Therapeutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma

Melanoma is the most dangerous and treatment-resistant skin cancer. Tumor resistance and recurrence are due to the persistence in the patient of aggressive cells with stem cell features, the cancer stem cells (CSC). Recent evidences have shown that CSC display a distinct metabolic profile as compared to tumor bulk population: a promising anti-tumor strategy is therefore to target specific metabolic pathways driving CSC behavior. Biguanides (metformin and phenformin) are anti-diabetic drugs able to perturb cellular metabolism and displaying anti-cancer activity. However, their ability to target the CSC compartment in melanoma is not known. Here we show that phenformin, but not metformin, strongly reduces melanoma cell viability, growth and invasion in both 2D and 3D (spheroids) models. While phenformin decreases melanoma CSC markers expression and the levels of the pro-survival factor MITF, MITF overexpression fails to prevent phenformin effects. Phenformin significantly reduces cell viability in melanoma by targeting both CSC (ALDHhigh) and non-CSC cells and by significantly reducing the number of viable cells in ALDHhighand ALDHlowderived spheroids. Consistently, phenformin reduces melanoma cell viability and growth independently from SOX2 levels. Our results show that phenformin is able to affect both CSC and non-CSC melanoma cell viability and growth and suggests its potential use as anti-cancer therapy in melanoma

TERT Promoter Mutations in Papillary Thyroid Microcarcinomas

Small papillary thyroid carcinomas have contributed to the worldwide increased incidence of differentiated thyroid cancer observed over the past decades. However, the mortality rate has not changed over the same period of time, raising questions about the possibility that thyroid cancer patients, especially those with small tumors, are overdiagnosed and overtreated. Molecular prognostic marker able to discriminate aggressive thyroid cancers from those with an indolent course would be of great relevance to tailor the therapeutic approach and reduce overtreatment. Mutations in the TERT promoter were recently reported to correlate strongly with aggressiveness in advanced forms of thyroid cancer, holding promise for a possible clinical application. The occurrence and potential clinical relevance of TERT mutations in papillary thyroid microcarcinomas (mPTCs) is currently unknown. This study aimed to analyze the occurrence of two TERT promoter mutations (-124C>T and -146C>T) and their potential association with unfavorable clinical features in a large cohort of mPTCs

Tuberculosis in Kindergarten and Primary School, Italy, 2008–2009

An outbreak of tuberculosis (TB) in Italy involved 19 schoolchildren with active TB and 43 with latent infection. The source of the outbreak was a school assistant born in Italy who had a family history of TB. This outbreak highlights the need for maintaining clinical and public health expertise in countries with low TB incidence

Genome sequences of three SARS-CoV-2 P.1 strains identified from patients returning from Brazil to Italy

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. We report the complete sequences of three SARS-CoV-2 P.1 strains obtained from nasopharyngeal swab specimens from three patients returning from Brazil to Italy

FOOT: a new experiment to measure nuclear fragmentation at intermediate energies

Summary: Charged particle therapy exploits proton or 12C beams to treat deep-seated solid tumors. Due to the advantageous characteristics of charged particles energy deposition in matter, the maximum of the dose is released to the tumor at the end of the beam range, in the Bragg peak region. However, the beam nuclear interactions with the patient tissues induces fragmentation both of projectile and target nuclei and needs to be carefully taken into account. In proton treatments, target fragmentation produces low energy, short range fragments along all the beam range, which deposit a non negligible dose in the entry channel. In 12C treatments the main concern is represented by long range fragments due to beam fragmentation that release their dose in the healthy tissues beyond the tumor. The FOOT experiment (FragmentatiOn Of Target) of INFN is designed to study these processes, in order to improve the nuclear fragmentation description in next generation Treatment Planning Systems and the treatment plans quality. Target (16O and 12C nuclei) fragmentation induced by –proton beams at therapeutic energies will be studied via an inverse kinematic approach, where 16O and 12C therapeutic beams impinge on graphite and hydrocarbon targets to provide the nuclear fragmentation cross section on hydrogen. Projectile fragmentation of 16O and 12C beams will be explored as well. The FOOT detector includes a magnetic spectrometer for the fragments momentum measurement, a plastic scintillator for ΔE and time of flight measurements and a crystal calorimeter to measure the fragments kinetic energy. These measurements will be combined in order to make an accurate fragment charge and isotopic identification. Keywords: Hadrontherapy, Nuclear fragmentation cross sections, Tracking detectors, Scintillating detector

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Monitoraggio di fauna ittica nelle zone interessate da barriere artificiali sommerse nelle acque costiere adriatiche della Regione Abruzzo

Le Province di Teramo e Pescara hanno installato tre barriere artificiali sommerse costituite da moduli in calcestruzzo e da massi naturali nelle acque costiere della regione Abruzzo per il ripopolamento della fauna ittica e per impedire la pesca a strascico illegale, utilizzando specifici finanziamenti europei. Le Province hanno affidato all’Istituto G. Caporale l’incarico di monitorare l’evoluzione delle popolazioni nectobentoniche mediante 3 campionamenti annuali in ciascuna barriera artificiale. Questo lavoro riporta i risultati dello studio condotto dal 2005 al 2007, ottenuti comparando le catture effettuate nelle aree interessate dalle barriere con quelle dei siti di controllo attraverso l’uso di alcuni indici di diversità. Le aree interessate da barriere artificiali mostrano una maggiore diversità e ricchezza di specie rispetto alle aree di controllo. Pertanto le barriere artificiali possono contribuire sia a risolvere i problemi legati allo scarso reddito della pesca artigianale e all’eccessivo sfruttamento delle risorse alieutiche, sia all’avvio di quei processi di diversificazione degli habitat che facilitano l’incremento della diversità biologica

Monitoring of ichthyic fauna in artificial reefs along the Adriatic coast of the Abruzzi Region of Italy

With the support of European Community funds, three submerged artificial reefs composed of concrete cubes, bell-shaped modules and natural rocks were deployed along the Adriatic coast of the Abruzzi Region to increase the fish population and to prevent illegal trawling. The Provincial governments of Teramo and Pescara requested the Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise ‘G. Caporale’ to monitor nectobenthic populations. Three sampling operations were conducted each year for each artificial reef. The authors present the results of a study conducted between 2005 and 2007, comparing the catches from the artificial reefs with those from the control sites using several diversity indexes. Artificial reef areas revealed greater species diversity and richness than the control sites. This study demonstrates the value of artificial reefs in response to the problem of low income, non-commercial fisheries as well as to the issue of over-exploitation of halieutic resources. In addition, the authors suggest that artificial reefs may be capable of activating habitat diversification processes that will increase biodiversity

Valutazione del ruolo delle IgM, IgG, IgA sieriche e delle IgA dello sputo nella diagnosi di polmonite comunitaria da Chlamydia pneumoniae: studio italiano policentrico

To evaluate the incidence of Chlamydia pneumoniae as etiologic agent of community acquired pneumonia (CAP), specific IgM and IgG antibodies anti-C. pneumoniae in serum and IgA in both serum and sputum were detected by a new ELISA-like test (EIA CP-IgG, IgA, IgM – Eurospital, Italy).The study was carried out from January 1999 to July 2001 in sixteen Italian Hospitals on a total of 141 patients with clinical signs of CAP. At a primary inspection (time T-0) serum and sputum samples were taken from 115/141 patients, whereas serum was collected from only 100/141 patients after 30 days (time T-30). At T-0 24/115 (20.8%) patients showed serological markers suggesting primary C. pneumoniae infection. In 23/24 patients the overall serological pattern found at T-0 was confirmed at T-30. In 32/115 patients (27.8%) serological markers of C. pneumoniae suggesting secondary infection were found positive and were confirmed 30 days later. Our data support the possible role played by C. pneumoniae as an important etiologic agent of CAP throughout different geographic areas of Italy.The test was suitable for the laboratory diagnosis of Chlamydia pneumoniae infection. In particular, the presence of specific IgA anti-Chlamydia pneumoniae in both serum and sputum revealed to be useful to define different stages and evolution of infection

Infezione da Borrelia burgdorferi: descrizione di un caso clinico atipico

La borreliosi o Malattia di Lyme (ML) è una malattia infettiva multisistemica causata da una spirocheta, Borrelia burgdorferi, trasmessa dal morso di una zecca del genere Ixodes.Viene descritto il caso clinico di una ragazza di venti anni. In un soggiorno estivo sul Monte Amiata, in Toscana, la giovane notò un arrossamento della pelle al fianco sinistro del corpo. Non osservò presenza della zecca nella zona di presumibile inoculo, da cui si sviluppò un eritema migrante (EM) ad andamento centrifugo, fino a raggiungere un diametro di circa 10 centimetri. Nei giorni successivi e durante il follow up non sono mai comparsi sintomi collaterali generali riferibili ad astenia, febbricola, artralgie, malessere, né a carico di organi bersaglio. Dopo circa due settimane, persistendo l’EM, sono stati eseguiti esami sierologici specifici per Borrelia burgdorferi. Al riscontro positivo dei test ELISA e western-blot IgG e IgM, il clnico ha prescritto terapia antibiotica a base di Amoxicillina 2g/die per 20 giorni.Dopo 8-10 giorni di terapia è avvenuta la scomparsa completa dell’eritema. Viene mostrato l’andamento dei test sierologici al momento della diagnosi e durante il follow up, per un periodo di circa cinque mesi