigeration was necessary to maintain high quality for up to one year. The use of modified atmosphere is recommended for long periods of storage. [Copyright &y& Elsevier]

Abstract: This work is a contribution to knowledge of the phenolic composition, antioxidant capacity and volatile profile of licuri (Syagrus coronata (Martius) Beccari) fruits. Samples of raw and roasted licuri were provided by an agricultural cooperative in the state of Bahia (Brazil). The phenolic composition was both estimated by spectrophotometric assays (by measuring the content of total phenolics, total flavonoids, and condensed tannins) and quantified by HPLC–MS. Antioxidant capacity was evaluated by ABTS and DPPH radical scavenging assays, while volatiles were determined by HS-SPME–GC/MS. An increase of total phenolics, total flavonoids and total condensed tannins was observed after the roasting process. Similarly, the antioxidant capacity of roasted seeds was higher than that of raw samples. Among phenolic compounds (+)-catechin, (−)-epicatechin, procyanidins B1 and B2, myricetin, quercetin, quercetin-3-O-glucoside, quercetin-3-O-rhamnoside, quercetin-3-O-rutinoside and luteolin were identified. The majority of these phenolics significantly increased during the roasting process. Among volatiles, carboxylic acids such as octanoic and hexanoic acids prevailed in raw licuri seeds. However, after roasting, these compounds decreased and Strecker aldehydes, δ-lactones and alkyl pyrazines, (all with high odor activity), became the most abundant. [Copyright &y& Elsevier]

Abstract: Wolfram syndrome (WS) is a rare autosomal recessive disorder characterized by diabetes insipidus (DI), insulin-dependent diabetes mellitus (DM), optic atrophy (OA) and deafness caused by mutations in WFS1 gene (4p16.1), which encodes an endoplasmic reticulum protein, called Wolframin. We describe the case of an infant who presented hypernatremia and severe hypoplasia of the left eyeball with alteration of visual evoked potentials. Persistent hypernatremia, iposmolar polyuria and high plasma osmolality suggested DI, confirmed by a normal urine concentration after vasopressin test. Treatment with vasopressin allowed a normalization of sodium levels and urine output. Brain magnetic resonance imaging showed absence of the neurohypophysis hyperintense signal, normal adenohypophysis and optic tracts hypoplasia. The concomitant presence of DI and OA, even in the absence of DM and deafness, prompted the suspicion of WS and complete genetic analysis was performed. Genomic DNA sequencing of WFS1 showed no inactivating mutations described to date, but suggested a structural mutation as markers genotyping revealed a segmental paternal heterodisomy involving the upstream regulatory region (promoter and 5′UTR). cDNA sequencing revealed the coexistence of the wild-type transcript and two splice variants; one variant, probably benign, is known in literature and the other one causes the loss of exon 2, containing the translation initiation site. Western blot confirmed a marked protein reduction. During the clinical follow-up child''s condition remained stable and glucose metabolism is still in the standard. In conclusion, the phenotype associated with this structural rearrangement, which substantially reduces the synthesis of Wolframin, confirms a tissue-specific pattern of expression of WFS1, suggests the presence of a different protein dosage sensitivity in different tissues and could be causative of DI and OA in our patient. The “incomplete” phenotype here described, usually absent in typical WS cases, is explained by the residual Wolframin expression that would preserve other organs, i.e. pancreatic islets. A careful longitudinal clinical follow-up will assess any changes in the phenotypic penetrance in our patient. [Copyright &y& Elsevier]

Abstract: Introduction: Myositis specific autoantibodies (MSAs) are useful in the diagnosis of idiopathic inflammatory myopathies and in the definition of disease subsets. The aim of this study was to set up an unlabelled protein immunoprecipitation technique for MSA identification in the sera of myositis patients, in order to identify and investigate new antibody reactivity, undetectable by currently used methods. Methods: Sera of 183 patients with connective tissue diseases (75 adult dermatomyositis, 12 juvenile dermatomyositis, 43 polymyositis, 53 other connective tissue diseases) and 30 healthy controls were screened by an in-house procedure of unlabelled protein immunoprecipitation. In the same sera MSAs and myositis associated antibodies were determined by immunoblotting and immunoprecipitation for RNA. Results: The analytical specificity of unlabelled protein immunoprecipitation was demonstrated by testing reference sera with known antibody reactivity. Sera from five patients, affected with dermatomyositis (5/75=7%), immunoprecipitated two proteins of 40 and 90kDa apparent molecular weights respectively, consistent with the subunits of the small ubiquitin like modifier activating enzyme heterodimer (SAE1/SAE2). The identity of putative SAE immunoprecipitated proteins was confirmed by immunoblotting on immunoprecipitates using commercial monospecific antibodies to SAE1 and SAE2. Major clinical features were compared between anti-SAE positive and negative patients. Interestingly, anti-SAE positive patients had mainly skin and muscle manifestations while dysphagia, interstitial lung disease, arthritis and constitutional symptoms were absent. Conclusions: Unlabelled protein immunoprecipitation is a specific analytical approach, appropriate for the identification of the recently described anti-SAE autoantibody. We confirmed the role of anti-SAE antibody as marker of dermatomyositis. [Copyright &y& Elsevier]

Growing attention is devoted to understand the influence of the short-term variations in air concentrations on the environmental fate of semivolatile organic compounds (SVOCs) such as polycyclic aromatic hydrocarbons (PAHs). These variations are ascribable to factors such as temperature-mediated air-surface exchange and variability of planetary boundary layer (PBL) height and structure. But when investigating the fate of SVOCs at a local scale, further variability can derive from specific point source contributions. In this context, a new modeling approach (AirPlus) which integrates a previously developed model (AirFug) with an air dispersion model (AERMOD) is presented. The integrated model is illustrated for two PAHs in a Northern Italy scenario. Results show how chemical contributions deriving from background advective inflows, local emissions and a point source interact in an hourly-varying meteorological scenario to determine air concentration rapid changes and the consequent response of the soil compartment. [Copyright &y& Elsevier]

Abstract: Annexins are a group of 12 highly conserved proteins which exert several regulatory functions on cell biology. There are involved in numerous cell processes including vesicle trafficking, calcium signaling, cell growth, division, and apoptosis. Autoantibodies directed toward annexin I, II, V and XI have been reported, but their role and their clinical correlates are controversial. Annexin I exerts an anti-inflammatory effect by suppressing the generation of inflammatory mediators and anti-annexin I antibodies were detected in patients affected with rheumatoid arthritis, systemic (SLE) and cutaneous lupus erythematosus. Annexin II and V have a high affinity for phospholipids playing a pivotal role in the regulation of coagulation cascade. Anti-annexin II and anti-annexin V antibodies were found in patients with arterial or venous thrombosis, especially in those with autoimmune rheumatic diseases (ARD) such as SLE, primary antiphospholipid syndrome (APS) or systemic sclerosis. Anti-annexin V antibodies were also found in patients with pregnancy loss with or without APS. Annexin XI is involved in several biological pathways, particularly apoptosis and cell proliferation. Anti-annexin XI antibodies have been found in patients with SLE, undifferentiated connective tissue disease, rheumatoid arthritis, Sjögren''s syndrome and APS. The metanalysis of studies published up to now showed that the Odds Ratio for having an ARD in anti-annexin XI positive patients was 5.08 (95% CI 2.06–12.58). [Copyright &y& Elsevier]

Monitoring campaigns from different locations have recently shown how air concentrations of persistent semivolatile contaminants such as polychlorinated biphenyls (PCBs) often exhibit short-term (less than 24 h) variations. The observed patterns have been ascribed to different factors, such as temperature-mediated air–surface exchange and variability of planetary boundary layer (PBL) height and dynamics. Here, we present a new modeling approach developed in order to investigate the short-term variability in air concentrations of organic pollutants at a local scale. A new dynamic multimedia box model is supplied by a meteorological preprocessor (AERMET) with hourly values of air compartment height and wind speed. The resulting model is tested against an existing dataset of PCB air concentrations measured in Zurich, Switzerland. Results show the importance of such modeling approach in elucidating the short- and long-term behavior of semivolatile contaminants in the air/soil system. [Copyright &y& Elsevier]

Abstract: Commercial blot assays are advanced applications of immunoblotting or dot immunobinding methodologies for the detection of specific autoantibodies in autoimmune diseases. Line(Dot) blots in particular have cost-effectively optimized a sort of multiparametric assay for simultaneous determination of several autoantibody reactivities. Efficient and wide-spectrum potentialities of recombinant DNA technology and proteomics are fruitfully employed by manufacturers in order to obtain highly purified antigens or novel targets to be spotted on blot matrices thus continuously implementing their multianalytic platforms. At present most widely used commercial blot assays for the diagnosis of connective tissue diseases can detect autoantibodies to several Extractable Nuclear Antigens or myositis and/or scleroderma associated autoantigens. They actually represent an important step-forward in the methodological panorama designed for the autoimmunity laboratory. However continuous effort in order to validate and improve clinical reliability of commercially available blot assays should be carried out. In this short review, our preliminary contribution on the validation of a commercial line blot assay for the laboratory diagnosis of autoimmune myositis is briefly reported. [Copyright &y& Elsevier]

Abstract: It has been demonstrated that atherosclerosis (ATS) is enhanced in autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE). The reason for this accelerated process is still debatable and, although traditional risk factors are more prevalent in SLE patients than in general population, they do not seem to fully explain the enhanced risk. ATS has the characteristics of an autoimmune chronic disease, involving both the innate and the adaptive immunity. Moreover, it satisfies the four criteria defining an autoimmune disease, proposed by Witebsky and Rose. It has been shown that some autoantibodies, including anti-oxLDL, anti-β2GPI, anti-HSP60/65, and more recently anti-oxLDL/β2GPI, play a key role in the pathogenesis of ATS. However the role of these autoantibodies in accelerated ATS in SLE patients is still controversial. In fact, some of them seem to be proatherogenic and other protective; moreover, it has been demonstrated that induced oral tolerance has a protective role against ATS. We have recently observed that the levels of oxLDL/β2GPI antigenic complexes and their antibodies were higher in patients with SLE than in healthy subjects, but we did not find a clear association between oxLDL/β2GPI complexes and IgG or IgM anti-oxLDL/β2GPI autoantibodies and subclinical ATS in SLE patients. Many other studies are required to explain the role of autoantibodies in the pathogenesis of ATS in SLE patients, because the characteristics of SLE seem to mask their effects for atherogenesis. [Copyright &y& Elsevier]

Cadmium yellows are a class of inorganic pigments introduced during the middle of the 19th c. and widely employed by modern painters. Recent research has reported the degradation of cadmium yellow paints in important artworks such as The Scream by Edward Munch, raising questions about its triggering factors. To address this issue, we investigated, for the first time, the historical production methods of Winsor & Newton, one of the leading suppliers of artists' materials. Starting from in-depth documentary research of the Winsor & Newton 19th c. archive database, the foundation for an informed selection of historical preparation methods of these yellow pigments was provided. This allowed us to replicate 19th c. recipes, enabling us to understand better historical synthesis processes and their impact on the properties of cadmium yellow pigments. The pigments prepared, as well as reference pigments, were characterized through surface-sensitive methods in a multi-faceted analytical approach. The results show that pigments synthesized following historical indications present polytype crystal structure and crystal grains and aggregates much smaller than reference pigments. More interestingly, the detection of chlorine ions on particles surface (in the form of Cl bonded to a metal) was possible by X-ray Photoelectron Spectroscopy analysis, allowing its exclusion as an environmental contaminant. Finally, we have observed a strong sensitivity of the photoluminescence emission to pigment crystallite and grain size, an occurrence which may significantly impact on the photo-reactivity of the pigment in artworks. Image 1 • Cadmium sulfide pigments were synthesized following instructions of the Winsor & Newton 19th c. archive database. • Synthesized pigments show polytipism, small grains and small aggregates with respect to reference pigments. • Chlorine ions, in the form of Cl bonded to a metal, were observed on particles surface of some of the synthesized pigments. • The synthesized pigments display an enhancement of the non-radiative decay channels with respect to reference pigments • All these properties may significantly impact on the photo-reactivity of the synthetized pigments. [ABSTRACT FROM AUTHOR]

Rh/Al 2 O 3 can be used as an effective chemo-selective reductive catalyst that combines the mild conditions of catalytic hydrogenation with high selectivity for azide moieties in the presence of other hydrogenolysis labile groups such as benzyl and benzyloxycarbonyl functionalities. The practicality of this strategy is exemplified with a range of azide-containing carbohydrate and amino acid derivatives. Image 1 • Rh/Al 2 O 3 can be used as a mild and effective chemo-selective reductive catalyst for azide moieties. • The method is chemoselective to azides in the presence of other hydrogenolysis labile groups (-OBn, -Cbz). • The reactions proceed cleanly and across a range of reactivity profiles. [ABSTRACT FROM AUTHOR]

Galectins are evolutionary conserved β-galactoside binding proteins with a carbohydrate-recognition domain (CRD) of approximately 130 amino acids. In mammals, 15 members of the galectin family have been identified and classified into three subtypes according to CRD organization: prototype, tandem repeat-type and chimera-type galectins. Galectin-3 (gal-3) is the only chimera type galectin in vertebrates containing one CRD linked to an unusual long N-terminal domain which displays non-lectin dependent activities. Although recent studies revealed unique, pleiotropic and context-dependent functions of gal-3 in both extracellular and intracellular space, gal-3 specific pathways and its ligands have not been clearly defined yet. In the kidney gal-3 is involved in later stages of nephrogenesis as well as in renal cell cancer. However, gal-3 has recently been associated with lupus glomerulonephritis, with Familial Mediterranean Fever-induced proteinuria and renal amyloidosis. Gal-3 has been studied in experimental acute kidney damage and in the subsequent regeneration phase as well as in several models of chronic kidney disease, including nephropathies induced by aging, ischemia, hypertension, diabetes, hyperlipidemia, unilateral ureteral obstruction and chronic allograft injury. Because of the pivotal role of gal-3 in the modulation of immune system, wound repair, fibrosis and tumorigenesis, it is not surprising that gal-3 can be an intriguing prognostic biomarker as well as a promising therapeutic target in a great variety of diseases, including chronic kidney disease, chronic heart failure and cardio-renal syndrome. This review summarizes the functions of gal-3 in kidney pathophysiology focusing on the reported role of gal-3 in autoimmune diseases. [ABSTRACT FROM AUTHOR]

N -linked glycosylation is a ubiquitous protein post-translational modification in which aberrant glycan biosynthesis has been linked to severe conditions like cancer. Accurate qualitative and quantitative analysis of N -glycans are crucial for investigating their physiological functions. Owing to the intrinsic absence of chromophores and high polarity of the glycans, current detection methods are restricted to liquid chromatography and mass spectrometry. Herein, we describe three new imidazolium-based glycan tags: 2'GITag, 3'GITag, and 4'GITag, that significantly improve both the limit of detection and limit of quantification of derivatized oligosaccharides, in terms of fluorescence intensity and ionisation efficiency. Our top-performing derivatisation agent, 4'GITag, shifted the detection sensitivity range from high femtomole to sub-femtomole levels in ESI-MS compared to traditional glycan label, 2AB, enabling the identification of 24 N -glycans in mouse serum, including those bearing sialic acids. Additionally, 4'GITag stabilized Na-salt forms of sialic acids, simplifying the simultaneous analysis of neutral and negative charged N -glycans significantly, avoiding the need for complex derivatisation procedures typically required for the detection of sialylated species. Overall, the favorable performance of imidazolium tags in the derivatisation and sensitive profiling of glycans has the potential for labeling tissue or live cells to explore disease biomarkers and for developing new targeted therapeutic strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

The early emergence of social smiles is an important milestone of infants' socio-emotional development. Our aim was to assess how the use of protective facemasks by adults affects the display of social smiles in preterm (PT) and full-term (FT) infants at 3 months (corrected age for prematurity). We enrolled 30 FT and 30 PT infants (gestational age ≤ 32 weeks). Infants' social smiles displays were assessed at 2–3-month-age (corrected) across a three-episode (masked mother; unmasked mother; masked adult female stranger) videotaped interactive task. During each episode, the adult was instructed to maintain specific facial expressions (happy-smiling, sad-frowning, neutral-unresponsive) for 15 second windows and then instructed to interact spontaneously for 45 s (of which the first 15 s were coded). FT and PT infants did not differ in the display of social smiles. In both groups, social smiles were mostly exhibited in response to happy/smiling and spontaneously interacting partners. Overall, no effect of wearing a protective facemask emerged. The use of protective facemasks did not result in a lower display of social smiles. The findings suggest that FT and PT might be equally sensitive to their adult interactive partners in terms of social smiles displays at 2–3-month-age. • Detrimental effect of mask wearing by adults for infants' emotional development has been suggested. • We tested social smiles display in 2-3-month-old infants facing different masked/unmasked adult partners. • Mask wearing did not result in lower social smiles display in 2-3-month-old infants. • FT and PT did not differ in social smiles display across the task. • Smiling or actively interacting adults elicited social smiles with highest probability in both groups. [ABSTRACT FROM AUTHOR]

Abstract: Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease, encompassing either mild or severe manifestations. SLE was originally labeled as being an immune complex-mediated disease, but further knowledge suggested its pathogenesis is motlier than that, involving complex interactions between predisposed individuals and their environment. People affected with SLE have their immune system skewed toward aberrant self-recognition usually after encountering a triggering agent. Defeats in early and late immune checkpoints contribute to tolerance breakdown and further generation and expansion of autoreactive cell-clones. B and T cells play a master role in SLE, however clues are emerging about other cell types and new light is being shed on SLE autoantibodies, since some of them display really harmful potential (pathogenic antibodies), while others are just connected with disease development (pathological antibodies) and may even be protective. Autoantibody generation is elicited by abnormal apoptosis and inefficient clearance of cellular debris causing intracellular autoantigens (e.g. nucleosomes) to persist in the extracellular environment, being further recognized by autoreactive cells. Here we explore the complexity of SLE pathogenesis through five core issues, i.e. genetic predisposition, B and T cell abnormalities, abnormal autoantigen availability, autoantibody generation and organ damage, relying on current knowledge and recent insights into SLE development. [Copyright &y& Elsevier]

Preterm newborns are considered at risk of acquired coagulopathy and are often prophylactically infused with fresh frozen plasma (FFP) even in the absence of bleeding. To assess the coagulation asset of preterm neonates and the biological plausibility of such infusions, we investigated at birth 87 very low birth weight (≤1500 g) preterm (gestational age <35 weeks) newborns and 64 full-term newborns. Preterm neonates were also investigated at different time-points up to 30 days after birth. Plasma from preterm and full-term neonates were subjected to the measurement of prothrombin and activated partial thromboplastin time (PT, APTT), pro- and anticoagulant factors as well as to thrombin-generation procedures both with and without thrombomodulin. PT and APTT of preterm newborns were longer than those of full-term neonates [PT: 15.9 s (11.7–51.2)-vs-13.8 (11.0–25.4), p < 0.001. APTT: 59.0 (37.8–97.5)-vs- 47.3 (28.1–71.9), p < 0.001] and tended to shortening after 30 days from birth. Thrombin-generation defined as endogenous thrombin potential (ETP) was increased in preterm as compared to full-term neonates at birth [1322 nM·min (474–2384)-vs-1006 (697–1612), p < 0.001] and did not change appreciably over time up to 30 days from birth. In conclusion, plasma from preterm neonates displays a procoagulant imbalance at birth as shown by increasing ETP, despite the prolongation of PT and APTT. The results define preterm newborns as having hyper- rather than hypo-coagulability and argue against the infusion of FFP when given prophylactically and/or based solely on prolongation of PT or APTT. • Thrombin generation in neonates is rebalanced because of the concomitant deficiency of pro- and anticoagulants, despite the prolongation of PT/APTT • Scanty observations are available for preterm neonates at birth and during the first month of life. • Thrombin generation in preterm neonates is higher than that in full-term neonates at birth. • Thrombin generation in preterm neonates remains high until the first month of life. • In the absence of bleeding, the prophylactic infusion of fresh frozen plasma to correct prolonged PT and APTT is not biologically plausible. [ABSTRACT FROM AUTHOR]

Roasted hazelnuts can be consumed as whole nuts, or as an ingredient in the confectionary and bakery industries and are highly appreciated for their typical taste, aroma and crunchy texture. In this work, two hazelnut types (TGT, Ordu) from two harvests were roasted using two different systems (hot air, infrared) at different time/temperature combinations, and the evolution of oxidative stability, the total phenolic content (TPC), the antioxidant capacity, the mechanical and acoustic properties and the sensory perception were determined during storage. The results showed that the oxidative stability was increased by roasting hazelnuts at 120 °C for 40 min with hot air system. Similar overall trends were not found for the TPC, the antioxidant capacity and the mechanical-acoustic properties. However, for the maintenance of high antioxidant activity, a storage time of 6 months at 4 °C is recommended. The two roasting systems gave hazelnuts with significant sensory differences only at high roasting temperature. [ABSTRACT FROM AUTHOR]

In an effort to find naturally occurring substances that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), statins were first discovered by Endo in 1972. With the widespread prescription and use of statins to decrease morbidity from myocardial infarction and stroke, it was noted that approximately 5% of all statin users experienced muscle pain and weakness during treatment. In a smaller proportion of patients, the myopathy progressed to severe morbidity marked by proximal weakness and severe muscle wasting. Remarkably, Mammen and colleagues were the first to discover that the molecular target of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is an autoantibody target in patients that develop an immune-mediated necrotizing myopathy (IMNM). These observations have been confirmed in a number of studies but, until today, a multi-center, international study of IMNM, related idiopathic inflammatory myopathies (IIM), other auto-inflammatory conditions and controls has not been published. Accordingly, an international, multi-center study investigated the utility of anti-HMGCR antibodies in the diagnosis of statin-associated IMNM in comparison to different forms of IIM and controls. This study included samples from patients with different forms of IIM ( n = 1250) and patients with other diseases ( n = 656) that were collected from twelve sites and tested for anti-HMGCR antibodies by ELISA. This study confirmed that anti-HMGCR autoantibodies, when found in conjunction with statin use, characterize a subset of IIM who are older and have necrosis on muscle biopsy. Taken together, the data to date indicates that testing for anti-HMGCR antibodies is important in the differential diagnosis of IIM and might be considered for future classification criteria. [ABSTRACT FROM AUTHOR]

In this study, the sanitization efficacy of decontamination techniques was evaluated on lemon balm (Melissa officinalis). Dried aromatic herbs are minor food components with widespread use and, despite their low water activity, they are often contaminated with microorganisms, including toxigenic and pathogenic ones. Gaseous ozone (GO) and electrolyzed water (EW) treatments were applied on lemon balm after and before drying (traditional at 40 °C and cold at 20 °C), respectively. Microbiological and entomological decontamination aspects were assessed as well as the sensory quality and compositional properties of the product in terms of essential oil, total polyphenol and ascorbic acid contents, and antioxidant capacity. The most interesting results concerned EW treatment (400 ppm × 1 min dipping) reducing aerobic mesophilic bacteria, Enterobacteriaceae , moulds and yeasts of about 4.0, 2.5, 2.0 and 1.0 Log cfu/g, respectively, thus below law limits. Moreover, 200 ppm EW x 1 min dipping was enough for limiting Bacillus cereus growth. However, sanitization against the beetle species Tribolium castaneum and Lasioderma serricorne was less efficient with EW (less than 40% mortality) compared with GO (200,000 ppm × min) (more than 95% mortality). Noteworthy, sensory analysis highlighted that lemon balm exposed to EW treatment did not lose organoleptic quality, in particular the color even seemed to improve in brightness when the herbs were subsequently cold dried. Furthermore, the loss in essential oils was not significant in terms of the overall content as well as total polyphenol, ascorbic acid and antioxidant capacity in EW treated lemon balm then submitted to cold drying. Differently, the combination of EW treatment and traditional drying led to a significant detriment of compositional properties. The results obtained in this study are encouraging and deserve to be discussed with producers. • EW treatment reduced microbial contamination below law limits in dried lemon balm. • EW treatment did not negatively affect sensorial quality of dried lemon balm. • EW treatment did not negatively affect chemical properties of cold dried lemon balm. • GO was more efficient than EW in insect control in lemon balm. • EW and GO were used to reduce microbial and insect contamination in lemon balm. [ABSTRACT FROM AUTHOR]

The aim of this work was to compare different texture test conditions for the evaluation of instrumental mechanical and acoustic properties of raw and roasted hazelnut ( Corylus avellana L.) kernels cv. Tonda Gentile Trilobata (TGT). A comparison of compression and shear tests, test speed (0.2, 1.0, 10.0 mm/s), and analyzed axis (x, y, z) combinations was performed. Joint mechanical and acoustic emission acquisitions were used for the first time on hazelnut kernels. The compression test method using 1.0 mm/s speed and analyzed on the x-axis showed the lowest variability of the results. These conditions were then used to evaluate raw kernels during 12 months of storage, conducted in-shell (at ambient temperature) and shelled (refrigerated, vacuum, frozen, with nitrogen modified atmosphere). The main differences among storage conditions were evidenced in rupture force, rupture slope and acoustic maximum peak parameters. [ABSTRACT FROM AUTHOR]

Abstract: Overlap Syndromes (OSs) have been defined as entities satisfying classification criteria of at least two connective tissue diseases (CTDs) occurring at the same or at different times in the same patient. CTDs include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PDM), and Sjögren syndrome (SS). Every combination between these disorders has been reported. In some OS a specific autoantibody has been indentified, supporting the hypothesis that these syndromes are not a mere association of two or more CTD in the same patient, but a well defined clinical entity with specific clinical characteristics. As an example, anti-t-RNA synthetase syndrome is characterized by the presence of anti-t-RNA synthetase antibodies. Notably, clinical manifestations observed in OS may be different from those observed in the single CTD. The treatment of OS is mainly based on the use of corticosteroids and immunosuppressants. Biologic drugs, i.e. anti-TNFα or anti-CD20 monoclonal antibodies, have been recently introduced as alternative treatments in refractory cases. Moreover, there are some concerns with the use of anti-TNF agents in patients with systemic autoimmune diseases due to the risk of triggering disease exacerbations. In this paper the most frequent OS are described with a special focus on the specific immunologic and clinical aspects. Furthermore, some personal data on anti-t-RNA synthetase syndrome and rhupus syndrome are reported. [Copyright &y& Elsevier]

Abstract: As soon as autoinflammatory diseases (AIDs) emerged as new entities, they have been linked to the well known world of autoimmunity. In fact, AIDs and systemic autoimmune diseases (ADs), share some characteristics: they start with the prefix “auto” to define a pathological process directed against self; they are systemic diseases, frequently involving musculoskeletal system; both include monogenic and polygenic diseases. From the pathogenetic point of view, they are characterized by a chronic activation of immune system, which eventually leads to tissue inflammation in genetically predisposed individuals. Nevertheless, the specific effectors of the damage are different in the two groups of diseases: in AIDs the innate immune system directly causes tissue inflammation, whereas in ADs the innate immune system activates the adaptive immune system which, in turn, is responsible for the inflammatory process. Mutations in inflammasome-related proteins, particularly in NOD-like receptor (NLR) genes, have been strongly associated to the occurrence of AIDs, whereas the link between inflammasome and ADs is less clear. However, a role for this multiprotein-complex in some ADs can be postulated, since a wide spectrum of endogenous danger signals can activate NLRs and inflammasome products, including IL-1ß, can activate adaptive immunity. An association between single nucleotide polymorphisms (SNPs) localized in the inflammasome gene NLRP1 and systemic lupus erythematosus has recently been reported. AIDs and ADs are currently subdivided into two different groups, but looking at their similarities they might be considered as a single group of diseases with a large immune pathological and clinical spectrum which includes at one end pure ADs and at the other end pure AIDs. [Copyright &y& Elsevier]

Abstract: Several autoantibodies are culprits in the pathogenesis of organ damage in systemic lupus erythematosus, by means of established or postulated mechanisms, whereby inducing a perturbation of cell structure and function, with consequent tissue–organ impairment. Common autoantibody-mediated mechanisms of damage include cell surface binding with or without cytolysis, immune complex-mediated damage, penetration into living cells, binding to cross-reactive extracellular molecules. Experimental data from both murine models and humans have recently clarified the key role of autoantibodies in severe organ involvements, including nephritis, neuropsychiatric (NP) dysfunction, and cerebrovascular disease (CVD). In lupus nephritis early and late phases are distinguishable and mediated by different processes in which anti-chromatin antibodies are both inducing and perpetuating agents, by immune-complex formation and massive deposition in mesangial matrix at first, and in glomerular basement membrane at end-stage. Also NP abnormalities occur very early, much earlier than other systemic manifestations, and exacerbate with the increase in autoantibody titers. Among the autoantibodies mainly implicated in neurolupus, anti-β2 glycoprotein I (β2GPI) antibodies are preferentially involved in focal NP events which are a consequence of non-inflammatory microangiopathy; otherwise, anti-ribosomal P protein antibodies and N-methyl-d-aspartate receptor (NMDAR) antibodies cause diffuse NP events through a direct cytotoxic effect on neuronal cells at specific brain zones. [Copyright &y& Elsevier]

Abstract: Around 1980 antinuclear antibody testing became widely used in routine laboratory practice leading to a tapering in the lag time between SLE onset and diagnosis. Since then nothing relevant has been introduced which could help us in making the diagnosis of SLE earlier than now. Notably, there is increasing evidence that early diagnosis and treatment could increase SLE remission rate and improve patient prognosis. Although it has been shown that autoantibodies appear before clinical manifestations in SLE patients, currently we cannot predict which autoantibody positive subjects will eventually develop the disease. Thus, great effort should be made in order to identify new biomarkers able to improve our diagnostic potential. B lymphocyte stimulator (BLyS), anti-ribosomal P protein and anti-C1q antibodies are among the most promising. In recent years, some therapeutic options have emerged as appropriate interventions for early SLE treatment, including antimalarials, vitamin D, statins and vaccination with self-derived peptides. All these immune modulators seem to be particularly useful when introduced in an early stage of the disease. [Copyright &y& Elsevier]

Abstract: The association between malignancy and autoimmune myositis has been largely described and confirmed by numerous epidemiological studies. The temporal relationship between the two pathologic conditions can vary: malignancy may occur before, at the same time or following the diagnosis of myositis. Beside these observations, the molecular mechanisms underlying this association are still unknown, even though it has been demonstrated a possible antigenic similarity between regenerating myoblasts and some cancer cell populations. To better identify peculiar histopathologic features common to cancer and myositis, we screened muscle biopsies from patients affected with polymyositis, dermatomyositis, myositis in association to cancer, and from patients affected with newly diagnosed cancer, but without myositis. Similarly to the histopatologic features that were observed in the muscle from myositis patients, especially in those with cancer associated myositis, in patients affected with malignancy at the clinical onset of disease we observed early sign of myopathy, characterized by internally nucleated and regenerating myofibers, most of them expressing the neural cell adhesion molecule. The hypothesis that in a particular subset of individuals genetically predisposed to autoimmunity, an initial subclinical tumor-induced myopathy may result in an autoimmune myositis, represents a further intriguing link behind the association of these two conditions. [Copyright &y& Elsevier]

Abstract: Background: A positive result for antinuclear antibodies (ANA), often as a fortuitous observation, may be cause for concern in idiopathic recurrent pericarditis (IRP), nevertheless data are lacking on their prevalence and clinical significance. This study is sought to investigate the prevalence and clinical significance of ANA in IRP. Methods: ANA titres were assessed in consecutive patients with recurrent pericarditis, and matched healthy controls. Baseline and follow-up data were recorded and compared according to ANA results. Results: A total of 145 consecutive patients with recurrent pericarditis were studied: 122 patients with IRP, 23 patients with pericarditis due to known etiologies (rheumatologic diagnoses and postpericardiotomy syndrome), and 122 healthy controls. ANA were detected in 53 of 122 (43.4%) patients with IRP, and in only 12 of 122 (9.8%) controls (p <0.001). Low titres (1/40–1/80) were found in the majority of cases, while moderate positivity (1/160–1/320) was more common in patients with a known rheumatic disease (26.7% vs. 5.7%; p =0.020). High concentrations of ANA (≥1/640) were not recorded. Women were at increased risk for ANA (OR 2.22 95%CI 1.07–4.60; p =0.033). During a mean follow-up of 32 months, complications and new diagnoses were similar in patients with or without ANA positivity. Conclusions: Low-positive titres are more common in patients with IRP than in controls, suggesting a possible autoimmune pathogenesis. Nevertheless, they are often a clinically non-specific finding. Routine serologic testing for ANA suggests a source for recurrent pericarditis in less than 10% of cases, and in these cases other evidence typically suggests the underlying disease. [Copyright &y& Elsevier]

Abstract: A growing body of experimental and clinical evidence supports the pivotal role of infections in the induction or exacerbation of systemic lupus erythematosus (SLE). Infections can be responsible for aberrant immune response leading to a loss of tolerance towards native proteins. Molecular mimicry, especially between Sm or Ro autoantigens and EBV Nuclear Antigen-1 response, as well as the over-expression of type 1 INF genes are among the major contributors to SLE development. On the other hand infections are very common in SLE patients, where they are responsible for 30–50% of morbidity and mortality. Several factors, either genetic, including complement deficiencies or mannose-binding lectin deficiency or acquired such as severe disease manifestations or immunosuppressant use, predispose SLE patients to infections. All types of infections, including bacterial, viral and opportunistic infections, have been reported and the most frequently involved sites of infections are the same as those observed in the general population, including respiratory, skin, and urinary tract infections. Some preventive measures could be adopted in order to reduce the rate of infections in SLE patients: i.e. screening for Mycobacterium tuberculosis and for some chronic viral infections before immunosuppressive treatment; adequate prophylaxes or drug adjustments when indicated, and pneumococcal and influenza vaccinations in patients with stable disease. [Copyright &y& Elsevier]