Overview of the benefitsand potential issues of the nonavalent HPV vaccine

HPV-related diseases affect anogenital and oropharyngeal regions, heavily affecting the psychosexual dimension of both male and female individuals. HPV vaccination programs based on a bivalent or quadrivalent vaccine have opened broad perspectives for primary prevention. A nonavalent HPV vaccine (9vHPV), covering nine genotypes (HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV45, HPV52, and HPV58), might provide further improvement in terms of direct protection. In the present report, efficacy and safety data from 9vHPV vaccine development programs are examined. Efficacy data come from a pivotal trial, which was conducted among women aged 16–26 years randomly assigned to receive either the 9vHPV or the quadrivalent HPV (4vHPV) vaccine. The 9vHPV vaccine was shown to have potential benefits as compared with 4vHPV, increasing the overall estimated rate of prevention to 90% for cervical cancer and up to 80% for precancerous cervical lesions. For all other HPV-related pre-invasive and invasive lesions, 9vHPV showed potentially greater disease reduction, depending on the anatomic region examined. Thus, the 9vHPV vaccine shows clinical potential for the prevention of HPV-related diseases in both sexes. Future adoption of 9vHPV will depend on factors including market price, cost-effectiveness data, use of a two-dose schedule, and safety and efficacy monitoring in real-life programs

Treatment responses to antiangiogenetic therapy and chemotherapy in nonsecreting paraganglioma (PGL4) of urinary bladder with SDHB mutation: a case report

Paraganglioma (PGL) is a rare neuroendocrine tumor. Currently, the malignancy is defined as the presence of metastatic spread at presentation or during follow-up. Several gene mutations are listed in the pathogenesis of PGL, among which succinate dehydrogenase (SDHX), particularly the SDHB isoform, is the main gene involved in malignancy. A 55-year-old male without evidence of catecholamine secretion had surgery for PGL of the urinary bladder. After 1 year, he showed a relapse of disease and demonstrated malignant PGL without evidence of catecholamine secretion with a germline heterozygous mutation of succinate dehydrogenase B (SDHB). After failure of a second surgery for relapse, he started medical treatment with sunitinib daily but discontinued due to serious side effects. Cyclophosphamide, vincristine, and dacarbazine (CVD) chemotherapeutic regimen stopped the disease progression for 7 months. Conclusion: Malignant PGL is a very rare tumor, and SDHB mutations must be always considered in molecular diagnosis because they represent a critical event in the progression of the oncological disease. Currently, there are few therapeutic protocols, and it is often difficult, as this case demonstrates, to decide on a treatment option according to a reasoned set of choices. Abbreviations: CVD = cyclophosphamide, vincristine and dacarbazine, HIF-1a = hypoxia inducible factor 1 alpha, PGL = paraganglioma, SDH = succinate dehydrogenase, VEGF = vasoendothelial growth factor

Evaluation of site effects by means of 3D numerical modeling of the Palatine Hill, Roman Forum, and Coliseum archaeological area

In this study we perform 3D nonlinear analyses of seismic site response of the Central Archaeological Area of Rome, which includes the Palatine Hill, Roman Forum, Circus Maximus, and Coliseum. The geological bedrock of the study area is constituted by a Pliocene marine sandy-clayey unit (MonteVaticano Formation, MVA). At top of this unit a continental Quaternary succession is superimposed. Previous studies available for this area (Pagliaroli et al. 2014a; Mancini et al. 2014; Moscatelli et al. 2014) enabled to define a detailed three-dimensional reconstruction of the subsoil conditions, characterized by complex surficial and buried morphology, lateral heterogeneities and dynamic properties of involved material, natural as well as anthropogenic. The area of Rome is affected by earthquakes from different seismogenic districts: i) the central Apennine mountain chain (D = 90–130km and M = 6.7–7.0); ii) the Colli Albani volcanic district (D = 20km and M=5.5); iii) Rome area itself, which is characterized by rare, shallow, low-magnitude events (M < 5). Both natural and artificial signals have been considered to define the input motion for the numerical modeling of the site response of the whole archeological area. This was accomplished by means of the finite differences code FLAC3D. To evaluate the seismic hazard and, consequently, to assess possible priorities for seismic retrofitting of the monuments, contour maps of Housner intensity amplification ratio FH (defined as the ratio between Housner intensity at the top of the model and the corresponding input at the bedrock outcrop), are carried out. To cover the entire range of natural periods pertaining to the monuments in the examined area, FH was evaluated over three ranges of period: 0.1–0.5s, 0.5–1.0s, and 1.0–2.0s. Numerical results shown that: 1) within the range of periods 0.1–0.5s, high values of FH = 2.2–2.6 occur both in correspondence of narrow valleys filled with soft alluvial deposits and at top of Palatine Hill; 2) within the range of periods 0.5–1.0s, high values of FH occur in correspondence of the deepest valleys; 3) within the range of periods 1.0–2.0s, low values of FH occur except in correspondence of the deepest valleys.Results show a good agreement with the previous 2D numerical modeling and with the microzonation maps (Pagliaroli et al 2014a, b), even if interesting differences show up highlighting the usefulness of 3D modeling in such complex settings. Such results are significantly relevant for the monumental and archaeological heritage of this area, as it is highly vulnerable due to its old age and state of conservation

The role of cell lysis and matrix deposition in tumor growth modeling

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A parametric study of a multiphase porous media model for tumor spheroids and environment interactions

Computational models for tumor growth provide an effective in silico tool to investigate the different stages of cancer growth. Recently, a series of computational models based on porous media theory has been proposed to predict tumor evolution and its interactions with the host tissue. In addition, a specialization of the original models, adapted for tumor spheroids, has been proposed and validated experimentally. However, due to the complexity of the modeling framework, a systematic understanding of the role of the parameters governing the equations is still lacking. In this work, we perform a parametric analysis on a set of fundamental parameters appearing in the model equations. We investigate the effects of a variation of these coefficients on the spheroid growth curves and, in particular, on the final radii reached by the cell aggregates in the growth saturation stage. Finally, we provide a discussion of the results and give a brief summary of our findings

Structure of the lectin mannose 6-phosphate receptor homology (MRH) domain of glucosidase II an enzyme that regulates glycoprotein folding quality control in the endoplasmic reticulum

Here we report for the first time the three-dimensional structure of a mannose 6-phosphate receptor homology (MRH) domain present in a protein with enzymatic activity, glucosidase II (GII). GII is involved in glycoprotein folding in the endoplasmic reticulum. GII removes the two innermost glucose residues from the Glc3Man9GlcNAc2 transferred to nascent proteins and the glucose added by UDP-Glc:glycoprotein glucosyltransferase. GII is composed of a catalytic GIIα subunit and a regulatory GIIβ subunit. GIIβ participates in the endoplasmic reticulum localization of GIIα and mediates in vivo enhancement of N-glycan trimming by GII through its C-terminal MRH domain. We determined the structure of a functional GIIβ MRH domain by NMR spectroscopy. It adopts a β-barrel fold similar to that of other MRH domains, but its binding pocket is the most shallow known to date as it accommodates a single mannose residue. In addition, we identified a conserved residue outside the binding pocket (Trp-409) present in GIIβ but not in other MRHs that influences GII glucose trimming activity.Fil: Olson, Linda J.. Medical College Of Wisconsin; Estados UnidosFil: Orsi, Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Alculumbre, Solana G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Peterson, Francis C.. Medical College Of Wisconsin; Estados UnidosFil: Stigliano, Ivan Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Parodi, Armando Jose A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: D'alessio, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires; ArgentinaFil: Dahms, Nancy M.. Medical College Of Wisconsin; Estados Unido

Aspirin Colorectal Cancer Prevention in Lynch Syndrome: Recommendations in the Era of Precision Medicine

Cancer prevention in the era of precision medicine has to consider integrated therapeutic approaches. Therapeutic cancer prevention should be offered to selected cohorts with increased cancer risk. Undoubtedly, carriers of hereditary cancer syndromes have a well-defined high cancer risk. Lynch Syndrome is one of the most frequent hereditary syndromes; it is mainly associated with colorectal cancer (CRC). Nonsteroidal anti-inflammatory drugs and, in particular, aspirin use, has been associated with reduced CRC risk in several studies, initially with contradictory results; however, longer follow-up confirmed a reduced CRC incidence and mortality. The CAPP2 study recruited 861 Lynch syndrome participants randomly assigned to 600 mg of aspirin versus placebo. Like sporadic CRCs, a significant CRC risk reduction was seen after an extended follow-up, with a median treatment time that was relatively short (2 years). The ongoing CAPP3 will address whether lower doses are equally effective. Based on pharmacology and clinical data on sporadic CRCs, the preventive effect should also be obtained with low-dose aspirin. The leading international guidelines suggest discussing with Lynch syndrome carriers the possibility of using low-dose aspirin for CRC prevention. We aim systematically promote this intervention with all Lynch syndrome carriers

Vitamins D and K as Factors Associated with Osteopathy in Chronic Pancreatitis. A Prospective Multicentre Study (P-BONE Study)

Background: Osteopathy is common in patients with chronic pancreatitis (CP), but previous studies carry several limitations. Vitamin K is essential for bone metabolism, but its role in this setting has never been investigated. Our aim is to assess the prevalence of osteoporosis and osteopenia in CP patients, and to investigate the association between osteopathy and CP features and nutritional parameters, especially vitamin D and K levels. Methods: Multicentre cross-sectional study on CP patients diagnosed according to M-ANNHEIM criteria. Bone density was evaluated by dual-energy X-ray absorptiometry and pancreatic function by faecal elastase. Nutritional evaluation included vitamin D and vitamin K. Differences between patients with or without osteopathy were evaluated. The association between investigated variables and bone density were analysed with logistic regression analysis. Results: In total, 211 CP patients were enrolled at eight Centres (67% men; mean age 60). In total, 18% had advanced-marked CP, 56% suffered from pancreatic exocrine insufficiency and disease aetiology was alcoholic in 43%. Vitamin D and K were deficient in 56% and 32%, respectively. Osteopenia was diagnosed in 42% and osteoporosis in 22%. In the multivariate analysis, female sex (OR 2.78), age (OR 1.07 per year) and higher BMI (OR 0.84) were associated with the presence of osteoporosis. In male patients, the only factor associated with osteoporosis was vitamin K deficiency (OR 4.23). Conclusion: The present data confirm a high rate of osteopathy in CP patients and highlight the relevance of vitamin K deficiency as only factor associated with osteoporosis in male patients for the first time

Geotechnical characterization of the upper Pleistocene-Holocene alluvial deposits of Roma (Italy) by means of multivariate geostatistics: Cross-validation results

We are presenting an attempt to evaluate the spatial variability of geotechnical parameters in the upper Pleistocene–Holocene alluvial deposits of Roma (Italy) by means of multivariate geostatistics. The upper Pleistocene–Holocene alluvial deposits of Roma are sensitive to high levels of geohazard. They occupy a sizable and significant part of the city, being the foundation for many monuments, historical neighborhoods, and archaeological areas, and the main host of the present and future subway lines. We have stored information from more than 2000 geotechnical boreholes crossing the alluvial deposits into a relational database. For the present study, only the boreholes with lithologic/textural interpretation and geotechnical information were selected. The set includes 283 boreholes and 719 samples, which have a set of geotechnical information comprising physical properties and mechanical parameters. Techniques of multivariate statistics and geostatistics were combined and compared to evaluate the estimation methods of the mechanical parameters, with special reference to the drained friction angle from direct shear test (φ′). Principal Component Analysis was applied to the dataset to highlight the relationships between the geotechnical parameters. Through cross-validation analysis, multiple linear regression, kriging, and cokriging were tested as estimators of φ′. Cross-validation demonstrates that the cokriging with granulometries as auxiliary variables is the most suitable method to estimate φ′. In addition to proving that cokriging is a good estimator of φ′, cross-validation demonstrates that input data are coherent and this allows us to use them for estimation of geotechnical parameters, although they come from different laboratories and different vintages. Nevertheless, to get the same good results of cross-validation in estimation, it is necessary for granulometries to be available at grid points. Since this information being not available at all grid points, it is expected that, in the future, textural information can be derived in an indirect way, i.e., from lithologic/textural spatial reconstructions.Published251-2682.3. TTC - Laboratori di chimica e fisica delle rocceJCR Journalope