Friction Stir Welding of Ti6Al4V complex geometries for aeronautical applications: a feasibility study

While Friction Stir Welding (FSW) of aluminium alloys can be considered a mature technology, even for complex joint morphologies, as T joints welded “in transparency”, welding of hard material still presents several open issues. In fact, welding of titanium alloys is a challenging process due to the chemical, mechanical and thermal characteristics of such materials which are subjected to atmosphere contamination resulting in joint hydrogen, oxygen and nitrogen embrittlement; additionally, due to the high melting temperature, large distortion and residual stress are found in joints obtained by traditional fusion welding processes as gas metal arc welding, electron beam welding and laser welding. In this way a solid-state process, as FSW, represents a valid choice in order to overcome problems related to the material melting. It should be noticed that FSW of titanium alloys is definitely more complex than the same process referred to aluminium alloys. In the proposed paper, a feasibility study on the production of Ti6Al4V T-joints in one welding pass, i.e. the so-called transparency welding, is presented. The main process parameters, i.e. tool rotation and feed rate have been fixed, and the main metallurgical and mechanical properties of the joint have been analysed. Macro and micro observations of the joints have been performed relating the final microstructure to the input process parameters utilized

Syncope with Surprise: An Unexpected Finding of Huge Gastric Diverticulum

A gastric diverticulum is a pouch protruding from the gastric wall. e vague long clinical history ranging between dyspepsia, postprandial fullness, and upper gastrointestinal bleeding makes this condition a diagnostic challenge. We present a case of large gastric diverticulum that has been diagnosed during clinical investigations for suspected cardiovascular issues in a patient admitted at the medical ward for syncope. A 51-year-old man presented to the medical department due to a syncopal episode occurring while he was resting on the beach a er having his lunch, with concomitant vague epimesogastric gravative pain without any other symptom. A diagnosis of neuromediated syncopal episode was made by the cardiologist. Due to the referred epimesogastric pain, an abdominal ultrasound scan was carried out, showing perisplenic uid. A CT scan of the abdomen was performed to exclude splenic lesions. e CT scan revealed a large diverticulum protruding from the gastric fundus. e upper gastrointestinal endoscopy visualized a large diverticular neck situated in the posterior wall of the gastric fundus, partially lled by undigested food. e patient underwent surgery, with an uneventful postoperative course. Histologic examination showed a full-thickness stomach specimen, indicative of a congenital diverticulum. At the 2nd month of follow-up, the patient was asymptomatic

The value of immunohistochemical research on PCNA, p53 and heat shock proteins in prostate cancer management: a review.

This review addresses the significance of the expression of proliferating cell nuclear antigen (PCNA), p53 and some heat shock proteins (Hsps) in prostate carcinoma (PC). In fact, PCNA and p53 are two widely discussed tools in PC diagno- sis, mainly because of the controversy regarding the signifi- cance of their expression during prostate cancer development and progression. At the same time, only few studies have shown the potential role of Hsps in carcinogenesis and their overexpression in pre-neoplastic and neoplastic lesions of the prostate. We briefly describe the physiological roles of Hsps in normal cells, and the significance of their immunohistochem- ical detection in PC as well as in pre-cancerous lesions of the prostate. We will also discuss the possible functional interac- tions of these molecules in both dysplastic and neoplastic cell

Localized strain sensing with fiber Bragg-grating ring cavities

We report the theoretical description and the experimental demonstration of an optical resonator formed by inserting a Fiber Bragg Grating (FBG) in a closed fiber loop. The spectral characteristics of such a resonator strongly depend on the reflectivity of the FBG. In the wavelength region where the FBG reflectivity R is negligible, the system behaves like a conventional ring resonator. On the other hand, when R is not vanishing, a split-mode structure can be observed, associated to the degeneracy removal of two counterpropagating resonant modes. The magnitude of the mode splitting can be used to sense small variations of the FBG physical parameters, such as length, temperature or group index. An example of strain sensing with this setup is reported, showing that the mode splitting is sensitive to a mechanical strain applied to the FBG, while it is almost insensitive to a strain applied to any other point of the resonator. This peculiar feature allows to perform cavity-enhanced, local strain measurements with a reduced sensitivity to environmental perturbations, which represents an important improvement in the framework of the fiber-optic sensors. (C)2013 Optical Society of Americ

Rapid Spread of the SARS-CoV-2 Variant of Concern 202012/01 in Southern Italy (December 2020–March 2021)

Epidemiological and virological studies have revealed that SARS-CoV-2 variants of concern (VOCs) are emerging globally, including in Europe. The aim of this study was to evaluate the spread of B.1.1.7-lineage SARS-CoV-2 in southern Italy from December 2020–March 2021 through the detection of the S gene target failure (SGTF), which could be considered a robust proxy of VOC B.1.1.7. SGTF was assessed on 3075 samples from week 52/2020 to week 10/2021. A subset of positive samples identified in the Apulia region during the study period was subjected to whole-genome sequencing (WGS). A descriptive and statistical analysis of the demographic and clinical characteristics of cases according to SGTF status was performed. Overall, 20.2% of samples showed SGTF; 155 strains were confirmed as VOC 202012/01 by WGS. The proportion of SGTF-positive samples rapidly increased over time, reaching 69.2% in week 10/2021. SGTF-positive cases were more likely to be symptomatic and to result in hospitalization (p < 0.0001). Despite the implementation of large-scale non-pharmaceutical interventions (NPIs), such as the closure of schools and local lockdowns, a rapid spread of VOC 202012/01 was observed in southern Italy. Strengthened NPIs and rapid vaccine deployment, first among priority groups and then among the general population, are crucial both to contain the spread of VOC 202012/01 and to flatten the curve of the third wav

Effect of mofezolac-galactose distance in conjugates targeting cyclooxygenase (COX)-1 and CNS GLUT-1 carrier

Neuroinflammation is the earliest stage of several neurological and neurodegenerative diseases. In the case of neurodegenerative disorders, it takes place about 15â 20 years before the appearance of specific neurodegenerative clinical symptoms. Constitutive microglial COX-1 is one of the pro-inflammatory players of the neuroinflammation. Novel compounds 3, 14 and 15 (Galmof0, Galmof5and Galmof11, respectively) were projected, and their synthetic methodologies developed, by linking by an ester bond, directly or through a C5 or C11 unit linker the highly selective COX-1 inhibitor mofezolac (COXs selectivity index > 6000) to galactose in order to obtain substances capable to cross blood-brain barrier (BBB) and control the CNS inflammatory response. 3, 14 and 15 (Galmofs) were prepared in good to fair yields. Galmof0(3) was found to be a selective COX-1 inhibitor (COX-1 IC50= 0.27 μM and COX-2 IC50= 3.1 μM, selectivity index = 11.5), chemically and metabolically stable, and capable to cross Caco-2 cell monolayer, resembling BBB, probing that its transport is GLUT-1-mediated. Furthermore, Galmof0(3) powerfully inhibits PGE2release higher than mofezolac (1) in LPS-stimulated mouse BV2 microglial cell line, a worldwide recognized neuroinflammation model. In addition, Fingerprints for Ligands and Proteins (FLAP) was used to explain the different binding interactions of Galmofs with the COX-1 active site

Subclinical Atrial Fibrillation on Prolonged ECG Holter Monitoring: Results from the Multicenter Real-World SAFARI (Silent Atrial Fibrillation ANCE-Sicily Research Initiative) Study

Background: The detection of subclinical/silent atrial fibrillation (SAF) in the general population is of the utmost importance, given its potential adverse consequences. Incident AF has been observed in 30% to 70% of patients with implanted devices, but its prevalence may indeed be lower in the general population. The prospective, multicentric, observational Silent Atrial Fibrillation ANCE Research Initiative (SAFARI) study aimed at assessing the SAF prevalence in a real-world outpatient setting by the means of a small, wearable, prolonged ECG Holter monitoring (>5 days) device (CGM HI 3-Lead ECG; CGM TELEMEDICINE, Piacenza, Italy). Methods: Patients = 55 years of age at risk for AF were screened according to the inclusion criteria to undergo prolonged 3-lead ECG Holter monitoring. SAF episodes were classified as follows: Class A, <30 s; Class B, 30 to 299 s; and Class C, =300 s. Results: In total, 119 patients were enrolled (64 men; median age 71 (IQR 55-85) years). At a median of 13.5 (IQR 5-21) days of monitoring, SAF episodes were found in 19 patients (16%). A total of 10,552 arrhythmic episodes were registered, 6901 in Class A (n = 7 patients), 2927 in Class B (n = 3), and 724 in Class C (n = 9), (Class A vs. B and C, p < 0.001). This latter group had multiple (all-class) episodes, and two patients had >1000 episodes. There were no clinical, echocardiographic, or laboratory findings able to discriminate patients with SAF from those in sinus rhythm in univariate and multivariable analyses; of note is that the Class C patients showed a higher diastolic blood pressure, resting heart rate, and indexed LA volume. Conclusions. Over a median of 13 days of Holter monitoring, the SAFARI study confirmed the usefulness of small wearable devices in detecting SAF episodes in real-world outpatients at risk for, but with no prior history of, AF

Decellularized silk fibroin scaffold primed with adipose mesenchymal stromal cells improves wound healing in diabetic mice

Introduction: Silk fibroin (SF) scaffolds have been shown to be a suitable substrate for tissue engineering and to improve tissue regeneration when cellularized with mesenchymal stromal cells (MSCs). We here demonstrate, for the first time, that electrospun nanofibrous SF patches, cellularized with human adipose-derived MSCs (Ad-MSCs-SF) or decellularized (D-Ad- MSCs-SF) are effective in the treatment of skin wounds, improving skin regeneration in db/db diabetic mice. Methods: The conformational and structural analyses of SF and D-Ad-MSCs-SF patches were performed by scanning electron microscopy, confocal microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. Wounds were performed by a 5mm punch biopsy tool on the mouse\u2019s back. Ad-MSCs-SF and D-Ad-MSCs-SF patches were transplanted and the efficacy of treatments was assessed by measuring the wound closure area, by histological examination and by gene expression profile. We further investigated the in vitro angiogenic properties of Ad-MSCs-SF and D-Ad-MSCs-SF patches by affecting migration of human umbilical vein endothelial cells (HUVECs), keratinocytes (KCs) and dermal fibroblasts (DFs), through the aortic ring assay and, finally, by evaluating the release of angiogenic factors. Results: We found that Ad-MSCs adhere and grow on SF, maintaining their phenotypic mesenchymal profile and differentiation capacity. Conformational and structural analyses on SF and D-Ad- MSCs-SF samples, showed that sterilization, decellularization, freezing and storing did not affect the SF structure. When grafted in wounds of diabetic mice, both Ad-MSCs-SF and DAd- MSCs-SF significantly improved tissue regeneration, reducing the wound area respectively by 40% and 35%, within three days, completing the process in around 10 days compared to 15-17 days of controls. RT2 gene profile analysis of the wounds treated with Ad- MSCs-SF and D-Ad-MSCs-SF showed an increment of genes involved in angiogenesis and matrix remodelling. Finally, Ad-MSCs-SF and D-Ad-MSCs-SF co-cultured with HUVECs, DFs and KCs, preferentially enhanced the HUVECs\u2019 migration and the release of angiogenic factors stimulating microvessel outgrowth in the aortic ring assay. Conclusions: Our results highlight for the first time that D-Ad-MSCs-SF patches are almost as effective as Ad-MSCs-SF patches in the treatment of diabetic wounds, acting through a complex mechanism that involves stimulation of angiogenesis. Our data suggest a potential use of DAd- MSCs-SF patches in chronic diabetic ulcers in humans

Beyond BRCA1 and BRCA2: deleterious variants in DNA repair pathway genes in italian families with breast/ovarian and pancreatic cancers

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches