Finite Fracture Mechanics extension to dynamic loading scenarios

The coupled criterion of Finite Fracture Mechanics (FFM) has already been successfully applied to assess the brittle failure initiation in cracked and notched structures subjected to quasi-static loading conditions. The FFM originality lies in addressing failure onset through the simultaneous fulfilment of a stress requirement and the energy balance, both computed over a finite distance ahead of the stress raiser. Accordingly, this length results to be a structural parameter, thus able to interact with the geometry under investigation. This work aims at extending the FFM failure criterion to dynamic loadings. To this end, the general requisites of a proper dynamic failure criterion are first shortlisted. The novel Dynamic extension of FFM (DFFM) is then put forward assuming the existence of a material time interval that is related to the coalescence period of microcracks upon macroscopic failure. On this basis, the DFFM model is investigated in case a one-to-one relation between the external solicitation and both the dynamic stress field and energy release rate holds true. Under such a condition, the DFFM is also validated against suitable experimental data on rock materials from the literature and proven to properly catch the increase of the failure load as the loading rate rises, thus proving to be a novel technique suitable for modelling the rate dependence of failure initiation in brittle and quasi-brittle materials

Transcriptional regulation of ascorbic acid during fruit ripening in pepper (Capsicum annuum) varieties with low and high antioxidants content

Research on plant antioxidants, such as ascorbic acid (AsA) and polyphenols, is of increasing interest in plant science because of the health benefits and preventive role in chronic diseases of these natural compounds. Pepper (Capiscum annuum L.) is a major dietary source of antioxidants, especially AsA. Although considerable advance has been made, our understanding of AsA biosynthesis and its regulation in higher plants is not yet exhaustive. For instance, while it is accepted that AsA content in cells is regulated at different levels (e.g., transcriptional and post-transcriptional), their relative prominence is not fully understood. In this work, we identified and studied two pepper varieties with low and high levels of AsA to shed light on the transcriptional mechanisms that can account for the observed phenotypes. We quantified AsA and polyphenols in leaves and during fruit maturation, and concurrently, we analyzed the transcription of 14 genes involved in AsA biosynthesis, degradation, and recycling. The differential transcriptional analysis indicated that the higher expression of genes involved in AsA accumulation is a likely explanation for the observed differences in fruits. This was also supported by the identification of gene-metabolite relations, which deserve further investigation. Our results provide new insights into AsA differential accumulation in pepper varieties and highlight the phenotypic diversity in local germplasm, a knowledge that may ultimately contribute to the increased level of health-related phytochemicals

Autoimmune thyroid disorders

Autoimmune thyroid diseases (AITD) result from a dysregulation of the immune system leading to an immune attack on the thyroid. AITD are T cell-mediated organ-specific autoimmune disorders. The prevalence of AITD is estimated to be 5%; however, the prevalence of antithyroid antibodies may be even higher. The AITD comprise two main clinical presentations: Graves' disease (GD) and Hashimoto's thyroiditis (HT), both characterized by lymphocytic infiltration of the thyroid parenchyma. The clinical hallmarks of GD and HT are thyrotoxicosis and hypothyroidism, respectively. The mechanisms that trigger the autoimmune attack to the thyroid are still under investigation. Epidemiological data suggest an interaction among genetic susceptibility and environmental triggers as the key factor leading to the breakdown of tolerance and the development of disease. Recent studies have shown the importance of cytokines and chemokines in the pathogenesis of AT and GD. In thyroid tissue, recruited T helper 1 (Th1) lymphocytes may be responsible for enhanced IFN-γ and TNF-α production, which in turn stimulates CXCL10 (the prototype of the IFN-γ-inducible Th1 chemokines) secretion from the thyroid cells, therefore creating an amplification feedback loop, initiating and perpetuating the autoimmune process. Associations exist between AITD and other organ specific (polyglandular autoimmune syndromes), or systemic autoimmune disorders (Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, cryoglobulinemia, sarcoidosis, psoriatic arthritis). Moreover, several studies have shown an association of AITD and papillary thyroid cancer. These data suggest that AITD patients should be accurately monitored for thyroid dysfunctions, the appearance of thyroid nodules, and other autoimmune disorders

Bone Involvement in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide variability of clinical manifestations due to the potential involvement of several tissues and internal organs, with a relapsing and remitting course. Dysregulation of innate and adaptive immune systems, due to genetic, hormonal and environmental factors, may be responsible for a broad spectrum of clinical manifestations, affecting quality of life, morbidity and mortality. Bone involvement represents one of the most common cause of morbidity and disability in SLE. Particularly, an increased incidence of osteoporosis, avascular necrosis of bone and osteomyelitis has been observed in SLE patients compared to the general population. Moreover, due to the improvement in diagnosis and therapy, the survival of SLE patient has improved, increasing long-term morbidities, including osteoporosis and related fractures. This review aims to highlight bone manifestations in SLE patients, deepening underlying etiopathogenetic mechanisms, diagnostic tools and available treatment

Increase of interferon-γ inducible α chemokine (C-X-C motif) ligand (CXCL)9 and CXCL11 serum levels in patients with active Graves' disease, and modulation by methimazole therapy.

Background: Chemokine (C-X-C motif) ligand (CXCL)9 and CXCL11 play an important role in the initial phases of autoimmune thyroiditis (AT); however their serum levels in patients with Graves'disease (GD) have never been evaluated in relation to thyroid function and treatment. Methods: To evaluate CXCL9 and CXCL11 serum levels in GD, to relate these parameters to the clinical phenotype, we measured CXCL9 and CXCL11 serum levels in 91 GD patients, 91 AT, 34 non-toxic multinodular goiters (MNG), 31 toxic nodular goiters (TNG) and 91 healthy controls (age- and sex-matched). Results: Mean CXCL9, or CXCL11, levels were higher in GD, in comparison with controls, or euthyroid AT, or MNG, or TNG (*p < 0.05, ANOVA; CXCL9: 274±265, *76±33, *132±78, *87±48, *112±56 pg/mL; CXCL11: 140±92, *64±20, 108±48, *76±33, *91±41 pg/mL; respectively). Hyperthyroid GD had significantly higher CXCL9 or CXCL11 than euthyroid or hypothyroid GD. GD with untreated hyperthyroidism had higher CXCL9 or CXCL11 than hyperthyroid or euthyroid GD under methimazole (MMI) treatment. Comparable CXCL9 and CXCL11 levels were observed in newly diagnosed untreated hyperthyroid GD vs. untreated patients with relapse of hyperthyroidism after a previous MMI course. Conclusions: Serum CXCL9, and CXCL11, levels are associated with the active phase of GD both in newly diagnosed and relapsing hyperthyroid patients. The reduction of serum CXCL9 and CXCL11 levels in treated patients with GD may be related to the immunomodulatory effects of MMI

Anti-cyclic-citrullinated-protein-antibodies in psoriatic arthritis patients: how autoimmune dysregulation could affect clinical characteristics, retention rate of methotrexate monotherapy and first line biotechnological drug survival. A single center retrospective study

Aim: Occasional findings of anti-cyclic-citrullinated-protein-antibodies (anti-CCP) were rarely observed in psoriatic arthritis (PsA). The aim of our study is to evaluate whether the presence of anti-CCP can determine different clinical subsets and influence methotrexate monotherapy survival, and biotechnological drug retention rate. Methods: We conducted a retrospective study on PsA patients. All patients were required to fulfill the CASPAR criteria for PsA, and to present juxta-articular osteo-proliferative signs at X-ray. The exclusion criteria were age less than 18 years old, satisfaction of rheumatoid arthritis classification criteria, and seropositivity for rheumatoid factor. Clinical characteristics, anti-CCP titer, drug survival and comorbidities information were recorded for each patient. Statistical significance was set at p ⩽ 0.05. Results: Of 407 patients with PsA screened 113 were recruited. Twelve patients were anti-CCP positive. Methotrexate monotherapy survival was shorter in patients with anti-CCP (150 ± 48.3 weeks versus 535.3 ± 65.3 weeks; p = 0.026) [discontinuation risk hazard ratio (HR) = 2.389, 95% confidence interval (CI) 1.043, 5.473; p = 0.039] than those without. Significant shorter survival of first-line biotechnological drugs (b-DMARDs) was observed in the anti-CCP positive group than in that without (102.05 ± 24.4 weeks versus 271.6 ± 41.7 weeks; p = 0.005) with higher discontinuation risk (HR = 3.230, 95% CI 1.299, 8.028; p = 0.012). A significant higher rate of multi-failure (more than second-line b-DMARDs) was found in anti-CCP positive patients than in those without (50% versus 14%, p = 0.035). Conclusion: Anti-CCP in PsA could be suggestive of more severe disease, with worse drug survival of both methotrexate monotherapy and first-line b-DMARDs, and higher chance to be b-DMARDs multi-failure. So, they can be considered for more intensive clinical management of these patients

CXCR3, CXCR5, CXCR6, and CXCR7 in Diabetes

Many studies have suggested that CXCR3, CXCR5, CXCR6 and CXCR7 chemokine receptors are determinant in type 1 diabetes (T1D), expecially in autoimmunity and β-cell destruction. In particular circulating CXCL10 level (the ligand of CXCR3) is high in T1D patients, and this suggests that CXCL10 may be a candidate for a predictive marker of T1D. Blocking the CXCL10/CXCR3 axis in newly onset of diabetes seems to be a potential strategy for the therapy of T1D. Attempts have been done in modulating or blocking CXCR5, CXCR6 and CXCR7 chemokine receptors in experimental settings of T1D. More researches are necessary to evaluate the interplay among cytokines, chemokines and the pathogenesis and therapy of T1D