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Play is an essential skill for children in early intervention settings and contributes to social and emotional development. Children with autism spectrum disorder (ASD) often show significant delays in action-on-object play skills, vocalizations during play, and novel responding. By assessing and targeting play, children with autism can acquire play skills which may increase the likelihood of inclusion in a classroom setting and provide increased opportunities for peer and adult interaction. The current study evaluated the effects of apps as a video model to increase the duration of play, independent and novel action-on-object play, and independent and novel vocalizations during play. Current assessment and intervention strategies, as well as the need for further research making use of current technology and apps to increase play skills for school-age children with autism are discussed.

Allantoin represents a compound widely employed in pharmaceutical and cosmetic fields. Its safety has been acknowledged by regulatory bodies such as the US Food and Drug Administration, the European Commission for Cosmetics and Consumer and Health and European Directorate for the Quality of Medicines & HealthCare. This justifies its wide use in dermatological/cosmetic formulations and allows their safe use.Allantoin possesses an asymmetric carbon atom, resulting in two enantiomers, with the (S)-enantiomer predominating in plants, although racemization may potentially occur during manufacturing processes. Notably, literature currently lacks enantioselective LC methods for allantoin analysis.In this study, two zwitterionic Cinchona alkaloid-based chiral stationary phases (CSPs), commercially known as CHIRALPAK® ZWIX(+) (CSP1) and CHIRALPAK® ZWIX(-) (CSP2), were utilized for the enantioseparation of allantoin under polar-ionic conditions. By employing a mobile phase consisting of acetonitrile/methanol/water/acetic acid (96:2:2:0.1, v/v/v/v), nearly complete baseline separation (with α=1.08) of allantoin enantiomers was achieved in less than 15 min with both CSPs. Due to the “pseudo-enantiomeric” nature of the two chiral selectors (quinine-based in CSP1 and quinidine-based in CSP2), an inversion of the enantiomer elution order was observed with the two CSPs under identical experimental conditions. Remarkably, this represents a rare instance where these CSPs demonstrate the ability to enantioseparate a non-ionic, non-ionizable species.The application of a molecular dynamics in silico protocol proved useful in elucidating the retention mechanism in depth, casting light on the central role of the H-bond formation and the involvement of the anionic moiety of the CSP 1.

Growing evidence suggests that impaired gut permeability and gut microbiota alterations are involved in the pathogenesis of Inflammatory Bowel Diseases (IBDs), which include Ulcerative Colitis (UC) and Crohn’s Disease (CD). Vedolizumab is an anti-α4β7 antibody approved for IBD treatment, used as the first treatment or second-line therapy when the first line results in inadequate effectiveness. The aim of this study is to develop a mathematical model capable of describing the pathophysiological mechanisms of Vedolizumab treatment in IBD patients. In particular, the relationship between drug concentration in the blood, colonic mucosal permeability and fecal microbiota composition was investigated and modeled to detect and predict trends in order to support and tailor Vedolizumab therapies. To pursue this aim, clinical data from a pilot study on a cluster of 11 IBD patients were analyzed. Enrolled patients underwent colonoscopy in three phases (before (t0), after 24 weeks of (t1) and after 52 weeks of (t2 ) Vedolizumab treatment) to collect mucosal biopsies for transepithelial electrical resistance (TEER) evaluation (permeability to ions), intestinal permeability measurement and histological analysis. Moreover, fecal samples were collected for the intestinal microbiota analysis at the three time points. The collected data were compared to those of 11 healthy subjects at t0, who underwent colonoscopy for screening surveillance, and used to implement a three-compartmental mathematical model (comprising central blood, peripheral blood and the intestine). The latter extends previous evidence from the literature, based on the regression of experimental data, to link drug concentration in the peripheral blood compartment with Roseburia abundance and intestinal permeability. The clinical data showed that Vedolizumab treatment leads to an increase in TEER and a reduction in intestinal permeability to a paracellular probe, improving tissue inflammation status. Microbiota analysis showed increasing values of Roseburia, albeit not statistically significant. This trend was adequately reproduced by the mathematical model, which offers a useful tool to describe the pathophysiological effects of Vedolizumab therapy on colonic mucosal permeability and fecal microbiota composition. The model’s satisfactory predictive capabilities and simplicity shed light on the relationship between the drug, the microbiota and permeability and allow for its straightforward extension to diverse therapeutic conditions.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the small joints of the hands and feet, characterized by pain, inflammation, and joint damage. In this context, magnetic resonance imaging (MRI) is useful to identify and monitor joint/tendon inflammation and the evolution of joint damage, playing a key role in treatment response evaluation, in addition to clinical measurements. Various methods to quantify joint inflammation and damage with MRI in RA have been developed, such as RA-MRI Score (RAMRIS), Early RA-MRI Score (ERAMRS), and Simplified RA-MRI Score (SAMIS). RAMRIS, introduced in 2002, offers an objective means to assess inflammation and damage via MRI in RA trials, encompassing findings such as synovitis, bone erosion, and edema/osteitis. Recently, an updated RAMRIS version was developed, which also includes the evaluation of joint space narrowing and tenosynovitis. The RAMRIS-5, which is a condensed RAMSIS version focusing on five hand joints only, has been proven to be a valuable resource for the semi-quantitative evaluation of RA joint damage, both in early and established disease. This narrative literature review will provide an overview of the MRI scoring systems that have been developed for the assessment of joint inflammation and structural damage in RA patients.

Molten salts such as 2LiF-BeF2 (FLiBe) have been proposed as coolants for advanced nuclear fission and fusion reactors. Critical to the design, licensing and operation of these reactors is characterization and understanding of the chemical behavior and mass transport of activation and fission products, corrosion products, and other solutes in the coolant. Electrochemical techniques are a powerful suite of tools for probing these phenomena. The design of an experimental cell for molten salt electrochemistry is described herein. As a demonstration of this design, details of the experimental methods used to conduct electrochemical experiments with molten FLiBe with addition of LiH are provided. Decommissioning of the cell is considered from the point of view of decontamination and waste generated. Main features of the cell include:•Suitable for operation up to 800 °C; suitable for operation inside and outside of a glovebox.•Enables sweep gas, gas sampling and analysis; enables addition of solid and liquid materials during operation.•Supports a variety of electrode materials and arrangements.

The present review provides a comprehensive examination of the intricate dynamics between α-synuclein, a protein crucially involved in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease and multiple system atrophy, and endogenously-produced bioactive lipids, which play a pivotal role in neuroinflammation and neurodegeneration. The interaction of α-synuclein with bioactive lipids is emerging as a critical factor in the development and progression of neurodegenerative and neuroinflammatory diseases, offering new insights into disease mechanisms and novel perspectives in the identification of potential biomarkers and therapeutic targets. We delve into the molecular pathways through which α-synuclein interacts with biological membranes and bioactive lipids, influencing the aggregation of α-synuclein and triggering neuroinflammatory responses, highlighting the potential of bioactive lipids as biomarkers for early disease detection and progression monitoring. Moreover, we explore innovative therapeutic strategies aimed at modulating the interaction between α-synuclein and bioactive lipids, including the development of small molecules and nutritional interventions. Finally, the review addresses the significance of the gut-to-brain axis in mediating the effects of bioactive lipids on α-synuclein pathology and discusses the role of altered gut lipid metabolism and microbiota composition in neuroinflammation and neurodegeneration. The present review aims to underscore the potential of targeting α-synuclein-lipid interactions as a multifaceted approach for the detection and treatment of neurodegenerative and neuroinflammatory diseases.

The aim of this paper is to identify factors associated with interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) and build an algorithm to better define this association for a personalised application in clinical practice. Methods. A total of 78 SSc patients underwent HRCT to assess ILD. Demographic, clinical and laboratory variables were collected, focusing on those associated either directly or indirectly with lung involvement. The discriminant value of each variable was determined using the operating characteristic curves (ROC) and included in a model to estimate the strength of ILD association in SSc. Results. Thirty-three (42.31%) patients showed ILD on HRCT. DLco, M-Borg, GERD-Q and capillary density were significantly associated with the presence of ILD-SSc. A model including these variables had a coefficient of determination (R2) of 0.697. DLco had an AUC of 0.861 (p < 0.001) with a cut-off of ≤72.3% (sensitivity 78.8%, specificity 91.1%, +LR 8.86). The m-Borg Scale showed an AUC of 0.883 (p < 0.001) with a cut-off >2 (sensitivity 84.8%, specificity 82.2%, +LR 4.77), GERD-Q had an AUC of 0.815 (p < 0.001) with a cut-off >7 (sensitivity 72.7%, specificity 86.7%, +LR 5.45). The capillary density showed an AUC of 0.815 (p < 0.001) with a cut-off of ≤4.78 (sensitivity 87.9%, specificity 68.9%, +LR 2.82). Based on the pre-test probability values, these four variables were applied to Fagan’s nomogram to calculate the post-test probability of this association. Conclusions. Our study identified four associated clinical factors of ILD in SSc patients. Moreover, their inclusion in an algorithm for the post-test probability, tailored to the specific patients’ characteristics, significantly increases the ability to find out the presence of SSc-ILD.

Vedolizumab (VDZ) is used for treating inflammatory bowel disease (IBD) patients. A study investigating colonic epithelial barrier function ex vivo following VDZ is lacking. This work aims to evaluate ex vivo the colonic epithelial barrier function in IBD patients at baseline and during VDZ treatment, and to investigate the relationships between barrier function and clinical parameters. Colonic specimens were obtained from 23 IBD patients before, and at 24 and 52 weeks after VDZ treatment, and from 26 healthy volunteers (HV). Transepithelial electrical resistance (TEER, permeability to ions) and paracellular permeability were measured in Ussing chambers. IBD patients showed increased epithelial permeability to ions (TEER, 13.80 ± 1.04 Ω × cm2 vs. HV 20.70 ± 1.52 Ω × cm2, p < 0.001) without changes in paracellular permeability of a 4 kDa probe. VDZ increased TEER (18.09 ± 1.44 Ω × cm2, p < 0.001) after 52 weeks. A clinical response was observed in 58% and 25% of patients at week 24, and in 62% and 50% at week 52, in ulcerative colitis and Crohn’s disease, respectively. Clinical and endoscopic scores were strongly associated with TEER. TEER < 14.65 Ω × cm2 predicted response to VDZ (OR 11; CI 2–59). VDZ reduces the increased permeability to ions observed in the colonic epithelium of IBD patients before treatment, in parallel to a clinical, histological (inflammatory infiltrate), and endoscopic improvement. A low TEER predicts clinical response to VDZ therapy.

Summary: Friedreich’s ataxia (FA) is a neurodegenerative disease resulting from a mutation in the FXN gene, leading to mitochondrial frataxin deficiency. FA patients exhibit increased visceral adiposity, inflammation, and heightened diabetes risk, negatively affecting prognosis. We investigated visceral white adipose tissue (vWAT) in a murine model (KIKO) to understand its role in FA-related metabolic complications. RNA-seq analysis revealed altered expression of inflammation, angiogenesis, and fibrosis genes. Diabetes-like traits, including larger adipocytes, immune cell infiltration, and increased lactate production, were observed in vWAT. FXN downregulation in cultured adipocytes mirrored vWAT diabetes-like features, showing metabolic shifts toward glycolysis and lactate production. Metagenomic analysis indicated a reduction in fecal butyrate-producing bacteria, known to exert antidiabetic effects. A butyrate-enriched diet restrained vWAT abnormalities and mitigated diabetes features in KIKO mice. Our work emphasizes the role of vWAT in FA-related metabolic issues and suggests butyrate as a safe and promising adjunct for FA management.

Abstract Background Macroscopic alterations of the affected rotator cuff (RC) are undoubtedly linked to microscopic changes, but they may underestimate the actual degree of the disease. Moreover, it remains unclear whether preoperative structural RC changes may alter clinical outcomes. Methods Supraspinatus tendon and muscle samples were collected from 47 patients undergoing RC surgery. Tendons were evaluated histologically according to the Bonar score; fatty infiltration and muscle atrophy were quantified using a software for biomedical image analysis (ImageJ) in percentage of area affected in the observed muscle section. Preoperative shoulder ROM and pain were evaluated. Radiological muscle atrophy was evaluated with the Tangent Sign and Occupation Ratio; fatty infiltration was assessed according to the Goutallier classification. Correlations between histological, radiological and clinical outcomes were assessed. Statistics were performed using the Spearman correlation coefficient. Intraobserver and interobserver agreement was calculated. Results Histopathologic fatty infiltration (r = 0.007, p = 0.962), muscle atrophy (r = 0.003, p = 0.984) and the total Bonar score (r = 0.157, p = 0.292) were not correlated to preoperative shoulder pain. Muscle atrophy showed a significant but weak negative correlation with the preoperative movement of abduction (r = -0.344, p = 0.018). A significant but weak positive correlation was found between muscle atrophy and the total Bonar score (r = 0.352, p = 0.015). No correlation between histological and radiological evaluation was found for both fatty infiltration (r = 0.099, p = 0.510) and muscle atrophy (Tangent Sign: r = -0.223, p = 0.131; Occupation Ratio: r = -0.148, p = 0.319). Our histological evaluation showed a modal value of 3 (out of 3) for fatty infiltration and an equal modal value of 2 and 3 (out of 3) for muscle atrophy. In contrast, the modal value of the Goutallier score was 1 (out of 4) and 28 patients out of 47 showed a negative Tangent sign. At histology, intraobserver agreement ranged from 0.59 to 0.81 and interobserver agreement from 0.57 to 0.64. On the MRI intraobserver agreement ranged from 0.57 to 0.71 and interobserver agreement ranged from 0.53 to 0.65. Conclusions Microscopic muscle atrophy appeared to negatively correlate with the movement of abduction leading to functional impairment. Shoulder pain did not show any relationship with microscopic changes. Radiological evaluation of the supraspinatus muscle alterations seemed to underestimate the degree of the same abnormalities evaluated at histology.

(1) Background: Type 2 diabetes is a major cause of incidences and the progression of peripheral artery disease (PAD). Bone marrow edema (BME) is an important finding suggestive of underlying bone inflammation in non-traumatic diabetic patients with PAD. Our aim was to evaluate the presence, severity, and clinical implications of BME detected by virtual non-calcium application (VNCa) of dual-energy CT angiography (DE-CTA). (2) Methods: A consecutive series of 76 diabetic patients (55 men; mean age 71.6 ± 11.2 yrs) submitted to lower limb DE-CTA for PAD evaluation and revascularization planning, which were retrospectively analyzed. VNCa images were independently and blindly revised for the presence, location, and severity of BME by two radiologists with 10 years of experience. BME and non-BME groups were evaluated in terms of PAD clinical severity and 6-month secondary major amputation rate. (3) Results: BME was present in 17 (22%) cases, while 59 (78%) patients were non-BME. The BME group showed a significantly higher incidence of major amputation (p < 0.001) and a significantly higher number of patients with advanced clinical stages of PAD compared to the non-BME group (p = 0.024). (4) Conclusions: Lower limb DE-CTA with VNCa application is a useful tool in the detection of BME in diabetic patients with PAD, simultaneously enabling the evaluation of the severity and location of the arterial disease for revascularization planning. BME presence could be a marker of clinically severe PAD and a possible risk factor for revascularization failure.

Constrictive pericarditis is a chronic inflammatory process that can lead to heart failure if not diagnosed and treated correctly. Although Epstein–Barr virus (EBV)–related pericarditis is a very rare condition, it should still be considered for a differential diagnosis. We report the case of an 18-year-old male, who was surgically treated for constrictive pericarditis, in which in situ hybridization to Epstein–Barr virus-encoded RNA (EBER) probe of the excised pericardium led to the subsequent etiological diagnosis of chronic pericarditis caused by EBV.

BackgroundAortic arch malformations (AAMs) should be suspected in the presence of persistent respiratory symptoms despite medical treatment or feeding problems at the pediatric age.AimWe report a descriptive cohort of patients with AAMs and the local management protocol applied.MethodsA total of 59 patients with AAM were retrospectively reviewed. Three groups were identified: double aortic arch (DAA), group 1; complete vascular ring (non-DAA), group 2; and anomalous origin of the innominate artery (IA), group 3.ResultsPrenatal diagnosis was available for 62.7% of the patients. In all, 49.2% of children were symptomatic. There was a significantly different prevalence of respiratory symptoms within the three groups: 73.7% in group 1, 24.2% in group 2, and 100% in group 3 (p-value: