Potential renal acid load and the risk of renal stone formation in a case–control study

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Contribution of polymorphic variation of inositol hexakisphosphate kinase 3 (IP6K3) gene promoter to the susceptibility to late onset Alzheimer's disease

Maintenance of electric potential and synaptic transmission are energetically demanding tasks that neuronal metabolism must continually satisfy. Inability to fulfil these energy requirements leads to the development of neurodegenerative disorders, including Alzheimer's disease. A prominent feature of Alzheimer's disease is in fact neuronal glucose hypometabolism. Thus understanding the fine control of energetic metabolism might help to understand neurodegenerative disorders. Recent research has indicated that a novel class of signalling molecules, the inositol pyrophosphates, act as energy sensors. They are able to alter the balance between mitochondrial oxidative phosphorylation and glycolytic flux, ultimately affecting the cellular level of ATP. The neuronal inositol pyrophosphate synthesis relies on the activity of the neuron enriched inositol hexakisphosphate kinase 3 (IP6K3) enzyme. To verify an involvement of inositol pyrophosphate signalling in neurodegenerative disorders, we performed tagging single nucleotide polymorphism (SNP) analysis of the IP6K3 gene in patients with familial and sporadic late onset Alzheimer's disease (LOAD). Two SNPs in the 5'-flanking promoter region of the IP6K3 gene were found to be associated with sporadic LOAD. Characterizing the functionality of the two polymorphisms by luciferase assay revealed that one of them (rs28607030) affects IP6K3 promoter activity, with the G allele showing an increased activity. As the same allele has a beneficial effect on disease risk, this may be related to upregulation of IP6K3 expression, with a consequent increase in inositol pyrophosphate synthesis. In conclusion, we provide the first evidence for a contribution of genetic variability in the IP6K3 gene to LOAD pathogenesis

INFLUENZA DELLA SALDATURA LASER SUL COMPORTAMENTO A MEMORIA DI FORMA A DUE VIE DI UNA LEGA NiTi

Nel presente lavoro è riportato lo studio del comportamento funzionale di un giunto saldato in lega NiTi a memoria di forma. In particolare, sono stati analizzati gli effetti della saldatura laser Nd:YAG sul comportamento a memoria di forma a due vie (Two Way Shape Memory Effect, TWSME) di una lega Ni- 51 at.% Ti, attraverso un confronto sistematico con i risultati relativi al materiale non saldato. Il TWSME è stato indotto nel materiale attraverso un opportuna procedura di training, che consiste nella ripetizione di cicli termomeccanici; successivamente, sono stati misurati i cicli di isteresi (temperatura-deformazione) caratteristici del TWSME. Sono stati valutati, inoltre, gli effetti del numero di cicli di training e delle deformazioni plastiche, che si generano nel materiale durante il processo di training, sul comportamento a memoria di forma del materiale. I risultati mostrano come il comportamento funzionale, e in particolare il TWSME, sia parzialmente preservato nel materiale saldato che, comunque, presenta valori di deformazioni plastiche maggiori rispetto al materiale base

multiaxial fatigue behavior of additive manufactured ti 6al 4v under in phase stresses

Abstract The development and application of additive manufacturing (AM) technologies is constantly increasing. However, in many applications, AM parts are subjected to multiaxial loads, arising from operating conditions and/or complex geometries. These make AM components serious candidates for crack initiation and propagation mechanisms. Therefore, a deep understanding of the multiaxial fatigue behavior of AM parts is essential in many applications where durability and reliability are core issues. In this study, multiaxial fatigue of Ti6Al4V thin-walled tubular specimens, made by Selective Laser Melting (SLM) process, was investigated by combined axial-torsional loads. Infrared thermography (IR) was also used to investigate the temperature evolution during fatigue tests. Results highlighted different damage mechanisms and failure modes in the low- and high-cycle fatigue regimes

Predictor Analysis in Radiofrequency Ablation of Benign Thyroid Nodules: A Single Center Experience

PURPOSE: To confirm the efficacy of ultrasound (US) guided radiofrequency ablation (RFA) in the treatment of benign thyroid nodules, we evaluated as primary outcome the technical efficacy and clinical success in a single center dataset. The secondary outcome was to find a correlation between nodules’ pre-treatment features and volume reduction rate (VRR) ≥75% at 12 months after RFA and during follow-up period. METHODS: This retrospective study included 119 consecutive patients (99 females, 20 males, 51.5 ± 14.4 years) with benign thyroid nodules treated in our hospital between October 2014 and December 2018 with a mean follow-up of 26.8 months (range 3–48). Clinical and US features before and after RFA were evaluated by a US examination at 1, 3, 6, 12 months and annually thereafter up to 48 months. RESULTS: The median pre-treatment volume was 22.4 ml; after RFA we observed a statistically significant volume reduction from the first month (11.7 ml) to the last follow-up (p 22.4 ml (HR 0.54, p 0.036) were found to be independent positive and negative predictors of VRR ≥75% respectively. One-month post RFA VRR ≥50% represented the best positive predictor of technical success. CONCLUSIONS: This study confirmed the efficacy of RFA in the treatment of benign thyroid nodules. In particular we show that by selecting macrocystic nodules smaller than 22.4 ml better long-term response can be achieved, which is predicted by an early shrinkage of the nodule

Clinical characteristics of patients with endometrial cancer and adenomyosis

open11noA better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been reported. Unfortunately, it is still unclear if this better prognosis is related to a more favorable clinical profile of adenomyosis patients. We aimed to evaluate differences in the clinical profiles of EC patients with and without adenomyosis. A systematic review and meta-analysis was performed by searching seven electronics databases for all studies that allowed extraction of data about clinical characteristics in EC patients with and without adenomyosis. Clinical characteristics assessed were: age, Body Mass Index (BMI), premenopausal status, and nulliparity. Mean difference in mean ± standard deviation (SD) or odds ratio (OR) for clinical characteristics between EC patients with and without adenomyosis were calculated for each included study and as a pooled estimate, and graphically reported on forest plots with a 95% confidence interval (CI). The Z test was used for assessing the overall effect by considering a p value < 0.05 as significant. Overall, eight studies with 5681 patients were included in the qualitative analysis, and seven studies with 4366 patients in the quantitative analysis. Pooled mean difference in mean ± SD between EC women with and without adenomyosis was −1.19 (95% CI: −3.18 to 0.80; p = 0.24) for age, and 0.23 (95% CI: −0.62 to 1.07; p = 0.60) for BMI. When compared to EC women without adenomyosis, EC women with adenomyosis showed a pooled OR of 1.53 (95% CI: 0.92 to 2.54; p = 0.10) for premenopausal status, and of 0.60 (95% CI: 0.41 to 0.87; p = 0.007) for nulliparity. In conclusion, there are not significant differences in clinical characteristics between EC patients with and without adenomyosis, with the exception for nulliparity. Clinical features seem to not underlie the better EC prognosis of patients with adenomyosis compared to patients without adenomyosis.openCasadio P.; Raffone A.; Maletta M.; Travaglino A.; Raimondo D.; Raimondo I.; Santoro A.; Paradisi R.; Zannoni G.F.; Mollo A.; Seracchioli R.Casadio P.; Raffone A.; Maletta M.; Travaglino A.; Raimondo D.; Raimondo I.; Santoro A.; Paradisi R.; Zannoni G.F.; Mollo A.; Seracchioli R

Multiaxial fatigue behavior of additively manufactured Ti6Al4V alloy: Axial–torsional proportional loads

Additive manufacturing (AM) techniques are under constant development and selective laser melting (SLM) is among the most promising ones. However, widespread use of AM techniques in many industries is limited by the different/unusual mechanical properties of AM metallic parts, with respect to traditionally processed ones, especially when dealing with complex fatigue loading conditions. In fact, crack formation and propagation mechanisms are mainly affected by the development of internal defects, residual stresses, and microstructural changes. This is actually one of the major issues the materials engineering community is facing today. In many applications, AM components are subjected to multiaxial fatigue loads, arising from operating conditions and/or from complex geometries, that unavoidably generate crack initiation and propagation mechanisms. The aim of this study is to investigate the multiaxial fatigue behavior of additively manufactured Ti6Al4V samples, made by SLM. Fatigue tests, combining proportional axial and torsional loads, were performed on thin-walled tubular specimens. Full-field measurement techniques, such as the infrared thermography and digital image correlation, were also used to capture temperature and strain evolutions, at both local scales and global scales. Fatigue results highlighted damage mechanisms, and failure modes are strongly related to the applied stress level

Uterine carcinosarcoma vs endometrial serous and clear cell carcinoma: a systematic review and meta-analysis of survival

Background: It is unclear whether uterine carcinosarcoma (UCS) is more aggressive than endometrial serous carcinoma (SC) and clear cell carcinoma (CCC). Objectives: To compare the prognosis of UCS to that of endometrial SC and CCC, through a systematic review and meta-analysis. Methods: Four electronic databases were searched from January 2000 to October 2020. All studies assessing hazard ratio (HR) for death in UCS vs SC and/or CCC. HRs for death with 95% confidence interval were extracted and pooled by using a random-effect model. A significant P-value <0.05 was adopted. Results: Six studies with 11 029 patients (4995 with UCS, 4634 with SC, 1346 with CCC and 54 with either SC or CCC) were included. UCS showed a significantly worse prognosis than SC/CCC both overall (HR = 1.51; P = 0.008) and at early stage (HR = 1.58; P < 0.001). Similar results were found for UCS vs SC (HR = 1.53; P < 0.001) and UCS vs CCC (HR = 1.60; P < 0.001). Conclusions: Compared to SC and CCC, UCS has a significantly worse prognosis, with a 1.5–1.6-fold increased risk of death. This might justify a more aggressive treatment for UCS compared to SC and CCC. Further studies are necessary to define the prognostic impact of different molecular subgroups

Absence of Phase Stiffness in the Quantum Rotor Phase Glass

We analyze here the consequence of local rotational-symmetry breaking in the quantum spin (or phase) glass state of the quantum random rotor model. By coupling the spin glass order parameter directly to a vector potential, we are able to compute whether the system is resilient (that is, possesses a phase stiffness) to a uniform rotation in the presence of random anisotropy. We show explicitly that the O(2) vector spin glass has no electromagnetic response indicative of a superconductor at mean-field and beyond, suggesting the absence of phase stiffness. This result confirms our earlier finding (PRL, {\bf 89}, 27001 (2002)) that the phase glass is metallic, due to the main contribution to the conductivity arising from fluctuations of the superconducting order parameter. In addition, our finding that the spin stiffness vanishes in the quantum rotor glass is consistent with the absence of a transverse stiffness in the Heisenberg spin glass found by Feigelman and Tsvelik (Sov. Phys. JETP, {\bf 50}, 1222 (1979).Comment: 8 pages, revised version with added references on the vanishing of the stiffness constant in the Heisenberg spin glas

IP6K3 and IPMK variations in LOAD and longevity: evidence for a multifaceted signaling network at the crossroad between neurodegeneration and survival

Several studies reported that genetic variants predisposing to neurodegeneration were at higher frequencies in centenarians than in younger controls, suggesting they might favor also longevity. IP6K3 and IPMK regulate many crucial biological functions by mediating synthesis of inositol poly- and pyrophosphates and by acting non-enzymatically via protein–protein interactions. Our previous studies suggested they affect Late Onset Alzheimer Disease (LOAD) and longevity, respectively. Here, in the same sample groups, we investigated whether variants of IP6K3 also affect longevity, and variants of IPMK also influence LOAD susceptibility. We found that: i) a SNP of IP6K3 previously associated with increased risk of LOAD increased the chance to become long-lived, ii) SNPs of IPMK, previously associated with decreased longevity, were protective factors for LOAD, as previously observed for UCP4. SNP-SNP interaction analysis, including our previous data, highlighted phenotype-specific interactions between sets of alleles. Moreover, linkage disequilibrium and eQTL data associated to analyzed variants suggested mitochondria as crossroad of interconnected pathways crucial for susceptibility to neurodegeneration and/or longevity. Overall, data support the view that in these traits interactions may be more important than single polymorphisms. This phenomenon may contribute to the non-additive heritability of neurodegeneration and longevity and be part of the missing heritability of these traits