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HPV vaccination is expected to reduce the incidence of cervical cancer. The greatest and the earliest health gains will be ensured by high vaccine coverage among all susceptible people. The high costs and the risk of a reduced cost/effectiveness ratio in sexually active girls still represent the main obstacles for a more widespread use of HPV vaccination in many countries. Data on the rate, risk factors, and HPV types in sexually active women could provide information for the evaluation of vaccination policies extended to broader age cohorts. Sexually active women aged 13-26 years enrolled in an Italian cohort study were screened for cervical HPV infections; HPV-DNA positive samples were genotyped by InnoLipa HPV Genotyping Extra or by RFLP genotype analysis. Among the 796 women meeting the inclusion criteria, 10.80% (95% CI 8.65-12.96) were HPV-DNA infected. Age >18 years, lifetime sexual partners >1, and history of STIs were associated to higher risk of HPV infection in the multivariable models adjusted for age, lifetime sexual partners, and time of sexual exposure. The global prevalence of the four HPV vaccine-types was 3.02% (95% CI 1.83-4.20) and the cumulative probability of infection from at least one vaccine-type was 12.82% in 26-years-old women and 0.78% in 18-years-old women. Our data confirm most of the previously reported findings on the risk factors for HPV infections. The low prevalence of the HPV vaccine-types found may be useful for the evaluation of the cost/efficacy and the cost/effectiveness of broader immunization programs beyond the 12-years-old cohort. © 2014 Landes Bioscience.

The domestication of the dog from the wolf was a key step in the pathway that led to the Neolithic revolution. The earliest fossil dogs, dated to the end of the last glacial period (17,000 to 12,000 years ago), have been found in Russia, Germany and the Middle East. No dogs are represented in the naturalistic art of the European Upper Palaeolithic, suggesting that dogs were introduced at a later date. Genetic studies of extant dog and wolf mitochondrial DNA sequences were interpreted in favour of multiple dog founding events as early as 135-76,000 years ago, or of a single origin in East Asia, 40,000 or 15,000 years ago. Our study included mitochondrial DNA sequences from Italian fossil bones attributed to three Late Pleistocene-Early Holocene wolves (dated from a15,000 to a10,000 14C years ago) and two dogs, dated to a4000 and a3000 14C years ago respectively. Taking paleogeography into account, our phylogenetic data point to a contribution of European wolves to the three major dog clades, in agreement with archaeozoological data. Our phylogeographic studies also suggest genetic differentiation of dogs and wolves related to isolation by geographic distance, supporting multicentric origins of dogs from wolves throughout their vast range of sympatry.

Background Pap screening, an effective method for cervical cancer prevention, is now supported by molecular human papillomavirus (HPV) testing. Recently commercialised preventive vaccines also provide new tools for the primary prevention of cervical cancer. To determine appropriate prevention strategies, the Health General Direction, Lombardy Region, funded a project that aims to characterize and monitor HPV infections and related cervical diseases in high-risk women. Methods/design VALHIDATE is a 5-year multicentre open prospective cohort study. It will recruit 7000 consenting women aged 13–65 years to provide information about the local biomolecular epidemiology of HPV infection and cervical diseases in high-risk women recruited from nine clinical centres and one faith-based organisation. The study will estimate the overall and type-specific prevalence of HPV infection and cervical abnormalities. It also aims to compare standard Pap screening with biomolecular screening, and to assist in the design of targeted regional prevention programs directed specifically at high-risk groups. Three groups of high-risk women: 1000 HIV-infected women (aged 26–65 years), 1000 recent migrant women (aged 26–65 years) and 3000 young women (aged 13–26 years) and 1 control group: 2000 women (aged 26–45 years) attending a spontaneous screening program, will be recruited. Sample sizes will be revised after the first year. Adult participants will undergo conventional cervical cytology, HPV DNA screening and genotyping. Paediatric participants will undergo HPV DNA testing and genotyping of urine samples. HPV DNA, cytological abnormalities and HPV types will be analysed according to demographic, epidemiological, behavioural, and clinical data collected in an electronic case report form. Overall and stratified prevalences will be estimated to analyse the associations between HPV infection and selected characteristics. Logistic regression models will be used to estimate crude and adjusted odds ratios. Cox proportional hazard models will be used to estimate hazard ratios over time and between groups. Discussion/main expected results This study will provide substantial insight into HPV infections and related cervical diseases in high-risk groups and will help determine appropriate regional cervical cancer prevention strategies.

Piera Rizzolo, Valentina Silvestri, Mario Falchetti, Laura OttiniDepartment of Molecular Medicine, "La Sapienza" University of Rome, Rome, ItalyAbstract: Breast cancer is the most common cancer among women, accounting for about 30% of all cancers. In contrast, breast cancer is a rare disease in men, accounting for less than 1% of all cancers. Up to 10% of all breast cancers are hereditary forms, caused by inherited germ-line mutations in "high-penetrance," "moderate-penetrance," and "low-penetrance" breast cancer susceptibility genes. The remaining 90% of breast cancers are due to acquired somatic genetic and epigenetic alterations. A heterogeneous set of somatic alterations, including mutations and gene amplification, are reported to be involved in the etiology of breast cancer. Promoter hypermethylation of genes involved in DNA repair and hormone-mediated cell signaling, as well as altered expression of micro RNAs predicted to regulate key breast cancer genes, play an equally important role as genetic factors in development of breast cancer. Elucidation of the inherited and acquired genetic and epigenetic alterations involved in breast cancer may not only clarify molecular pathways involved in the development and progression of breast cancer itself, but may also have an important clinical and therapeutic impact on improving the management of patients with the disease.Keywords: breast cancer, inherited susceptibility, acquired alterations, epigenetics

Tuberculosis represents one of the humankind's most socially devastating diseases. Despite a long history of medical research and the development of effective therapies, this disease remains a global health danger even in the 21st century. Tuberculosis may cause death but infected people with effective immunity may remain healthy for years, suggesting long-term host-pathogen co-existence. Because of its antiquity, a supposed association with human settlements and the tendency to leave typical lesions on skeletal and mummified remains, tuberculosis has been the object of intensive multidisciplinary studies, including paleo-pathological research. During the past 10 years molecular paleo-pathology developed as a new scientific discipline allowing the study of ancient pathogens by direct detection of their DNA. In this work, we reviewed evidences for tuberculosis in ancient human remains, current methods for identifying ancient mycobacterial DNA and explored current theories of Mycobacterium tuberculosis evolution and their implications in the global development of tuberculosis looking into the past and present at the same time.

On April the 9th 1898 Golgi presented the discovery of the Apparato Reticolare Interno or internal reticular apparatus to the Società Medico-Chirurgica in Pavia. The internal reticular apparatus was described as "a fine and elegant network within the cell body" of Purkinje cells. The discovery of this new intracellular structure can be considered a byproduct of Golgi studies devoted to the analysis of the nervous system histology. Golgi and his co-workers detected the internal reticular apparatus in many cell types and described the organelle pleiomorphism due to specific physiological or pathological conditions. However, the real existence of the apparatus was questioned until the organelle was finally identified by electron microscopy in 1954. At this point Golgi apparatus became an actual intracellular structure without any clear function. The involvement in cell secretion processes was verified by using biochemical and molecular investigations from the 1960s. Nowadays, Golgi apparatus is clearly known to be involved in different cell functions as growth, homeostasis and division. The correct execution of these functions lies on the ability to maintain an equilibrated balance between the proteins therein resident. Recently, Golgi apparatus has been involved also in human pathology as mutations in proteins localized in the organelle are linked to some hereditary disorders like the Lowe syndrome. Golgi apparatus has been debated since its discovery. From the Golgi milestones discussed here it is evident that controversies that have arisen were often resolved by information resulting from the application of new technical developments. Indeed the compound dynamic structure and the relevance in cell physiology and in human pathology render Golgi apparatus an open object for future studies. Overall, the history of the Golgi apparatus represents an excellent model not only to follow the transition of the study approaches from cellular biology to molecular cell biology but also to understand the current attention paid to integrate the molecular function and the organelle structure in order to explain what goes wrong in the context of human disease.

OBJECTIVE: To investigate epidemiologic, clinical and pathologic aspects of various grades of vulvar intraepithelial neoplasia (VIN). STUDY DESIGN: A retrospective, multicenter study of 370 cases of vulvar intraepithelial neoplasia (VIN) wits performed by the Italian Study Group on Vulvar Disease. RESULTS: Of the 370 cases, 148 were VIN 1 (40.0%), 53 were VIN 2 (14.3%), and 169 were VIN 3 (45.7%). The mean age of the patients was 52.6 years. During the study period an increase in the rate of human papillomavirus-associated VIN was observed. In addition, while VIN 1 and 2 were associated mostly with squamous cell hyperplasia, VIN 3 was almost equally associated with lichen sclerosus and squamous cell hyperplasia; the difference was statistically significant. Intraepithelial or invasive squamous neoplasia of the lower genital tract was associated in 22% of the cases (82/370). CONCLUSION The results of the investigation, although not allowing firm conclusions due to the retrospective and multicentered nature of the study, demonstrate the extreme heterogeneity of VIN lesions.