An open day for children: The Bambineide in Arcetri

We briefly review the outreach activities at the Arcetri Astrophysical Observatory, and in particular the annual open day for children called Bambineide

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Dopaminergic drugs and neurotoxins affecting pancreatic beta cells physiology and survival: similarities between dopaminergic neurons and pancreatic beta cells.

The main aim of my thesis is to investigate the role of the dopaminergic system in pancreatic β- cells’ physiology and to underline similarities between dopaminergic neurons and β-cells concerning the sensibility to toxins and pharmacological agents capable to protect both cell types. My dissertation is divided into five themed chapters: the role of the dopaminergic system in β-cells; the pharmacology of dopaminergic drugs affecting β-cells function and viability; to study the correlation between Parkinson and diabetes in terms of epidemiology; to analyse the effect of parkinsonian neurotoxins on β-cells survival; to analyse protective factors for the toxicity induced by neurotoxins. More specifically, data from several studies suggest that neurotoxins like 1-methyl-4- phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA) and rotenone are extremely toxic to dopaminergic neurons. Furthermore, epidemiological studies have highlighted how parkinsonian patients are more likely to develop type 2 diabetes and vice versa. Another characteristic that have in common dopaminergic neurons and β-cells is the expression of dopamine receptors (D1–D5), dopamine transporter and enzymes for dopamine production (tyrosine hydroxylase and aromatic amino-acid decarboxylase) and degradation (MAO-A and B). With these premises, we investigated if there are similarities between β-cells and dopaminergic neurons in terms of vulnerability to different toxins. The cell lines analyzed are rat insulinoma cell line (INS-1 832/13) and mouse insulinoma cell line (MIN6). We showed that rotenone is the most potent for reducing β-cells viability and altering mitochondrial structure and bioenergetics in the low nanomolar range, similar to that found in dopaminergic cell lines. MPP+ and 6-OHDA show comparative impacts yet at higher concentration. Rotenone-induced toxicity was counteracted by α-tocopherol and partially by metformin, which are endowed with strong antioxidative and cytoprotective properties. The methodological procedure taken in this study is a mixed approach based on the evaluation of toxicity on different cell lines, the analysis of cell morphology after exposure to toxic substances, the analysis of mitochondrial functionality and verification of the protection induced by some compounds like dopamine agonists, metformin and α-tocopherol. Regarding mitochondrial functionality, I have deepened the generation of ROS and associated signalling. These experiments have allowed us to understand the relevance of some dopaminergic elements present in β-cells, at a physiological, pharmacological level and with regard to cellular vulnerability to environmental toxins, thus offering new potential therapeutic targets for both the treatment of diabetes and Parkinson's

A 5-Year Study of Lithium and Valproic Acid Drug Monitoring in Patients with Bipolar Disorders in an Italian Clinical Center

Therapeutic drug monitoring (TDM) is an effective tool used to improve the pharmacological treatment in clinical practice, especially to detect subtherapeutic drug plasma concentration (Cp) in order to consider a change of dosage during treatment and reach its putative therapeutic range. In this study, we report the Cp values of lithium and valproic acid (VPA), alone and in combination, mostly in bipolar patients admitted to an Italian clinical center of the University of Pisa during the years 2016–2020, which include 12,294 samples of VPA, 7449 of lithium and 1118 of both in combination. Lithium and VPA are the most utilized drugs in treating bipolar disorders, and their TDM is strongly recommended by recent guidelines. In relation to lithium Cp monitoring, several studies have underlined that 0.5–0.8 mmol/L is the optimal range for chronic treatment, and below 0.4 mmol/L, it is unlikely to produce a clinical response. For VPA, the therapeutic range is 50–100 μg/mL and a linear correlation between Cp and clinical efficacy has been proposed, where below 50 μg/mL, the clinical efficacy of VPA has not been proven thus far. Toxic levels of both drugs were rarely found in our study, while a high percentage of patients, about one-third, had sub-therapeutic Cp during their treatments. In addition, in several cases of patients receiving multiple blood sampling, the initial subtherapeutic Cp changed only partially without reaching its therapeutic window. In relation to age, we found a higher percentage of lithium and VPA Cp values in range in the adolescents than in the adults and elderly groups. No differences were reported when analyzing the distribution of Cp values in males and females. In conclusion, this present study suggests that TDM is widely used by many specialists, but there is still a window of improvement for optimizing pharmacological treatments in clinical practice

MAGNUM survey: A MUSE-Chandra resolved view on ionized outflows and photoionization in the Seyfert galaxy NGC 1365

Context. Ionized outflows, revealed by broad asymmetric wings of the [O III] lambda 5007 line, are commonly observed in active galactic nuclei (AGN) but the low intrinsic spatial resolution of the observations has generally prevented a detailed characterization of their properties. The MAGNUM survey aims at overcoming these limitations by focusing on the nearest AGN, including NGC 1365, a nearby Seyfert galaxy (D similar to 17 Mpc), hosting a low-luminosity active nucleus (L-bol similar to 2 x 10(43) erg s(-1)). Aims. We want to obtain a detailed picture of the ionized gas in the central similar to 5 kpc of NGC 1365 in terms of physical properties, kinematics, and ionization mechanisms. We also aim to characterize the warm ionized outflow as a function of distance from the nucleus and its relation with the nuclear X-ray wind. Methods. We employed optical integral-field spectroscopic observations from VLT/MUSE to investigate the warm ionized gas and Chandra ACIS-S X-ray data for the hot highly-ionized phase. We obtained flux, kinematic, and diagnostic maps of the optical emission lines, which we used to disentangle outflows from gravitational motions in the disk and measure the gas properties down to a spatial resolution of similar to 70 pc. We then performed imaging spectroscopy on Chandra ACIS-S data guided by the matching with MUSE maps. Results. The [O III] emission mostly traces a kpc-scale biconical outflow ionized by the AGN having velocities up to similar to 200 km s(-1). H alpha emission traces instead star formation in a circumnuclear ring and along the bar, where we detect non-circular streaming gas motions. Soft X-rays are predominantly due to thermal emission from the star-forming regions, but we manage to isolate the AGN photoionized component which nicely matches the [O III] emission. The mass outflow rate of the extended ionized outflow is similar to that of the nuclear X-ray wind and then decreases with radius, implying that the outflow either slows down or that the AGN activity has recently increased. However, the hard X-ray emission from the circumnuclear ring suggests that star formation might in principle contribute to the outflow. The integrated mass outflow rate, kinetic energy rate, and outflow velocity are broadly consistent with the typical relations observed in more luminous AGN

Effect of centre volume on pathological outcomes and postoperative complications after surgery for colorectal cancer: results of a multicentre national study

Background: The association between volume, complications and pathological outcomes is still under debate regarding colorectal cancer surgery. The aim of the study was to assess the association between centre volume and severe complications, mortality, less-than-radical oncologic surgery, and indications for neoadjuvant therapy.Methods: Retrospective analysis of 16,883 colorectal cancer cases from 80 centres (2018-2021). Outcomes: 30-day mortality; Clavien-Dindo grade >2 complications; removal of >= 12 lymph nodes; non-radical resection; neoadjuvant therapy. Quartiles of hospital volumes were classified as LOW, MEDIUM, HIGH, and VERY HIGH. Independent predictors, both overall and for rectal cancer, were evaluated using logistic regression including age, gender, AJCC stage and cancer site.Results: LOW-volume centres reported a higher rate of severe postoperative complications (OR 1.50, 95% c.i. 1.15-1.096, P = 0.003). The rate of >= 12 lymph nodes removed in LOW-volume (OR 0.68, 95% c.i. 0.56-0.85, P = 12 lymph nodes removed was lower in LOW-volume than in VERY HIGH-volume centres (OR 0.57, 95% c.i. 0.41-0.80, P = 0.001). A lower rate of neoadjuvant chemoradiation was associated with HIGH (OR 0.66, 95% c.i. 0.56-0.77, P < 0.001), MEDIUM (OR 0.75, 95% c.i. 0.60-0.92, P = 0.006), and LOW (OR 0.70, 95% c.i. 0.52-0.94, P = 0.019) volume centres (vs. VERY HIGH).Conclusion: Colorectal cancer surgery in low-volume centres is at higher risk of suboptimal management, poor postoperative outcomes, and less-than-adequate oncologic resections. Centralisation of rectal cancer cases should be taken into consideration to optimise the outcomes