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In recent years, habits related to smoking have been changing. An increasing portion of light/occasional smokers tend to define themselves as non-smokers, leading to an incorrect perception of the risks that smoking even a few cigarettes can entail. In this study, we investigated the nicotine-induced cognitive distortion in young, higher-education students with low/moderate dependence (as indexed by the Fagerstrom questionnaire). The study involved 111 participants (62 female; mean age 24.43 ± 3.77) divided into smokers and non-smokers, who responded to specific questionnaires to evaluate their attachment style, emotion dysregulation, and state anxiety. Their response to smoking-related cues following emotional stimulation was experimentally evaluated, with participants being made to choose between care- or smoking-related images, following the presentation of threatening or neutral stimuli. The results show a cognitive bias in smokers, with participants choosing smoking-related stimuli significantly more often than non-smokers, with a slower reaction time, regardless of emotional cues. Emotion dysregulation and attachment style were also significantly correlated with response choice but not with response latency. Overall, our data indicate that there is no such thing as light use of nicotine and that smoking, even if not continuous, determines cognitive biases that lead to a vision of the environment as a function of substance seeking.

Background: Donation-related fears are prevalent even among regular donors and can hinder both recruitment and retention. This cross-sectional study aimed to estimate the prevalence of these fears in Italian whole-blood and plasma donors, across different levels of donation experience., Study Design and Methods: A sample of 615 voluntary, unpaid donors from Italy (64.1% male, mean age 45.42 ± 11.80 years) completed an online survey assessing their fear of common donation-related stimuli (fear of blood, needles, pain, and fainting), experience of vasovagal symptoms at the last donation, and their intention to donate again. Donors were grouped based on donation history and their most recent donation type (whole-blood or plasma)., Results: A significant negative relationship was found between donation history and most types of donation-related fears, suggesting that greater experience corresponds to reduced fear. Plasma donors reported lower levels of fear across all stimuli compared to whole-blood donors. Despite this, nearly one-third of the most experienced whole-blood donors and 20% of plasma donors still reported some level of fear. Greater fear was associated with increased reports of pain and vasovagal symptoms during donation, regardless of donation type. However, no significant association emerged between donation-related fears and the intention to donate again., Discussion: Donation-related fear persists even among experienced donors, for both whole-blood and plasma donors. Given its potential to impact donor comfort and retention, the assessment and management of donation-related fears should be integrated into donor care, with appropriate strategies to help donors regulate their fear throughout their donation careers., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background and Objectives: Facemasks represent an essential measure of prevention against the spread of infectious diseases; however, they lessen the ability to convey and understand emotions through facial expressions. In blood donation settings, facemask wearing could interfere with professionals' tasks, reduce the satisfaction of blood donors and affect their future blood donation behaviour. This preliminary cross-sectional study explored the association of mandatory facemask wearing with the quality of the blood donation process at the end of the coronavirus 2019 (COVID-19) pandemic., Materials and Methods: A sample of 615 voluntary unpaid Italian blood and plasma donors completed an online survey assessing their attitude towards facemask wearing, the perceived distress due to facemasks in the different steps of the donation process, self-reported vasovagal reactions after donation and the intention to donate again., Results: Nearly 24% of donors reported a worsened quality of the donation process due to facemask wearing, and 36% reported moderate to severe distress during the donation itself. Donors with a more negative attitude towards facemasks reported a worse donation experience, mainly related to the interactions and the communication with physicians and nurses, and a higher probability of experiencing vasovagal reactions at their last donation. No significant correlations were observed between negative facemask attitudes towards facemask wearing, distress or future intention to donate blood/plasma., Conclusion: Facemasks have worsened the quality of blood and plasma donations for one fourth of donors, confirming the interference with the quality of communications and relationships with healthcare professionals., (© 2024 The Author(s). Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Background &aim: Post-colonoscopy colorectal cancer (PCCRC) is a colorectal cancer (CRC) diagnosed after a colonoscopy in which no cancer is detected (index colonoscopy). Although the overall cumulative rates of PCCRC are low in both the general population and inflammatory bowel disease (IBD) patients, the overall incidence of PCCRC in IBD is greater than that documented in the general population. This study aimed to identify the index colonoscopy-related factors and patients' characteristics influencing IBD-associated PCCRC development., Materials and Methods: We carried out an observational, retrospective study in which IBD-associated PCCRCs were diagnosed between 2010 and 2023. The PCCRC group was compared to a control cohort of IBD patients without CRC matched 1:1 by several demographic and clinical features as well as characteristics of index colonoscopy to minimize selection bias., Results: Among 61 CRCs identified, 37 (61%) were PCCRC. Twelve of 37 (32%) PCCRC were diagnosed within 12 months after the previous negative colonoscopy, 15 (41%) within 12-36 months, and 10 (27%) within 36-60 months. In the multivariate analysis, the inadequate bowel preparation of the index colonoscopy (OR: 5.9; 95% CI: 11.1- 31.4) and the presence of high-risk factors for CRC (OR: 24.03; 95% CI: 3.1-187.8) were independently associated with PCCRC. Conversely, prior exposure to immunosuppressors/biologics (OR: 0.17; 95% CI: 0.03-0.83) and random biopsies sampling at index colonoscopy (OR:0.19; 95% CI: 0.04-0.85) were inversely associated with PCCRC., Conclusions: More than 50% of CRCs in our population were PCCRC. PCCRCs were associated with previous inadequate cleansing and occurred more frequently in high-risk patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Nesbit's procedure remains a cornerstone in surgical management of Peyronie's disease, despite the subjective loss of penile length. This retrospective study demonstrates that the perceived length loss has already occurred prior to surgery and that the Nesbit's procedure does not produce additional loss of length. Ninety-one patients who had undergone Nesbit's procedure between 2017 and 2022 at the Department of Urology of the University of Trieste were enrolled in the study. Preoperative stretched penile length and postoperative stretched penile length were measured. The curvature was uniplanar in 78 patients and biplanar in the remainder. Mean degree of the main curvature was 52.58° ± 14.13° and mean number of plications was 2.42 ± 1.07. Analysis revealed that the median of the differences between preoperative stretched penile length and postoperative stretched penile length was not significant (p = 0.466). According to our results, no significant penile shortening occurs as immediate consequence of Nesbit's procedure, as length is defined by the shorter side of the shaft affected by Peyronie's disease. Hence the length loss should have to be attributed to Peyronie's disease itself and could have been accurately predicted preoperatively allowing for a more accurate counseling of patients. Further studies are pending to assess potential postoperative loss of length due to scarring contracture., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

A small chlorite vial, discovered among numerous artifacts looted and recovered in the Jiroft region of Kerman province, southeastern Iran, contains a deep red cosmetic preparation that is likely a lip-coloring paint or paste. Through analytical research involving XRD (X-ray diffraction), SEM-EDS (scanning electron microscopy-energy-dispersive spectroscopy), and HPLC-MS (high-performance liquid chromatography-mass spectrometry) analyses, the mineral components of the reddish substance were identified as hematite, darkened with manganite and braunite, and traces of galena and anglesite, mixed with vegetal waxes and other organic substances. The mixture, thus observed, bears a striking resemblance to the recipes of contemporary lipsticks. We also report the first radiocarbon date ever obtained from a Bronze age cosmetic in the ancient Near East: results place the pigment in the early 2nd millennium BCE, a date compatible with several mentions of the powerful eastern-iranian civilization of Marḫaši in coeval cuneiform texts of Mesopotamia, as well as with its currently emerging archaeological picture., (© 2024. The Author(s).)

Background: Intestinal ultrasonography (US) allows for the characterization of the intestinal lesions and provides information on transmural inflammation. The aim of the study was to assess the clinical relevance of echopattern and correlation with Crohn's disease (CD) behavior and activity., Methods: We performed a prospective study including CD patients assessed by intestinal US. The echopattern was classified as hypoechoic, hyperechoic and stratified. Color-doppler US was also performed in the thickest segment., Results: One hundred CD patients were enrolled. The hypoechoic echopattern was significantly correlated with penetrating behavior (r = 0.44, p<0.0001), active disease (r = 0.21, p = 0.034), C-reactive protein/Fecal Calprotectin (r = 0.31, p = 0.004; r = 0.34, p = 0.031, respectively) and steroids (r = 0.33, p = 0.0008). Hypoechoic echopattern was associated with younger age than stratified (p = 0.046) and hyperechoic (p = 0.018) echopatterns. Bowel wall thickness was greater in the hypoechoic group than in the hyperechoic/stratified groups (p = 0.011 and p<0.0001, respectively). Hypoechoic echopattern was associated with fistulas (r = 0.52, p<0.0001) and increased vascularization (r = 0.32, p = 0.001). The hyperechoic echopattern showed a significant correlation with stricturing disease and an inverse correlation with fistulas. During a follow up period of 6 months, patients with hypoechoic echopattern had an increased risk of biological therapy need or surgery., Conclusions: The characterization of bowel wall echopattern allows for the identification of different CD behaviors., Competing Interests: Conflict of Interest EDC: None to declare LM: None to declare EL: None to declare LB: None to declare GM: served as a consultant for First Wave BioPharma and filed a patent related to the treatment of inflammatory bowel diseases with Smad7 antisense oligonucleotides. EC: Served as a speaker for AbbVie, Takeda, MSD and Janssen FZ: Served as a speaker for Janssen, Takeda, (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Statistical analysis of the properties of single microparticles, such as cells, bacteria or plastic slivers, has attracted increasing interest in recent years. In this regard, field flow cytometry is considered the gold standard technique, but commercially available instruments are bulky, expensive, and not suitable for use in point-of-care (PoC) testing. Microfluidic flow cytometers, on the other hand, are small, cheap and can be used for on-site analyses. However, in order to detect small particles, they require complex geometries and the aid of external optical components. To overcome these limitations, here, we present an opto-fluidic flow cytometer with an integrated 3D in-plane spherical mirror for enhanced optical signal collection. As a result, the signal-to-noise ratio is increased by a factor of six, enabling the detection of particle sizes down to 1.5 µm. The proposed optofluidic detection scheme enables the simultaneous collection of particle fluorescence and scattering using a single optical fiber, which is crucial to easily distinguishing particle populations with different optical properties. The devices have been fully characterized using fluorescent polystyrene beads of different sizes. As a proof of concept for potential real-world applications, signals from fluorescent HEK cells and Escherichia coli bacteria were analyzed.

Objective: Fever contributes to the inflammatory response; in some infections, antipyretics could prolong the illness. The objective of our study was to evaluate the impact of antipyretic treatments on the evolution of acute upper and lower respiratory tract infections (RTI)., Method: A systematic literature review of randomized controlled trials (RCTs) with meta-analysis was conducted. Our primary endpoint was the time to recovery from illness. Our prespecified secondary endpoints were quality of life, duration and number of fever episodes, repeated medical visits, and adverse events., Results: Out of the 1466 references found, 25 RCTs were included. There were two studies assessing mean fever clearance time, and five studies examining the duration of symptoms associated with the illness studied. No statistically significant differences were found when pooling the results of the different studies. The assessment of adverse events showed a significant difference disadvantaging non-steroidal anti-inflammatory drugs. No meta-analysis could be performed for our other secondary endpoints. The quality of the evidence is limited by the small number of studies included for our primary endpoint and by heterogeneity between the studies., Conclusion: Our results suggest that the use of antipyretics does not prolong or shorten illness duration in acute upper and lower RTI. The symptomatic efficacy of antipyretics must be weighed against their adverse effects, particularly when fever is well-tolerated., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Sentinel node biopsy (SNB) for prostate cancer (PCa) represents an innovative technique aimed at improving nodal staging accuracy. The routinary adoption of this procedure in patients undergoing radical prostatectomy (RP) might be crucial to identify candidates who could effectively benefit from extensive pelvic lymph nodal dissection (ePLND). Despite some promising results, SNB for PCa is still considered experimental due to the lack of solid evidence and procedural standardization. In this regard, our narrative review aimed to analyze the most recent literature in this field, providing an overview of both the diagnostic accuracy measures and the oncological outcomes of SNB.

Current endoscopic surveillance programs do not consider inflammatory bowel disease (IBD)-associated post-inflammatory polyps (pseudopolyps) per se clinically relevant, even though their presence seems to increase the risk of colorectal cancer (CRC). However, it remains unclear whether the link between pseudopolyps and CRC is indirect or whether some subsets of pseudopolyp-like lesions might eventually undergo neoplastic transformation. This study aimed to assess the frequency and predictors of dysplasia in pseudopolyp-like lesions in a population with long-standing colonic IBD. This was a retrospective, single-center study including patients with a colonic IBD (median disease duration of 192 months) and at least a pseudopolyp-like lesion biopsied or resected in the period from April 2021 to November 2022. One hundred and five pseudopolyps were identified in 105 patients (80 with ulcerative colitis and 25 with Crohn's disease). Twenty-three out of 105 pseudopolyp samples (22%) had dysplastic foci, and half of the dysplastic lesions were hyperplastic. Multivariate analysis showed that the age of the patients (odds ratio (OR) 1.1; p = 0.0012), size (OR 1.39; p = 0.0005), and right colonic location (OR 5.32; p = 0.04) were independent predictors of dysplasia, while previous exposure to immunosuppressors/biologics and left colonic location of the lesions were inversely correlated to dysplasia (OR 0.11; p = 0.005, and OR 0.09; p = 0.0008, respectively). No differences were seen between ulcerative colitis and Crohn's disease patients. Lesions with a size greater than 5 mm had a sensitivity of 87% and a specificity of 63% to be dysplastic. These data show that one-fourth of pseudopolyp-like lesions evident during surveillance colonoscopy in patients with longstanding IBD bear dysplastic foci and suggest treating such lesions properly.

Therapeutic targets in Crohn's disease (CD) have evolved greatly over the past several decades to include endoscopic improvement along with clinical remission. Yet CD is characterized by transmural damage, and there is increasing evidence of improved outcomes associated with transmural healing. Intestinal ultrasonography is a noninvasive, highly accurate imaging modality that provides real-time results and can assess for transmural healing in CD. In this review, we present the definition of transmural healing by ultrasonography, its comparison with other imaging modalities and with endoscopy, the efficacy of diverse therapies on achieving transmural healing, and data on patient outcomes in those achieving transmural healing. This review can guide clinicians who care for patients with inflammatory bowel disease on the added value of achieving transmural healing and its eventual incorporation as a target of therapy., (Copyright © 2023 by The American College of Gastroenterology.)

Tire wear particles (TWPs) are one of the environment's most important emission sources of microplastics. In this work, chemical identification of these particles was carried out in highway stormwater runoff through cross-validation techniques for the first time. Optimization of a pre-treatment method (i.e., extraction and purification) was provided to extract TWPs, avoiding their degradation and denaturation, to prevent getting low recognizable identification and consequently underestimates in the quantification. Specific markers were used for TWPs identification comparing real stormwater samples and reference materials via FTIR-ATR, Micro-FTIR, and Pyrolysis-gas-chromatography-mass spectrometry (Pyr-GC/MS). Quantification of TWPs was carried out via Micro-FTIR (microscopic counting); the abundance ranged from 220,371 ± 651 TWPs/L to 358,915 ± 831 TWPs/L, while the higher mass was 39,6 ± 9 mg TWPs/L and the lowest 31,0 ± 8 mg TWPs/L. Most of the TWPs analyzed were less than 100 μm in size. The sizes were also confirmed using a scanning electron microscope (SEM), including the presence of potential nano TWPs in the samples. Elemental analysis via SEM supported that a complex mixture of heterogeneous composition characterizes these particles by agglomerating organic and inorganic particles that could derive from brake and road wear, road pavement, road dust, asphalts, and construction road work. Due to the analytical lack of knowledge about TWPs chemical identification and quantification in scientific literature, this study significantly contributes to providing a novel pre-treatment and analytical methodology for these emerging contaminants in highway stormwater runoff. The results of this study highlight the uttermost necessity to employ cross-validation techniques, i.e., FTIR-ATR, Micro-FTIR, Pyr-GC/MS, and SEM for the TWPs identification and quantification in the real environmental samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Two nanomicas of similar composition, containing muscovite and quartz, but with different particle size distributions, have been used to prepare transparent epoxy nanocomposites. Their homogeneous dispersion, due to the nano-size, was achieved even without being organically modified, and no aggregation of the nanoparticles was observed, thus maximizing the specific interface between matrix and nanofiller. No exfoliation or intercalation has been observed by XRD, despite the significant dispersion of the filler in the matrix which produced nanocomposites with a loss in transparency in the visible domain of less than 10% in the presence of 1% wt and 3% wt of mica fillers. The presence of micas does not affect the thermal behavior of the nanocomposites, which remains similar to that of the neat epoxy resin. The mechanical characterization of the epoxy resin composites revealed an increased Young's modulus, whereas tensile strength was reduced. A peridynamics-based representative volume element approach has been implemented to estimate the effective Young's modulus of the nanomodified materials. The results obtained through this homogenization procedure have been used as input for the analysis of the nanocomposite fracture toughness, which has been carried out by a classical continuum mechanics-peridynamics coupling approach. Comparison with the experimental data confirms the capability of the peridynamics-based strategies to properly model the effective Young's modulus and fracture toughness of epoxy-resin nanocomposites. Finally, the new mica-based composites exhibit high values of volume resistivity, thus being excellent candidates as insulating materials.

Biodegradable stent coatings have shown great potential in terms of delivering drugs to a damaged vessel wall, and their release profiles are key elements governing the overall performance of drug-eluting stents (DESs). However, release and degradation kinetics are usually not tested under simulated physiological conditions or in dynamic environments, both essential aspects in the design of novel DESs. To bridge this gap, fused silica-based microfluidic systems, with either round or square channel cross-sections, were designed to mimic the microenvironment of a stented vessel. In particular, we fabricated and characterized microfluidic chips based on customizable channels, which were spray-coated with a naturally-derived, rutin-loaded zein solution, to perform a comprehensive study under flow conditions. Dynamic assays after 6 hours showed how the degradation of the zein matrix was affected by the cross-sectional conformation (∼69% vs. ∼61%, square and round channel, respectively) and the simulated blood fluid components (∼55%, round channel with a more viscous solution). The released amount of rutin was ∼81% vs. ∼77% and ∼78% vs. ∼74% from the square and round channels, using the less and more viscous blood-simulated fluids, respectively. Fitting the drug release data to Korsmeyer-Peppas and first-order mathematical models provided further insight into the mechanism of rutin release and coating behavior under flowing conditions. More importantly, whole blood tests with our newly developed microfluidic platforms confirmed the hemocompatibility of our zein-based coating. In detail, in-flow and static studies on the blood cell behavior showed a significant reduction of platelet adhesion (∼73%) and activation (∼93%) compared to the stainless-steel substrate, confirming the benefits of using such naturally-derived coatings to avoid clogging. Overall, our microfluidic designs can provide a key practical tool for assessing polymer degradation and drug release from degradable matrices under flowing conditions, thus aiding future studies on the development of hemocompatible, controlled-release coatings for DESs.

The paper reports the results of the analyses on mortar-based materials from the Roman theatre of Aquileia (Friuli Venezia Giulia, Northern Italy), recently dated between the mid-1st Century BCE and the mid-1st Century CE. Samples were characterized by Polarized Light Microscopy on thin sections (PLM), Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM-EDS) and Quantitative Phase Analysis by X-Ray Powder Diffraction (QPA-XRPD). Pyroclastic aggregates (mainly pumices and scattered tuffs), incompatible with the regional geology, were found in two samples from the preparation layers of the ground floor of the building. Their provenance was determined by means of QPA-XRPD, SEM-EDS, X-Ray Fluorescence (XRF) and Laser-Ablation Inductively-Coupled-Plasma Mass-Spectrometry (LA-ICP-MS). Mineralogical and geochemical analyses demonstrated their provenance from the Bay of Naples, thus recognizing them as pulvis puteolana, a type of pozzolanic aggregate outcropping around the modern town of Pozzuoli and prescribed by Vitruvius (De Architectura, 2.6.1) in mortar-based materials to strengthen masonries and produce hydraulic concrete for harbor piers. This evidence represents the oldest analytically-established case of pulvis puteolana exploitation in Northern Italy up to now, and an early use of the material out of Campania adapted for civil constructions in a non-strictly maritime-related environment. Indeed, the theatre was built in the low-lying Aquileia's deltaic plain, prone to water infiltrations that are typical in lagoon-like environments. The data highlight the craftsmen's resilience in adapting and reinterpreting the traditional use of the Neapolitan volcanic materials to deal with the geomorphological challenges of Aquileia's lowland., (© 2023. The Author(s).)

A laboratory experiment lasting 28 days was run to simulate a typical landfill system and to investigate the compositional changes affecting the main components (CH 4 , CO 2 , and H 2 ) and nonmethane volatile organic compounds from biogas generated by anaerobic digestion of food waste and passing through a soil column. Gas samples were periodically collected from both the digester headspace and the soil column at increasing distances from the biogas source. CH 4 and H 2 were efficiently degraded along the soil column. The isotopic values of δ 13 C measured in CH 4 and CO 2 from the soil column were relatively enriched in 13 C compared to the biogas. Aromatics and alkanes were the most abundant groups in the biogas samples. Among these compounds, alkylated benzenes and long-chain C 3+ alkanes were significantly degraded within the soil column, whereas benzene and short-chain alkanes were recalcitrant. Terpene and O-substituted compounds were relatively stable under oxidising conditions. Cyclic, alkene, S-substituted, and halogenated compounds, which exhibited minor amounts in the digester headspace, were virtually absent in the soil column. These results pointed out how many recalcitrant potentially toxic and polluting compounds tend to be relatively enriched along the soil column, claiming action to minimise diffuse landfill gas (LFG) emissions. The proposed experimental approach represents a reliable tool for investigating the attenuation capacities of landfill cover soils for LFG components and developing optimised covers by adopting proper soil treatments and operating conditions to improve their degradation efficiencies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Prevotella copri is the most abundant member of the genus Prevotella that inhabits the human large intestines. Evidences correlated the increase in Prevotella abundance to inflammatory disorders, suggesting a pathobiont role., Objectives: The aim of this study was to investigate the phylogenetic dynamics of P. copri in patients with irritable bowel syndrome (IBS), inflammatory bowel diseases (IBDs) and in healthy volunteers (CTRL)., Design: A phylogenetic approach was used to characterize 64 P. copri 16S rRNA sequences, selected from a metagenomic database of fecal and mucosal samples from 52 patients affected by IBD, 44 by IBS and 59 healthy., Methods: Phylogenetic reconstructions were carried out using the maximum likelihood (ML) and Bayesian methods., Results: Maximum likelihood phylogenetic tree applied onto reference and data sets, assigned all the reads to P. copri clade, in agreement with the taxonomic classification previously obtained. The longer mean genetic distances were observed for both the couples IBD and CTRL and IBD and IBS, respect to the distance between IBS and CTRL, for fecal samples. The intra-group mean genetic distance increased going from IBS to CTRLs to IBD, indicating elevated genetic variability within IBD of P. copri sequences. None clustering based on the tissue inflammation or on the disease status was evidenced, leading to infer that the variability seemed to not be influenced by concomitant diseases, disease phenotypes or tissue inflammation. Moreover, patients with IBS appeared colonized by different strains of P. copri . In IBS, a correlation between isolates and disease grading was observed., Conclusion: The characterization of P. copri phylogeny is relevant to better understand the interactions between microbiota and pathophysiology of IBD and IBS, especially for future development of therapies based on microbes (e.g. probiotics and synbiotics), to restore the microbiota in these bowel diseases., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

SPIDER is the 100 keV full-size Negative Ion Source prototype of the ITER Neutral Beam Injector, operating at Consorzio RFX in Padova, Italy. The largest Negative Ion Source in the world, SPIDER generates an RF driven plasma from which Deuterium or Hydrogen negative ions are produced and extracted. At the end of 2021, a scheduled long-term shutdown started to introduce major modifications and improvements aiming to solve issues and drawbacks identified during the first three years of SPIDER operations. The first action of the shutdown period was the disassembly and characterization of the SPIDER beam source after removal from the vacuum vessel and its placement inside the clean room. Each component was carefully assessed and catalogued, following a documented procedure. Some source components, i.e., the Plasma Grid, Extraction Grid and Bias Plate, revealed the presence of different and non-uniform red, white and green coatings that might be correlated to back-streaming positive ions impinging on grid surfaces, electrical discharges and caesium evaporation. Thus, several analyses have been carried out to understand the nature of such coatings, with the study still ongoing. The evidence of caesium evaporation and deposition on molybdenum-coated SPIDER components, such as the formation of oxides and hydroxides, is demonstrated through surface characterization analyses with the use of the Scanning Electron Microscope (SEM), X-ray Diffraction (XRD) and X-ray Photoelectron Spectroscopy (XPS).

Background: Endoscopic-post-operative-recurrence [ePOR] in Crohn's disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting., Methods: A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents., Results: The study included 297 patients (53.9% males, age at diagnosis 24 years [19-32], age at ICR 34 years [26-43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01-2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25-1.19], OR = 1.86 [95% CI: 0.79-4.38]), respectively., Conclusion: Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Owing to the high level of patient and operative complexity, vascular surgery represents a major driver for elevating case mix index within health care institutions. Although several specialty services are recruited in the care of these patients, it has been difficult to quantify the financial impact of these vascular patient across the health care enterprise. This study aims to quantify all revenues attributable to the introduction of vascular surgery patients within a tertiary health care system., Methods: Billing data from 2017 to 2020 for all new vascular surgery patients entering a tertiary health care system were captured, and segregated by encounter type--inpatient versus outpatient. Within these major categories, vascular revenue streams were analyzed according to procedural pathology types, such as aneurysm, peripheral vascular disease, cerebrovascular, and venous. Subsequent revenues for nonvascular services were also captured for both inpatient and outpatient encounters that were tied to the initial vascular surgical encounter. Revenues attributable to vascular patients were analyzed and followed with respect to other hospital service lines., Results: A total of 1115 new patients were introduced to the health care system for the first time by vascular surgery. These new patients generated more than $26 million in gross revenue and more than $10 million in contribution margin to the hospital during this time interval in aggregate. From a procedural standpoint, aortic surgery generated more than $7.4 million in revenue and $2.9 million in health system contribution margin. Peripheral vascular disease contributed $7.3 million and $2.6 million in revenue and contribution margins, respectively. Aortic surgery cases generated the highest margin per encounter encompassing the total sum of contributions. Subtracting all revenue attributable to vascular billing (spin-off), new patients brought in by vascular generated $9.6 million in revenue and $4.3 million in contribution margin from other service lines. Vascular access procedures produced the greatest spin-off margin per encounter at $10,985, and ancillary inpatient/outpatient generated the greatest number of spin-off encounters (n = 597) and revenue ($8,181,708)., Conclusions: Patients introduced by a tertiary care vascular surgery program produce a significant revenue/margin for the parent health care system. When considering the fiscal health of a vascular program within a tertiary health care system, spin-off and downstream revenue should be considered in terms of overall value., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Dye-based chromoendoscopy (DCE) with targeted biopsies is recommended for surveillance of patients with long-standing inflammatory bowel diseases (IBD), but endoscopic features that predict dysplasia are not fully clarified. We here aimed at identifying predictive factors of dysplastic/neoplastic lesions in IBD patients undergoing DCE. Two-hundred-and-nineteen patients were consecutively and prospectively enrolled from October 2019 to March 2022. One-hundred-and-forty-five out of 219 patients underwent DCE, and 148 lesions were detected in 79/145 (54%) patients. Thirty-nine lesions (26%) were dysplastic and one of them contained a CRC. Among these lesions, 7 (17.9%) had Kudo pit pattern I-II and 32 (82.1%) had a neoplastic pit pattern (Kudo III-IV). Multivariate analysis showed that neoplastic lesions Kudo III-IV (OR: 5.8, 95% CI: 2.3−14.6; p = 0.0002), lesion’s size (OR 1.16, 95% CI: 1.06−1.26; p = 0.0009), and polypoid lesions according to Paris Classification (OR 7.4, 95% CI: 2.7−20.2; p = 0.0001) were independent predictors of dysplasia. A cut-off of lesion’s size > 7 mm was identified as the best predictor of dysplasia. Among such features, Kudo pit pattern III-IV had the highest sensitivity and specificity to predict dysplasia (79% and 80%, respectively). Lesions with all three endoscopic features had a sensitivity of 90% and specificity of 100% to predict dysplasia. In contrast, non-polypoid lesions were inversely associated with dysplasia (OR 0.13, 95% CI: 0.05−0.36; p = 0.0001). These findings indicate that, in IBD patients, DCE-evidenced polypoid lesions with Kudo pit pattern III-IV and size > 7 mm are frequently dysplastic.

A unique specimen of argyria is preserved in the Morgagni Museum of Pathological Anatomy at the University of Padua (Italy). It is a stuffed head belonging to a man who decided to cure his syphilis by himself with the so-called infernal stone (silver nitrate) every day for years, thus developing argyria in the second half of the nineteenth century. Paleopathological and historical studies were performed on the specimen to confirm the diagnosis of argyria. Furthermore, a morphological investigation of the specimen was conducted with histological and ultrastructural investigations, including environmental scanning electron microscopy and electron dispersive x-ray spectroscopy, recording high presence of silver in the dermis and epidermis and also other chemical elements correlated to the "infernal stone." A comparison with actual cases may also lead to a common feature: a potential dependence on the perceived benefits brought by silver compound that may sustain a further prolonged intake., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background & Aims: Bowel ultrasonography (BUS) is a noninvasive tool for evaluating bowel activity in Crohn's disease (CD) patients. Aim of our multicenter study was to assess whether BUS helps to monitor intestinal activity improvement/resolution following different biological therapies., Methods: Adult CD patients were prospectively enrolled at 16 sites in Italy. Changes in BUS parameters [i.e. bowel wall thickening (BWT), lesion length, echo pattern, blood flow changes and transmural healing (TH: normalization of all BUS parameters)] were analyzed at baseline and after 3, 6 and 12 months of different biological therapies., Results: One hundred eighty-eight out of 201 CD patients were enrolled and analyzed (116 males [62%]; median age 36 years). Fifty-five percent of patients were treated with adalimumab, 16% with infliximab, 13% with vedolizumab and 16% with ustekinumab. TH rates at 12 months were 27.5% with an NNT of 3.6. TH at 12 months after adalimumab was 26.8%, 37% after infliximab, 27.2% after vedolizumab and 20% after ustekinumab. Mean BWT improvement from baseline was statistically significant at 3 and 12 months (P < .0001). Median Harvey-Bradshaw index, C-reactive protein and fecal calprotectin decreased after 12 months from baseline (P < .0001). Logistic regression analysis showed colonic lesion was associated with a higher risk of TH at 3 months and a greater BWT at baseline was associated with a lower risk of TH at 3 months [P = .03 (OR 0.70, 95% CI 0.50-0.97)] and 12 months [P = .01 (OR 0.58, 95% CI 0.38-0.89)]. At 3 months therapy optimization during the study was the only independent factor associated with a higher risk of no ultrasonographic response [P = .02 (OR 3.34, 95% CI 1.18-9.47)] and at 12 months disease duration [P = .02 (OR 3.03, 95% CI 1.15-7.94)]., Conclusions: Data indicate that BUS is useful to monitor biologics-induced bowel activity improvement/resolution in CD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and aims: Intravenous corticosteroids (IVCS) and rescue therapy with infliximab (IFX) are useful for managing patients with acute severe ulcerative colitis (ASUC). However, nearly one fifth of responders undergo colectomy. Predictive factors of colectomy in this subset of patients are not fully known. We retrospectively examined the long-term risk and the predictors of colectomy in ASUC patients achieving clinical remission following treatment with IVCS or IFX. Patients and methods: Clinical and demographic characteristics were evaluated in consecutive ASUC patients who were admitted to the “Tor Vergata University” hospital between 2010 and 2020 and responded to IVCS or IFX. A multivariate logistic regression model was constructed to identify independent predictors of colectomy. Results: A total of 116 ASUC patients responding to IVCS (98 patients) or IFX (18 patients) were followed up for a median of 46 months. After discharge, 29 patients (25%) underwent colectomy. Multivariate analysis showed that a serum albumin level <3 g/dL and colonic dilation >5.5 cm on admission were independent predictors of colectomy (OR: 6.9, 95% CI: 2.08−22.8, and OR 8.5, 95% CI: 1.23−58.3, respectively). Patients with both these factors had a risk of colectomy 13 times greater than those with no risk factor. Conclusions: A low serum albumin level and colonic dilation are risk factors of long-term colectomy in ASUC patients responding to IVCS or IFX.

Background and Aims : Treatment with intravenous corticosteroids (IVCS) is a mainstay in the management of acute severe ulcerative colitis (UC). Although most patients respond to IVCS, little is known about the long-term outcomes. In this study, we assessed the long-term outcomes of IVCS in a real-life cohort. Methods : Disease activity, clinical relapse (partial Mayo score >4), the need for steroids or other maintenance therapies and the rates of colectomy and re-hospitalization were evaluated in consecutive patients admitted to the Tor Vergata University hospital between 2010 and 2020 for acute severe UC who responded to IVCS. Results: Eighty-eight patients were followed up with for a median period of 46 (range 6-133) months. Of these, 56 (64%) patients were treated with 5-aminosalycilic acid and 32 (36%) with immunomodulators or biologics after discharge. A total of 60 out of 88 patients (68%) relapsed, 28 (32%) were re-hospitalized, and 15 (17%) underwent a colectomy with no difference between the two maintenance therapy groups. The multivariate analysis showed that patients in clinical remission 6 months after discharge had a lower risk of relapse during the follow-up. Conclusions: Nearly two-thirds of patients with acute UC responding to IVCS experienced relapse after a median follow-up of 4 years, and this was not influenced by the maintenance therapy.

Serrated lesions represent a group of lesions with different genetic and biological features causing important clinical repercussions. Three types of serrated lesions are identified: hyperplastic, sessile adenomas (with and without dysplasia) and traditional serrated adenomas. Such lesions are now recognized as precancerous lesions.The carcinogenic process of serrated lesions follows a pathway including: alterations concerning activation of mitogen and protein kinase regulating the extracellular signal of other intracellular kinases (MAPK-ERK), inhibition of the apoptosis and hypermethylation of DNA and instability of microsatellites. Like for adenomatous polyps, the risk factors for serrated lesions are environmental factors, related to lifestyle and diet. The cancerogenic risk is increased by excessive alcohol consumption, obesity and poor intake of folate. When a high number of colorectal polyps with architecture serrated is diagnosed, it could be considered as serrated polyposis syndrome (SPS). According the most recent ESGE guidelines, the diagnostic criteria of the SPS, are: at least 5 polyps resected proximal to the sigmoid colon, 2 of which> 10 mm, or >20 serrated lesions of any size distributed in the entire colon. This condition presents a high risk for personal and/or familiar CRC, for this reason a regular screening colonoscopy should be performed in these patients and in their first-degree relatives.

Thermochromic dynamic cool materials present a reversible change of their properties wherein by increasing the temperature, the reflectance, conductivity, and transmittance change due to a reversible crystalline phase transition. In particular, vanadium (IV) dioxide shows a reversible phase transition, accompanied by a change in optical properties, from monoclinic VO 2 (M1) to tetragonal VO 2 (R). In this paper, we report on a systematic exploration of the parameters for the synthesis of vanadium dioxide VO 2 (M1) via an easy, sustainable, reproducible, fast, scalable, and low-cost hydrothermal route without hazardous chemicals, followed by an annealing treatment. The metastable phase VO 2 (B), obtained via a hydrothermal route, was converted into the stable VO 2 (M1), which shows a metal-insulator transition (MIT) at 68 °C that is useful for different applications, from energy-efficient smart windows to dynamic concrete. Within this scenario, a further functionalization of the oxide nanostructures with tetraethyl orthosilicate (TEOS), characterized by an extreme alkaline environment, was carried out to ensure compatibility with the concrete matrix. Structural properties of the synthesized vanadium dioxides were investigated using temperature-dependent X-ray Diffraction analysis (XRD), while compositional and morphological properties were assessed using Scanning Electron Microscopy, Energy Dispersive X-ray Analysis (SEM-EDX), and Transmission Electron Microscopy (TEM). Differential Scanning Calorimetry (DSC) analysis was used to investigate the thermal behavior.

In total, ~25% of familial breast cancer (BC) is attributed to germline mutations of the BRCA1 and BRCA2 genes, while the rest of the cases are included in the BRCAX group. BC is also known to affect men, with a worldwide incidence of 1%. Epigenetic alterations, including DNA methylation, have been rarely studied in male breast cancer (MBC) on a genome-wide level. The aim of the present study was to examine the global DNA methylation profiles of patients with BC to identify differences between familial female breast cancer (FBC) and MBC, and according to BRCA1, BRCA2 or BRCAX mutation status. The genomic DNA of formalin-fixed paraffin-embedded tissues from 17 women and 7 men with BC was subjected to methylated DNA immunoprecipitation and hybridized on human promoter microarrays. The comparison between FBC and MBC revealed 2,846 significant differentially methylated regions corresponding to 2,486 annotated genes. Gene Ontology enrichment analysis revealed molecular function terms, such as the GTPase superfamily genes (particularly the GTPase Rho GAP/GEF and GTPase RAB), and cellular component terms associated with cytoskeletal architecture, such as 'cytoskeletal part', 'keratin filament' and 'intermediate filament'. When only FBC was considered, several cancer-associated pathways were among the most enriched KEGG pathways of differentially methylated genes when the BRCA2 group was compared with the BRCAX or BRCA1+BRCAX groups. The comparison between the BRCA1 and BRCA2+BRCAX groups comprised the molecular function term 'cytoskeletal protein binding'. Finally, the functional annotation of differentially methylated genes between the BRCAX and BRCA1+BRCA2 groups indicated that the most enriched molecular function terms were associated with GTPase activity. In conclusion, to the best of our knowledge, the present study was the first to compare the global DNA methylation profile of familial FBC and MBC. The results may provide useful insights into the epigenomic subtyping of BC and shed light on a possible novel molecular mechanism underlying BC carcinogenesis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Abeni et al.)

The addition of magnetic particles to inorganic matrices can produce new composites exhibiting intriguing properties for practical applications. It has been previously reported that the addition of magnetite to concrete improves its mechanical properties and durability in terms of water and chloride ions absorption. Here we describe the preparation of novel magnetic geopolymers based on two different matrices (G1 without inert aggregates and G2 with inert quartz aggregates) containing commercial SrFe 12 O 19 particles with two weight concentrations, 6% and 11%. The composites' characterization, including chemical, structural, morphological, and mechanical determinations together with magnetic and electrical measurements, was carried out. The magnetic study revealed that, on average, the SrFe 12 O 19 magnetic particles can be relatively well dispersed in the inorganic matrix. A substantial increase in the composite samples' remanent magnetization was obtained by embedding in the geopolymer SrFe 12 O 19 anisotropic particles at a high concentration under the action of an external magnetic field during the solidification process. The new composites exhibit good mechanical properties (as compressive strength), higher than those reported for high weight concretes bearing a similar content of magnetite. The impedance measurements indicate that the electrical resistance is mainly controlled by the matrix's chemical composition and can be used to evaluate the geopolymerization degree.

Competing Interests: Declaration of Competing Interest None

Background: In Crohn's disease (CD), one of the major inflammatory bowel disease (IBD) in human beings, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine TGF-β1. The aim of this study was to assess whether Smad7 over-expression occurs in the early and/or late phases of CD., Methods: Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with or without (early CD) post-operative endoscopic recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (late CD). Smad7 was examined by immunohistochemistry and cytokine expression was analysed by flow-cytometry., Results: Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of Smad7-expressing cells in both the epithelial and lamina propria compartments. Transition from this stage to endoscopic recurrence was marked by persistence of high number of Smad7-positive cells, which reduced significantly in the late stages of the disease, where Smad7 expression remained, however, greater than that seen in normal controls. In samples with early lesions, Smad7 expression positively correlated with the number of interferon-γ-secreting cells., Conclusions: Smad7 induction is an early event in the inflammatory sequence occurring in CD, thus suggesting that knockdown of Smad7 can help prevent post-operative recurrence.

Background & Aims: Mucosal healing, determined by ileocolonoscopy, is a goal for treatment of Crohn's disease (CD), but this is an invasive assessment procedure. We investigated whether response to tumor necrosis factor (TNF) antagonists, determined by small-intestine contrast ultrasonography, associates with long-term outcomes., Methods: We performed observational study of 80 patients with CD treated with anti-TNF agents for at least 1 year who underwent serial small intestine contrast ultrasonography (SICUS) at the University of Rome, in Italy. SICUS was used to evaluate disease site (based on bowel wall thickness), extent of lesions, and presence of complications. Inclusion criteria required pre-therapy SICUS with follow-up SICUS after 18 months. At second SICUS, patients were assigned to categories of complete or partial responder or non-responder. CD-related outcomes (corticosteroid need, hospitalization, and surgery) were assessed at 1 year from the second SICUS, using multivariate models, and were analyzed after long term follow up (5 years) using Kaplan-Meier survival analysis., Results: Based on SICUS, after a median of 18 months, 36 patients (51%) were complete responders, 30 were partial responders (34%), and 13 were non-responders (15%). At 1 year from the second SICUS, no patients with a complete response, based on ultrasonography, underwent surgery, in comparison to partial responders (P = .0003) or non-responders (P = .001). Complete responders used smaller amounts of corticosteroids than partial responders (P = .0001) or non-responders (P < .0001). Complete responders required fewer hospitalizations than non-responders (P = .001). Kaplan-Meier survival analysis of long-term follow up data demonstrated a lower cumulative probability of need for surgery, hospitalization, and need for steroids among SICUS-categorized complete responders (P < .0001, P = .003 and P = .0001 respectively) than SICUS-categorized non-responders., Conclusions: In patients with CD, response to anti-TNF agents, determined by SICUS, is associated with better long-term outcomes than partial or no response. Ultrasonographic assessment therefore provides a relatively non-invasive method for monitoring response to treatment in patients with CD., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Rosette-forming glioneuronal tumors (RGNTs) with multifocal growth throughout the ventricular system are extremely rare, and only 1 case of RGNT with dissemination limited to supratentorial ventricles has previously been reported. Recent evidence based on molecular data suggest that low-grade glioneuronal tumors (GNT) involving the septum pellucidum and the lateral ventricles, with either dysembryoplastic neuroepithelial tumor-like or RGNT-like features, may belong to a neuropathologic entity distinct from cortical dysembryoplastic neuroepithelial tumor and "typical" fourth ventricle RGNT, respectively. Given their rarity, the classification of these neoplasms is still uncertain and their clinicopathological and radiological aspects are only partially known., Case Description: A 24-year-old male presented a GNT with RGNT-like morphological features centered in the septum pellucidum with multifocal masses occupying the lateral ventricles and the third ventricle with extraventricular infiltration of the frontal lobe. The patient underwent subtotal resection and 4 years follow-up. The clinicopathological and radiological features of the neoplasm are discussed., Conclusions: Advanced magnetic resonance imaging (magnetic resonance spectroscopy and perfusion-weighted imaging) may provide valuable information in the differential diagnosis between rare GNTs and other more frequent intraventricular neoplasms. In the present case, the enhancing remnant portion of the tumor showed remarkable contrast enhancement variability during the follow-up with slow in situ progression. However, available data suggest that spontaneous contrast enhancement "fluctuations" over time in RGNT may not represent a reliable indicator of tumor behavior., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Highly porous bioceramics, based on a complex hardystonite solid solution, were developed from silicone resins and micro-sized oxide fillers fired in air at 950 °C. Besides CaO, SrO, MgO, and ZnO precursors, and the commercial embedded silicone resins, calcium borate was essential in providing the liquid phase upon firing and favouring the formation of an unprecedented hardystonite solid solution, corresponding to the formula (Ca 0.70 Sr 0.30 ) 2 (Zn 0.72 Mg 0.15 Si 0.13 ) (Si 0.85 B 0.15 ) 2 O 7 . Silicone-filler mixtures could be used in the form of thick pastes for direct ink writing of reticulated scaffolds or for direct foaming. The latter shaping option benefited from the use of hydrated calcium borate, which underwent dehydration, with water vapour release, at a low temperature (420 °C). Both scaffolds and foams confirmed the already-obtained phase assemblage, after firing, and exhibited remarkable strength-to-density ratios. Finally, preliminary cell tests excluded any cytotoxicity that could be derived from the formation of a boro-silicate glassy phase.

Aim: The human gastrointestinal tract harbors diverse, abundant microbiota and Akkermansia muciniphila is involved in this community. The aim of this study is to characterize 16 new A. muciniphila 16S ribosomal RNA sequences selected from a metagenomic database from stools of patients with irritable bowel syndrome (IBS), inflammatory bowel diseases and control (CTRLs) subjects by a phylogenetic approach. Materials & methods: A phylogenetic approach was used to study the genetic diversity and SNPs in 16 A. muciniphila 16S ribosomal RNA sequences from stools of 107 individuals, 36 of which were patients affected by IBS, 30 by inflammatory bowel disease and 41 were CTRLs. Results: Phylogenetic analysis confirmed the subdivision into different supported clusters. An increase of variability in IBS has been identified. Conclusion: The genetic variation combined to the relative abundance, contribute to the protective role of A. muciniphila . Phylogenesis represent an additional approach to investigate genetic variability.

An imbalance in the bacterial species resulting in the loss of intestinal homeostasis has been described in inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). In this prospective study, we investigated whether IBD and IBS patients exhibit specific changes in richness and distribution of fecal and mucosal-associated microbiota. Additionally, we assessed potential 16S rRNA gene amplicons biomarkers for IBD, IBS, and controls (CTRLs) by comparison of taxonomic composition. The relative abundance of bacteria, at phylum and genus/species levels, and the bacterial diversity were determined through 16S rRNA sequence-based fecal and mucosal microbiota analysis. Linear discriminant analysis effect size (LEfSe) was used for biomarker discovery associated to IBD and IBS as compared to CTRLs. In fecal and mucosal samples, the microbiota richness was characterized by a microbial diversity reduction, going from CTRLs to IBS to IBD. β-diversity analysis showed a clear separation between IBD and CTRLs and between IBD and IBS with no significant separation between IBS and CTRLs. β-diversity showed a clear separation between mucosa and stool samples in all the groups. In IBD, there was no difference between inflamed and not inflamed mucosa. Based upon the LEfSe data, the Anaerostipes and Ruminococcaceae were identified as the most differentially abundant bacterial taxa in CTRLs. Erysipelotrichi was identified as potential biomarker for IBS, while Gammaproteobacteria, Enterococcus , and Enterococcaceae for IBD. This study provides an overview of the alterations of microbiota and may aid in identifying potential 16S rRNA gene amplicons mucosal biomarkers for IBD and IBS.

Purpose: The current clinical investigation for primary aldosteronism (PA) diagnosis requires complex expensive tests from the initial suspicion to the final subtype classification, including invasive approaches; therefore, appropriate markers for subtype definition are greatly desirable. The present study performs a metabolomics analysis to further examine specific molecular signatures of PA urines EXPERIMENTAL DESIGN: The study considered PA subtype and gender-related differences using two orthogonal advanced UHPLC-MS metabolomics approaches. Patients with essential hypertension (n = 36) and PA (n = 50) who were referred to the outpatient hypertension clinic and matched healthy subjects (n = 10) are investigated., Results: Statistically significant changes (p < 0.05 ANOVA, Fc > 1.5) of metabolites involved in central carbon, energy, and nitrogen metabolism are identified, especially purine and pyrimidine nucleosides and precursors, and free amino acids. PLS-DA interpretation provides strong evidence of a disease-specific metabolic pattern with dAMP, diiodothyronine, and 5-methoxytryptophan as leading factors, and a sex-specific metabolic pattern associated with orotidine 5-phosphate, N-acetylalanine, hydroxyproline, and cysteine. The results are verified using an independent sample set, which confirms the identification of specific signatures., Conclusions and Clinical Relevance: Metabolomics is used to identify low molecular weight molecular markers of PA, which paves the way for follow-up validation studies in larger cohorts., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sickle cell disease is an autosomal recessive genetic red cell disorder with a worldwide distribution. Growing evidence suggests a possible involvement of complement activation in the severity of clinical complications of sickle cell disease. In this study we found activation of the alternative complement pathway with microvascular deposition of C5b-9 on skin biopsies from patients with sickle cell disease. There was also deposition of C3b on sickle red cell membranes, which is promoted locally by the exposure of phosphatidylserine. In addition, we showed for the first time a peculiar "stop-and-go" motion of sickle cell red blood cells on tumor factor-α-activated vascular endothelial surfaces. Using the C3b/iC3b binding plasma protein factor Has an inhibitor of C3b cell-cell interactions, we found that factor H and its domains 19-20 prevent the adhesion of sickle red cells to the endothelium, normalizing speed transition times of red cells. We documented that factor H acts by preventing the adhesion of sickle red cells to P-selectin and/or the Mac-1 receptor (CD11b/CD18), supporting the activation of the alternative pathway of complement as an additional mechanism in the pathogenesis of acute sickle cell related vaso-occlusive crises. Our data provide a rationale for further investigation of the potential contribution of factor H and other modulators of the alternative complement pathway with potential implications for the treatment of sickle cell disease., (Copyright© 2019 Ferrata Storti Foundation.)

Self-injurious behaviors and suicide attempts are more frequent in prison settings than in the general population and represent a crucial problem. The aims of this work are to assess the prevalence of self-injurious behaviors and suicide attempts in an Italian prison setting, to determine whether inmates could be differentiated based on profiles of psychological distress and impulsiveness, and to assess the predictive power of the proposed profiles. A sample of 1422 male inmates of a north Italian penitentiary was assessed upon admission with a clinical interview and completed a set of self-report questionnaires to assess psychological distress and impulsiveness; the number of self-injurious behaviors and suicide attempts occurring in the first year of detention was recorded. A cluster analysis approach was used. Prevalence of self-Injurious behaviors and suicide attempts is similar to what has been observed in previous work. Cluster analysis revealed four clusters: dysregulated (high impulsivity and distress), impulsive (high impulsivity and mean distress), mildly distressed (mean impulsivity and moderate distress) and well-balanced (low impulsivity and distress). The four clusters help to discriminate subjects more at risk of self-injurious behaviors and suicide attempts and are confirmed by the inclusion of risk factors such as marital status and relatives'/social support. Clinical implications are discussed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Although gout is a common disease, the presence of gouty tophi outside joints is rare and in literature, there is to date only one report of hepatic tophaceous nodule. We would like to highlight here the difficult diagnostic workup in a patient with history of cancer and the presence of a tophus inside the liver. Moreover, we address the possible etiologic role of chronic inflammation related to tophi and liver cancer., Case Presentation: We present the case of a 72-year-old man with a localization of gouty tophus in the liver, who thereafter developed a hepatocellular carcinoma (HCC) in the same site. The patient was followed up after surgery for left renal cancer from 1992 to 2011, when a hepatic nodule was discovered for the first time. After a detailed evaluation, the nodule was classified as a urate tophus of the liver. However, further follow-up showed that the nodule increased in size and changed its characteristics, bringing to the diagnosis of HCC., Conclusions: With the present case report, we would discuss the possible neoplastic degeneration of a gouty tophus and its etiologic role favouring cellular degeneration linked to chronic inflammation. We would also highlight the importance of histopathological evaluation of hepatic lesions in gouty patients at high risk of liver neoplasm, due to the difficulty in characterizing gouty tophi by imaging.

Sickle cell disease (SCD; ORPHA232; OMIM # 603903) is a chronic and invalidating disorder distributed worldwide, with high morbidity and mortality. Given the disease complexity and the multiplicity of pathophysiological targets, development of new therapeutic options is critical, despite the positive effects of hydroxyurea (HU), for many years the only approved drug for SCD. New therapeutic strategies might be divided into (1) pathophysiology-related novel therapies and (2) innovations in curative therapeutic options such as hematopoietic stem cell transplantation and gene therapy. The pathophysiology related novel therapies are: a) Agents which reduce sickling or prevent sickle red cell dehydration; b) Agents targeting SCD vasculopathy and sickle cell-endothelial adhesive events; c) Anti-oxidant agents. This review highlights new therapeutic strategies in SCD and discusses future developments, research implications, and possible innovative clinical trials., Competing Interests: Competing interests: The authors have declared that no competing interests exist. Competing Interests and Funding. The Authors declare that they have no conflict of interest. This work was supported by FUR-UNIVR (LDF).

Background: The desire for pregnancy in sickle cell disease (SCD) women has become a true challenge for hematologists, requiring a multidisciplinary approach. Erythrocytapheresis (ECP) is an important therapeutic tool in SCD, but only limited data on starting time and the effects of ECP during pregnancy are available., Study Design and Methods: This is a double-center retrospective cross-sectional study on a total of 46 single pregnancies in SCD women from January 2008 to June 2017. ECP was started at 10.7 ± 5.2 weeks of gestation, and prophylactic enoxaparin (4,000 U daily) was introduced due to the reported high prevalence of thromboembolic events in pregnant SCD women., Results: The alloimmunization ratio was 2.1 per 1,000 and the alloimmunization rate was 5.6%. In early ECP-treated SCD women, no severe vaso-occlusive crisis, sepsis or severe infection, or preeclampsia or eclampsia were observed. We found normal umbilical arterial impedance during pregnancy, suggesting an optimal uteroplacental function in early ECP-treated SCD women. This was also supported by the improvement in newborn birthweights compared to previous studies. In our cohort, three SCD women were started later on ECP (20-25 weeks), and gestation ended with late fetal loss. Placenta pathology documented SCD-related damage and erythroblasts in placental vessels, indicating fetal hypoxia., Conclusions: Collectively, our data generate a rationale to support a larger clinical trial of early ECP program in SCD pregnancy., (© 2018 AABB.)

Background: The unavailability of standardized parameters in bowel ultrasonography (US) commonly used in Crohn's disease (CD) and the shortage of skilled ultrasonographers are 2 limiting factors in the use of this imaging modality around the world. The aim of this study is to evaluate interobserver agreement among experienced sonographers in the evaluation of bowel US parameters in order to improve standardization in imaging reporting and interpretation., Methods: Fifteen patients with an established diagnosis of CD underwent blinded bowel US performed by 6 experienced sonographers. Prior to the evaluation, the sonographers and clinical and radiological IBD experts met to formally define the US parameters. Interobserver agreement was tested with the Quatto method (s)., Results: All operators agreed on the presence/absence of CD lesions and distinguished absence of/mild activity or moderate/severe lesions in all patients. S values were moderate for bowel wall thickness (s = 0.48, P = n.s.), bowel wall pattern (s = 0.41, P = n.s.), vascularization (s = 0.52, P = n.s.), and presence of lymphnodes (s = 0.61, P = n.s.). Agreement was substantial for lesion location (s = 0.68, P = n.s.), fistula (s = 0.74, P = n.s.), phlegmon (s = 0.78, P = 0.04), and was almost perfect for abscess (s = 0.95, P = 0.02). Poor agreement was observed for mesenteric adipose tissue alteration, lesion extent, stenosis, and prestenotic dilation., Conclusions: In this study, the majority of the US parameters used in CD showed moderate/substantial agreement. The development of shared US imaging interpretation patterns among sonographers will lead to improved comparability of US results among centers and facilitate the development of multicenter studies and the spread of bowel US training, thereby allowing a wider adoption of this useful technique., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)