Multilevel examination of minor salivary gland biopsy for Sjögren's syndrome significantly improves diagnostic performance of AECG classification criteria

The recently observed low reproducibility of focus score (FS) assessment at different section depths in a series of single minor salivary gland biopsies highlighted the need for a standardized protocol of extensive histopathological examination of such biopsies in Sjögren's syndrome. For this purpose, a cumulative focus score (cFS) was evaluated on three slides cut at 200-μm intervals from each of a series of 120 salivary biopsies. The cFS was substituted for the baseline FS in the American–European Consensus Group (AECG) criteria set for Sjögren's syndrome classification, and then test specificity and sensitivity were assessed against clinical patient re-evaluation. Test performances of the AECG classification with the original FS and the score obtained after multilevel examination were statistically compared using receiver operating characteristic (ROC) curve analysis. The diagnostic performance of AECG classification significantly improved when the cFS was entered in the AECG classification; the improvement was mostly due to increased specificity in biopsies with a baseline FS ≥ 1 but <2. The assessment of a cFS obtained at three different section levels on minor salivary gland biopsies can be useful especially in biopsies with baseline FSs between 1 and 2.     

Genomic analysis reveals association of specific SNPs with athletic performance and susceptibility to injuries in professional soccer players

The development of specific and individualized training programs is a possible way to improve athletic performance and minimize injuries in professional athletes. The information regarding the sport's physical demands and the athletes’ physical profile have been, so far, considered as exhaustive for the design of effective training programs. However, it is currently emerging that the genetic profile has to be also taken into consideration. By merging medical and genetic data, it is thus possible to identify the athlete's specific attitude to respond to training, diet, and physical stress. In this context, we performed a study in which 30 professional soccer players, subjected to standard sport medical evaluation and practices, were also screened for genetic polymorphism in five key genes (ACTN3, COL5A1, MCT1, VEGF, and HFE). This genetic analysis represents the central point of a multidisciplinary method that can be adopted by elite soccer teams to obtain an improvement in athletic performance and a concomitant reduction of injuries by tailoring training and nutritional programs. The genetic fingerprinting of single athletes led to the identification of two performance-enhancing polymorphisms (ACTN3 18705C>T, VEGF-634C>G) significantly enriched. Moreover, we derived a genetic model based on the gene set analyzed, which was tentatively used to reduce athletes’ predisposition to injuries, by dictating a personalized nutrition and training program. The potential usefulness of this approach is concordant with data showing that this team has been classified as the healthiest and least injured team in Europe while covering the highest distance/match with the highest number of high-intensity actions/match.     

Characterization of an in vitro model to study the possible role of polyomavirus BK in prostate cancer

Prostate cancer (PCa) is the most common male neoplasms in the Western world. Various risk factors may lead to carcinogenesis, including infectious agents such as polyomavirus BK (BKPyV), which infects the human renourinary tract, establishes latency, and encodes oncoproteins. Previous studies suggested that BKPyV plays a role in PCa pathogenesis. However, the unspecific tropism of BKPyV and the lack of in vitro models of BKPyV-infected prostate cells cast doubt on this hypothesis. The aim of the present study was to determine whether BKPyV could (a) infect normal and/or tumoral epithelial prostate cells and (b) affect their phenotype. Normal epithelial prostate RWPE-1 cells and PCa PC-3 cells were infected with BKPyV for 21 days. Cell proliferation, cytokine production, adhesion, invasion ability, and epithelial-to-mesenchymal transition (EMT) markers were analyzed. Our results show that (a) RWPE-1 and PC-3 cells are both infectable with BKPyV, but the outcome of the infection varies, (b) cell proliferation and TNF-α production were increased in BKPyV-infected RWPE-1, but not in PC-3 cells, (c) adhesion to matrigel and invasion abilities were elevated in BKPyV-infected RWPE-1 cells, and (d) loss of E-cadherin and expression of vimentin occurred in both uninfected and infected RWPE-1 cells. In conclusion, BKPyV may change some features of the normal prostate cells but is not needed for maintaining the transformed phenotype in the PCa cells The fact that RWPE-1 cells exhibit some phenotype modifications related to EMT represents a limit of this in vitro model.     

Colonoscopic surveillance of first-degree relatives of colorectal cancer patients in a faecal occult blood screening programme

Background: In some Italian areas, colonoscopic surveillance of first-degree relatives (FDRs) of colorectal cancer (CRC) patients is provided as a part of local population-based faecal occult blood test (FOBT) screening programmes. The objective of the present study was to assess the feasibility and early results of this surveillance model. Methods: Data from district screening centres were used to evaluate the process of identification and selection of eligible FDRs (residence in the Emilia-Romagna Region, age 40–75 years, no recent colonoscopy) of screen-detected CRC patients and the detected prevalence of disease. The probability for an FDR to undergo colonoscopy and to be diagnosed with CRC and advanced adenoma was estimated using the Kaplan–Meier method. The sex- and age-standardised ratio of detected prevalence to that expected based on results from a colonoscopy screening study of the Italian general population was estimated. Results: Between 2005 and 2011, 9319 FDRs of 2437 screen-detected CRC patients (3.8 per patient) were identified and contacted. Their likelihood of being eligible for, and accepting, colonoscopy was 0.11 (95% confidence interval: 0.11–0.12). Among the 926 subjects undergoing colonoscopy, the prevalence of previous negative screening FOBT was 63%. Eleven CRCs (1.2%) and 100 advanced adenomas (10.8%) were detected. The standardised ratio of detected prevalence to that expected was 0.91 (95% confidence interval: 0.19–2.66) for CRC and 1.48 (1.04–2.05) for advanced adenoma. Conclusions: The procedure of selection of FDRs was extremely ineffective. Due to previous negative screening tests, the prevalence of disease was less than expected. A population-based FOBT screening programme is a highly unsuitable setting for the provision of surveillance to FDRs of CRC patients.     

Role of the N-methyl-d-aspartate receptors complex in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease pathologically characterized by the massive loss of motor neurons in the spinal cord, brain stem and cerebral cortex. There is a consensus in the field that ALS is a multifactorial pathology and a number of possible mechanisms have been suggested. Among the proposed hypothesis, glutamate toxicity has been one of the most investigated. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor mediated cell death and impairment of the glutamate-transport system have been suggested to play a central role in the glutamate-mediated motor neuron degeneration. In this context, the role played by the N-methyl-d-aspartate (NMDA) receptor has received considerable less attention notwithstanding its high Ca^2 + permeability, expression in motor neurons and its importance in excitotoxicity. This review overviews the critical role of NMDA-mediated toxicity in ALS, with a particular emphasis on the endogenous modulators of the NMDAR.     

Role of modern radiation therapy in early stage Hodgkin's lymphoma: A young radiation oncologists’ perspective

The role of radiotherapy is well established in combined modality programs for early stage Hodgkin's lymphoma, but still debated with regards to late toxicity issues. Modern radiotherapy prescribing attitudes include lower doses and smaller fields, together with the implementation of sophisticated and dedicated delivery techniques. Aim of this review is to briefly discuss the current role of radiotherapy in this field and the potential future developments. Major trials conducted in recent years in early stage Hodgkin's lymphoma are critically reviewed and discussed with a focus on radiotherapy-related issues and with an attention to current treatment options by a “young” radiation oncologists’ perspective.