Cortactin phosphorylation regulates cell invasion through a pH-dependent pathway

Cortactin phosphorylation induces recruitment of the sodium-hydrogen exchanger NHE1 to invadopodia, resulting in pH changes that regulate cortactin-cofilin binding and invadopodium dynamics

Spark location adaptive process control in meso-micro EDM

Time-synchronised high-speed imaging and electrical signal measurements are performed in near-real erosion conditions to analyse the feasibility of determining spark location based on its electrical signals in die-sinking electrical discharge machining (EDM). Using this novel research platform, a correlation between the discharge voltage and the geometric location of a discharge on an electrode has been established. Through the derived understanding, a microsecond level spark location adaptive process control has been conceptualised and demonstrated. The parameter control of each spark according to its probabilistic location on the electrode results in low wear of micro- to macroscale electrode features, higher material removal rate and higher form precision despite of electrode complexity. Reduction in the required number of electrodes achieved through the novel spark location adaptive process control increases the economic and energy efficiency of die-sinking EDM

Spark location adaptive process control in meso-micro EDM

Time-synchronised high-speed imaging and electrical signal measurements are performed in near-real erosion conditions to analyse the feasibility of determining spark location based on its electrical signals in die-sinking electrical discharge machining (EDM). Using this novel research platform, a correlation between the discharge voltage and the geometric location of a discharge on an electrode has been established. Through the derived understanding, a microsecond level spark location adaptive process control has been conceptualised and demonstrated. The parameter control of each spark according to its probabilistic location on the electrode results in low wear of micro- to macroscale electrode features, higher material removal rate and higher form precision despite of electrode complexity. Reduction in the required number of electrodes achieved through the novel spark location adaptive process control increases the economic and energy efficiency of die-sinking EDM.ISSN:0268-3768ISSN:1433-301

Potentially Inappropriate Prescribing of Oral Solid Medications in Elderly Dysphagic Patients

Pharmaceutical formulations suitable for dysphagic patients are not always commercially available, motivating caregivers to crush tablets or open capsules to facilitate swallowing. Since this action may modify the characteristics of the medicine, it should be considered potentially inappropriate. This paper is the first to focus on how hospitalization affected the rate of potentially inappropriate prescriptions (PIPs) and the incidence of dosage form-related PIPs in elderly patients with dysphagia. Data was collected by reviewing patient medical records in the Italian National Research Center on Aging of Ancona. The therapy at admission and discharge was analysed in terms of: inappropriate drug associations, inappropriate drugs for dysphagic patients, inappropriate dosage forms and inappropriate dosage form modifications. Forty-one dysphagic patients with an average age of 88.3 years were included in the study and 451 prescriptions were analysed. PIPs were widespread at admission, and hospitalization did not improve the situation in a statistically significant manner. The most common PIPs identified (>80%) were related to dosage form selection and modification. This study highlights a clear need for continuing medical education about prescription appropriateness and modification of solid dosage forms in patients with dysphagia

Effects of zinc-fotified drinking skim milk (as functional food) on cytokine release and thymic hormone activity in very old persons: a pilot study

Zinc is a relevant nutritional factor for the whole life of an organism because it affects the inflammatory/immune response and antioxidant activity, leading to an healthy state. Despite its important function, the dietary intake of zinc is inadequate in elderly. Possible interventions include food fortification, because it does not require changes in dietary patterns, the cost is low and it can reach a large portion of the elderly population, including very old subjects. Studies evaluating the impact of Zn-fortified foods on functional parameters in elderly, in particular in very old individuals, are missing. The objective of this study was to evaluate the efficacy of consumption of a zinc-fortified drinking skim milk (Zn-FMilk) for a period of two months in comparison to standard non-fortified milk (No-FMilk) on some biochemical parameters, zinc status, inflammatory/immune response and on a key parameter of the T-cell mediated immunity (thymulin hormone) in healthy very old subjects. The treatment with zinc-fortified milk (Zn-FMilk) is a good omen to increase the cell-mediated immunity in very old age represented by thymulin activity and some cytokine (IL-12p70, IFN-γ) release. At clinical level, a good healthy state occurs in 70% of the subjects with no hospitalization after one year of the follow-up in comparison to very old control subjects that did not participate to crossover design. In conclusion, the Zn-FMilk can be considered a good functional food for elderly, including older people. It might be a good replacement to the zinc tablets or lozenges taking into account the attitude of old people to uptake milk as a preferential food

Effect of ZIP2 Gln/Arg/Leu (rs2234632) polymorphism on zinc homeostasis and inflammatory response following zinc supplementation

Zinc dyshomeostasis may lead to an augmented production of proinflammatory cytokines promoting chronic inflammation and increasing the susceptibility to age-related diseases. Several studies suggest that the zinc transporter protein ZIP2 may play a relevant role in the immune system especially during zinc deficiency, while a polymorphism on the coding region of ZIP2 gene (Gln/Arg/Leu) has been associated with severe carotid artery disease. The aim of this study is to investigate the role of ZIP2 SNP on zinc and inflammatory status in 1090 elderly healthy free-living subjects enrolled in the ZincAge project and to assess the effect of zinc supplementation on zinc status, inflammatory mediators, and zinc transporter expression depending on ZIP2 genotype. ZIP2 Leu- (Arg43Arg) carriers showed enhanced IL-6, TNF-α, and RANTES plasma levels associated with decreased free cytosolic zinc in PBMCs and an upregulation of zinc transporters ZIP2, ZIP8, and Znt1. Moreover, Leu- subjects displayed significant decrement of inflammatory mediators such as MCP-1, TNF-α, and RANTES following zinc supplementation. In summary, this investigation provides new evidence on the effect of ZIP2 Gln/Arg/Leu polymorphism on proinflammatory mediators and zinc homeostasis in elderly population with a more pronounced anti-inflammatory effect of zinc supplementation in subjects carrying ZIP2 Leu- (Arg43Arg) genotype. These novel findings could be useful in identifying elderly subjects who may benefit of zinc intervention to decrease the inflammatory status and to prevent or delay the development of age-related diseases

Clinical impact of multiple resheathing during transcatheter aortic valve implantation with Evolut self-expanding valves

Background: The possibility to resheath some transcatheter heart valves (THV) facilitates the optimization of self-expandable devices implantation. However, resheating manoeuvres (expecially when repeated) increase the interaction between the transcatheter prosthesis and the patient's tissues potentially causing side-effects. Aims: To assess the clinical outcomes of resheathing at midterm follow-up with a focus on the safety of multiple resheathing. Methods: This retrospective observational study included all consecutive patients who underwent TAVI with a self-expandable supra-annular THV between December 2018 and December 2022. Primary endpoint was a composite of cardiovascular (CV) mortality, neurological events, non-fatal acute myocardial infarction and CV rehospitalizations. All clinical endpoints were assessed according to VARC-3 criteria. Results: 469 TAVI procedures with self-expandable supra-annular THV were included in the study. The attempt to resheath and the resheath manoeuvres number was prospectively recorded into an electronic database. Resheating was attempted in 253 (53.9%) cases; 1, 2 and ≥ 3 resheathing were performed in respectively 122 (26.0%), 63 (13.4%) and 68 (14.5%) procedures. At a median follow-up of 640 days (interquartile range 340-1033 days), the incidence of the primary endpoint did not differ between 0 vs. ≥1 (22.7 vs. 26.1%, LogRank p = 0.584) and < 3 vs. ≥3 resheathing groups (24.2 vs. 26.5% LogRank p = 0.963). Furthermore, no significant differences in the primary endpoint were observed between 0, 1-2 and ≥ 3 resheathing (p = 0.84). Conclusions: Our study found that resheathing of self-expandable THVs during TAVI did not result in worse clinical outcomes compared with no resheathing at mid-term follow-up. These results are independent from the number of resheathing, underling the safety of multiple resheathing in terms of peri-procedural and mid-term outcome. Condensed abstract: In this retrospective observational study of 469 patients undergoing transcatheter aortic valve implantation (TAVI) for symptomatic severe aortic stenosis with self-expanding valves, we investigated the influence of resheathing on mid-term clinical outcomes. Specifically, we focused on the safety of multiple resheathing procedures. Our findings revealed no significant impact of resheathing on medium-term outcomes. The primary endpoint, a composite of cardiovascular mortality, neurological events, non-fatal acute myocardial infarction, and cardiovascular rehospitalizations, did not show statistically significant differences between no resheathing, single resheathing and multiple resheathing groups. Our study suggests that resheathing, even when performed multiple times, does not appear to significantly affect clinical outcomes at mid-term follow-up

Anatomical Annulus Predictors of New Permanent Pacemaker Implantation Risk after Balloon-expandable Trans-catheter Aortic Valve Implantation

: New-generation transcatheter-heart-valves (THV) have significantly improved technical success and procedural safety of transcatheter-aortic-valve-implantation (TAVI) procedures, but incidence of permanent pacemaker implantation (PPI) remains a concern.The study aimed to assess the role of anatomical annulus features in determining peri-procedural conduction disturbances leading to new-PPI following TAVI with the last generation Edwards Sapien balloon-expandable valves (BEV). In the context of a prospective single-center registry, we integrated clinical and procedural predictors of PPI with anatomical data derived from multi-slice-computed-tomography (MSCT). A total of 210 consecutive patients treated with balloon expandable Edwards THV were included in the study from 2015 to 2023. Technical success was achieved in 197 (93.8%) procedures, and 26 patients (12.4%) required new-PPI at 30-day follow-up (median time-to-implantation 3 days). At the univariable logistic-regression analysis, pre-procedural right bundle branch block (RBBB; OR:2.24 [95%CI:1.01-4.97], p=0.047), annulus eccentricity ≥0.25 (OR:5.43 [95%CI:2.21-13.36], p<0.001), calcium volume at annulus of the right coronary cusp (RCC) >48 mm3 (OR:2.60 [95%CI:1.13-5.96], p=0.024) and prosthesis implantation depth greater than membranous septum length (OR:2.17 [95%CI: 1.10-4.28], p=0.026) were associated with new-PPI risk. At multivariable analysis pre-procedural RBBB (OR:2.81 [95%CI:1.01-7.85], p=0.049), annulus eccentricity ≥0.25 (OR:4.14 [95%CI:1.85-9.27], p<0.001), and annulusRCC calcium >48 mm3 (OR:2.89 [95%CI:1.07-7.82], p=0.037) were confirmed as independent predictors of new-PPI. In conclusion, specific anatomical features of the aortic valve annulus might have an additive role in determining the occurrence of conduction disturbances in patients undergoing TAVI with BEV. This suggests the possibility to use the MSCT to improve the prediction of post-TAVI new-PPI risk

Spark location adaptive process control in meso-micro EDM

ISSN:0268-3768ISSN:1433-301