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The diagnosis and management of graft-versus-host disease (GVHD) have remained important challenges in allogeneic stem cell transplantation (allo-SCT). Novel diagnostic methods and therapeutic interventions are needed to further improve on patient outcomes. Extracellular vesicles (EV) are microvesicles formed by the inversion of the phospholipid bilayer of different cellular subtypes and have been described as biomarkers of cellular damage, activation, and intercellular signaling in numerous clinical scenarios. We studied the association between the levels of EV and the incidence of acute GVHD (aGVHD). Forty patients undergoing allo-SCT for hematological malignancies had their plasma collected at neutrophil engraftment. Using flow cytometry combined with fluorescent beads, the total circulating EV count (TEV) was established with annexin V positivity; CD61 positivity was used for platelet-derived EV (PEV), and CD235 positivity, for erythrocyte-derived EV (EryEV). TEV counts greater than 516/μL were associated with a higher cumulative incidence (CI) of grade II to IV aGVHD (54% vs. 21%; p = 0.02), as were EryEV counts above 357 /μL (CI of aGVHD: 59% vs. 26%; p = 0.04). In patients who are exposed to reduced intensity conditioning (RIC), stronger associations of both high TEV and EryEV counts with aGVHD were observed (77% vs. 22%; p = 0.003 and 89% vs. 27%; p = 0.002, respectively). PEV levels were not associated with the risk of aGVHD. Our data suggest that the measurement of cell-derived EV at engraftment can be used as a preemptive biomarker for acute GVHD.

Purpose : Removal of impacted third molars, can be associated with complications such as pain, edema, trismus, that can increase the morbidity of this procedure. The purpose of this study is to determine whether the Er:YAG laser is effective in reducing pain, swelling and trismus compared to rotary instruments in removing impacted lower third molars (3 LM`s). Methods : For this systematic review the searches were carried out independently by 2 researchers and the articles were selected according to the inclusion and exclusion criteria previously established. The predictor variable was the study group (Er:YAG laser versus rotatory instruments). The main outcome was the analysis of post-operative pain, edema and trismus after third molars extractions. Data analysis included the risk of bias evaluation (RoB 2 Cochrane) and meta-analysis with random effects I2 based heterogeneity and 95% confidence. Results : In the initial results, 1371 articles were found and 6 RCT were selected to compose this study. A total of 299 3 LM`s were removed, 126 with the Er:YAG laser, 142 with a drill and 31 with a piezoelectric instrument. The results of this meta-analysis showed that in the laser group there was a significant reduction in edema (1.82 [CI95% = -3.06 to -0.57] cm (p=0.004)) and complications (p=0.0004), a slight reduction in pain after 2 days (p =0.030) and there was no variation in trismus (p=0.200) when compared to the drill group. The surgery/osteotomy time was shorter in the drill group. Only 1 study presented low risk of bias. Conclusion : The Er:YAG laser has been shown to be effective in reducing edema, pain and complications in impacted lower third molar surgeries. however due to the lack of standardization in Er:YAG laser therapy, new controlled and standardized studies should be performed with the aim of proving the efficacy of this therapeutic modality.

Objective: The characteristics and outcomes of patients undergoing vascular surgery hospitalised and managed in Lombardy are described with a comparison of patients tested positive for COVID-19 (CV19-pos) vs. those tested negative (CV19-neg). Methods: This was a multicentre, retrospective, observational cohort study which involved all vascular surgery services in Lombardy, Northern Italy. Data were retrospectively merged into a combined dataset covering the nine weeks of the Italian COVID-19 pandemic phase 1 (8 March 2020 to 3 May 2020). The primary outcome was freedom from in hospital death, secondary outcomes were re-thrombosis rate after peripheral revascularisation, and freedom from post-operative complication. Results: Among 674 patients managed during the outbreak, 659 (97.8%) were included in the final analysis: 121 (18.4%) were CV19-pos. CV19-pos status was associated with a higher rate of complications (OR 4.5; p < .001, 95% CI 2.64 – 7.84), and a higher rate of re-thrombosis after peripheral arterial revascularisation (OR 2.2; p = .004, 95% CI 1.29 – 3.88). In hospital mortality was higher in CV19-pos patients (24.8% vs. 5.6%; OR 5.4, p < .001;95% CI 2.86 – 8.92). Binary logistic regression analysis identified CV19-pos status (OR 7.6; p < .001, 95% CI 3.75 – 15.28) and age > 80 years (OR 3.2; p = .001, 95% CI 1.61 – 6.57) to be predictors of in hospital death. Conclusion: In this experience of the vascular surgery group of Lombardy, COVID-19 infection was a marker of poor outcomes in terms of mortality and post-operative complications for patients undergoing vascular surgery treatments.

Background Long-standing overt ventriculomegaly in adults is a chronic form of hydrocephalus without a clear pathophysiological description and a consensus about the treatment. We present the results of endoscopic third ventriculostomy (ETV) in a consecutive series with a mean follow-up of 79 ± 23 months, highlighting how the preoperative lumbar infusion test could facilitate understanding the pathophysiology of the disease. Methods We retrospectively collected data regarding clinical assessment, neuroradiological findings, and preoperative lumbar infusion tests in 22 symptomatic patients. Results In the majority of cases, patients reported imbalance and gait disorders, and 8 subjects had headaches. The preoperative lumbar infusion test demonstrated a mean opening pressure of 13.95 ± 2.88 mm Hg, with plateau values ranging from 22 to 39 mm Hg. The resistance to outflow was 11.21 ± 2.00 mm Hg/mL/min. After the procedure, all patients reported improvement or halted progression in their presenting symptoms, whereas no significant reduction was demonstrated in Evans' index. One subject underwent a second ETV procedure after more than 2 years because of the failure of the endoscopic approach. Conclusions A progressive exhaustion of brain compliance plays an important role in explaining the dichotomy between severe ventriculomegaly and mild clinical symptoms in patients with long-standing overt ventriculomegaly in adults. The role of the aqueductal stenosis as a diagnostic criterion might be reconsidered. The preoperative infusion test data support this observation. Preoperative assessment should include not only clinical and neuroradiological evaluation but also the study of cerebrospinal fluid dynamics. ETV should be considered the treatment of choice because of its safety and efficacy. Long-term follow-up is mandatory.

Background Despite their lethality and ensuing clinical and therapeutic relevance, circulating tumor cells (CTCs) from colorectal carcinoma (CRC) remain elusive, poorly characterized biological entities. Methods and findings We perfected a cell system of stable, primary lines from human CRC showing that they possess the full complement of ex- and in-vivo, in xenogeneic models, characteristics of CRC stem cells (CCSCs). Here we show how tumor-initiating, CCSCs cells can establish faithful orthotopic phenocopies of the original disease, which contain cells that spread into the circulatory system. While in the vascular bed, these cells retain stemness, thus qualifying as circulating CCSCs (cCCSCs). This is followed by the establishment of lesions in distant organs, which also contain resident metastatic CCSCs (mCCSCs). Interpretation Our results support the concept that throughout all the stages of CRC, stemness is retained as a continuous property by some of their tumor cells. Importantly, we describe a useful standardized model that can enable isolation and stable perpetuation of human CRC's CCSCs, cCCSCs and mCCSCs, providing a useful platform for studies of CRC initiation and progression that is suitable for the discovery of reliable stage-specific biomarkers and the refinement of new patient-tailored therapies. Fund This work was financially supported by grants from "Ministero della Salute Italiano"(GR-2011-02351534, RC1703IC36 and RC1803IC35) to Elena Binda and from "Associazione Italiana Cancro" (IG-14368) Angelo L. Vescovi. None of the above funders have any role in study design, data collection, data analysis, interpretation, writing the project.

The isotope used in this research was supplied by the United States Department of Energy Office of Science by the Isotope Program in the Office of Nuclear Physics., The neutron capture cross section of 154Gd was measured from 1 eV to 300 keV in the experimental area located 185 m from the CERN n_TOF neutron spallation source, using a metallic sample of gadolinium, enriched to 67% in 154Gd. The capture measurement, performed with four C6D6 scintillation detectors, has been complemented by a transmission measurement performed at the GELINA time-of-flight facility (JRC-Geel), thus minimising the uncertainty related to sample composition. An accurate Maxwellian averaged capture cross section (MACS) was deduced over the temperature range of interest for s process nucleosynthesis modelling. We report a value of 880(50) mb for the MACS at kT = 30 keV, significantly lower compared to values available in literature. The new adopted 154Gd(n,γ ) cross section reduces the discrepancy between observed and calculated solar s-only isotopic abundances predicted by s-process nucleosynthesis models., EUFRAT open access programme of the Joint Research Centre at Geel

Mucopolysaccharidosis type II (Hunter Syndrome) is a rare X-linked inherited lysosomal storage disorder presenting a wide genetic heterogeneity. It is due to pathogenic variants in the IDS gene, causing the deficit of the lysosomal hydrolase iduronate 2-sulfatase, degrading the glycosaminoglycans (GAGs) heparan- and dermatan-sulfate. Based on the presence/absence of neurocognitive signs, commonly two forms are recognized, the severe and the attenuate ones. Here we describe a line of induced pluripotent stem cells, generated from dermal fibroblasts, carrying the mutation c.479C>T, and obtained from a patient showing an attenuated phenotype. The line will be useful to study the disease neuropathogenesis.

This work focuses on the behaviour of granular materials under unsteady, simple shear conditions and, in particular, on from solid- to fluid-like phase transition. The authors introduce a theoretical model, based on continuum mechanics, able of predicting the mechanical behaviour of granular media under both quasi-static and dynamic conditions. The model assumes a parallel scheme where confining and shear stresses are computed as the sum of two contributions: the quasi-static and the collisional one. The quasi-static contribution is obtained by employing an elastic–plastic model including the critical state concept, while the collisional one is derived from the kinetic theory of granular gases. In order to test the model under unsteady conditions, DEM numerical simulations of time evolving homogeneous shear flows have been performed by considering an assembly of frictional, deformable spheres, under constant volume conditions. Simulations have been performed by systematically changing both void ratio and shear rate. The comparison between theoretical model predictions and DEM results is done in terms of time evolution of stresses and granular temperature. Suitable initial conditions are imposed to reproduce both solid to fluid (liquefaction) and fluid to solid (solidification) phase transitions.

Charcot-Marie-Tooth type 4B3 (CMT4B3) is a rare subtype of hereditary neuropathy associated with variants in the MTMR5/SBF1 gene. Herein, we report the generation and characterization of a hiPSC line from a 12-year-old Italian girl with early onset severe polyneuropathy with motor and axonal involvement, harboring biallelic variants in the MTMR5/SBF1 gene. Fibroblasts were reprogrammed using non-integrating episomal plasmids, and iPSCs successfully passed the stemness and pluripotency tests. Patient-specific hiPSCs were produced to obtain a disease model for the study of this rare condition.

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by developmental delay, behavioural problems and circadian rhythm dysregulation. About 90% of SMS cases are due to a 17p11.2 deletion containing retinoic acid induced1 (RAI1) gene, 10% are due to heterozygous mutations affecting RAI1 coding region. Little is known about RAI1 role.

Joubert Syndrome (JS) is a rare autosomal recessive or X-linked condition characterized by a peculiar cerebellar malformation, known as the molar tooth sign (MTS), associated with other neurological phenotypes and multiorgan involvement. JS is a ciliopathy, a spectrum of disorders whose causative genes encode proteins involved in the primary cilium apparatus. In order to elucidate ciliopathy-associated molecular mechanisms, human induced pluripotent stem cells (hiPSCs) were derived from a patient affected by JS carrying a homozygous missense mutation in the AHI1 gene (p.H896R) that encodes a protein named Jouberin.

Summary Background Malnutrition is a common finding in allogeneic hematopoietic stem cell transplantation (alloHSCT) patients, and there is some evidence that malnutrition might negatively affect the transplant outcomes. Method We performed a retrospective study with 148 patients aged 18–75 years, who underwent alloHSCT between 2011 and 2017. Patients were classified according to the body mass index (BMI) and the Subjective Global Assessment (SGA). The SGA was assessed on the day of hospitalization for the transplant, and classifies patients into three groups: A (well-nourished), B (moderately malnourished) and C (severely malnourished). Results The SGA classified 49 (33%) patients as well-nourished, 54 (37%) as moderately malnourished, and 45 (30%) as severely malnourished. SGA-C was also associated with severe acute graft versus host disease (aGVHD) with a cumulative incidence (CI) of 31% vs. a CI of 14% for combined well-nourished or moderately malnourished group (SGA-A or –B, P = 0.017). In multivariate analysis, SGA-C compared to SGA-A or –B, remained as an independent risk factor for aGVHD (hazard ratio - HR 1.68, 95% confidence interval - 95% CI 1.02–2.74), and nonrelapse mortality (NRM - HR 3.63, 95% CI 1.76–7.46), worse progression free survival (HR 2.12, 95% CI 1.25–3.60), and worse overall survival (HR 3.27, 95% CI 1.90–5.64). Conclusion Malnutrition increases the risk of aGVHD and NRM and has a negative impact on survival.

Objectives The present review provides information about which molecules appear to be the main fluorophores in skin and oral mucosa, together with their clinical applications. Design The MEDLINE database was searched, using “oral mucosa AND fluorophores”, “skin AND fluorophores”, “epidermal AND fluorophores”, “dermal AND fluorophores” and “cutaneous AND fluorophores” as entry terms. We searched the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The level of evidence in the studies was assessed using the Classification of the Oxford Centre for Evidence-based Medicine (CEBM) Levels for Diagnosis. Results Five papers and 17 were primarily focused on description of fluorophores in oral mucosa and skin Evidence exists that fluorophores of oral mucosa and skin are mainly proteins such as collagen, elastin, keratin and tryptophan. Other possible fluorophores identified are: porphyrins, advanced glycation end products, flavins, lipopigment, nicotinamide adenine dinucleotide, flavin adenine dinucleotide, pheomelanin, eumelanin and components of lipofuscin. Clinical applications of oral mucosal autofluorescence (AF) are related to management of malignant and potentially malignant lesions. In the skin, AF has been used for acne assessment, diagnosis of sweat-gland pathologies, glycemic control and management of malignant lesions and as a marker for skin aging. Conclusion Fluorophores stimulated through AF devices are implied in different physiologic and pathologic processes. AF seems to be useful for several clinical applications, especially in skin department. Because most of the studies show a low level of evidence, further studies are necessary in such a promising and fascinating field.

Particulate contamination in the form of nanoparticles (NPs) can occur not only in the environment but also in the food production chain, making human exposure almost inevitable. In the present study the potentialities of Environmental Scanning Electron Microscopy coupled with Energy-Dispersive X-ray Spectroscopy (ESEM-EDS) were exploited for the detection and visualization of inorganic NPs in air, raw materials and food products along the pasta production chain (wheat ear, wheat, semolina and pasta). Investigation of the elemental composition of NPs in the same samples was also carried out by using two independent techniques: ESEM-EDS and Inductively Coupled Plasma Mass Spectrometry (ICP-MS). As for airborne particles, size-fractionated sampling was performed by an eight-stage cascade impactor located near the production plant with different exposition times for both ESEM-EDS and gravimetric analysis, respectively. In the case of raw materials and food products, the particles were collected on polycarbonate filters after immersion in milli-Q water in order to recover the NPs deriving from external environmental contamination. Only particle sizes lower than 0.8 µm were taken into consideration when ESEM-EDS analysis was carried out. NPs containing mainly Fe and Ti having dimensions0.15 µm were identified in the filters used for wheat ear, wheat, semolina and pasta samples. As for air monitoring, gravimetric analysis showed an increase in the concentration levels of total particles during winter, particularly in the case of fine particulate matter (PM

The purpose of this work is to evaluate the influence of co-lamination vs. co-bonding on the failure behavior, and namely the fracture toughness, of carbon fibre reinforced (CFR) composite laminate joints in order to assess comparatively their performance. Since the strength of the laminate and ply texture are parameters affecting the strength of the joint, the comparison is extended to two different types of CFR pre-preg fibers, a satin T1100 with 2573 Nanoalloy® epoxy resin supplied by Toray and a twill T700 with ER450 toughened epoxy resin supplied by CIT, Toray group, representative of two different fields of application, racing and automotive, respectively.