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

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

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

Effectiveness of a phone-based nurse monitoring assessment and intervention for chemotherapy-related toxicity: A randomized multicenter trial

PurposeAnticancer treatment-related toxicities can impact morbidity and mortality, hamper the administration of treatment, worsen the quality of life and increase the burden on the healthcare system. Therefore, their prompt identification is crucial. NICSO (Italian Network for Supportive Care in Cancer) conducted a nationwide randomized trial to evaluate the role of a planned, weekly phone-based nurse monitoring intervention to prevent and treat chemotherapy, targeted therapy- and immunotherapy-related toxicities. Here, we report the results from the chemotherapy arm. MethodsThis was a nationwide, randomized, open-label trial conducted among 29 Italian centers (NCT04726020) involving adult patients with breast, colon, or lung cancer and a life expectancy >= 6 months receiving adjuvant chemotherapy. Patients received either a weekly nurse monitoring phone call and an educational leaflet reporting practical advice about prevention and treatment of toxicities (experimental group) or the educational leaflet only (control group). ResultsThe addition of a nurse monitoring intervention may help reduce time spent with severe toxicities (grade >= 3), particularly those less frequently reported in clinical practice, such as fatigue. When considering grade 1-2 AEs, times with mild/moderate diarrhea, mucositis, fatigue and pain were shorter in the experimental arm. Time spent without AEs was significantly longer in the experimental arms for all the toxicities. The requirement for special medical attention was comparable between groups. ConclusionThis study suggests the need for implementing a better system of toxicity assessment and management for patients treated with adjuvant chemotherapy to promote effective preventive and/or therapeutic intervention against these events

NKp46-expressing human gut-resident intraepithelial V\u3b41 T cell subpopulation exhibits high anti-tumor activity against colorectal cancer

\u3b3\u3b4 T cells account for a large fraction of human intestinal intraepithelial lymphocytes (IELs) endowed with potent anti-tumor activities. However, little is known about their origin, phenotype and clinical relevance in colorectal cancer (CRC). To determine \u3b3\u3b4 IEL gut-specificity, homing and functions, \u3b3\u3b4 T cells were purified from human healthy blood, lymph nodes, liver, skin, intestine either disease-free or affected by CRC or generated from thymic precursors. The constitutive expression of NKp46 specifically identifies a new subset of cytotoxic V\u3b41 T cells representing the largest fraction of gut-resident IELs. The ontogeny and gut-tropism of NKp46pos/V\u3b41 IELs depends both on distinctive features of V\u3b41 thymic precursors and gut-environmental factors. Either the constitutive presence of NKp46 on tissue-resident V\u3b41 intestinal IELs or its induced-expression on IL-2/IL-15 activated V\u3b41 thymocytes are associated with anti-tumor functions. Higher frequencies of NKp46pos/V\u3b41 IELs in tumor-free specimens from CRC patients correlate with a lower risk of developing metastatic III/IV disease stages. Additionally, our in vitro settings reproducing CRC tumor-microenvironment inhibited the expansion of NKp46pos/V\u3b41 cells from activated thymic precursors. These results parallel the very low frequencies of NKp46pos/V\u3b41 IELs able to infiltrate CRC, thus providing new insights to either follow-up cancer progression or develop novel adoptive cellular therapies

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN)

Background Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. Methods This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed >= 12, and proximal and distal free resection margins length >= 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. Results A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to infinity). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to infinity). Conclusions Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection

Perinatal outcomes among immigrant mothers over two periods in a region of central Italy

<p>Abstract</p> <p>Background</p> <p>The number of immigrants has increased in Italy in the last twenty years (7.2% of the Italian population), as have infants of foreign-born parents, but scanty evidence on perinatal outcomes is available. The aim of this study was to investigate whether infants of foreign-born mothers living in Italy have different odds of adverse perinatal outcomes compared to those of native-born mothers, and if such measures changed over two periods.</p> <p>Methods</p> <p>The source of this area-based study was the regional hospital discharge database that records perinatal information on all births in the Lazio region. We analysed 296,739 singleton births born between 1996-1998 and 2006-2008. The exposure variable was the mother's region of birth. We considered five outcomes of perinatal health. We estimated crude and adjusted odds ratios and 95% confidence intervals (CIs) to evaluate the association between mother's region of birth and perinatal outcomes.</p> <p>Results</p> <p>Perinatal outcomes were worse among infants of immigrant compared to Italian mothers, especially for sub-Saharan and west Africans, with the following crude ORs (in 1996-1998 and 2006-2008 respectively): 1.80 (95%CI:1.44-2.28) and 1.95 (95%CI:1.72-2.21) for very preterm births, and 1.32 (95%CI:1.16-1.50) and 1.32 (95%CI:1.25-1.39) for preterm births; 1.18 (95%CI:0.99-1.40) and 1.17 (95%CI:1.03-1.34) for a low Apgar score; 1.22 (95%CI:1.15-1.31) and 1.24 (95%CI:1.17-1.32) for the presence of respiratory diseases; 1.47 (95%CI:1.30-1.66) and 1.45 (95%CI:1.34-1.57) for the need for special or intensive neonatal care/in-hospital deaths; and 1.03 (95%CI:0.93-1.15) and 1.07 (95%CI:1.00-1.15) for congenital malformations. Overall, time did not affect the odds of outcomes differently between immigrant and Italian mothers and most outcomes improved over time among all infants. None of the risk factors considered confounded the associations.</p> <p>Conclusion</p> <p>Our findings suggest that migrant status is a risk factor for adverse perinatal health. Moreover, they suggest that perinatal outcomes improved over time in some immigrant women. This could be due to a general improvement in immigrants' health in the past decade, or it may indicate successful application of policies that increase accessibility to mother-child health services during the periconception and prenatal periods for legal and illegal immigrant women in Italy.</p