An easy access to furan fused polyheterocyclic systems

Nitrostilbenes characterized by two different or differently substituted aryl moieties can be obtained from the initial ring-opening of 3-nitrobenzo[b]thiophene with amines. Such versatile building blocks couple the well-recognized double electrophilic reactivity of the nitrovinyl moiety (addition to the double bond, followed by, e.g., intramolecular replacement of the nitro group) with the possibility to exploit a conjugated system of double bonds within an electrocyclization process. Herein, nitrostilbenes are reacted with different aromatic enols provided by a double (carbon and oxygen) nucleophilicity, leading to novel, interesting naphthodihydrofurans. From these, as a viable application, aromatization and electrocyclization lead in turn to valuable polycondensed, fully aromatic O-heterocycles. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Comparative spectroscopic and electrochemical study of N-1 or N-2-alkylated 4-nitro and 7-nitroindazoles

Abstract Our research groups are by long time involved in the study of the reactivity and the pharmacological activity of nitrogen-containing heterocyclic compounds: in this line we have now examined the behaviour of some substituted 4- and 7-nitroindazoles. Considering the fact that nitroreduction processes are often essential steps for the biological activity of nitro compounds and remembering that some nitroindazoles show interesting biological activities, we have collected nuclear magnetic resonance, electron spin resonance, and cyclic voltammetry data and carried out density functional theory computations on the above compounds thus obtaining an accurate picture of electronic distribution and reduction processes of the examined substrates as a function of their chemical structure. Looking also to our previous results obtained examining the behaviour of 5- and 6-nitroindazoles, we have confirmed the different general behaviour of 1- and 2-alkyl substituted nitroindazoles strictly related to the known different electronic distribution in these two classes of compounds. Interestingly, cyclic voltammetry data have confirmed the ability of N-1 H nitroindazoles to give rise to the formation of dimers, already observed by us studying 5- and 6-nitroindazoles

Autism Spectrum Disorder and screen time during lockdown: an Italian study.

Background: Lockdown due to Covid-19 pandemic brought deep changes to the daily lives of children with Autism Spectrum Disorder (ASD), greatly increasing their amount of time spent at home. Methods: A cohort of 243 parents of children with ASD (2-15 years old) completed an original online survey regarding the child's screen time and the modification of the ASD symptomatology during lockdown to investigate the relationship between them. Results: The data show that high solitary screen time is related with the worsening of ASD core symptoms. Conclusions: This study may help to increase awareness in the excessive use of screen in children with ASD during the lockdown, both during the pandemic as well as after it ends

Individual patient data meta‐analysis of patients treated with a heparin‐bonded Viabahn in the femoropopliteal artery for chronic limb‐threatening ischemia

ObjectivesThe aim of the study was to analyze available data on patients treated for chronic limb-threatening ischemia (CLTI) with the heparin-bonded Viabahn endoprosthesis.BackgroundThe patency of self-expanding covered stents in patients with complex femoropopliteal lesions is encouraging. However, data were mostly derived in patients with intermittent claudication. Patients with CLTI often have more advanced disease and worse outcome.MethodsAfter the abstract screening, full-text papers were checked. Authors were approached to consider joining the consortium. Data were sent anonymously, databases were merged and an individual patient data meta-analysis was performed. Kaplan–Meier curves were used to calculate the freedom from amputations, the amputation-free survival, and patency rates.ResultsSeven studies were enrolled, representing 161 limbs that were treated for CLTI. Median lesion length was 28.0 cm (interquartile range 25.0–33.0 cm) and 82.7% were chronic total occlusions. The technical success rate was 98.1% and the 30-day mortality 1.9%. Through 2-year follow-up, the freedom-from-major-amputations was 99.3%, with an amputation-free survival of 78.8%. The freedom-from-loss-of primary, primary-assisted, and secondary patency was 70.4%, 71.8%, and 88.2%, respectively, at 1-year and 59.5%, 62.7%, and 86.1% at 2-year follow-up, respectively. The reintervention-free survival was 62.2% at a 2-year follow-up.ConclusionsTreatment of femoropopliteal disease in CLTI patients with the use of the heparin-bonded Viabahn is safe and effective with favorable clinical outcomes and low amputation rates. Reinterventions are needed in a subset of the population to maintain endoprosthesis patency. Close follow-up using duplex is recommended to detect potential edge stenosis, allowing treatment before device occlusion.</p

Contribution of MUTYH variants to male breast cancer risk: results from a multicenter study in Italy

Inherited mutations in BRCA1, and, mainly, BRCA2 genes are associated with increased risk of male breast cancer (MBC). Mutations in PALB2 and CHEK2 genes may also increase MBC risk. Overall, these genes are functionally linked to DNA repair pathways, highlighting the central role of genome maintenance in MBC genetic predisposition. MUTYH is a DNA repair gene whose biallelic germline variants cause MUTYH-associated polyposis (MAP) syndrome. Monoallelic MUTYH variants have been reported in families with both colorectal and breast cancer and there is some evidence on increased breast cancer risk in women with monoallelic variants. In this study, we aimed to investigate whether MUTYH germline variants may contribute to MBC susceptibility. To this aim, we screened the entire coding region of MUTYH in 503 BRCA1/2 mutation negative MBC cases by multigene panel analysis. Moreover, we genotyped selected variants, including p.Tyr179Cys, p.Gly396Asp, p.Arg245His, p.Gly264Trpfs*7, and p.Gln338His, in a total of 560 MBC cases and 1,540 male controls. Biallelic MUTYH pathogenic variants (p.Tyr179Cys/p.Arg241Trp) were identified in one MBC patient with phenotypic manifestation of adenomatous polyposis. Monoallelic pathogenic variants were identified in 14 (2.5%) MBC patients, in particular, p.Tyr179Cys was detected in seven cases, p.Gly396Asp in five cases, p.Arg245His and p.Gly264Trpfs*7 in one case each. The majority of MBC cases with MUTYH pathogenic variants had family history of cancer including breast, colorectal, and gastric cancers. In the case-control study, an association between the variant p.Tyr179Cys and increased MBC risk emerged by multivariate analysis [odds ratio (OR) = 4.54; 95% confidence interval (CI): 1.17-17.58; p = 0.028]. Overall, our study suggests that MUTYH pathogenic variants may have a role in MBC and, in particular, the p.Tyr179Cys variant may be a low/moderate penetrance risk allele for MBC. Moreover, our results suggest that MBC may be part of the tumor spectrum associated with MAP syndrome, with implication in the clinical management of patients and their relatives. Large-scale collaborative studies are needed to validate these findings

Pegaso: an ultra-light long duration stratospheric

Launched from the Mario Zuccelli Station (Baia Terra Nova) in Antarctica during the 2005/06 austral summer, the PEGASO-D payload lifted into the stratospheric anticyclone over the southern polar region. This effort marks the first Long Duration Scientific payload to be launched from this location and is the fourth such payload launched in the polar regions. Performing in the framework of the NOBILE/AMUNDSEN collaborative LDB development between ASI-ARR. The Italian Institute of Geophysics and Volcanology (INGV), with the sponsorship of the Italian Antarctic Program (PNRA) and the Italian Space Agency (ASI),designed and built the Ultra-Light system together with three Universities in Italy. The Pegaso program has been created to investigate the Earth magnetic field and provide a precursor series of small payload launches for the bigger LDB program such as OLIMPO, BOOMERanG and BArSPOrt through this collaboration between ASI and ARR. The Italian scientific community, aware of the big advantages that LDB balloons can offer to their experiments, proposed to extend the LDB program to Southern polar regions, besides performing launches from the newly initiated Nobile/Amundsen Stratospheric Balloon Center in Svalbard, Norway.Three PEGASO (Polar Explorer for Geomagnetics And other Scientific Observations) payloads have been launched from the Svalbard (No) in collaboration with Andoya Rocket Range, ASI and ISTAR (Operations and logistics) during the past two northern summers. These stratospheric (altitude m.35000) small 10kmc balloons have floated in the stratosphere between 14 to 39 days measuring the magnetic field of polar regions, by means of a 3-axys-fluxgate magnetometer, during a three year campaign. The study of the magnetic field and its variations is done through permanent observatories. They provide us with high quality data but their spatial distribution is not quite regular, specially in Antarctica due to logistic difficulties. The coverage is improved through marine and aeromagnetic surveys, and also through satellite missions. There exists nevertheless a gap in the wavelengths of the magnetic field represented by these kind of measurements. Satellite data are too far away from Earth's surface to individuate wavelengths lower than 1000 km, and near-ground sur- veys are not able to represent wavelengths longer than the dimensions of the surveyed area. Moreover, there is a region empty of data around the geographical pole for the satellite measurements. The size of these gaps depends on the orbital parameters, but it can reach up to 10 degrees around the pole. PEGASO allows to bridge this gap in the measurements of the magnetic field. Surveys carried out at 35 km height allow the study of crustal anomalies in the range between, we can say, 60 and 1000 km. Taking into account that pathfinders (smaller non-recoverable balloon systems) are usually sent to explore the atmospheric currents, the use of PEGASO as pathfinder allows us to obtain all these results at a very affordable cost. The PEGASO payload was also developed as a single source system integrating science, housekeeping and operational control of the entire balloon borne configuration.Satellite telemetry sent the scientific (magnetometric) data, house-keeping (temperature, solar panel voltage and current, altitude and time) and telecommand (four ballast, two parachute release system, system reset), and powered the terminate system. Data flows through the IRIDIUM telephone service. The onboard systems were kept inside a vessel (white painted and pressurizzed vessel due to power dissipation) except for external flexible solar panels and magnetometer, attached to an external boom. Two redundant tracking systems have been used: a first GPS was integrated inside the on-board telemetry system, necessary to reconstruct position and time of scientific data, while an independent GPS-ARGOS system gave the balloon trajectory, including its descent. Continuous trajectory predictions were made during the missions; they have been necessary, in particular, for the flight safety requirements of the northern hemisphere. The evaluation of the statistical error is proposed. The PEGASO payload was developed to be a light, cost effective way to explore the potential of Ultra-Light Long Duration Ballooning for science as well as an introduction to the earth-space possibilities for students.PublishedBeijing, China1A. Geomagnetismo e Paleomagnetism

High-fat diet leads to reduced protein o-glcnacylation and mitochondrial defects promoting the development of alzheimer\u2019s disease signatures

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer\u2019s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process

How do we estimate survival? External validation of a tool for survival estimation in patients with metastatic bone disease-decision analysis and comparison of three international patient populations

How do we estimate survival? External validation of a tool for survival estimation in patients with metastatic bone disease-decision analysis and comparison of three international patient population