L'Analisi della composizione corporea rivela l'esistenza di un'intrinseca eterogeneità clinica nel diabete latente autoimmune dell'adulto (LADA)

Background and aim: Latent autoimmune diabetes in adults (LADA) is characterized by the presence of islet autoantibodies in adult (over 35 years) patients with the phenotype of type 2 diabetes (T2D) at diagnosis, and not requiring insulin for at least 6 months after diagnosis. Although a low BMI was reported to be associated with a faster progression of the disease, the body composition in LADA is scarcely known. In this study the body composition of a large (n=251) LADA cohort was thoroughly investigated. Methods: We determined the body composition in 251 LADA patients, 251 T2D patients and 135 late-onset type 1 diabetes (T1D) patients of Sardinian origin. Weight, height, fat mass and lean mass were evaluated in a sample of patients using anthropometry, electric bioimpedance analysis (EBIA) and Dual Energy X-rays Absorption (DXA). Results: in LADA patients BMI shows a clear bimodal distribution with peaks at 28 and 33 kg/m², whereas in late-onset T1D and T2D the distribution is strictly unimodal. Visceral fat, but not total fat amount, is significantly lower in LADA compared to T2D. BMI-adjusted resting energy expenditure (REE) is also significantly increased in LADA compared to T2D. Conclusion: The bimodal distribution of BMI in LADA suggests the existence of two subgroups of patients with different body composition and fat distribution, and further underline the clinical heterogeneity of this subtype of diabetes

Full Load Testing Of A 12.5 MW Vertical High Speed Subsea Motorcompressor

Lecturepg. 79-92In late 2006 Authors’ company was awarded a contract for the motorcompressor for the Ormen Lange Subsea Compression Pilot. This Pilot represents the first subsea motorcompressor unit ever built in a fully marinized version and tested in a water pit, which was developed specifically for the project at the customer’s site (Nhyamna, Norway). The prototype unit is a 12.5MW (16763HP) integrated motorcompressor, which runs up to 10.5krpm in a vertical configuration with the following features: Single casing; High-speed motor rigidly coupled to a multistage centrifugal compressor (3 journal bearings shaft line); Canned Active Magnetic Bearings (AMBs); Process gas used as cooling fluid for the Electric Motor; Internal separation system (to protect the bearings and the electric motor from the intrusion of solid and liquid materials); Fully marinized AMBs control system; The design and validation plan for this complex equipment were developed through a four years program where many challenging milestones were achieved. The Ormen Lange Subsea Compression Pilot motorcompressor has successfully completed an intensive full load testing campaign in the Authors’ Company plant including the following: Static-dynamic tuning of the AMBs; Mechanical Running Test; Compressor Performance Test (ASME PTC-10 Type 2 + Full Load test); Electric Motor Performance Test; Overall cooling system check; Landing test (partial landing and full speed delevitation test). The test campaign has fully demonstrated the functionality of this prototype unit capable of operation in the service conditions. The Next step will be the shipment to the costumer site where the submerged testing will be conducted. This paper will provide a detailed description of the main test results of the subsea motorcompressor covering all aspects of the test program including rotordynamic behaviour, compressor thermodynamic performance, axial load variation versus operating conditions (monitored thanks to the thrust AMB), electric motor cooling system behaviour, electric motor performance, AMBs and control system operability. Of special interest is the rotor delevitation test from full speed consisting in the two ton rotor running at 10.5krpm dropping onto the mechanical emergency bearings until the machine reached a complete stop condition. This test, which was repeated 5 times, provided a full-scale verification of the landing numerical simulation developed by the authors (Ransom et al., 2009)

The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction

Previous studies based on low oxygen concentrations in the incubation atmosphere revealed that metabolic factors govern the maintenance of normal hematopoietic or leukemic stem cells (HSC and LSC). The physiological oxygen concentration in tissues ranges between 0.1 and 5.0%. Stem cell niches (SCN) are placed in tissue areas at the lower end of this range (“hypoxic” SCN), to which stem cells are metabolically adapted and where they are selectively hosted. The data reported here indicated that driver oncogenic proteins of several leukemias are suppressed following cell incubation at oxygen concentration compatible with SCN physiology. This suppression is likely to represent a key positive regulator of LSC survival and maintenance (self-renewal) within the SCN. On the other hand, LSC committed to differentiation, unable to stand suppression because of addiction to oncogenic signalling, would be unfit to home in SCN. The loss of oncogene addiction in SCN-adapted LSC has a consequence of crucial practical relevance: the refractoriness to inhibitors of the biological activity of oncogenic protein due to the lack of their molecular target. Thus, LSC hosted in SCN are suited to sustain the long-term maintenance of therapy-resistant minimal residual disease

Life-course socioeconomic status and DNA methylation of genes regulating inflammation

Background: In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment. Methods: The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study. Results: Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals. Conclusions: Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease ris

Epidemiological surveillance of West Nile neuroinvasive diseases in Italy, 2008 to 2011.

Binary file ES_Abstracts_Final_ECDC.txt matche

Differentially methylated microRNAs in prediagnostic samples of subjects who developed breast cancer in the european prospective investigation into nutrition and cancer (EPIC-Italy) cohort

The crosstalk between microRNAs (miRNAs) and other epigenetic factors may lead to novel hypotheses about carcinogenesis identifying new targets for research. Because a single miRNA can regulate multiple downstream target genes, its altered expression may potentially be a sensitive biomarker to detect early malignant transformation and improve diagnosis and prognosis. In the current study, we tested the hypothesis that altered methylation of miRNA encoding genes, associated with deregulated mature miRNA expression, may be related to dietary and lifestyle factors and may contribute to cancer development. In a case-control study nested in a prospective cohort (EPIC-Italy), we analysed DNA methylation levels of miRNA encoding genes (2191 CpG probes related to 517 genes) that are present in the Infinium Human Methylation450 BeadChip array in prediagnostic peripheral white blood cells of subjects who developed colorectal cancer (CRC, n = 159) or breast cancer (BC, n = 166) and matched subjects who remained clinically healthy. In the whole cohort, several differentially methylated miRNA genes were observed in association with age, sex, smoking habits and physical activity. Interestingly, in the case-control study, eight differentially methylated miRNAs were identified in subjects who went on to develop BC (miR-328, miR-675, miR-1307, miR-1286, miR-1275, miR-1910, miR-24-1 and miR-548a-1; all Bonferroni-adjusted P < 0.05). No significant associations were found with CRC. Assuming that altered methylation of miRNAs detectable in blood may be present before diagnosis, it may represent a biomarker for early detection or risk of cancer and may help to understand the cascade of events preceding tumour onset

Surgical site infection after caesarean section. Space for post-discharge surveillance improvements and reliable comparisons

Surgical site infections (SSI) after caesarean section (CS) represent a substantial health system concern. Surveying SSI has been associated with a reduction in SSI incidence. We report the findings of three (2008, 2011 and 2013) regional active SSI surveillances after CS in community hospital of the Latium region determining the incidence of SSI. Each CS was surveyed for SSI occurrence by trained staff up to 30 post-operative days, and association of SSI with relevant characteristics was assessed using binomial logistic regression. A total of 3,685 CS were included in the study. A complete 30 day post-operation follow-up was achieved in over 94% of procedures. Overall 145 SSI were observed (3.9% cumulative incidence) of which 131 (90.3%) were superficial and 14 (9.7%) complex (deep or organ/space) SSI; overall 129 SSI (of which 89.9% superficial) were diagnosed post-discharge. Only higher NNIS score was significantly associated with SSI occurrence in the regression analysis. Our work provides the first regional data on CS-associated SSI incidence, highlighting the need for a post-discharge surveillance which should assure 30 days post-operation to not miss data on complex SSI, as well as being less labour intensive

The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort

Background: In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). Methods and Findings: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45, 52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of fullterm pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for >= 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95% CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Conclusions: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors