Evaluation of the QTc interval during lenvatinib treatment in radioiodine-refractory differentiated thyroid cancer: reports from the real-life clinical practice.

As for other tyrosine kinase inhibitors, a prolongation of ECG-recorded QTc intervals may be observed during lenvatinib treatment; a warning on this phenomenon has been stated. However, methods and frequency of ECG recordings have seldom been reported in this context. We present two cases of patients treated with lenvatinib for radioiodine-refractory differentiated thyroid cancer in whom the QTc interval was long monitored through a weekly 12-lead ECG registration. Overall, the maximum QTc increase above baseline was 3 and 31 ms in the first and second patient, respectively. QTc interval did not reach the toxicity value for drug withdrawal in either of the patients. These data may provide further information on cardiac safety profile of lenvatinib in a real-life practice

Enhanced adsorption capacity of porous titanium dioxide nanoparticles synthetized in alkaline sol

Abstract In recent years, the exploitation of natural resources and industrial development have led to the production of harmful pollutants. Much of these contaminants end up in water resources, reducing the availability of drinking water. Therefore, it is necessary to find remedies to this situation. Solutions could be the adsorption or the degradation through photocatalysis of these compounds. A good candidate for this task is titanium dioxide (TiO2), due to its non-toxicity, stability and low cost. In this work, we propose a novel synthesis of TiO2 nanoparticles (NPs), with high adsorption capacity, produced at low temperature in alkaline environment. Adsorption tests were conducted using methylene blue and diclofenac as model pollutants. Moreover, the obtained NPs have been characterized through Raman spectroscopy, Scanning and Transmission electron microscopies and with thermogravimetric analysis. The results showed a porous structure with a high surface area, able to efficiently adsorb large amounts of dye from the aqueous solution. These properties make the obtained TiO2 powders suitable for applications devoted to the adsorption and recovery of harmful compounds. Graphic abstrac

Binge-like administration of alcohol mixed to energy drinks to male adolescent rats severely impacts on mesocortical dopaminergic function in adulthood: A behavioral, neurochemical and electrophysiological study

A growing body of evidence indicates that the practice of consuming alcohol mixed with energy drinks (ED) (AMED) in a binge drinking pattern is significantly diffusing among the adolescent population. This behavior, aimed at increasing the intake of alcohol, raises serious concerns about its long-term effects. Epidemiological studies suggest that AMED consumption might increase vulnerability to alcohol abuse and have a gating effect on the use of illicit drugs. The medial prefrontal cortex (mPFC) is involved in the modulation of the reinforcing effects of alcohol and of impulsive behavior and plays a key role in the development of addiction. In our study, we used a binge-like protocol of administration of alcohol, ED, or AMED in male adolescent rats, to mimic the binge-like intake behavior observed in humans, in order to evaluate whether these treatments could differentially affect the function of mesocortical dopaminergic neurons in adulthood. We did so by measuring: i) physiological sensorimotor gating; ii) voluntary alcohol consumption and dopamine transmission before, during, and after presentation of alcohol; iii) electrophysiological activity of VTA dopaminergic neurons and their sensitivity to a challenge with alcohol. Our results indicate that exposure to alcohol, ED, or AMED during adolescence induces differential adaptive changes in the function of mesocortical dopaminergic neurons and, in particular, that AMED exposure decreases their sensitivity to external stimuli, possibly laying the foundation for the altered behaviors observed in adulthood

Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease

Background Current evidence suggests a role of neuroinflammation in the pathogenesis of Parkinson's disease (PD) and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of basal ganglia injury. Reportedly, nonsteroidal anti-inflammatory drugs (NSAIDs) mitigate DAergic neurotoxicity in rodent models of PD. Consistent with these findings, epidemiological analysis indicated that certain NSAIDs may prevent or delay the progression of PD. However, a serious impediment of chronic NSAID therapy, particularly in the elderly, is gastric, renal and cardiac toxicity. Nitric oxide (NO)-donating NSAIDs, have a safer profile while maintaining anti-inflammatory activity of parent compounds. We have investigated the oral activity of the NO-donating derivative of flurbiprofen, [2-fluoro-α-methyl (1,1'-biphenyl)-4-acetic-4-(nitrooxy)butyl ester], HCT1026 (30 mg kg-1 daily in rodent chow) in mice exposed to the parkinsonian neurotoxin MPTP. Methods Ageing mice were fed with a control, flurbiprofen, or HCT1026 diet starting ten days before MPTP administration and continuing for all the experimental period. Striatal high affinity synaptosomial dopamine up-take, motor coordination assessed with the rotarod, tyrosine hydroxylase (TH)- and dopamine transporter (DAT) fiber staining, stereological cell counts, immunoblotting and gene expression analyses were used to assess MPTP-induced nigrostriatal DAergic toxicity and glial activation 1-40 days post-MPTP. Results HCT1026 was well tolerated and did not cause any measurable toxic effect, whereas flurbiprofen fed mice showed severe gastrointestinal side-effects. HCT1026 efficiently counteracted motor impairment and reversed MPTP-induced decreased synaptosomal [3H]dopamine uptake, TH- and DAT-stained fibers in striatum and TH+ neuron loss in subtantia nigra pars compacta (SNpc), as opposed to age-matched mice fed with a control diet. These effects were associated to a significant decrease in reactive macrophage antigen-1 (Mac-1)-positive microglial cells within the striatum and ventral midbrain, decreased expression of iNOS, Mac-1 and NADPH oxidase (PHOX), and downregulation of 3-Nitrotyrosine, a peroxynitrite finger print, in SNpc DAergic neurons. Conclusions Oral treatment with HCT1026 has a safe profile and a significant efficacy in counteracting MPTP-induced dopaminergic (DAergic) neurotoxicity, motor impairment and microglia activation in ageing mice. HCT1026 provides a novel promising approach towards the development of effective pharmacological neuroprotective strategies against PD

The vaccinaTion & Hpv Knowledge (THinK) questionnaire: a reliability and validity study on a sample of women living in Sicily (southern-Italy)

Objective The aim of this study was to introduce the VaccinaTion & Hpv Knowledge (THinK) questionnaire to assess knowledge about human papillomavirus (HPV) and attitude to HPV-vaccination. Its reliability and validity was demonstrated in a sample of women living in Sicily (southern Italy). Methods A cross-sectional survey was conducted on a sample of 220 women at the “Paolo Giaccone” University Hospital in Palermo (Sicily), aged 18–61. Data were analyzed through Cronbach’s alpha and exploratory factor analysis, followed by a structural equation model with measurement component. The two-level data structure was explicitly considered. Results Three dimensions were found: “knowledge of HPV infection (kHPV), “Attitude to be vaccinated against HPV (aHPV)” and “Knowledge about vaccines (KV)” (97% overall explained variance). Internal consistency was good for the whole questionnaire (0.82) and the first dimension (0.88) and acceptable for the second (0.78) and the third dimension (0.73). 23% of women showed no or little knowledge of HPV and 44.3% of women had no or little knowledge about HPV induced lesions. Discussion The use of a validated questionnaire may serve as a useful measure to assess general knowledge about HPV and attitude towards vaccination against HPV in the primary prevention setting

Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

Shorter androgen receptor polyQ alleles protect against life-threatening COVID-19 disease in European males

Background: While SARS-CoV-2 similarly infects men and women, COVID-19 outcome is less favorable in men. Variability in COVID-19 severity may be explained by differences in the host genome. Methods: We compared poly-amino acids variability from WES data in severely affected COVID-19 patients versus SARS-CoV-2 PCR-positive oligo-asymptomatic subjects. Findings: Shorter polyQ alleles (≤22) in the androgen receptor (AR) conferred protection against severe outcome in COVID-19 in the first tested cohort (both males and females) of 638 Italian subjects. The association between long polyQ alleles (≥23) and severe clinical outcome (p = 0.024) was also validated in an independent cohort of Spanish men <60 years of age (p = 0.014). Testosterone was higher in subjects with AR long-polyQ, possibly indicating receptor resistance (p = 0.042 Mann-Whitney U test). Inappropriately low serum testosterone level among carriers of the long-polyQ alleles (p = 0.0004 Mann-Whitney U test) predicted the need for intensive care in COVID-19 infected men. In agreement with the known anti-inflammatory action of testosterone, patients with long-polyQ and age ≥60 years had increased levels of CRP (p = 0.018, not accounting for multiple testing). Interpretation: We identify the first genetic polymorphism that appears to predispose some men to develop more severe disease. Failure of the endocrine feedback to overcome AR signaling defects by increasing testosterone levels during the infection leads to the polyQ tract becoming dominant to serum testosterone levels for the clinical outcome. These results may contribute to designing reliable clinical and public health measures and provide a rationale to test testosterone as adjuvant therapy in men with COVID-19 expressing long AR polyQ repeats. Funding: MIUR project "Dipartimenti di Eccellenza 2018-2020" to Department of Medical Biotechnologies University of Siena, Italy (Italian D.L. n.18 March 17, 2020) and "Bando Ricerca COVID-19 Toscana" project to Azienda Ospedaliero-Universitaria Senese. Private donors for COVID-19 research and charity funds from Intesa San Paolo

Tracing rejuvenation events in nearby S0 galaxies

With the aim of characterizing rejuvenation processes in early-type galaxies, we analyzed five barred S0 galaxies showing prominent outer ring in ultraviolet (UV) imaging. We analyzed GALEX far- (FUV) and near- (NUV) UV and optical data using stellar population models and estimated the age and the stellar mass of the entire galaxies and of the UV-bright ring structures. Outer rings consist of young (<200 Myr old) stellar populations, accounting for up to 70% of the FUV flux but containing only a few % of the total stellar mass. Integrated photometry of the whole galaxies places four of these objects on the green valley, indicating a globally evolving nature. We suggest such galaxy evolution is likely driven by bar induced instabilities, i.e. inner secular evolution, that conveys gas to the nucleus and to the outer rings. At the same time, HI observations of NGC 1533 and NGC 2962 suggest external gas re-fueling can play a role in the rejuvenation processes of such galaxies.Comment: 23 pages, 5 figures and 2 tables, Accepted for publication in The Astrophysical Journa