Annurca apple (M. pumila Miller cv Annurca) extracts act against stress and ageing in S. cerevisiae yeast cells

During the past years, a number of studies have demonstrated the positive effect of apple on ageing and different diseases such as cancer, degenerative and cardiovascular diseases. The unicellular yeast Saccharomyces cerevisiae represents a simple eukaryotic model to study the effects of different compounds on lifespan. We previously demonstrated that apple extracts have anti-ageing effects in this organism because of their antioxidant properties. In particular, the effect is related to the presence in this fruit of polyphenols, which give a large contribution to the antioxidant activity of apples

A predictive index of intra-dialysis IDH. A statistical clinical data mining approach.

Intra-Dialysis Hypotension (IDH) is one of the main hemodialysis related complications, occurring in 25-30% of the sessions. The factors involved in the onset of hypotension in patients undergoing dialysis are due both to clinical conditions (e.g. presence of vascular or cardiac diseases, neuropathology, anemia) and treatment settings such as temperature of the dialysate, sodium concentration, buffer composition, ultrafiltration rate, etc. The patient’s peculiar reaction to the treatment implies difficulties in preventing IDH episodes. This work explores the possibility to use a multivariate analysis of clinical data to quantify the risk to develop IDH at the beginning of each session. The study is framed in the DialysIS project (Dialysis therapy between Italy and Switzerland) funded by INTERREG – Italy – Switzerland and Co-funded by European Union. Data referring to a total of 516 sessions performed on 70 adult patients undergoing dialysis treatment (50 patients enrolled at A. Manzoni Hospital Lecco, Italy and 20 patients at Regional Hospital of Lugano, Switzerland) were collected. Clinical prescriptions, hydration status, dialysis machine data and hematochemical data were recorded and stored in a unique flexible structured MySQL® database. A statistical analysis was performed to find the potential risk factor related to IDH onset. IDH episodes were automatically detected during the monitored sessions, according to the literature criteria. Patients suffering from IDH in 2 or more sessions were classified as Hypotension Prone (HP), the others as Hypotension Resistant (HR). Initial values of potassium concentration [K+], systolic (SBP) and diastolic (DBP) blood pressure, and weight gain (ΔW) from the end of the previous treatment result to be statistically different between the HP and HR groups. A new index, J, was defined as a weighted patient-specific combination of these parameters and calculated for each session of each patient. The weight of the index coefficients can be dynamically adjourned based on the longitudinal analysis of [K+], SBP, DBP, and ΔW. The results reported in this paper were calculated based on a longitudinal analysis of a minimum of three sessions for each patient. The accuracy of the J index in predicting IDH events has been evaluated and quantified in terms of percentage number of predicted IDH events, with respect to the total number of IDHs. Values of J index higher than 1 point out the risk of IDH onset. J allows the prediction of 100% of IDH episodes using 5 sessions, the 90% using 3 sessions. More specifically, at Lecco Hospital 43 IDH events were detected by the automatic system of which 100% and 95% were respectively predicted by the new index calculated using 5 or 3 sessions. Similarly, at Lugano Hospital 58 IDH were detected by the automatic system of which 100% and 87,5% were predicted using 5 or 3 sessions respectively. A longer longitudinal dataset will allow a higher matching of J to actual IDH episodes. In conclusion, the evaluation of this new index at the beginning of the dialysis session prior to connecting the patient to the machine can provide the clinician with useful information about the risk for the patient to develop cardiovascular instabilities (IDH) during the treatment and can advise the physician about the need to modify the prescription

Electrophysiological profile remodeling via selective suppression of voltage-gated currents by CLN1/PPT1 overexpression in human neuronal-like cells.

CLN1 disease (OMIM #256730) is an inherited neurological disorder of early childhood with epileptic seizures and premature death. It is associated with mutations in CLN1 coding for Palmitoyl-Protein Thioesterase 1 (PPT1), a lysosomal enzyme which affects the recycling and degradation of lipid-modified (S-acylated) proteins by removing palmitate residues. Transcriptomic evidence from a neuronal-like cellular model derived from differentiated SH-SY5Y cells disclosed the potential negative roles of CLN1 overexpression, affecting the elongation of neuronal processes and the expression of selected proteins of the synaptic region. Bioinformatic inquiries of transcriptomic data pinpointed a dysregulated expression of several genes coding for proteins related to voltage-gated ion channels, including subunits of calcium and potassium channels (VGCC and VGKC). In SH-SY5Y cells overexpressing CLN1 (SH-CLN1 cells), the resting potential and the membrane conductance in the range of voltages close to the resting potential were not affected. However, patch-clamp recordings indicated a reduction of Ba2+ currents through VGCC of SH-CLN1 cells; Ca2+ imaging revealed reduced Ca2+ influx in the same cellular setting. The results of the biochemical and morphological investigations of CACNA2D2/α2δ-2, an accessory subunit of VGCC, were in accordance with the downregulation of the corresponding gene and consistent with the hypothesis that a lower number of functional channels may reach the plasma membrane. The combined use of 4-AP and NS-1643, two drugs with opposing effects on Kv11 and Kv12 subfamilies of VGKC coded by the KCNH gene family, provides evidence for reduced functional Kv12 channels in SH-CLN1 cells, consistent with transcriptomic data indicating the downregulation of KCNH4. The lack of compelling evidence supporting the palmitoylation of many ion channels subunits investigated in this study stimulates inquiries about the role of PPT1 in the trafficking of channels to the plasma membrane. Altogether, these results indicate a reduction of functional voltage-gated ion channels in response to CLN1/PPT1 overexpression in differentiated SH-SY5Y cells and provide new insights into the altered neuronal excitability which may underlie the severe epileptic phenotype of CLN1 disease. It remains to be shown if remodeling of such functional channels on plasma membrane can occur as a downstream effect of CLN1 disease.Peer reviewe

Detecting particles flowing through interdigitated 3D microelectrodes

Counting cells in a large microchannel remains challenging and is particularly critical for in vitro assays, such as cell adhesion assays. This paper addresses this issue, by presenting the development of interdigitated three-dimensional electrodes, which are fabricated around passivated pillarshaped silicon microstructures, to detect particles in a flow. The arrays of micropillars occupy the entire channel height and detect the passage of the particle through their gaps by monitoring changes in the electrical resistance. Impedance measurements were employed in order to characterize the electrical equivalent model of the system and to detect the passage of particles in real-time. Three different geometrical micropillar configurations were evaluated and numerical simulations that supported the experimental activity were used to characterize the sensitive volume in the channel. Moreover, the signal-to-noise-ratio related to the passage of a single particle through an array was plotted as a function of the dimension and num ber of micropillars

A novel mutation in NDUFB11 unveils a new clinical phenotype associated with lactic acidosis and sideroblastic anemia

NDUFB11, a component of mitochondrial complex I, is a relatively small integral membrane protein, belonging to the 'supernumerary' group of subunits, but proved to be absolutely essential for the assembly of an active complex I. Mutations in in the X-linked nuclear encoded NDUFB11 gene have recently been discovered in association with two distinct phenotypes, i.e. microphthalmia with linear skin defects and histiocytoid cardiomyopathy. We report on a male with complex I deficiency, caused by a de novo mutation in NDUFB11 and displaying early onset sideroblastic anemia as the unique feature. This is the third report that describes a mutation in NDUFB11 but all are associated to a different phenotype. Our results further expand the molecular spectrum and associated clinical phenotype of NDUFB11 defects

School in Italy: a safe place for children and adolescents

Background: During the first SARS-CoV-2 pandemic phase, the sudden closure of schools was one of the main measures to minimize the spread of the virus. In the second phase, several safety procedures were implemented to avoid school closure. To evaluate if the school is a safe place, students and staff of two school complexes of Rome were monitored to evaluate the efficacy of prevention measures inside the school buildings. Methods: Oral secretions specimens were collected from 1262 subjects for a total of 3431 samples, collected over a 3 months period. Detection of Coronavirus SARS-CoV-2 was performed by real-time PCR. Target genes were represented by E gene, RdRP/S gene and N gene. Results: Among the 3431 samples analyzed, just 16 sample resulted as positive or low positive: 1 sample in the first month, 12 samples in the second month and 3 in the third month. In each period of evaluation, all positive children attended different classes. Conclusions: Even if the school has the potential for spreading viruses, our preliminary results show the efficacy of the implementations undertaken in this setting to minimize virus diffusion. Our evidence suggests that school does not act as an amplifier for transmission of SARS-CoV-2 and can be really considered a safe place for students

Navigating challenges:STI policies for sustainable and inclusive development in Latin America

This paper explores the challenges and opportunities for Latin America in adopting sustainable development strategies, with a particular focus on Science, Technology and Innovattion (STI) policies. It gathers the insights of a group of distinguished scholars on STI policies, social inclusion and sustainability from the region who participated in the panel organized by the UNESCO Chair during the LALICS* conference held in Asuncion, Paraguay, on 19-21 June 2023.It addresses the challenges that hinder Latin America’s inclusive, sustainable and innovative development process from different perspectives. Highlighted challenges include strong inequality, high informality levels, and low R&D expenditure, heterogeneous productive structure posing obstacles to innovation and their governance. Scholars highlight the role of STI policies and the engagement of academia, government, and business in reducing inequality and promoting social protection, and discuss the technological capabilities needed to address climate change and digitalisation in the region

Navigating challenges:STI policies for sustainable and inclusive development in Latin America

This paper explores the challenges and opportunities for Latin America in adopting sustainable development strategies, with a particular focus on Science, Technology and Innovattion (STI) policies. It gathers the insights of a group of distinguished scholars on STI policies, social inclusion and sustainability from the region who participated in the panel organized by the UNESCO Chair during the LALICS* conference held in Asuncion, Paraguay, on 19-21 June 2023.It addresses the challenges that hinder Latin America’s inclusive, sustainable and innovative development process from different perspectives. Highlighted challenges include strong inequality, high informality levels, and low R&D expenditure, heterogeneous productive structure posing obstacles to innovation and their governance. Scholars highlight the role of STI policies and the engagement of academia, government, and business in reducing inequality and promoting social protection, and discuss the technological capabilities needed to address climate change and digitalisation in the region

Modified radical retropubic prostatectomy: Personal technical variation "tension free continuum-urethral anastomosis (T.F.C.U.A)" with optical magnification in the preservation of the bladder neck, and estimation of the urinary continence

Objective: To reassess the double continence technique for open retropubic radical prostatectomy, proposed by Malizia and employed by Pagano et al., with the "tension free continuum-urethral anastomosis" (T.F.C.U.A.) personal modification and the use of image magnification optical systems and appropriate and delicate surgical tools. Materials and methods: A total of 173 radical retropubic prostatectomies, performed by the same surgeon, were evaluated in terms of early and late continence. Results: The presence of residual prostate cancer cells within the muscle layer was always excluded by the histopathological examination that also demonstrated that the muscle layer was well represented; satisfactory outcomes were obtained in terms of both early urinary continence (60%) and urinary continence at 6-12 month follow-up (92.4% for the whole series and 97.2% for the last series of patients). Conclusions: The "tension free" anastomosis obtained by the suspension of the anterior bladder wall to the the pubis along the median line allowed to achieve satisfactory outcomes in terms of urinary continence, even if these data obviously need to be confirmed by other series and comparative trials