High-resolution 40Ar/39Ar chronostratigraphy of the post-caldera (<20 ka) volcanic activity at Pantelleria, Sicily Strait

The island of Pantelleria (Sicily Strait), the type locality for pantellerite, has been the locus of major calderaforming eruptions that culminated, ca. 50 ka ago, in the formation of the Cinque Denti caldera produced by the Green Tuff eruption. The post-caldera silicic activity since that time has been mostly confined inside the caldera and consists of smaller-energy eruptions represented by more than twenty coalescing pantelleritic centers structurally controlled by resurgence and trapdoor faulting of the caldera floor. A high-resolution 40Ar/39Ar study was conducted on key units spanning the recent (post-20 ka) intracaldera activity to better characterize the present-day status (and forecast the short-term behavior of) the system based on the temporal evolution of the latest eruptions. The new 40Ar/39Ar data capture a long-term (N15 ka) decline in eruption frequency with a shift in eruptive pace from 3.5 ka−1 to 0.8 ka−1 associated with a prominent paleosol horizon marking the only recognizable volcanic stasis around 12–14 ka. This shift in extraction frequency occurswithoutmajor changes in eruptive style, and is paralleled by a subtle trend of decreasingmelt differentiation index. We speculate that this decline probably occurred (i) without short-term variations in melt production/differentiation rate in a steadystate compositionally-zoned silicic reservoir progressively tapped deeper through the sequence, and (ii) that it was possibly modulated by outboard eustatic forcing due to the 140 m sea level rise over the past 21 ka. The intracaldera system is experiencing a protracted stasis since 7 ka. Coupled with recent geodetic evidence of deflation and subsidence of the caldera floor, the system appears today to be on a wane with no temporal evidence for a short-term silicic eruption

Skeletal muscle Na+K+-ATPase function in Type II diabetes

Insulin resistance is a common factor in metabolic disorders, such as obesity and Type II diabetes mellitus. In skeletal muscle, insulin can induce the translocation of both glucose transporters and the &amp;alpha;-subunit of the Na+K+-ATPase to the plasma membrane. Whilst the detrimental effects of insulin resistance upon insulin-mediated glucose uptake is well recognized, little is known about the effect on Na+K+-ATPase function and the potential benefits antidiabetic therapies, such as exercise training and Rosiglitazone can have on Na+K+-ATPase function in insulin resistant skeletal muscle. Therefore the primary aim of this dissertation was to determine the effect of insulin resistance on Na+K+-ATPase content and maximal in vitro activity in skeletal muscle and the possible beneficial effects of the insulin sensitising drug, Rosiglitazone and exercise training on Na+K+-ATPase. Since Na+K+-ATPase is a membrane-bound enzyme and its function is dependant upon the membrane lipid milieu surrounding it, a second focus of this thesis was to examine a possible link between changes in enzyme activities and membrane phospholipids. The results of the studies undertaken for this thesis repeatedly demonstrated that insulin resistance has a detrimental effect on Na+K+-ATPase function in skeletal muscle. This was shown in both the genetically predisposed obese Zucker and high fat (HF) diet induced Sprague Dawley rat models of insulin resistance. This may have been due to changes seen in the phospholipid profile however this may depend on the insulin resistant animal model used. The findings indicate compromised Na+K+-ATPase function, causing a reduced reserve for Na+K+-ATPase activation in insulin resistant skeletal muscle. This may predispose diabetics to early muscle fatigue with associated impaired exercise tolerance and may further progress the development of type II diabetes and its associated complications. Despite insulin sensitivity increasing through Rosiglitazone, Na+K+-ATPase activity was reduced in the lean rats only. Rosiglitazone had either no effect on Na+K+-ATPase in skeletal muscle of obese Zucker rats or, its effect was not seen because it was not additive to the decrease already observed with insulin resistance alone. Rosiglitazone treatment also did not have any effect on Na+K+-ATPase function in skeletal muscle of the HF fed rats. The other important finding from this thesis was the positive effect exercise training had on the reduced Na+K+-ATPase capacity found with insulin resistance. For the first time, it was shown that chronic exercise training increased Na+K+-ATPase activity and content, reversing the negative effect of insulin resistance on Na+K+-ATPase function

Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in children allergic to Parietaria pollen treated with inhaled fluticasone propionate

Immunotherapy is a recognized treatment for allergic respiratory diseases

Health-related quality of life and functional changes in DMD:A 12-month longitudinal cohort study

Family caregivers of people with amyotrophic lateral sclerosis (ALS) live stressful lives in which they spend most of their time caring for their loved ones and managing difficult situations, thereby reducing the time spent in taking care of themselves. This situation may last several years. Previous literature has widely highlighted that this situation reduces caregivers' quality of life and increases their psychological distress and risk of health problems, but there is a lack of studies that focus on psychological interventions for these situations. This qualitative study examined a pilot experience of two mutual support groups for family caregivers of people with ALS. The aim was to identify caregivers' needs, the prominent aspects of their experience, and to understand whether and how this intervention strategy might help them. Six partners (four men and two women) and six adult children (five women and one man) participated in the groups, which were conducted in northern Italy. After the support groups finished, participants underwent semi-structured interviews. The authors conducted a content analysis of the transcripts of the interviews and the 20 group sessions. The thematic areas identified were "caregiving," "being the son/daughter of a person with ALS," "being the partner of a person with ALS," "group experience" and "group evaluation." The caregiving experience was profoundly different depending on whether the caregiver was a son/daughter or a partner of a patient with ALS. Moreover, comparison with peers and mutual support helped participants to better cope with ALS and its consequences, to improve their care for their relatives and to overcome typical caregiver isolation. These results suggest the usefulness of involving communities in caregiver support in order to create new networks and activate personal and social resources for well-being

Expression of telomeric repeat binding factor-1 in astroglial brain tumors

OBJECTIVE: In human somatic cells, telomeres shorten with successive cell divisions, resulting in progressive genomic instability, altered gene expression, and cell death. Recently, telomere-specific deoxyribonucleic acid-binding proteins, such as telomeric repeat binding factor-1 (TRF1), have been proposed as candidates for the role of molecules regulating telomerase activity, and they have been suggested to play key roles in the maintenance of telomere function. The present study was designed to assess TRF1 expression in human astroglial brain tumors and to speculate on the clinical implications of its expression. METHODS: Twenty flash-frozen surgical specimens obtained from adult patients who underwent craniotomy for microsurgical tumor resection, histologically verified as World Health Organization Grade II to IV astrocytomas, were used. Expression of TRF1 in astrocytomas of different grades was studied by means of both immunohistochemical and Western blotting analysis. The correlation between the extent of TRF1 expression and histological grading, performance status, and length of survival of patients underwent statistical analyses. RESULTS: TRF1 was expressed in all tumor samples. The level of its expression was variable, decreasing from low-grade through high-grade astrocytomas (P 0.0032). TRF1 expression correlated with the patient’s length of survival (P 0.001) and performance status (P 0.001) and proved to be an independent indicator of length of survival. CONCLUSION: Our findings suggest that the loss of TRF1 expression capability, as a result of down-regulation of TRF1 expression in malignant gliomas cells, may play a role in the malignant progression of astroglial brain tumors

Effect of solid waste landfill organic pollutants on groundwater in three areas of Sicily (Italy) characterized by different vulnerability

The aim of this study was to obtain information on the presence and levels of hazardous organic pollutants in groundwater located close to solid waste landfills. Eighty-two environmental contaminants, including 16 polycyclic aromatic hydrocarbons (PAHs), 20 volatile organic compounds (VOCs), 29 polychlorinated biphenyls (PCBs), 7 dioxins (polychlorinated dibenzo-p-dioxins, PCDDs) and 10 furans (polychlorinated dibenzofurans, PCDFs) were monitored in areas characterised by different geological environments surrounding three municipal solid waste landfills (Palermo, Siculiana and Ragusa) in Sicily (Italy) in three sampling campaigns. The total concentrations of the 16 PAHs were always below the legal threshold. Overall, the Fl/Fl + Py diagnostic ratio revealed that PAHs had a petrogenic origin. VOC levels, except for two notable exceptions near Palermo landfill, were always below the legal limit. As concerns PCB levels, several samples were found positive with levels exceeding the legal limits. It is worth noting that the % PCB distribution differs from that of commercial compositions. In parallel, some samples of groundwater containing PCDDs and PCDFs exceeding the legal threshold were also found. Among the 17 congeners monitored, the most abundant were the highest molecular weight ones

A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days

Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial. Preclinical studies showed antitumour activity in a broad range of human tumour xenografts. A phase I trial was performed with a 7-day b.i.d. p.o. schedule. Twenty-one patients (median age 62 years, range: 39–73 years) were treated with doses of 100, 200 and 800 b.i.d. Dose-limiting toxicities were seen at 800 mg b.i.d.; grade 3 fatigue, grade 3 skin rash, grade 3 hyponatraemia and grade 4 hypokalaemia. Other toxicities included reversible raised creatinine (grade 2), reversible grade 3 abnormal liver function and grade 2 emesis. An 800 mg portion was investigated further in 12 patients, three of whom had MAG3 renograms. One patient with a rapid increase in creatinine on day 3 had a reversible fall in renal perfusion, with full recovery by day 14, and no changes suggestive of renal tubular damage. Further dose escalation was precluded by hypokalaemia. Seliciclib reached peak plasma concentrations between 1 and 4 h and elimination half-life was 2–5 h. Inhibition of retinoblastoma protein phosphorylation was not demonstrated in peripheral blood mononuclear cells. No objective tumour responses were noted, but disease stabilisation was recorded in eight patients; this lasted for a total of six courses (18 weeks) in a patient with ovarian cancer

Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation

<p>Abstract</p> <p>Background</p> <p>In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m²weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting.</p> <p>Methods</p> <p>40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m²to 100 mg/m². Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.</p> <p>Results</p> <p>Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine.</p> <p>Conclusion</p> <p>Low-dose fotemustine at 65–75 mg/m²(induction phase) followed by 75–85 mg/m²(maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.</p

Anthropometric measures at different ages and endometrial cancer risk

BACKGROUND: Endometrial cancer is strongly associated with body mass index (BMI), but the influence of BMI history and of different types of obesity is uncertain. METHODS: A case\u2013control study was carried out in Italy including 454 cases and 908 controls admitted to hospital for acute non-hormone-related conditions. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using multivariate logistic and spline regression models. RESULTS: The OR for BMI 430 at diagnosis compared with 20 to o25 kgm 2 was 4.08 (95% CI: 2.90\u20135.74). The association for BMI was monotonic with a possible steeper increase for BMI above 28. Conversely, waist-to-hip ratio (WHR) showed a bell shaped curve with increased OR (2.10; 95% CI: 1.43\u20133.09) in the intermediate tertile only. After stratification by BMI at diagnosis, history of weight loss and BMI at age 30 did not influence endometrial cancer risk. History of obesity in middle age had a weak and not significant adverse effect among obese women (OR\ubc1.60; 95% CI: 0.52\u20134.96). CONCLUSION: The predominant importance of recent weight compared to lifetime history, justifies encouraging weight reduction in women at any age

A Snapshot on the On-Label and Off-Label Use of the Interleukin-1 Inhibitors in Italy among Rheumatologists and Pediatric Rheumatologists: A Nationwide Multi-Center Retrospective Observational Study.

Background: Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis. Objectives: To perform a nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults. Methods: We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016. Results: Five hundred and twenty-six treatment courses given to 475 patients (195 males, 280 females; 111 children and 364 adults) were evaluated. ANA was administered in 421 (80.04%) courses, CAN in 105 (19.96%). Sixty-two (32.1%) patients had been treated with both agents. IL-1 inhibitors were employed in 38 different indications (37 with ANA, 16 with CAN). Off-label use was more frequent for ANA than CAN (p < 0.0001). ANA was employed as first-line biologic approach in 323 (76.7%) cases, while CAN in 37 cases (35.2%). IL-1 inhibitors were associated with corticosteroids in 285 (54.18%) courses and disease modifying anti-rheumatic drugs (DMARDs) in 156 (29.65%). ANA dosage ranged from 30 to 200 mg/day (or 1.0-2.0 mg/kg/day) among adults and 2-4 mg/kg/day among children; regarding CAN, the most frequently used posologies were 150mg every 8 weeks, 150mg every 4 weeks and 150mg every 6 weeks. The frequency of failure was higher among patients treated with ANA at a dosage of 100 mg/day than those treated with 2 mg/kg/day (p = 0.03). Seventy-six patients (14.4%) reported an adverse event (AE) and 10 (1.9%) a severe AE. AEs occurred more frequently after the age of 65 compared to both children and patients aged between 16 and 65 (p = 0.003 and p = 0.03, respectively). Conclusions: IL-1 inhibitors are mostly used off-label, especially ANA, during adulthood. The high frequency of good clinical responses suggests that IL-1 inhibitors are used with awareness of pathogenetic mechanisms; adult healthcare physicians generally employ standard dosages, while pediatricians are more prone in using a weight-based posology. Dose adjustments and switching between different agents showed to be effective treatment strategies. Our data confirm the good safety profile of IL-1 inhibitors