Endothelin-dependent vasoconstrictor activity in metabolically healthy and unhealthy obese patients

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Physical exercise and synaptic protection in human and pre-clinical models of multiple sclerosis

: In multiple sclerosis, only immunomodulatory and immunosuppressive drugs are recognized as disease-modifying therapies. however, in recent years, several data from pre-clinical and clinical studies suggested a possible role of physical exercise as disease-modifying therapy in multiple sclerosis. current evidence is sparse and often conflicting, and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated. Data, mainly derived from pre-clinical studies, suggest that exercise could enhance long-term potentiation and thus neuroplasticity, could reduce neuroinflammation and synaptopathy, and dampen astrogliosis and microgliosis. In humans, most trials focused on direct clinical and MRI outcomes, as investigating synaptic, neuroinflammatory, and pathological changes is not straightforward compared to animal models. the present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies

Brown Tumour in a Patient with Secondary Hyperparathyroidism Resistant to Medical Therapy: Case Report on Successful Treatment after Subtotal Parathyroidectomy

Brown tumour represents a serious complication of hyperparathyroidism. Differential diagnosis, based on histological examination, is only presumptive and clinical, radiological and laboratory data are necessary for definitive diagnosis. Here we describe a case of a brown tumour localised in the maxilla due to secondary hyperparathyroidism in a young women with chronic renal failure. Hemodialysis and pharmacological treatment were unsuccessful in controlling secondary hyperparathyroidism making it necessary to proceed with a subtotal parathyroidectomy. The proper timing of the parathyroidectomy and its favourable effect on regression of the brown tumor made it possible to avoid a potentially disfiguring surgical removal of the brown tumor

Differences in the vascular and metabolic profiles between metabolically healthy and unhealthy obesity

Abstract Individuals suffering from severe obesity but not presenting the typical metabolic alterations, are included in a subclass of obesity defined Metabolically Healthy Obesity (MHO). The physiological factors underlying what seems a protective and favourable metabolic profile remain unclear. MHO individuals are more insulin-sensitive, have relatively lower visceral/ectopic fat accumulation and reduced levels of chronic low-grade inflammation, compared to obese subjects with co-morbidities. The study of MHO subjects represents a great opportunity for the recognition of the mechanisms that lead to the vascular and metabolic complications in obesity. Finding the differences among the metabolic profile of visceral adipose tissue between metabolically healthy and unhealthy obesity may lead to future personalized and stratified therapies.This review article summarizes the pathomechanisms and metabolic changes in MHO and metabolically unhealthy obesity (MUO), reviews clinical studies on the subject, and discusses preventive and therapeutic options

Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma

renal cell carcinoma originates from the lining of the proximal convoluted renal tubule and represents the most common type of kidney cancer. risk factors and comorbidities might be associated to renal cell carcinoma, while a small fraction of 2-3% emerges from patients with predisposing cancer syndromes, typically associated to hereditary mutations in VHL, folliculin, fumarate hydratase or MET genes. here, we report a case of renal cell carcinoma in patient with concurrent germline mutations in BRCA1 and RAD51 genes. this case displays an unusual high mutational burden and chromosomal aberrations compared to the typical profile of renal cell carcinoma. mutational analysis on whole genome sequencing revealed an enrichment of the MMR2 mutational signature, which is indicative of impaired DNA repair capacity. overall, the tumor displayed a profile of unusual high genomic instability which suggests a possible origin from germline predisposing mutations in the DNA repair genes BRCA1 and RAD51. while BRCA1 and RAD51 germline mutations are well-characterised in breast and ovarian cancer, their role in renal cell carcinoma is still largely unexplored. the genomic instability detected in this case of renal cell carcinoma, along with the presence of unusual mutations, might offer support to clinicians for the development of patient-tailored therapies

A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient

: Triple-negative breast cancer (TNBC) is the most aggressive subtype of mammary carcinoma. Here, we describe a case of an 81-year-old female diagnosed with ductal triple negative breast cancer with a germline pathogenic variant in BReast CAncer gene2 (BRCA2). Genetic testing also revealed the presence of four somatic mutations in the ephrin type-A receptor 3 (EphA3), TP53, BRCA1-associated protein (BAP1), and MYB genes. The BRCA2, TP53, and BAP1 gene mutations are highly predictive of a defective homologous recombination repair system and subsequent chromosomal instability in this patient. Coherently, the patient displayed a strong homologous recombination deficiency signature and high tumor mutational burden status, which are generally associated with increased probability of immune neoantigens formation and presentation, and with tumor immunogenicity. Analysis of immune checkpoint revealed high expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), programmed death 1 (PD1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), suggesting that the patient might likely benefit from immunotherapies. Altogether, these findings support an unveiled link between BRCA2 inactivation, HR deficiency and increased expression of immune checkpoints in TNBC. This clinical case highlights the importance of screening TNBC patients for genetic mutations and TMB biomarkers in order to predict the potential efficacy of immunotherapy

Case Report Brown Tumour in a Patient with Secondary Hyperparathyroidism Resistant to Medical Therapy: Case Report on Successful Treatment after Subtotal Parathyroidectomy

Brown tumour represents a serious complication of hyperparathyroidism. Differential diagnosis, based on histological examination, is only presumptive and clinical, radiological and laboratory data are necessary for definitive diagnosis. Here we describe a case of a brown tumour localised in the maxilla due to secondary hyperparathyroidism in a young women with chronic renal failure. Hemodialysis and pharmacological treatment were unsuccessful in controlling secondary hyperparathyroidism making it necessary to proceed with a subtotal parathyroidectomy. The proper timing of the parathyroidectomy and its favourable effect on regression of the brown tumor made it possible to avoid a potentially disfiguring surgical removal of the brown tumor

New insights to assess the consolidation of stone materials used in built heritage: the case study of ancient graffiti (Tituli Picti) in the archaeological site of Pompeii

Abstract Tituli Picti are an ancient form of urban graffiti very common in the archaeological site of Pompeii (Naples, South—Italy). They are generally made of red pigments applied on walls of Campanian ignimbrite. This paper deals with a scientific investigation aimed to their conservation. This is a challenging task since it requires a multidisciplinary approach that includes restorers, archaeologists and conservation scientists. The study has provided suggestions on the proper way to conserve Tituli Picti over time. In the present work, several specimens of Campanian ignimbrite were painted with red earth pigment; lime and Arabic gum have been used as binders as well. Such painted stones were treated with three consolidants: a suspension of reactive nanoparticles of silica, ethyl silicate and an acrylic microemulsion. Treated and untreated specimens were subjected to thermal aging, artificial solar radiation and induced crystallization decay. It has been assessed the colorimetric variations induced by treatments. Moreover, the micromorphologic features of the consolidated surfaces have been highlighted by means of electron microscope observations. The scotch tape test allowed to compare the superficial cohesion induced by the three used products. According to the results, ethyl silicate seems to represent the most successful product

Aged mesenchymal stem cells and inflammation: from pathology to potential therapeutic strategies

Natural ageing of organisms and corresponding age-related diseases result mainly from stem cell ageing and "inflammaging". Mesenchymal stem cells (MSCs) exhibit very high immune-regulating capacity and are promising candidates for immune-related disease treatment. However, the effect of MSC application is not satisfactory for some patients, especially in elderly individuals. With ageing, MSCs undergo many changes, including altered cell population reduction and differentiation ability, reduced migratory and homing capacity and, most important, defective immunosuppression. It is necessary to explore the relationship between the "inflammaging" and aged MSCs to prevent age-related diseases and increase the therapeutic effects of MSCs. In this review, we discuss changes in naturally ageing MSCs mainly from an inflammation perspective and propose some ideas for rejuvenating aged MSCs in future treatments