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The fatigue behavior of composite materials is still a very challenging issue for the scientific community. So far, several numerical methodologies allow us to faithfully simulate the propagation of delamination due to fatigue. However, the reduction of material properties due to the applied cyclic load should be considered. The main objective of this work is to investigate the role of the material property degradation and the intralaminar damages on the propagation of delamination in composite laminates under fatigue loads. The numerical tool FT-SMXB, based on the Paris Law and virtual crack closure technique, for the mimic of fatigue-driven delamination, has been integrated with a user material subroutine, based on the generalized residual material property 7degradation model and the Hashin fatigue failure criteria. Typical aeronautical stiffened panel has been considered as test case. Matrix damages and strength degradation due to fatigue cycles have been found to influence the propagation of delamination.

Autologous gastrointestinal reconstructive surgery (AGIR) has become a key component of intestinal rehabilitation programs. However, the best surgical option for short bowel syndrome (SBS) remains unknown. This paper presents our experience using combined procedures as primary treatment.We collected data on SBS patients who underwent surgery from 2008 to 2021 in two tertiary European Centres. Combined procedures were defined as more than one technique used on the same patient. Charts were reviewed for demographics, type of procedures, complications, and outcomes. Data are presented as median and IQR. Wilcoxon signed rank was used for all paired analyses.Twenty-one children (12 females) underwent combined procedures. Preoperative median small bowel length was 20 cm (IQR: 15-35 cm); after lengthening, it was 35.5 cm (IQR: 30.75-50.50 cm) (P 0.001). Combined procedures were simultaneous in 15 patients and sequential in 6. At a median of 9.2 years (IQR: 7.55-9.78 years) follow-up, complications were three bowel obstructions after strictures of anastomosis and two wound infections. Two patients achieved enteral autonomy, and others followed a weaning home parenteral nutrition regimen with a median of 4 nights off (IQR: 3-4 nights) starting with a median of 7 nights (IQR: 7-7 nights).Combined AGIR techniques are practical and safe in SBS treatment when tailored to meet patients' needs, combining lengthening, tailoring, and reducing transit time procedures. Therefore, combined AGIR may be considered a resource in intestinal rehabilitation units' armamentarium.

The update of the review on the effects of switching from agalsidase beta to alfa showed, in comparison to the previous review, an increased number of clinical events, a significant loss of renal function, and an increase in lyso Gb-3 levels, underscoring the importance of dose in the treatment of FD.

Cyclodextrins are nanometric cyclic oligosaccharides with amphiphilic characteristics that increase the stability of drugs in pharmaceutical forms and bioavailability, in addition to protecting them against oxidation and UV radiation. Some of its characteristics are low toxicity, biodegradability and biocompatibility. They are divided into α-, β- and γ-cyclodextrins, each with its own particularities. They can undergo surface modification to improve their performance. Furthermore, their drug inclusion complexes can be made by various methods, including lyophilization, spray drying, magnetic stirring, kneading and others. Cyclodextins can solve several problems in drug stability when incorporated into dosage forms (including tablets, gels, films, nanoparticles and suppositories) and allow the best topical biological effect of drugs at administration sites such as skin, eyeballs and oral, nasal, vaginal and rectal cavities. However, as they are nanostructured systems and some of them can cause mild toxicity depending on the application site, they must be evaluated for their nanotoxicology and nanosafety aspects. Moreover, there is evidence that they can cause severe ototoxicity, killing cells from the ear canal even when applied by other adminsitration routes. Therefore, they should be avoided in otologic administration and should have their permeation/penetration profiles evaluated to certify that they will be safe and will not cause hearing loss.

Aims: To evaluate whether angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) combination therapy is more nephroprotective than ACE inhibitor or ARB monotherapy in people with type 2 diabetes and overt nephropathy. Materials and methods: In this prospective, randomized, open, blind-endpoint phase III trial sponsored by the Italian Drug Agency, 103 consenting patients with type 2 diabetes, aged >40 years, with serum creatinine levels 159 to 309 μmol/L, spot morning urinary albumin–creatinine ratio > 1000 mg/g (or > 500 mg/g in those on ACE inhibitor or ARB therapy at inclusion) were stratified by centre and randomized to 4.5-year treatment with valsartan 320 mg/d (n = 36), benazepril 20 mg/d (n = 34) or halved doses of both medications (n = 33). The primary endpoint was end-stage renal disease (ESRD). Modified intention-to-treat analyses were performed. Results: Recruitment took place between June 2007 and February 2013 at 10 centres in Italy and one in Slovenia. A total of 77 participants completed the study and 26 were prematurely withdrawn. During a median (interquartile range) of 41 (18–54) months, 12 participants on benazepril (35.3%) and nine on combination therapy (27.3%) progressed to ESRD, versus five on valsartan (13.9%). Differences between benazepril (hazard ratio [HR] 3.59, 95% confidence interval [CI] 1.25–10.30; P = 0.018) or combination therapy (HR 3.28, 95% CI 1.07–10.0; P = 0.038) and valsartan were significant, even after adjustment for age, gender and baseline serum creatinine, systolic blood pressure and 24-hour proteinuria (HR 5.16, 95% CI 1.50–17.75, P = 0.009 and HR 4.75, 95% CI 1.01–22.39, P = 0.049, respectively). Adverse events were distributed similarly among the groups. Conclusions: In people with type 2 diabetes with nephropathy, valsartan (320 mg/d) safely postponed ESRD more effectively than benazepril (20 mg/d) or than halved doses of both medications.

Four individuals from two families presented with a multisystemic condition of suspected genetic origin that was diagnosed only after genome analysis. The main phenotypic features were immune system dysregulation (severe immunodeficiency with autoimmunity) and intellectual disability. The four individuals were found to be homozygous for a 4.4 Kb deletion removing exons 20 to 23 (NM_003291.4) of the TPP2 gene, predicting a frameshift with premature termination of the protein. The deletion was located on a shared chromosome 13 haplotype indicating a Swiss founder mutation. Tripeptidyl peptidase 2 (TPP2) is a protease involved in HLA/antigen complex processing and amino acid homeostasis. Biallelic variants in TPP2 have been described in ten individuals with variable features including immune deficiency, autoimmune cytopenias, and intellectual disability or chronic sterile brain inflammation mimicking multiple sclerosis. Our observations further delineate this severe condition not yet included in the OMIM catalog. Timely recognition of TPP2 deficiency is crucial since (1) immune surveillance is needed and hematopoietic stem cell transplantation may be necessary, and (2) for provision of genetic counseling. Additionally, enzyme replacement therapy, as already established for TPP1 deficiency, might be an option in the future. This article is protected by copyright. All rights reserved.

Background: Speckle tracking advancements make now available the analysis of layer-specific myocardial deformation. This study investigated multilayer longitudinal strain in Anderson-Fabry disease (AFD) patients at diagnosis. Methods: In a case-control study, 33 newly diagnosed, untreated AFD patients and 33 healthy age- and sex-matched healthy controls underwent a complete echocardiogram, including assessment of left ventricular (LV) transmural global longitudinal strain (GLS), subendocardial longitudinal strain (LSsubendo), subepicardial longitudinal strain (LSsubepi), and strain gradient (LSsubendo-LSsubpepi). Results: Anderson-Fabry disease patients had similar blood pressure, heart rate, and ejection fraction but higher body mass index in comparison with controls. LV mass index, maximal, and relative wall thickness were significantly greater in AFD patients. LSsubendo was significantly higher than LSsubepi in both groups, but GLS (P

This paper deals with the fatigue failure of composite coupon characterized by circular hole and subjected to tensile cyclic loading conditions. A limited sensitivity analysis has been performed to study the onset and propagation of intralaminar damages, in terms of fibers and matrix failure. The residual strength material properties degradation model, proposed by Shokrieh and Lessard, has been implemented in the FEM code ANSYS Mechanical and employed to study the damages induced by stress concentrations and assess the effects of the stacking sequence and the geometrical parameters on the fatigue damage.

The use of nanomodified epoxy resins can potentially increase composites application to aeronautical structural components, thanks to the potential enhancement, in terms of physical and mechanical properties, when compared to the neat epoxy matrix. In this work, the effects of silica nanoparticles (NPs) on the fracture toughness and, consequently, the crack growth resistance of fiber-reinforced polymers (FRPs) have been numerically investigated. The skin-stringer debonding initiation and growth have been studied by a tailored innovative numerical procedure considering an aeronautical panel reinforced with a single T-shape stringer, made of carbon fibers/epoxy resin material, and subjected to compressive load. An analytical model has been used to evaluate the Mode I fracture toughness value of the nanomodified resin, and the Virtual Crack Closure Technique methodology has been employed to assess the delamination growth in the frame of a Finite Elements (FE) analysis performed in the Ansys FE environment. Numerical results presenting the comparison between charged and neat configurations have been assessed to provide a first understanding of the influence of nanoparticles on the static delamination growth in geometrically complex composite structures.

A strong increase in the use of composite materials has been observed in all the industrial fields, related to manufacturing of lightweight load-bearing components. However, despite the excellent mechanical properties that characterize such innovative materials, uncertainties still exist on their complex failure mechanisms. Hence, the use of non-destructive techniques and experimental tests is needed to increase the understanding of composite materials damage evolution. This paper deals with the use of the Digital Image Correlation (DIC) technique to investigate the failure mechanisms of delaminated composite panels under compressive loading conditions, accounting for the complex phenomena related to unstable delamination growth due to buckling snap-through. The panels have been produced by tuning manufacturing parameters to test their influence on toughening mechanisms such as fiber bridging. The main aim is to understand how to improve laminate out-of-plane performance and delay the delamination growth phenomenon. The obtained data in terms of strain and displacements distributions has been used to assess the phenomenon of delamination propagation related to local delamination and global panels’ instabilities.

The recent explosive increase in the number of works on gut microbiota has been accompanied by the spread of rather vague or improper definitions, chosen more for common use than for experimental evidence. Among them are those defining the human gut microbiota as an organ of our body or as a commensal. But, is the human gut microbiota an organ or a commensal? Here, we address this issue to spearhead a reflection on the real roles of the human gut microbiota in our life. Actually, the misuse of the vocabulary used to describe the properties and functions of the gut microbiota may generate confusion and cause misunderstandings both in the scientific community and among the general public.