Defective DNA repair mechanisms in prostate cancer: impact of olaparib

The field of prostate oncology has continued to change dramatically. It has truly become a field that is intensely linked to molecular genetic alterations, especially DNA-repair defects. Germline breast cancer 1 gene (BRCA1) and breast cancer 2 gene (BRCA2) mutations are implicated in the highest risk of prostate cancer (PC) predisposition and aggressiveness. Poly adenosine diphosphate ribose polymerase (PARP) proteins play a key role in DNA repair mechanisms and represent a valid target for new therapies. Olaparib is an oral PARP inhibitor that blocks DNA repair pathway and coupled with BRCA mutated-disease results in tumor cell death. In phase II clinical trials, including patients with advanced castration-resistant PC, olaparib seems to be efficacious and well tolerated. Waiting for randomized phase III trials, olaparib should be considered as a promising treatment option for PC

Predicted properties of Galactic and Magellanic Classical Cepheids in the SDSS filters

We present the first extensive and detailed theoretical scenario for the interpretation of Cepheid properties observed in the SDSS filters. Three sets of nonlinear convective pulsation models, corresponding to the chemical compositions of Cepheids in the Milky Way, the Large Magellanic Cloud and the Small Magellanic Cloud respectively, are transformed into the SDSS bands by relying on updated model atmospheres. The resulting observables, namely the instability strip boundaries and the light curves, as well as the Period-Luminosity, the Wesenheit and the Period-Luminosity-Colour relations, are discussed as a function of the metal content, for both the fundamental and the first overtone mode. The fundamental PL relations are found to deviate from linear relations when computed over the whole observed Cepheid period range, especially at the shorter wavelenghts, confirming previous findings in the Johnson-Cousins bands. The obtained slopes are found to be mildly steeper than the ones of the semiempirical and the empirical relations available in the literature and covering roughly the same period range, with the discrepancy ranging from about 13% in u-band to about 3% in z.Comment: Accepted for publication in MNRA

Radiation therapy and serum salivary amylase in head and neck cancer

Radiation therapy (RT) is a valid treatment option for head and neck cancer (HNC). The risk of RT-induced toxicities is significant, especially due to extended treatment fields. The raise in amylase activity is strictly dependent on the volume of salivary glands included in the irradiated target volume and it is firmly related to the dose. The aim of this review is to report the effects on salivary amylase activity after radiation exposure of salivary glands, in patients with HNC

Dwarf spheroidal satellites of M31: I. Variable stars and stellar populations in Andromeda XIX

We present B,V time-series photometry of Andromeda XIX (And XIX), the most extended (half-light radius of 6.2') of Andromeda's dwarf spheroidal companions, that we observed with the Large Binocular Cameras at the Large Binocular Telescope. We surveyed a 23'x 23' area centered on And XIX and present the deepest color magnitude diagram (CMD) ever obtained for this galaxy, reaching, at V~26.3 mag, about one magnitude below the horizontal branch (HB). The CMD shows a prominent and slightly widened red giant branch, along with a predominantly red HB, which, however, extends to the blue to significantly populate the classical instability strip. We have identified 39 pulsating variable stars, of which 31 are of RR Lyrae type and 8 are Anomalous Cepheids (ACs). Twelve of the RR Lyrae variables and 3 of the ACs are located within And XIX's half light radius. The average period of the fundamental mode RR Lyrae stars ( = 0.62 d, \sigma= 0.03 d) and the period-amplitude diagram qualify And XIX as an Oosterhoff-Intermediate system. From the average luminosity of the RR Lyrae stars ( = 25.34 mag, \sigma= 0.10 mag) we determine a distance modulus of (m-M)$_0$=$24.52\pm0.23$ mag in a scale where the distance to the Large Magellanic Cloud (LMC) is $18.5\pm0.1$ mag. The ACs follow a well defined Period-Wesenheit (PW) relation that appears to be in very good agreement with the PW relationship defined by the ACs in the LMC.Comment: accepted for publication in Ap

Canine faecal contamination and parasitic risk in the city of Naples (southern Italy)

BACKGROUND: Dogs are associated with more than 60 zoonotic diseases among which, parasitosis and, in particular, helminthosis, can pose serious public-health concerns worldwide. Many canine gastrointestinal parasites eliminate their dispersion elements (eggs, larvae, oocysts) by the faecal route. The quantity of canine faeces deposited on public and private property in cities worldwide is both a perennial nuisance and an important health issue. Public sites such as playgrounds, parks, gardens, public squares and sandpits may be an important source of human infection. The aim of this study was to evaluate the extent of both canine faecal contamination in the city of Naples (southern Italy), and presence of canine parasitic elements, with particular regard to those which are potential agents of zoonosis. A regular grid of sub-areas (1 km × 700 m) was overlaid on the city map using a Geographical Information System (GIS). In each sub-area the straightest 1 km transect was drawn and digitalized on-screen in the GIS. Between February and May 2005 canine faeces were counted along the 1 km transects in 143 sub-areas, and 415 canine faecal samples were collected and submitted to coprological examinations. Negative binomial regression models and Gaussian random effects models were used to analyze the association between faeces count and human population density taking into account for extraPoisson variability. Logistic regression model was used to evaluate the association between positivity to parasitic elements and number of canine faeces. RESULTS: Out of the 143 studied sub-areas, 141 (98.6%) contained canine faeces. There was a strong spatial gradient with 48% of the total variability accounted by between neighbourhood variability; a positive association between the number of faeces and the human population density was found. Seventy (over 415, 16.9%) canine faecal samples were positive for parasitic elements. There was no association between positivity to parasitic elements and the number of canine faeces. Eggs of Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Trichuris vulpis were found, as well as oocysts of Isospora canis. CONCLUSION: In conclusion, the results of the present study, conducted using GIS both for planning and sampling and for evaluation and presentation of findings, showed the presence of canine faecal contamination in the city of Naples, and the presence of canine parasitic elements, some of which are potential agents of zoonosis

HIV screening in patients with anal condylomatosis. An overview about ethical and legal issues

: Although there is a strong evidence of prevalence of condylomata in the HIV-positive population, literature on HIV prevalence in HIV-unscreened population diagnosed with condylomata is still unconclusive. Our aim is to review literature about HIV screening and diagnosis of anal condylomata in order to evaluate medical aspects, ethical and legal issues concerning the management of this disease. We undertook an online search on Pubmed for the keywords "HIV", "screening" and "anal condylomata" and 23 papers were analysed, 2 being randomized controlled trial, 11 comparative studies and 10 reviews. A total of 1270 patients were reviewed. All authors strongly recommend HIV testing in patients with clinical evidence of anal condylomata. In undeveloped countries with high prevalence of HIV, a proctological evaluation could be a could represent an unexpected therapeutic option for HIV infected male patients to prevent anal cancer. Clinical trials and prospective studies are necessary to validate this interesting hypothesis. KEY WORDS: Anal condylomatosis, HIV screening, Papilloma virus

Variable stars in the ultra-faint dwarf spheroidal galaxy Ursa Major I

We have performed the first study of the variable star population of Ursa Major I (UMa I), an ultra-faint dwarf satellite recently discovered around the Milky Way by the Sloan Digital Sky Survey. Combining time series observations in the B and V bands from four different telescopes, we have identified seven RR Lyrae stars in UMa I, of which five are fundamental-mode (RRab) and two are first-overtone pulsators (RRc). Our V, B-V color-magnitude diagram of UMa I reaches V~23 mag (at a signal-to-noise ratio of ~ 6) and shows features typical of a single old stellar population. The mean pulsation period of the RRab stars = 0.628, {\sigma} = 0.071 days (or = 0.599, {\sigma} = 0.032 days, if V4, the longest period and brightest variable, is discarded) and the position on the period-amplitude diagram suggest an Oosterhoff-intermediate classification for the galaxy. The RR Lyrae stars trace the galaxy horizontal branch at an average apparent magnitude of = 20.43 +/- 0.02 mag (average on 6 stars and discarding V4), giving in turn a distance modulus for UMa I of (m-M)0 = 19.94 +/- 0.13 mag, distance d= 97.3 +6.0/-5.7 kpc, in the scale where the distance modulus of the Large Magellanic Cloud is 18.5 +/- 0.1 mag. Isodensity contours of UMa I red giants and horizontal branch stars (including the RR Lyrae stars identified in this study) show that the galaxy has an S-shaped structure, which is likely caused by the tidal interaction with the Milky Way. Photometric metallicities were derived for six of the UMa I RR Lyrae stars from the parameters of the Fourier decomposition of the V-band light curves, leading to an average metal abundance of [Fe/H] = -2.29 dex ({\sigma} = 0.06 dex, average on 6 stars) on the Carretta et al. metallicity scale.Comment: Accepted for publication in Ap

Weekly versus three weeks chemotherapy for advanced ovarian cancer. A meta-analysis

Aim: Three weeks paclitaxel and carboplatin has been considered the standard of care for primary treatment of ovarian cancer (OC). Whether weekly therapy will further improve the clinical outcomes or not is still unclear. We conducted a meta-analysis to compare the two regimens. Method: Articles were selected with a systematic approach, using PubMed databases. Trials concerning comparison between carboplatin plus weekly paclitaxel (dose-dense regimen) and carboplatin plus paclitaxel every 3 weeks were considered. Outcomes included overall survival (OS), progression free survival (PFS) and severe acute toxicity. Results: Dose-dense regimen was associated with significant improvement of PFS compared with standard schedule, with HR of 0.73 (95% CI 0.61-0.88, p = 0.001). There was no difference in OS between treatment regimens (HR 0.95, 95% CI 0.77-1.16, p=0.06), as well as in term of severe acute toxicity. Conclusion: Dose-dense regimen is superior to standard schedule in terms of PFS. Further studies are necessary to firmly confirm this evidence in advanced OC treatment

Efficacy and toxicity of bevacizumab in recurrent ovarian disease: an update meta-analysis on phase III trials

Background: To analyze the efficacy and toxicity of bevacizumab on survival outcomes in recurrent ovarian cancer. Results: Bevacizumab was associated with significant improvement of PFS and OS compared with standard treatment with HRs of 0.53 (95% CI 0.44 - 0.63; p < 0.00001) and 0.87 (95% CI, 0.77 to 0.99; p = 0.03), respectively. Bevacizumab increased the incidence of G3/G4 hypertension (RR 19.01, 95% CI 7.77 - 46.55; p < 0.00001), proteinuria (RR 17.31, 95% CI 5.42 - 55.25; p < 0.00001), arterial thromboembolic events (ATE) (RR 4.99, 95% CI 1.29 - 19.27; p = 0.02) and bleeding (RR 3.14, 95% CI 1.35 - 7.32; p = 0.008). Materials and Methods: Three randomized phase III trials representing 1502 patients were identified. Pooled hazard ratio (HR), odd ratio (OR), risk ratio (RR) with 95% confidence interval (CI) were calculated using fixed or random effects model. Conclusions: Adding bevacizumab to standard chemotherapy improved ORR, PFS and OS, and it had a higher, but manageable, incidence of toxicities graded 3 to 4