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Abstract We have developed a state-of-the-art apparatus for laser-based spin- and angle-resolved photoemission spectroscopy with micrometer spatial resolution (µ-SARPES). This equipment is realized by the combination of a high-resolution photoelectron spectrometer, a 6 eV laser with high photon flux that is focused down to a few micrometers, a high-precision sample stage control system, and a double very-low-energy-electron-diffraction spin detector. The setup achieves an energy resolution of 1.5 (5.5) meV without (with) the spin detection mode, compatible with a spatial resolution better than 10 µm. This enables us to probe both spatially-resolved electronic structures and vector information of spin polarization in three dimensions. The performance of µ-SARPES apparatus is demonstrated by presenting ARPES and SARPES results from topological insulators and Au photolithography patterns on a Si (001) substrate.

The autophagy process recycles dysfunctional cellular components and protein aggregates by sequestering them in autophagosomes directed to lysosomes for enzymatic degradation. A basal level of autophagy is essential for skeletal muscle maintenance. Increased autophagy occurs in several forms of muscular dystrophy and in the merosin-deficient congenital muscular dystrophy 1A mouse model (dy3k/dy3k) lacking the laminin-α2 chain. This pilot study aimed to compare autophagy marker expression and autophagosomes presence using light and electron microscopes and western blotting in diagnostic muscle biopsies from newborns affected by different congenital muscular myopathies and dystrophies. Morphological examination showed dystrophic muscle features, predominance of type 2A myofibers, accumulation of autophagosomes in the subsarcolemmal areas, increased number of autophagosomes overexpressing LC3b, Beclin-1 and ATG5, in the merosin-deficient newborn suggesting an increased autophagy. In Duchenne muscular dystrophy, nemaline myopathy, and spinal muscular atrophy the predominant accumulation of p62+ puncta rather suggests an autophagy impairment.

Several studies have shown the relevance among students of the quality of their interpersonal relationships for their academic achievement. Nevertheless, most studies available have explored the relation between the cognitive functioning and academic achievement without taking into account the quality of the relationships experienced in the school environment. Furthermore, the studies that have begun to consider the joint role of these factors in the prediction of academic achievement are scant. Therefore, it appears of relevance to deepen the relation between cognitive functioning and quality of school relationships in order to support students' academic achievement and the potential of youth. In this paper, we examined the moderating role of the quality of student-teacher relationships and school bonding (STR-SB) in the associations of fluid intelligence (Gf) with academic achievement among adolescents (N = 219). A multiple-group structural equation modelling analysis revealed that STR-SB quality moderated unexpectedly only the link between Gf and mathematics. The findings support the idea that the quality of student-teacher relationships may be a relevant dimension to be considered to clarify the association between cognitive functioning and academic achievement.

Extraintestinal manifestations (EIMs) are common in inflammatory bowel disease (IBD), in both Crohn's disease and ulcerative colitis. Almost any organ system can be affected, including the musculoskeletal, dermatologic, renal, hepatopancreatobiliary, pulmonary and ocular systems. However, the musculoskeletal and dermatologic systems are the most commonly involved sites of manifestations. While some manifestations such as peripheral arthritis and erythema nodosum have an association with IBD activity, others such as axial arthropathy, pyoderma gangrenosum and primary sclerosing cholangitis have an independent disease course. This review provides a summary of the most common EIMs in IBD and their prevalence and management.

Abstract Background Many genome- and epigenome-wide association studies (GWAS and EWAS) and studies of promoter methylation of candidate genes for inflammatory bowel disease (IBD) have demonstrated significant associations between genetic and epigenetic changes and IBD. Independent GWA studies have identified genetic variants in the BACH2, IL6ST, LAMB1, IKZF1, and MGAT3 loci to be associated with both IBD and immunoglobulin G (IgG) glycosylation. Methods Using bisulfite pyrosequencing, we analyzed CpG methylation in promoter regions of these five genes from peripheral blood of several hundred IBD patients and healthy controls (HCs) from two independent cohorts, respectively. Results We found significant differences in the methylation levels in the MGAT3 and BACH2 genes between both Crohn’s disease and ulcerative colitis when compared to HC. The same pattern of methylation changes was identified for both genes in CD19+ B cells isolated from the whole blood of a subset of the IBD patients. A correlation analysis was performed between the MGAT3 and BACH2 promoter methylation and individual IgG glycans, measured in the same individuals of the two large cohorts. MGAT3 promoter methylation correlated significantly with galactosylation, sialylation, and bisecting GlcNAc on IgG of the same patients, suggesting that activity of the GnT-III enzyme, encoded by this gene, might be altered in IBD. The correlations between the BACH2 promoter methylation and IgG glycans were less obvious, since BACH2 is not a glycosyltransferase and therefore may affect IgG glycosylation only indirectly. Conclusions Our results suggest that epigenetic deregulation of key glycosylation genes might lead to an increase in pro-inflammatory properties of IgG in IBD through a decrease in galactosylation and sialylation and an increase of bisecting GlcNAc on digalactosylated glycan structures. Finally, we showed that CpG methylation in the promoter of the MGAT3 gene is altered in CD3+ T cells isolated from inflamed mucosa of patients with ulcerative colitis from a third smaller cohort, for which biopsies were available, suggesting a functional role of this glyco-gene in IBD pathogenesis.

Abstract Acidic glycerophospholipids play an important role in determining the resistance of Gram-negative bacteria to stress conditions and antibiotics. Acinetobacter baumannii, an opportunistic human pathogen which is responsible for an increasing number of nosocomial infections, exhibits broad antibiotic resistances. Here lipids of A. baumannii have been analyzed by combined MALDI-TOF/MS and TLC analyses; in addition GC-MS analyses of fatty acid methyl esters released by methanolysis of membrane phospholipids have been performed. The main glycerophospholipids are phosphatidylethanolamine, phosphatidylglycerol, acyl-phosphatidylglycerol and cardiolipin together with monolysocardiolipin, a lysophospholipid only rarely detected in bacterial membranes. The major acyl chains in the phospholipids are C16:0 and C18:1, plus minor amounts of short chain fatty acids. The structures of the cardiolipin and monolysocardiolipin have been elucidated by post source decay mass spectrometry analysis. A large variety of cardiolipin and monolysocardiolipin species were found in A. baumannii. Similar lysocardiolipin levels were found in the two clinical strains A. baumannii ATCC19606 T and AYE whereas in the nonpathogenic strain Acinetobacter baylyi ADP1 lysocardiolipin levels were highly reduced.

During experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis associated with blood-brain barrier (BBB) disruption, oligodendrocyte precursor cells (OPCs) overexpress proteoglycan nerve/glial antigen 2 (NG2), proliferate, and make contacts with the microvessel wall. To explore whether OPCs may actually be recruited within the neurovascular unit (NVU), de facto intervening in its cellular and molecular composition, we quantified by immunoconfocal morphometry the presence of OPCs in contact with brain microvessels, during postnatal cerebral cortex vascularization at postnatal day 6, in wild-type (WT) and NG2 knock-out (NG2KO) mice, and in the cortex of adult naïve and EAE-affected WT and NG2KO mice. As observed in WT mice during postnatal development, a higher number of juxtavascular and perivascular OPCs was revealed in adult WT mice during EAE compared to adult naïve WT mice. In EAE-affected mice, OPCs were mostly associated with microvessels that showed altered claudin-5 and occludin tight junction (TJ) staining patterns and barrier leakage. In contrast, EAE-affected NG2KO mice, which did not show any significant increase in vessel-associated OPCs, seemed to retain better preserved TJs and BBB integrity. As expected, absence of NG2, in both OPCs and pericytes, led to a reduced content of vessel basal lamina molecules, laminin, collagen VI, and collagen IV. In addition, analysis of the major ligand/receptor systems known to promote OPC proliferation and migration indicated that vascular endothelial growth factor A (VEGF-A), platelet-derived growth factor-AA (PDGF-AA), and the transforming growth factor-β (TGF-β) were the molecules most likely involved in proliferation and recruitment of vascular OPCs during EAE. These results were confirmed by real time-PCR that showed Fgf2, Pdgfa and Tgfb expression on isolated cerebral cortex microvessels and by dual RNAscope-immunohistochemistry/in situ hybridization (IHC/ISH), which detected Vegfa and Vegfr2 transcripts on cerebral cortex sections. Overall, this study suggests that vascular OPCs, in virtue of their developmental arrangement and response to neuroinflammation and growth factors, could be integrated among the classical NVU cell components. Moreover, the synchronized activation of vascular OPCs and pericytes during both BBB development and dysfunction, points to NG2 as a key regulator of vascular interactions.

La qualità dell’ambiente di apprendimento risulta essere un importante fattore influenzante l’esperienza degli studenti infermieri. La valutazione della qualità dovrebbe includere la classificazione delle percezioni dello studente sui fattori che influenzano il loro apprendimento clinico. L’obiettivo di questo studio è comprendere come gli studenti infermieri percepiscono l’ambiente clinico di apprendimento nei Corsi di Laurea in Infermieristica della Regione Molise utilizzando lo strumento “Student Evaluation of the Clinical Education Environment Inventory”(SECEE)[1]. Il campione è rappresentato dagli studenti del secondo e del terzo anno dei Corsi di Laurea in Infermieristica della Regione Molise. I risultati evidenziano una significativa predisposizione degli studenti infermieri ad esprimersi positivamente circa il proprio ambiente clinico di apprendimento. L’originalità del presente progetto di ricerca risiede fondamentalmente nella volontà di proporre un’analisi che considera e osserva le percezioni e le opinioni degli studenti infermieri attraverso un metodo quali-quantitativo.

Inflammation is the driving force in inflammatory bowel disease (IBD) and its link to oxidative stress and carcinogenesis has long been accepted. The antioxidant system of the intestinal mucosa in IBD is compromised resulting in increased oxidative injury. This defective antioxidant system may be the result of genetic variants in antioxidant genes, which can represent susceptibility factors for IBD, namely Crohn's disease (CD) and ulcerative colitis (UC). Single nucleotide polymorphisms (SNPs) in the antioxidant genes SOD2 (rs4880) and GPX1 (rs1050450) were genotyped in a Portuguese population comprising 436 Crohn's disease and 367 ulcerative colitis patients, and 434 healthy controls. We found that the AA genotype in GPX1 is associated with ulcerative colitis (OR = 1.93, adjusted P-value = 0.037). Moreover, we found nominal significant associations between SOD2 and Crohn's disease susceptibility and disease subphenotypes but these did not withstand the correction for multiple testing. These findings indicate a possible link between disease phenotypes and antioxidant genes. These results suggest a potential role for antioxidant genes in IBD pathogenesis and should be considered in future association studies.

Objectives: To determine the role of antiphospholipid antibodies (aPL) and of Raynaud’s phenomenon (RP) in the development of migraine in patients with systemic lupus erythematosus (SLE). Methods: 50 unselected SLE patients and 20 rheumatoid arthritis (RA) controls underwent an interview to define the presence of migraine according to the guidelines of the International Headache Society (1988). Serological tests for aPL were performed in all patients. SLE patients were divided according to positivity for RP and/or aPL into 4 subsets: R-/aPL-, R-/aPL+, R+/aPL- and R+/aPL+. Data were analysed using Fisher’s exact test, Chi-square test and U Mann-Whitney test. Results: SLE and RA patients were similar for demographic and clinical features; aPL positivity was found in a greater proportion of SLE patients versus RA controls (68% vs 25%, p=0.0036). 31 of the 50 lupic patients (62%) and 7 of the 20 RA controls (35%) suffered from migraine (OR=3, CI:1-8.9). Among SLE and RA patients, migraine was associated with aPL positivity (p=0.027 and p=0.019). Analysing the combined effect of aPL and RP on migraine, in R+/aPL+ patients we detected an higher frequency of migraine (85.7%) with respect to the patients negative for these two features (27%, p=0.0051, OR=16, CI:2.2-118) and to the patients positive only for aPL (65%, p=0.0031, OR=6.2, CI:1.2-32). Conclusions: Migraine in SLE and RA associates with aPL positivity. The simultaneous presence of RP increases by 2,5 times the probability of having migraine, suggesting that cerebral vasospasm might be more common in patients with peripheral vasospasm, given the presence of aPL.

BackgroundRecent evidence suggests that the IL-33/IL1RL1 axis plays a critical role in several autoimmune and inflammatory disorders; however, its mechanistic role in inflammatory bowel disease (IBD) has not been clearly defined. We investigated the contribution of IL-33 and IL1RL1 polymorphisms to IBD risk, and possible correlations with phenotype in an Italian cohort of adult and pediatric patients.MethodsWe evaluated the association of six SNPs in IL-33 and IL1RL1 genes, in 805 Crohn's disease (CD), 816 ulcerative colitis (UC), and 752 controls, using Taqman. IL-33 and IL1RL1 mRNA expression was also analyzed.ResultsSignificant allele and genotype associations with IL-33 rs3939286 were found in CD (P = 0.004; P = 0.035) and UC patients (P = 0.002; P = 0.038). After stratifying the cohort for age at diagnosis, the differences remained significant only in the IBD adult-onset. Significant associations were also obtained in CD patients with two IL1RL1 polymorphisms (rs13015714 and rs2058660, PConclusionsCommon IL-33 and IL1RL1 polymorphisms contribute to the risk of IBD in an Italian cohort of adult and pediatric patients, with some influence on sub-phenotypes.

This work addresses a new approach developed in our laboratory, consisting in the application of isolated dimethyldioxirane (DDO, 1a) labelled with 18O for synthesis of epoxidized glyceryl linoleate (Gly-LLL, 2). We expect that this work could contribute in improving analytical methods for the determination of epoxidized soybean oil (ESBO) in complex food matrices by adopting an 18O-labelled-epoxidized triacylglycerol as an internal standard.

BACKGROUND: Recent GWAs and meta-analyses have outlined about 100 susceptibility genes/loci for inflammatory bowel diseases (IBD). In this study we aimed to investigate the influence of SNPs tagging the genes/loci PTGER4, TNFSF15, NKX2-3, ZNF365, IFNG, PTPN2, PSMG1, and HLA in a large pediatric- and adult-onset IBD Italian cohort. METHODS: Eight SNPs were assessed in 1,070 Crohn's disease (CD), 1,213 ulcerative colitis (UC), 557 of whom being diagnosed at the age of ≤16 years, and 789 healthy controls. Correlations with sub-phenotypes and major variants of NOD2 gene were investigated. RESULTS: The SNPs tagging the TNFSF15, NKX2-3, ZNF365, and PTPN2 genes were associated with CD (P values ranging from 0.037 to 7×10(-6)). The SNPs tagging the PTGER4, NKX2-3, ZNF365, IFNG, PSMG1, and HLA area were associated with UC (P values 0.047 to 4×10(-5)). In the pediatric cohort the associations of TNFSF15, NKX2-3 with CD, and PTGER4, NKX2-3, ZNF365, IFNG, PSMG1 with UC, were confirmed. Association with TNFSF15 and pediatric UC was also reported. A correlation with NKX2-3 and need for surgery (P = 0.038), and with HLA and steroid-responsiveness (P = 0.024) in UC patients was observed. Moreover, significant association in our CD cohort with TNFSF15 SNP and colonic involvement (P = 0.021), and with ZNF365 and ileal location (P = 0.024) was demonstrated. CONCLUSIONS: We confirmed in a large Italian cohort the associations with CD and UC of newly identified genes, both in adult and pediatric cohort of patients, with some influence on sub-phenotypes.

Diabetic nephropathy affects a subset of about 30% of patients with type 1 Diabetes Mellitus (DM); it also develops in a less defined percentage (20–30%) of patients with type 2, after a period of 15–20 years. It is usually divided into stages. The aim of this study is to assess the usefulness of duplex sonography with Doppler wave form analysis in the evaluation of early diabetic nephropathy, in order to detect patients at risk for irreversible renal disease. 262 patients (61 males, 201 females; age range: 48–81 years) with type 2 diabetes mellitus were studied; 100 healthy volunteers with no evidence of diabetes mellitus (74 females, 26 males; age range: 50–80 years) composed the control group. All of them underwent duplex Doppler sonography of the kidneys; a scanner with a 3.5 MHz transducer (Toshiba 270 SSA) was used, Pulsatily Index (P.I.) and Resistive Index (R.I.) of Doppler waveform were obtained at the intrarenal arteries; the average value of 3 bilateral measurements was taken. Doppler sonography was done by the same authors without knowledge of the patient group (case or control). Both indexes (PI. and R.I.) resulted to be higher in patients with DM compared to controls in patients with microalbuminuria: PI. = 1.49 +/- 0.34 vs. 1.07 +/- 0.06, p< 0.05; R.I. = 0.79 +/- 0.15 vs 0.60 +/- 0.03, p

Objective: To assess the agreement between presence and location of central nervous system (CNS) structural damage and neuropsychological performance. Methods: 21 unselected SLE patients underwent a 3 hours-long battery of neuropsychological tests sampling 15 cognitive functions. A neuropsychologist hypothesized for each SLE patient the most likely site of possible involvement, according to the neuropsychological performance. Patients underwent MRI scans within 6 months (3 months before or after) from neuropsychological tests and SPECT. Results: 14 of the 21 SLE patients (66,6%) were impaired in at least 1 function; among these, 7 patients (33,3%) were mildly impaired and 7 (33,3%) had more than 3 functions impaired. 10 patients (48%) had abnormal MRI scan. Negative and positive agreements between neuropsychological performance and MRI scan were detected in 15 patients (71%; χ2 with Yates’correction 6,09, p 0,007, measure K for concordance 0,44, p 0,03). All the 6 negative agreements had no records of major neurologic or psychiatric events; among the 9 positive agreements, 6 presented previous major neurologic events and 2 minor neuropsychiatric symptoms. Among the subjects with disagreement, 1 was unimpaired with positive MRI and without neuropsychiatric symptoms, 5 were mildly impaired with negative MRI. Conclusions: A detailed neuropsychological evaluation along with MRI arose as a valid method to esclude or to identify, localize and clinically interpret CNS involvement in SLE. Disagreement between MRI and neuropsychological tests was detected mainly for mild cognitive impairment that might be the expression of functional (inflammatory or ischemic) processes.