The ambitious role of anti angiogenesis molecules: Turning a cold tumor into a hot one

In renal cancer emerging treatment options are becoming available and there is a strong need to combine therapies to reformulate and adjourn clinical practice. We here highlight and discuss the need to take advantage of the common immune targets to design combined strategies to increase clinical responses

Commissioning of a Novel Test Apparatus for the Identification of the Dynamic Coefficients of Large Tilting Pad Journal Bearings

This paper describes the commissioning of a novel test bench for the static and dynamic characterization of large tilting pad journal bearings, realized within a collaboration of the Department of Civil and Industrial Engineering of the University of Pisa, BHGE and AM Testing. The adopted test bench configuration has the test article (TA) floating at the mid-span of a rotor supported by two rolling bearings. The TA is statically loaded vertically upwards by a hydraulic actuator and excited dynamically by two orthogonal hydraulic actuators with multiple frequency sinusoidal forces. The test rig is capable of testing bearings with a diameter from 150 to 300 mm. It includes very complex mechanical, hydraulic, electrical and electronic components, and needs, for the whole plant, about 1 MW of electric power. The commissioning of the testing system involved several aspects and presented various issues. This work focuses on measuring systems and data acquisition of high-frequency data (forces, accelerations and relative displacements) and on data processing for the identification of the bearing dynamic coefficients. The identification procedure is based on the linearity assumption and the principle of superposition, operating in the frequency domain with the fast Fourier transforms of the applied forces and displacement signals. First results, referred to a 4-pad bearing, are in satisfactory agreement with theoretical ones

Risk adjustment for inter-hospital comparison of caesarean delivery rates in low-risk deliveries

BACKGROUND: Caesarean delivery (CD) rates have been frequently used as quality measures for maternity service comparisons. More recently, primary CD rates (CD in women without previous CD) or CD rates within selected categories such as nulliparous, term, cephalic singleton deliveries (NTCS) have been used. The objective of this study is to determine the extent to which risk adjustment for clinical and socio-demographic variables is needed for inter-hospital comparisons of CD rates in women without previous CD and in NTCS deliveries. METHODS: Hospital discharge records of women who delivered in Emilia-Romagna Region (Italy) from January, 2007 to June 2009 and in Tuscany Region for year 2009 were linked with birth certificates. Adjusted RRs of CD in women without a previous Caesarean and NTCS were estimated using Poisson regression. Percentage differences in RR before and after adjustment were calculated and hospital rankings, based on crude and adjusted RRs, were examined. RESULTS: Adjusted RR differed substantially from crude RR in women without a previous Caesarean and only marginally in NTCS group. Hospital ranking was markedly affected by adjustment in women without a previous CD, but less in NTCS. CONCLUSION: Risk adjustment is warranted for inter-hospital comparisons of primary CD rates but not for NTCS CD rates. Crude NTCS CD rates are a reliable estimate of adjusted NTCS CD

Demography of the bottlenose dolphin Tursiops truncatus (Mammalia: Delphinidae) in the Eastern Ligurian Sea (NW Mediterranean): quantification of female reproductive parameters

AbstractThe reproductive histories of 41 adult bottlenose dolphin females were analysed using photo-identification data collected between 2006 and 2014 in four sub-areas of the eastern Ligurian Sea (northwest Mediterranean). The Rapallo sub-area revealed the highest (highly significant) frequency of encounters (per unit effort) of reproductive females in association with young individuals, therefore emerging as a candidate nursery area in the region. The estimated fertility rate of adult females ranged between 290 and 407 births per 1000 individuals per year, higher than that of other known bottlenose dolphin populations, with a calving interval between 2.45 and 3.5 years. These results will be useful for projecting future trends of this (sub)population

Ehrlichia infection in Italy.

Immunoglobulin M seroconversion to Ehrlichia chaffeensis was documented in U.S. citizens bitten by ticks in Sardinia. Seven cases of suspected ehrlichiosis in local residents were not confirmed by laboratory tests. In Alpine areas antibodies to E. phagocytophila were detected in persons at high risk, i.e., foresters (8.6%) and hunters (5.5%), and in controls (1.5%). Of 153 persons bitten by ticks, only one was Ehrlichia antibody-positive after 6 months

Network analysis of gut microbiome and metabolome to discover microbiota-linked biomarkers in patients affected by non-small cell lung cancer

Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients

Network analysis of gut microbiome and metabolome to discover microbiota-linked biomarkers in patients affected by non-small cell lung cancer

Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients

Di-(2-ethylhexyl) phthalate metabolites in urine show age-related changes and associations with adiposity and parameters of insulin sensitivity in childhood

Objectives: Phthalates might be implicated with obesity and insulin sensitivity. We evaluated the levels of primary and secondary metabolites of Di-(2-ethylhexyl) phthalate (DEHP) in urine in obese and normal-weight subjects both before and during puberty, and investigated their relationships with auxological parameters and indexes of insulin sensitivity. Design and Methods: DEHP metabolites (MEHP, 6-OH-MEHP, 5-oxo-MEHP, 5-OH-MEHP, and 5-CX-MEHP), were measured in urine by RP-HPLC-ESI-MS. Traditional statistical analysis and a data mining analysis using the Auto-CM analysis were able to offer an insight into the complex biological connections between the studied variables. Results: The data showed changes in DEHP metabolites in urine related with obesity, puberty, and presence of insulin resistance. Changes in urine metabolites were related with age, height and weight, waist circumference and waist to height ratio, thus to fat distribution. In addition, clear relationships in both obese and normal-weight subjects were detected among MEHP, its products of oxidation and measurements of insulin sensitivity. Conclusion: It remains to be elucidated whether exposure to phthalates per se is actually the risk factor or if the ability of the body to metabolize phthalates is actually the key point. Further studies that span from conception to elderly subjects besides further understanding of DEHP metabolism are warranted to clarify these aspects

Discovery of chemotherapy-associated ovarian cancer antigens by interrogating memory T cells

According to the immunogenic cell death hypothesis, clinical chemotherapy treatments may result in CD8(+) and CD4(+) T-cell responses against tumor cells. To discover chemotherapy-associated antigens (CAAs), T cells derived from ovarian cancer (OC) patients (who had been treated with appropriate chemotherapy protocols) were interrogated with proteins isolated from primary OC cells. We screened for immunogenicity using two-dimensional electrophoresis gel-eluted OC proteins. Only the selected immunogenic antigens were molecularly characterized by mass-spectrometry-based analysis. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were correlated with prolonged survival in response to chemotherapy, supporting the model of chemotherapy-induced apoptosis as an adjuvant of anti-tumor immunity. The strength of both memory CD4(+) and CD8(+) T cells producing either IFN- or IL-17 in response to apoptotic OC antigens was also significantly greater in Responders to chemotherapy than in nonresponders. Immunogenicity of some of these antigens was confirmed using recombinant proteins in an independent set of patients. The T-cell interrogation system represents a strategy of reverse tumor immunology that proposes to identify CAAs, which may then be validated as possible prognostic tumor biomarkers or cancer vaccines