Functional and morphological correlates in the drosophila LRRK2 loss-of-function model of Parkinson's disease: drug effects of Withania somnifera (Dunal) administration

The common fruit fly Drosophila melanogaster (Dm) is a simple animal species that contributed significantly to the development of neurobiology whose leucine-rich repeat kinase 2 mutants (LRRK2) loss-of-function in the WD40 domain represent a very interesting tool to look into physiopathology of Parkinson's disease (PD). Accordingly, LRRK2 Dm have also the potential to contribute to reveal innovative therapeutic approaches to its treatment. Withania somnifera Dunal, a plant that grows spontaneously also in Mediterranean regions, is known in folk medicine for its anti-inflammatory and protective properties against neurodegeneration. The aim of this study was to evaluate the neuroprotective effects of its standardized root methanolic extract (Wse) on the LRRK2 loss-of-function Dm model of PD. To this end mutant and wild type (WT) flies were administered Wse, through diet, at different concentrations as larvae and adults (L+/A+) or as adults (L-/A+) only. LRRK2 mutants have a significantly reduced lifespan and compromised motor function and mitochondrial morphology compared toWT flies 1% Wse-enriched diet, administered to Dm LRRK2 as L-/A+and improved a) locomotor activity b) muscle electrophysiological response to stimuli and also c) protected against mitochondria degeneration. In contrast, the administration of Wse to Dm LRRK2 as L+/A+, no matter at which concentration, worsened lifespan and determined the appearance of increased endosomal activity in the thoracic ganglia. These results, while confirming that the LRRK2 loss-of-function in the WD40 domain represents a valid model of PD, reveal that under appropriate concentrations Wse can be usefully employed to counteract some deficits associated with the disease. However, a careful assessment of the risks, likely related to the impaired endosomal activity, is require

A Measurement of the Branching Ratio of KL→e+e−γγK_L \to e^+e^-\gamma\gamma

We report on a study of the decay $K_L \to e^+e^-\gamma\gamma$ carried out as a part of the KTeV/E799 experiment at Fermilab. The 1997 data yielded a sample of 1543 events, including an expected background of $56 \pm 8$ events. An effective form factor was determined from the observed distribution of the $e^+e^-$ invariant mass. Using this form factor in the calculation of the detector acceptance, the branching ratio was measured to be ${\mathcal B}(K_L \to e^+ e^- \gamma \gamma, E^*_\gamma > 5 {MeV}) = (5.84 \pm 0.15 {\rm ~(stat)} \pm 0.32 {\rm ~(sys)})\times 10^{-7}$.Comment: 5 pages, 4 figure

Cardiac rehabilitation after transcatheter versus surgical prosthetic valve implantation for aortic stenosis in the elderly

Background: Transcatheter aortic valve implantation plays a leading role in the management of aortic stenosis in patients with comorbidities but no data are available about cardiac rehabilitation in these subjects. This study aimed to compare safety and efficacy of an early, exercise-based, cardiac rehabilitation programme in octogenarians after a traditional surgical aortic valve replacement versus transcatheter aortic valve implantation.Methods: Seventy-eight consecutive transcatheter aortic valve implantation patients were studied in order to evaluate the effect of an exercise-based cardiac rehabilitation programme in comparison to 80 of a similar age having surgical aortic valve replacement. Functional capacity was assessed by a 6 min walking test on admission and at the end of the programme. When possible, a cardiopulmonary exercise test was also performed before discharge.Results: The two groups were similar in terms of gender and length of stay in cardiac rehabilitation; as expected, the transcatheter aortic valve implantation group had more comorbidities but no major complications occurred in either group during rehabilitation. All patients enhanced autonomy and mobility and were able to walk at least with the assistance of a stick. In those patients who were able to perform the 6 min walking test, the distance walked at discharge did not significantly differ between the groups (272.7.108 vs. 294.2. 101 m, p=0.42), neither did the exercise capacity assessed by cardiopulmonary exercise test (peak-VO2 12.5.3.6 vs. 13.9.2.7 ml/kg/min, p=0.16).Conclusions: Cardiac rehabilitation is feasible, safe and effective in octogenarian patients after transcatheter aortic valve implantation as well as after traditional surgery. An early cardiac rehabilitation programme enhances independence, mobility and functional capacity and should be highly encouraged

Intermuscular technique for implantation of the subcutaneous implantable defibrillator: a propensity-matched case-control study

Aims A previous randomized study demonstrated that the subcutaneous implantable cardioverter defibrillator (S-ICD) was noninferior to transvenous ICD with respect to device-related complications and inappropriate shocks. However, that was performed prior to the widespread adoption of pulse generator implantation in the intermuscular (IM) space instead of the traditional subcutaneous (SC) pocket. The aim of this analysis was to compare survival from device-related complications and inappropriate shocks between patients who underwent S-ICD implantation with the generator positioned in an IM position in comparison with an SC pocket. Methods and results We analysed 1577 consecutive patients who had undergone S-ICD implantation from 2013 to 2021 and were followed up until December 2021. Subcutaneous patients (n = 290) were propensity matched with patients of the IM group (n = 290), and their outcomes were compared. : During a median follow-up of 28 months, device-related complications were reported in 28 (4.8%) patients and inappropriate shocks were reported in 37 (6.4%) patients. The risk of complication was lower in the matched IM group than in the SC group [hazard ratio 0.41, 95% confidence interval (CI) 0.17-0.99, P = 0.041], as well as the composite of complications and inappropriate shocks (hazard ratio 0.50, 95% CI 0.30-0.86, P = 0.013). The risk of appropriate shocks was similar between groups (hazard ratio 0.90, 95% CI 0.50-1.61, P = 0.721). There was no significant interaction between generator positioning and variables such as gender, age, body mass index, and ejection fraction. Conclusion Our data showed the superiority of the IM S-ICD generator positioning in reducing device-related complications and inappropriate shocks

A measurement of the transverse polarization of Lambda-hyperons produced in inelastic pN-reactions at 450 GeV proton energy

A study of the polarization of Λ hyperons produced in inelastic pN reactions induced by the 450 GeV proton beam from the CERN SPS has been performed with the NA48 detector. The Λ hyperons were detected at a fixed angle of 4.2 mrad in the momentum range from 50 GeV/c to 200 GeV/c. The polarization changes from −0.053 ± 0.034 to −0.298 ± 0.074 for a transverse momentum range of the Λ between 0.28 GeV/c and 0.86 GeV/c. The antiΛ polarization is consistent with zero