On the structural optimization in presence of base isolating devices

The minimum volume design of plane frames constituted by elastic perfectly plastic material and subjected to appropriate combinations of fixed, cyclic and dynamic loads is studied. The influence on the design, in terms of cost (volume) and behavioural features, of seismic protecting devices is particularly focused. The considered protecting device is a lead rubber bearing base isolation system. Two optimal design problem formulations are proposed for the structure with or without the protecting device, both based on the so-called statical approach. The minimum volume frame is reached accounting for three different resistance limits: the purely elastic limit, the (elastic) shakedown limit and the instantaneous collapse limit. The adopted load combinations are alternatively characterized by the presence of only fixed loads, of amplified fixed loads and quasi-static perfect cyclic loads due to the wind action, of suitably reduced fixed loads and dynamic actions due to the earthquake. The linear elastic effects of the dynamic actions are studied by utilizing a modal technique. Reference is made to the most recent Italian code related to the structural analysis and design. The solution of the optimization problem is reached by using a suitable subroutine available into the optimization toolbox of MATLAB\uae appropriate to the proposed formulations. A flexural frame is studied with and without the relevant seismic protecting device in order to study the influence on the design of such a base isolation system. The related minimum volume structures are obtained assuming the stiffness and the damping feature of the base isolation system as variables within assigned suitable ranges. The Bree diagrams of the obtained optimal designs are also determined in order to characterize and compare their structural and safety behaviou

MOLECULAR CHARACTERIZATION OF K26 GENE OF LEISHMANIA INFANTUM, ISOLATE BY HUMAN PATIENTS FROM SICILY REGION

Human Leishmaniasis is an emerging problem in Italy and increase in the Sicily region. In the present work, we explored the genetic polymorphism of Leishmania isolates from twenty-five cases of human Leishmaniasis: two cases of visceral Leishmaniasis (VL) and twenty-three of cutaneous Leishmaniasis (CL). The characterization is carried out in comparison with twenty five human isolates of leishmania and one reference strain, L. infantum MHOM/TN/80IPT1 (MON-1). MON-1 is the most common zymodeme responsible for Leishmaniasis in Italy. The aim of the study is to genotype Leishmania isolates from Sicily by PCR ,analyzing size polymorphism of K26 gene to discriminate between MON-1 and non MON-1 zymodemes. K26 is a protein belonging to the Hydrofilic acylated surface protein B (HASPB) family. It is characterized by repeated aminoacidal domains and shows polymorphisms. The k26 polymorphism of MON-1 zymodeme is determinate in the size of 626 bp. The analysis show that all the 25 isolates belong to the L. infantum species, in particular the product size of 626 bp is detect in six patients affected by cutaneous Leishmaniasis. The molecular tools applied in this study can constitute a helpful support for parasite tracking and for a better understanding of the epidemiological evolution of Leishmaniasis

G-protein-coupled receptor kinase 5 polymorphism and Takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TTC) is an increasingly reported clinical syndrome that mimics acute myocardial infarction without obstructive coronary artery disease and is characterized by transient systolic dysfunction of the apical and/or mid-segments of the left ventricle. The syndrome mainly occurs in postmenopausal women with high adrenergic state conditions. Nowadays, the pathophysiology of TTC is not yet known and the possibility of a genetic predisposition is controversial. AIMS: The purpose of this study was to assess the genetic susceptibility to TTC through analysis of the L41Q polymorphism of the G-protein-coupled receptor kinase 5 (GRK5). METHODS AND RESULTS: In a cohort of 20 patients enrolled in two tertiary Italian centers with diagnosis of TTC, accordingly to the commonly accepted Mayo Clinic criteria and in 22 healthy individuals (control) we have evaluated the polymorphism in GRK5 gene. The TTC patients had a mean age of 65 ± 9 years and 19 of 20 were women. The presence of one or two L41 alleles of GRK5 was significantly more frequent in TTC group than in the control group (40 vs. 8%, P = 0.0372). CONCLUSION: In our study, we have found a significant difference in the frequency of GRK5 polymorphism between TTC patients and controls, supporting a genetic predisposition to this cardiac syndrome

An in vitro study of the mTORC1/2 inhibitor PP242 in glioblastoma multiforme

mTOR is a kinase complex involved in cell growth, proliferation, survival, metabolism and migration. The aberrant activation of mTOR has been previously demonstrated in glioblastoma multiforme (GBM), making it an interesting target for therapeutic approaches [1]. Unfortunately, the attempts to block mTOR activity made so far had disappointing clinical efficacy, as the mTOR inhibitor Rapamycin and analogs only target mTOR complex 1 (mTORC1) while mTOR actually exists in two distinct complexes, namely mTORC1 and mTOR complex 2 (mTORC2) that differ in terms of both regulation mechanisms and functions [2,3]. mTORC1 is inhibited by Rapamycin and acts as a downstream effector of the PTEN/PI3K/Akt pathway, linking growth factors, amino acids, ATP and O2 signals to protein translation, cell growth, proliferation and survival. Differently, mTORC2 is insensible to Rapamycin and acts as an upstream activator of Akt via phosphorylation of serine 473 [3]. To analyze the contribution of mTORC1/2 to GBM biology, we studied the in vitro effect of PP242, a novel mTORC1/2 inhibitor, on glioma cell lines of different malignancy degree, and compared it to the effect of Rapamycin and of the irreversible PI3K inhibitor, Wortmannin. Our results suggest that the inhibition of both mTOR complexes with PP242 induces sustained levels of autophagy that causes G0/G1 cell cycle arrest and a significantly reduction of cell viability, proliferation and migration. Additionally, we observed that administration of PP242 in U87MG cell line prevents stem cell growth, which results in the inhibition of neurospheres formation. This data confirms the pivotal role of mTOR in glioblastoma cells biology and expand upon this evidence suggesting a prominent role of the mTOR complex 2 in glioblastoma cell growth, migration and survival, and indicate that the mTORC2 might represent clinically valuable target in GMB

Current exposure of Italian women of reproductive age to PFOS and PFOA: a human biomonitoring study

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) concentrations were determined in serum samples collected in 2011-2012 from 549 nulliparous Italian women of reproductive age who resided in six different Italian Regions. Assessment of exposure to perfluorinated compounds was part of a large human biomonitoring study (Project Life Plus "Womenbiopop") that aimed at examining the exposure of women of reproductive age to priority organic pollutants. The median concentrations of PFOS and PFOA were 2.43, and 1.55ngg-1, respectively. Significant differences in the concentrations of both compounds were observed among the six Regions. Women from central Italy had the highest levels of both compounds, followed by women from northern Italy, and southern Italy. No differences in the PFOS concentrations were found between women from urban/industrial areas and women from rural areas, whereas the levels of PFOA were significantly higher in women residing in urban/industrial areas than in women residing in rural areas. Taken together, the observed concentrations confirm that the overall exposure of the Italian population is among the lowest observed in industrialized countries. A downward temporal trend in exposure was observed for both compounds when comparing the results from the present study with those assessed in a study conducted in 2008

Kidney transplantation from living donor with monolateral renal artery fibromuscular dysplasia using a cryopreserved iliac graft for arterial reconstruction: a case report and review of the literature

Background Aging and mortality of patients on waiting lists for kidney transplantation have increased, as a result of the shortage of organs available all over the world. Living donor grafts represent a significant source to maintain the donor pool, and resorting successfully to allografts with arterial disease has become a necessity. The incidence of renal artery fibromuscular dysplasia (FMD) in potential living renal donors is reported to be 2-6%, and up to 4% of them present concurrent extra-renal involvement. Case presentation We present a case of renal transplantation using a kidney from a living donor with monolateral FMD. Resection of the affected arterial segment and its subsequent replacement with a cryopreserved iliac artery graft from a deceased donor were performed. No intraoperative nor post-operative complications were reported. The allograft function promptly resumed, with satisfying creatinine clearance, and adequate patency of the vascular anastomoses was detected by Doppler ultrasounds. Conclusion Literature lacks clear guidelines on the eligibility of potential living renal donors with asymptomatic FMD. Preliminary assessment of the FMD living donor should always rule out any extra-renal involvement. Whenever possible, resection and reconstruction of the affected arterial segment should be taken into consideration as this condition may progress after implantation

Am J Prev Med

CC999999/Intramural CDC HHS/United States2017-02-19T00:00:00Z26456878PMC531651

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry

[Abstract] Aims. Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. Methods and results. We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66±13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease. Conclusion. Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease