A case-driven hypothesis for multi-stage crack growth mechanism in fourth-generation ceramic head fracture

Background Ceramic bearings are used in total hip arthroplasty due to their excellent wear behaviour and biocompatibility. The major concern related to their use is material brittleness, which significantly impacts on the risk of fracture of ceramic components. Fracture toughness improvement has contributed to the decrease in fracture rate, at least of the prosthetic head. However, the root cause behind these rare events is not fully understood. This study evaluated head fracture occurrence in a sizeable cohort of patients with fourth-generation ceramic-on-ceramic implants and described the circumstances reported by patients in the rare cases of head fracture. Methods The clinical survivorship of 29,495 hip prostheses, with fourth-generation ceramic bearings, was determined using data from a joint replacement registry. The average follow-up period was 5.2 years (range 0.1-15.6). Retrieval analysis was performed in one case for which the ceramic components were available. Results Clinical outcomes confirmed the extremely low fracture rate of fourth-generation ceramic heads: only two out of 29,495 heads fractured. The two fractures, both involving 36 mm heads, occurred without a concurrent or previous remarkable trauma. Considering the feature of the fractured head, a multi-stage crack growth mechanism has been hypothesized to occur following damage at the head-neck taper interface. Conclusions Surgeons must continue to pay attention to the assembly of the femoral head: achieving a proper head seating on a clean taper is a prerequisite to decrease the risk of occurrence of any damage process within head-neck junction, which may cause high stress concentration at the contact surface, promoting crack nucleation and propagation even in toughened ceramics

The Citrus Flavanone Naringenin Protects Myocardial Cells against Age-Associated Damage

In recent years, the health-promoting effects of the citrus flavanone naringenin have been examined. The results have provided evidence for the modulation of some key mechanisms involved in cellular damage by this compound. In particular, naringenin has been revealed to have protective properties such as an antioxidant effect in cardiometabolic disorders. Very recently, beneficial effects of naringenin have been demonstrated in old rats. Because aging has been demonstrated to be directly related to the occurrence of cardiac disorders, in the present study, the ability of naringenin to prevent cardiac cell senescence was investigated. For this purpose, a cellular model of senescent myocardial cells was set up and evaluated using colorimetric, fluorimetric, and immunometric techniques. Relevant cellular senescence markers, such as X-gal staining, cell cycle regulator levels, and the percentage of cell cycle-arrested cells, were found to be reduced in the presence of naringenin. In addition, cardiac markers of aging-induced damage, including radical oxidative species levels, mitochondrial metabolic activity, mitochondrial calcium buffer capacity, and estrogenic signaling functions, were also modulated by the compound. These results suggested that naringenin has antiaging effects on myocardial cells

Effects of P4 Antagonist RU486 on VEGF and Its Receptors' Signaling during the In Vivo Transition from the Preovulatory to Periovulatory Phase of Ovarian Follicles

The development of an adequate blood vessel network is crucial for the accomplishment of ovarian follicle growth and ovulation, which is necessary to support the proliferative and endocrine functions of the follicular cells. Although the Vascular Endothelial Growth Factor (VEGF) through gonadotropins guides ovarian angiogenesis, the role exerted by the switch on of Progesterone (P4) during the periovulatory phase remains to be clarified. The present research aimed to investigate in vivo VEGF-mediated mechanisms by inducing the development of periovulatory follicles using a pharmacologically validated synchronization treatment carried out in presence or absence of P4 receptor antagonist RU486. Spatio-temporal expression profiles of VEGF, FLT1, and FLK1 receptors and the two major MAPK/ERKs and PI3K/AKT downstream pathways were analyzed on granulosa and on theca compartment. For the first time, the results demonstrated that in vivo administration of P4 antagonist RU486 inhibits follicular VEGF receptors' signaling mainly acting on the theca layer by downregulating the activation of ERKs and AKTs. Under the effect of RU486, periovulatory follicles' microarchitecture did not move towards the periovulatory stage. The present evidence provides new insights on P4 in vivo biological effects in driving vascular and tissue remodeling during the periovulatory phase

SGSI project at CNAF

The Italian Tier1 center is mainly focused on LHC and physics experiments in general. Recently we tried to widen our area of activity and established a collaboration with the University of Bologna to set-up an area inside our computing center for hosting experiments with high demands of security and privacy requirements on stored data. The first experiment we are going to host is Harmony, a project part of IMI's Big Data for Better Outcomes programme (IMI stands for Innovative Medicines Initiative). In order to be able to accept this kind of data we had to make a subset of our computing center compliant with the ISO 27001 regulation. In this article we will describe the SGSI project (Sistema Gestione Sicurezza Informazioni, Information Security Management System) with details of all the processes we have been through in order to become ISO 27001 compliant, with a particular focus on the separation of the project dedicated resources from all the others hosted in the center. We will also describe the software solutions adopted to allow this project to accept in the future any experiment or collaboration in need for this kind of security procedures

A Cloud-Edge Orchestration Platform for the Innovative Industrial Scenarios of the IoTwins Project

The concept of digital twins has growing more and more interest not only in the academic field but also among industrial environments thanks to the fact that the Internet of Things has enabled its cost-effective implementation. Digital twins (or digital models) refer to a virtual representation of a physical product or process that integrate data from various sources such as data APIs, historical data, embedded sensors and open data, giving to the manufacturers an unprecedented view into how their products are performing. The EU-funded IoTwins project plans to build testbeds for digital twins in order to run real-time computation as close to the data origin as possible (e.g., IoT Gateway or Edge nodes), and whilst batch-wise tasks such as Big Data analytics and Machine Learning model training are advised to run on the Cloud, where computing resources are abundant. In this paper, the basic concepts of the IoTwins project, its reference architecture, functionalities and components have been presented and discussed

Persistent immune stimulation exacerbates genetically driven myeloproliferative disorders via stromal remodeling

Systemic immune stimulation has been associated with increased risk of myeloid malignancies, but the pathogenic link is unknown. We demonstrate in animal models that experimental systemic immune activation alters the bone marrow stromal microenvironment, disarranging extracellular matrix (ECM) microarchitecture, with downregulation of secreted protein acidic and rich in cysteine (SPARC) and collagen-I and induction of complement activation. These changes were accompanied by a decrease in Treg frequency and by an increase in activated effector T cells. Under these conditions, hematopoietic precursors harboring nucleophosmin-1 (NPM1) mutation generated myeloid cells unfit for normal hematopoiesis but prone to immunogenic death, leading to neutrophil extracellular trap (NET) formation. NET fostered the progression of the indolent NPM1-driven myeloproliferation toward an exacerbated and proliferative dysplastic phenotype. Enrichment in NET structures was found in the bone marrow of patients with autoimmune disorders and in NPM1-mutated acute myelogenous leukemia (AML) patients. Genes involved in NET formation in the animal model were used to design a NET-related inflammatory gene signature for human myeloid malignancies. This signature identified two AML subsets with different genetic complexity and different enrichment in NPM1 mutation and predicted the response to immunomodulatory drugs. Our results indicate that stromal/ECM changes and priming of bone marrow NETosis by systemic inflammatory conditions can complement genetic and epigenetic events towards the development and progression of myeloid malignancy

Different biological and prognostic breast cancer populations identified by FDG-PET in sentinel node-positive patients: Results and clinical implications after eight-years follow-up

Abstract Background Sentinel node (SN) biopsy is the standard method to evaluate axillary node involvement in breast cancer (BC). Positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (FDG-PET) provides a non-invasive tool to evaluate regional nodes in BC in a metabolic-dependent, biomolecular-related way. In 1999, we initiated a prospective non-randomized study to compare these two methods and to test the hypothesis that FDG-PET results reflect biomolecular characteristics of the primary tumor, thereby yielding valuable prognostic information. Patients and methods A total of 145 cT1N0 BC patients, aged 24–70 years, underwent FDG-PET and lymphoscintigraphy before surgery. SN biopsy was followed in all cases by complete axillary dissection. Pathologic evaluation in tissue sections for involvement of the SN and other non-SN nodes served as the basis of the comparison between FDG-PET imaging and SN biopsy. Results FDG-PET and SN biopsy sensitivity was 72.6% and 88.7%, respectively, and negative predictive values were 80.5% and 92.2%, respectively. A subgroup of more aggressive tumors (ER-GIII, Her2+) was found mainly in the FDG-PET true-positive (FDG-PET+) patients, whereas LuminalA, Mib1 low-rate BCs were significantly undetected ( p = 0.009) in FDG-PET false-negative (FDG-PET−) patients. Kaplan–Meier survival estimates after a median follow-up of more than 8 years showed significantly worse overall survival for FDG-PET+ patients in node-positive (N+) patients ( p = 0.035) as compared to N+/FDG-PET− patients, which overlapped with survival curves of N− and FDG-PET+ or − patients. Conclusions Our findings suggest that FDG-PET results reflect intrinsic biologic features of primary BC tumors and have prognostic value with respect to nodal metastases. FDG-PET false negative cases appear to identify less aggressive indolent metastases. The possibility to identify a subgroup of N+ BC patients with an outcome comparable with N− BC patients could reduce the surgical and adjuvant therapeutic intervention

Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma

The International Extranodal Lymphoma Study Group (IELSG) 26 study was designed to evaluate the role of (18)F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) in the management of primary mediastinal (thymic) large B-cell lymphoma (PMBCL). We examined the prognostic impact of functional PET parameters at diagnosis. Metabolic activity defined by the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) was measured on baseline 18FDG PET/CT following a standard protocol in a prospectively enrolled cohort of 103 PMBCL patients. All received combination chemoimmunotherapy with doxorubicin- and rituximab-based regimens; 93 had consolidation radiotherapy. Cutoff values were determined using the receiver-operating characteristic curve. At a median follow-up of 36 months, progression-free survival (PFS) and overall survival (OS) were 87% and 94%, respectively. In univariate analysis, elevated MTV and TLG were significantly associated with worse PFS and OS. Only TLG retained statistical significance for both OS (P = .001) and PFS (P < .001) in multivariate analysis. At 5 years, OS was 100% for patients with low TLG vs 80% for those with high TLG (P = .0001), whereas PFS was 99% vs 64%, respectively (P < .0001). TLG on baseline PET appeared to be a powerful predictor of PMBCL outcomes and warrants further validation as a biomarker. The IELSG 26 study was registered at www.clinicaltrials.gov as #NCT00944567

Whole genome sequence analysis of Brucella abortus isolates from various regions of South Africa

The availability of whole genome sequences in public databases permits genome-wide comparative studies of various bacterial species. Whole genome sequence-single nucleotide polymorphisms (WGS-SNP) analysis has been used in recent studies and allows the discrimination of various Brucella species and strains. In the present study, 13 Brucella spp. strains from cattle of various locations in provinces of South Africa were typed and discriminated. WGS-SNP analysis indicated a maximum pairwise distance ranging from 4 to 77 single nucleotide polymorphisms (SNPs) between the South African Brucella abortus virulent field strains. Moreover, it was shown that the South African B. abortus strains grouped closely to B. abortus strains from Mozambique and Zimbabwe, as well as other Eurasian countries, such as Portugal and India. WGS-SNP analysis of South African B. abortus strains demonstrated that the same genotype circulated in one farm (Farm 1), whereas another farm (Farm 2) in the same province had two different genotypes. This indicated that brucellosis in South Africa spreads within the herd on some farms, whereas the introduction of infected animals is the mode of transmission on other farms. Three B. abortus vaccine S19 strains isolated from tissue and aborted material were identical, even though they originated from different herds and regions of South Africa. This might be due to the incorrect vaccination of animals older than the recommended age of 4–8 months or might be a problem associated with vaccine production.SUPPLEMENTARY TABLES: Table S1: Sample order used in Bruce-ladder (A) and AMOS (B) multiplex PCR assays and the descriptive information of the gel images, Table S2: Clean unique variants of the South African strains (refer to Table 2 for the sample names (in column 1) and sample ID (in column 2)).The Gauteng Department of Agriculture and Rural Development (GDARD), National Research Foundation, South Africa and Institute of Tropical Medicine, Belgium.https://www.mdpi.com/journal/microorganismsam2022Veterinary Tropical Disease