Experimental analysis of "bovedas tabicadas"

A particular type of vaulted structures, known as b\uf3vedas tabicadas (Catalan vaults), made with alternate layers of bricks and mortar and characterized by a very low thickness in comparison to the other two dimensions, are studied. The research has been faced under the historical aspect as well as under the mechanical one, developing experimental and numerical analysis regarding real existing structures. In particular, the experimental analysis, performed by effecting compression and bending tests on samples taken from a real structure, has been devoted to the constitutive material identification and the characterization is made by considering the material as an ideal homogeneous; further experimental tests have been made on a real vault and the related numerical analyses have been developed by utilizing a suitable FEM discretization

On fractional Choquard equations

We investigate a class of nonlinear Schrodinger equations with a generalized Choquard nonlinearity and fractional diffusion. We obtain regularity, existence, nonexistence, symmetry as well as decays properties.Comment: revised version, 22 page

BAG3 (Bcl-2 associated athanogene 3)

Bcl2-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that interacts with the ATPase domain of the heat shock protein (Hsp) 70 through BAG domain. BAG3 is induced by stressful stimuli, mainly through the activity of heat shock factor 1 on bag3 gene promoter.In addition to the BAG domain, BAG3 contains also a WW domain and a proline-rich (PXXP) repeat, that mediate binding to partners different from Hsp70.These multifaceted interactions underlie BAG3 ability to modulate major biological processes, that is, apoptosis, development, cytoskeleton organization and autophagy, thereby mediating cell adaptive responses to stressful stimuli. In normal cells, BAG3 is constitutively present in a very few cell types, including cardiomyocytes and skeletal muscle cells, in which the protein appears to contribute to cell resistance to mechanical stress. BAG3 is expressed also in several tumor types where it sustains cell survival, resistance to therapy, and/or motility and metastatization (Rosati et al., 2011)

The Impact of Repeated Abutment Changes on Peri-implant Tissue Stability: Five-year Post-loading Results From a Multicentre Randomised Controlled Trial

PURPOSE. To evaluate the impact of at least three abutment disconnections on hard and soft tissues around conventionally loaded implants versus definitive immediately non-oc-clusally loaded abutments in implants. A secondary aim was to evaluate whether the presence of less than 2 mm of keratinised mucosa is associated with increased soft tissue recession and/or peri-implant marginal bone loss. MATERIALS AND METHODS. Eighty patients requiring one single crown or one fixed partial prosthesis supported by a maximum of three implants were randomised, after implant placement at greater than 35 Ncm, according to a parallel-group design to receive either definitive immediately loaded abutments (definitive abutment or immediate loading group) or transmucosal abutments which were loaded after a delay of 3 months and removed at least three times. Patients were treated in four centres, and each patient contributed to the study with only one prosthesis, which was followed up for 5 years after initial loading. Outcome measures were: prosthesis failures, implant failures, complica-tions, pink aesthetic score (PES), buccal recessions, patient satisfaction, peri-implant marginal bone-level changes and height of the keratinised mucosa. RESULTS. Forty patients were randomly allocated to each group according to a paral-lel-group design. Seven patients from the definitive abutment group versus six from the repeated disconnection group dropped out or died. No patient from the definitive group had implant failures versus three patients who lost five implants in the repeated disconnection group (difference = 9.1%; CI95%:-0.7% to 18.9% to; P = 0.227). Nine patients from the repeated disconnection group lost or had to have their prosthesis remade (four provisional and five definitive prostheses) versus one provisional prosthesis failure in the definitive abutment group; this difference was statistically significant (difference = 23.5%; CI95%: 7.6% to 39.4%; P = 0.017), but was due to the erroneous use of non-indexed abutments in indexed implants in patients from the repeated disconnection group alone. Seven patients from the definitive abutment group versus nine patients from the repeated disconnection group were affected by complications (difference =-5.9%; CI95%:-26.0% to 14.2%; P = 0.775), the difference being not statistically significant. PES scores assessed at 5 years post-loading were 12.1±1.8 for the definitive abutment group and 11.9±1.7 for the repeated abutment changes group (difference = 0.2; CI95%:-0.7 to 1.1; P = 0.615); however, there was a statistically significant difference of 0.20 out of a maximum score of 2 in favour of the definitive abutment group for soft tissue contour alone (P = 0.045). Buccal recessions at 5 years post-loading amounted to-0.19±0.77 mm for the definitive abutment group and-0.07±1.24 mm for the repeated abutment changes group (difference = 0.12 mm CI95%:-0.42 to 0.66; P = 0.662). All patients declared being very satisfied or sati-sfied with the function and aesthetics of their prosthesis and would undergo the same procedure again. Mean peri-implant marginal bone loss 5 years after loading was 0.11±0.30 mm for the definitive abutment group and 0.48±0.73 mm for the repeated abutment change group (difference =-0.37 [SE=0.14] mm; CI95%:-0.66 to-0.09; P = 0.012), the difference being statistically significant. The height of keratinised mucosa at 5 years post-loading was 2.81±1.46 mm in the definitive abutment group and 2.83±1.84 mm in the repeated abutment change group (difference =-0.02 mm; CI95%:-0.85 to 0.80; P = 0.956), and there were no significant differences in marginal bone loss (difference = 0.00 mm; CI95%:-0.32 to 0.32, P = 0.990) or buccal recession (difference = 0.05 mm, CI95%:-0.43 to 0.54, P = 0.826) at implants having less than 2 mm of keratinised mucosa at loading compared to those having more than 2 mm of keratinised mucosa. CONCLUSIONS. Five-year post-loading data show that at least three repeated abutment disconnections significantly increased bone loss by 0.37 mm when compared to no di-sconnection, but this difference may not be clinically significant. While it might be advi-sable to avoid unnecessary abutment disconnection whenever possible, if disconnections are required, no clinically significant side effects may be expected. Immediately non-oc-clusally loaded dental implants are a viable alternative to conventional loading, and no increased bone loss or buccal recessions were noted even at implants with less than 2 mm of keratinised mucosa

Accurate detection and quantification of SARS-CoV-2 genomic and subgenomic mRNAs by ddPCR and meta-transcriptomics analysis

SARS-CoV-2 replication requires the synthesis of a set of structural proteins expressed through discontinuous transcription of ten subgenomic mRNAs (sgmRNAs). Here, we have fine-tuned droplet digital PCR (ddPCR) assays to accurately detect and quantify SARS-CoV-2 genomic ORF1ab and sgmRNAs for the nucleocapsid (N) and spike (S) proteins. We analyzed 166 RNA samples from anonymized SARS-CoV-2 positive subjects and we observed a recurrent and characteristic pattern of sgmRNAs expression in relation to the total viral RNA content. Additionally, expression profiles of sgmRNAs, as determined by meta-transcriptomics sequencing of a subset of 110 RNA samples, were highly correlated with those obtained by ddPCR. By providing a comprehensive and dynamic snapshot of the levels of SARS-CoV-2 sgmRNAs in infected individuals, our results may contribute a better understanding of the dynamics of transcription and expression of the genome of SARS-CoV-2 and facilitate the development of more accurate molecular diagnostic tools for the stratification of COVID-19 patients

miR-29b and miR-198 overexpression in CD8⁺ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction

Background: Mammalian microRNAs (miR) regulate the expression of genes relevant for the development of adaptive and innate immunity against cancer. Since T cell dysfunction has previously been reported in patients with renal cell carcinoma (RCC; clear cell type), we aimed to analyze these immune cells for genetic and protein differences when compared to normal donor T cells freshly after isolation and 35 days after in vitro stimulation (IVS) with HLA-matched RCC tumor cells. Methods: We investigated gene expression profiles of tumor-reactive CD8+ T cells obtained from RCC patient and compared with their HLA-matched healthy sibling donors using a microarray approach. In addition, miRNAs analysis was performed in a validation cohort of peripheral blood CD8+ T cells from 25 RCC patients compared to 15 healthy volunteers. Results: We observed that CD8+ T cells from RCC patients expressed reduced levels of anti-apoptotic and proliferation-associated gene products when compared with normal donor T cells both pre- and post-IVS. In particular, JAK3 and MCL-1 were down-regulated in patient CD8+ T cells versus their normal counterparts, likely due to defective suppressor activity of miR-29b and miR-198 in RCC CD8+ T cells. Indeed, specific inhibition of miR-29b or miR-198 in peripheral blood mononuclear cells (PBMCs) isolated from RCC patients, resulted in the up-regulation of JAK3 and MCL-1 proteins and significant improvement of cell survival in vitro. Conclusions: Our results suggest that miR-29b and miR-198 dysregulation in RCC patient CD8+ T cells is associated with dysfunctional immunity and foreshadow the development of miR-targeted therapeutics to correct such T cell defects in vivo

miR-29b and miR-198 overexpression in CD8+ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction.

Background: Mammalian microRNAs (miR) regulate the expression of genes relevant for the development of adaptive and innate immunity against cancer. Since T cell dysfunction has previously been reported in patients with renal cell carcinoma (RCC; clear cell type), we aimed to analyze these immune cells for genetic and protein differences when compared to normal donor T cells freshly after isolation and 35 days after in vitro stimulation (IVS) with HLAmatched RCC tumor cells. Methods: We investigated gene expression profiles of tumor-reactive CD8+ T cells obtained from RCC patient and compared with their HLA-matched healthy sibling donors using a microarray approach. In addition, miRNAs analysis was performed in a validation cohort of peripheral blood CD8+ T cells from 25 RCC patients compared to 15 healthy volunteers. Results: We observed that CD8+ T cells from RCC patients expressed reduced levels of anti-apoptotic and proliferation- associated gene products when compared with normal donor T cells both pre- and post-IVS. In particular, JAK3 and MCL-1 were down-regulated in patient CD8+ T cells versus their normal counterparts, likely due to defective suppressor activity of miR-29b and miR-198 in RCC CD8+ T cells. Indeed, specific inhibition of miR-29b or miR-198 in peripheral blood mononuclear cells (PBMCs) isolated from RCC patients, resulted in the up-regulation of JAK3 and MCL-1 proteins and significant improvement of cell survival in vitro. Conclusions: Our results suggest that miR-29b and miR-198 dysregulation in RCC patient CD8+ T cells is associated with dysfunctional immunity and foreshadow the development of miR-targeted therapeutics to correct such T cell defects in vivo

Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: A retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database

Aims Oral glucose-lowering medications are associated with excess risk of heart failure (HF). Given the absence of comparative data among drug classes, we performed a retrospective study in 32 Health Services of 16 Italian regions accounting for a population of 18 million individuals, to assess the association between HF risk and use of sulphonylureas, DPP-4i, and glitazones. Methods and results We extracted data on patients with type 2 diabetes who initiated treatment with DPP-4i, thiazolidinediones, or sulphonylureas alone or in combination with metformin during an accrual time of 2 years. The endpoint was hospitalization for HF (HHF) occurring after the first 6 months of therapy, and the observation was extended for up to 4 years. A total of 127 555 patients were included, of whom 14.3% were on DPP-4i, 72.5% on sulphonylurea, 13.2% on thiazolidinediones, with average 70.7% being on metformin as combination therapy. Patients in the three groups differed significantly for baseline characteristics: age, sex, Charlson index, concurrent medications, and previous cardiovascular events. During an average 2.6-year follow-up, after adjusting for measured confounders, use of DPP-4i was associated with a reduced risk of HHF compared with sulphonylureas [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.62-0.97; P = 0.026]. After propensity matching, the analysis was restricted to 39 465 patients, and the use of DPP-4i was still associated with a lower risk of HHF (HR 0.70; 95% CI 0.52-0.94; P = 0.018). Conclusion In a very large observational study, the use of DPP-4i was associated with a reduced risk of HHF when compared with sulphonylureas

BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential

Existence results for a doubly nonlocal equation

In this note we expose some results proved in d’Avenia et al. [8] concerning an elliptic problem in RN which involves two nonlocal operators: the fractional Laplacian and a convolution term of Hartree type. This equation has been called fractional Choquard equation. The results obtained concern regularity of weak solutions, existence and properties of ground states, as well as multiplicity and nonexistence of solutions