Radiation therapy technologists' involvement and opinion in research: A national survey in Italy.

INTRODUCTION: This survey describes Italian RTTs' involvement and opinions in research activities related to radiation oncology. Primary aim was to assess the degree of involvement of the national RTTs community in research and to describe how RTTs can integrate their skills collaborating with other professionals. MATERIALS AND METHODS: A ten-items multiple-choice questionnaire, with 2-8 possible responses, was developed by a steering committee and generated on a survey platform. Links were sent via email to Italian RTTs.The questions were divided in 3 domains: demographic data; scientific research and activity; opinions about RTTs role in scientific research. The survey started on October 1, 2018 and ended on January 31, 2019. RESULTS: One hundred thirty-five out of 509 (26.5%) RTTs responded to the questionnaire at its expiring date; 97.73% think to be valid contributors in radiation oncology research, expressing clear interest in "data collection" tasks (52.71%); 38.64% feel unsupported by other professionals in the research team and 59.85% of the respondents are not members in any scientific society. CONCLUSIONS: The role of Italian RTTs in research is heterogeneous. Mainly RTTs in the age range from 30 to 40 years responded to the survey showing their interest in scientific research. This might be related to different informatics and educational skills as well as to personal attitudes. RTTs particular skills, like data management and technical hypothesis generation abilities, are of benefit to realize research projects. Therefore, engaging RTTs in research activities is strongly suggested.

Antisense transcription at the TRPM2 locus as a novel prognostic marker and therapeutic target in prostate cancer.

Overwhelming evidence indicates that cancer is a genetic disease caused by the accumulation of mutations in oncogenes and tumor suppressor genes. It is also increasingly apparent, however, that cancer depends not only on mutations in these coding genes but also on alterations in the large class of non-coding RNAs. Here, we report that one such long non-coding RNA, TRPM2-AS, an antisense transcript of TRPM2, which encodes an oxidative stress-activated ion channel, is overexpressed in prostate cancer (PCa). The high expression of TRPM2-AS and its related gene signature were found to be linked to poor clinical outcome, with the related gene signature working also independently of the patient's Gleason score. Mechanistically, TRPM2-AS knockdown led to PCa cell apoptosis, with a transcriptional profile that indicated an unbearable increase in cellular stress in the dying cells, which was coupled to cell cycle arrest, an increase in intracellular hydrogen peroxide and activation of the sense TRPM2 gene. Moreover, targets of existing drugs and treatments were found to be consistently associated with high TRPM2-AS levels in both targeted cells and patients, ultimately suggesting that the measurement of the expression levels of TRPM2-AS allows not only for the early identification of aggressive PCa tumors, but also identifies a subset of at-risk patients who would benefit from currently available, but mostly differently purposed, therapeutic agents.

Regulation of stem cell differentiation by histone methyltransferases and demethylases.

The generation of different cell types from stem cells containing identical genetic information and their organization into tissues and organs during development is a highly complex process that requires defined transcriptional programs. Maintenance of such programs is epigenetically regulated and the factors involved in these processes are often essential for development. The activities required for cell-fate decisions are frequently deregulated in human tumors, and the elucidation of the molecular mechanisms that regulate these processes is therefore important for understanding both developmental processes and tumorigenesis.

Changing concepts in long-term central venous access: catheter selection and cost savings.

BACKGROUND AND OBJECTIVES: Long-term central venous access is becoming an increasingly important component of health care today. Long-term central venous access is important therapeutically for a multitude of reasons, including the administration of chemotherapy, antibiotics, and total parenteral nutrition. Central venous access can be established in a variety of ways varying from catheters inserted at the bedside to surgically placed ports. Furthermore, in an effort to control costs, many traditionally inpatient therapies have moved to an outpatient setting. This raises many questions regarding catheter selection. Which catheter will result in the best outcome at the least cost? It has become apparent in our hospital that traditionally placed surgical catheters (ie, Hickmans and central venous ports) may no longer be the only options. The objective of this study was to explore the various modalities for establishing central venous access comparing indications, costs, and complications to guide the clinician in choosing the appropriate catheter with the best outcome at the least cost. METHODS: We evaluated our institution's central venous catheter use during a 3-year period from 1995 through 1997. Data was obtained retrospectively through chart review. In addition to demographic data, specific information regarding catheter type, placement technique, indications, complications, and catheter history were recorded. Cost data were obtained from several departments including surgery, radiology, nursing, anesthesia, pharmacy, and the hospital purchasing department. RESULTS: During a 30-month period, 684 attempted central venous catheter insertions were identified, including 126 surgically placed central venous catheters, 264 peripherally inserted central catheters by the nursing service, and 294 radiologically inserted peripheral ports. Overall complications were rare but tended to be more severe in the surgical group. Relative cost differences between the groups were significant. Charges for peripherally inserted central catheters were $401 per procedure, compared with $3870 for radiologically placed peripheral ports and $3532 to $4296 for surgically placed catheters. CONCLUSIONS: Traditional surgically placed central catheters are increasingly being replaced by peripherally inserted central venous access devices. Significant cost savings and fewer severe complications can be realized by preferential use of peripherally inserted central catheters when clinically indicated. Cost savings may not be as significant when comparing radiologically placed versus surgically placed catheters. However, significant cost savings and fewer severe complications are associated with peripheral central venous access versus the surgical or radiologic approach.

Degradation of gonadotropin beta-subunits retained in the endoplasmic reticulum of the gonadotropes of castrated rats.

LH and FSH are composed of a common alpha-subunit and a noncovalently associated hormone-specific beta-subunit. Unassociated beta LH and beta FSH can be retained in the cisternae of endoplasmic reticulum (ER). This phenomenon is particularly evident in gonadotropes of castrated animals where beta-subunits are expressed in larger amounts than the alpha-subunit. Because little was known about the fate of the gonadotropin beta-subunits retained in the ER, we carried out immunocytochemical studies on ultrathin frozen sections of anterior pituitaries of castrated rats. After castration, the intracellular levels of the beta-subunits were found to increase more than that of the alpha-subunit. When the subcellular localization of the alpha- and beta-subunits and secretogranin II (a regulated secretory protein present in the secretory granules of gonadotropes of many species) was investigated by double immunoelectron microscopy, both gonadotropin subunits were colocalized in secretory granules with secretogranin II. However, only the beta-subunits, not the alpha-subunit and secretogranin II, were localized in the dilated cisternae of the ER as well as in irregularly shaped vacuoles. Using markers for the endoplasmic reticulum, the prelysosomal compartment and lysosomes (cathepsin D and lgp120), we found that these vacuoles correspond to a degradative compartment with two types of intermediates: 1) one with small amounts of lgp120, and cathepsin D preferentially localized at the periphery of a central dense matrix; and 2) the other with larger amounts of lgp120, and cathepsin D present all over the matrix of the vacuole. These vacuoles do not derive from autophagy because vesicles surrounded by a double or multilamellar membrane containing profiles of ER cisternae together with small amounts of the cytoplasm were never detected. Moreover, they do not correspond to crinophagic bodies because the latter contained beta-subunits as well as alpha-subunit and SgII. Our data indicate that gonadotropin beta-subunits, probably retained as unassociated subunits in the endoplasmic reticulum of castrated rat gonadotropes, undergo degradation in vacuoles that acquire lysosomal enzymes. This process appears different from the classical autophagy, but similar to the nonautophagic pathway for the diversion to lysosomes of the intracisternal granules accumulated in the ER of hyperstimulated thyrotropes.

Patterns of dyspepsia in patients with no clinical evidence of organic diseases.

We studied 2000 dyspeptic patients with no obvious signs of organic disease at their first examination, in order to (1) verify how many diagnoses of idiopathic dyspepsia had really been made after exhaustive diagnostic procedures and (2) evaluate the diagnostic power of the symptoms in distinguishing organic from idiopathic dyspepsia. This latter was considered only when no structural abnormalities were found. In all the other cases, a distinction was made between "related" and "associated" organic dyspepsia according to whether or not there was a certain relationship between the abnormalities and the dyspeptic symptoms. The patients were referred to us as follows: (1) spontaneously, (2) sent by physicians collaborating with us, (3) referred to our open access endoscopic service. The results show the frequency of idiopathic dyspepsia was 26%, whereas associated structural abnormalities were present in 45.4%. Obvious organic causes of dyspepsia were seen in 28.6% (24% benign and 4.6% malignant diseases). When considered separately, no symptom alone allows a correct diagnosis. The simultaneous evaluation of the symptoms with linear discriminant analysis distinguishes between idiopathic and organic dyspeptic patients in about 70% of the cases. A higher discrimination percentage in about 70% of the cases. A higher discrimination percentage could probably be obtained using a wider range of clinical parameters and/or a more complex statistical analysis of the interrelationships which exist between the clinical symptoms and the final diagnosis.