MicroRNAs’ crucial role in salivary gland cancers’ onset and prognosis

Simple Summary: Salivary gland cancers are incredibly heterogeneous, both in the physical onset and in the aggressiveness. Setting up a novel diagnostic and prognostic detection method based on the noninvasive microRNAs’ profiling might represent a goal for the clinical management of those particular malignancies, saving precious time for the patients. Abstract: Salivary gland cancer (SGC) is an uncommon and heterogeneous disease that accounts for around 8.5% of all head and neck cancers. MicroRNAs (miRNAs) consist of a class of highly conserved, short, single-stranded segments (18–25 nucleotides) of noncoding RNA that represent key gene-transcription regulators in physiological and pathological human conditions. However, their role in SGC development and progression is not completely clear. This review aims to compile and summarize the recent findings on the topic, focusing on the prognostic and diagnostic value of the major modulated and validated microRNAs in SGC. Their differential expression could possibly aid the clinician in delivering an early diagnosis, therapeutic strategy and precision medicine

Norrbottnian clinical variant of Gaucher disease in Southern Italy

The Norrbottnian type of Gaucher disease (GD), as described many years ago, is due to a unique neuronopathic variant (c.1448T>G; L444P) that may have appeared during or before the sixteenth century in northern Sweden. It is a well-defined nosological entity with a characteristic course of clinical manifestations. In particular, Norrbottnian patients described in Sweden and Poland seem to share identical clinical histories characterized by the early onset of significant hepatosplenomegaly, often requiring splenectomy at an early age. Neurological involvement generally appears during the first or second decade of life, and includes horizontal gaze palsy, epilepsy, myoclonic movements, ataxia, dementia and cognitive impairment. Osteopenia occurs primarily in the spine, causing a severe and progressive thoracic kyphosis, although the involvement of other skeletal sites cannot be excluded. Here, we report on four Gaucher type 3 patients with Southern Italian ancestry presenting with clinical features and disease progression comparable to those of the 'Norrbottnian' Swedish phenotype, particularly regarding skeletal involvement with poor responsiveness to any therapeutical approach. Although a common ancestry among Southern Italian and Swedish Norrbottnian GD patients could not be investigated, the genotype [L444P]+[L444P] is the most frequently encountered in Southern Italy

Biokinetics and Internal Dosimetry of Tritiated Steel Particles

International audienceDecommissioning fission and fusion facilities can result in the production of airborne particles containing tritium that could inadvertently be inhaled by workers directly involved in the operations, and potentially others, resulting in internal exposures to tritium. Of particular interest in this context, given the potentially large masses of material involved, is tritiated steel. The International Commission on Radiological Protection (ICRP) has recommended committed effective dose coefficients for inhalation of some tritiated materials, but not specifically for tritiated steel. The lack of a dose coefficient for tritiated steel is a concern given the potential importance of the material. To address this knowledge gap, a “dissolution” study, in vivo biokinetic study in a rodent model (1 MBq intratracheal instillation, 3-month follow-up) and associated state-of-the-art modelling were undertaken to derive dose coefficients for model tritiated steel particles. A committed effective dose coefficient for the inhalation of 3.3 × 10−12 Sv Bq−1 was evaluated for the particles, reflecting an activity median aerodynamic diameter (AMAD) of 13.3 µm, with the value for a reference AMAD for workers (5 µm) of 5.6 × 10−12 Sv Bq−1 that may be applied to occupational inhalation exposure to tritiated steel particles

Novel A-ring and B-ring modified combretastatin A-4 (CA-4) analogues endowed with interesting cytotoxic activity.

A novel class of combretastatins, modified at A-ring or both A- and B-rings, mainly by replacement with benzofuran or benzo[b]thiophene, were synthesized. The new heterocombretastatins showed good cytotoxic activity on BMEC and H-460 cell lines. The aminocombretastatin 9f potently inhibits cell growth of BMEC and combretastatin-resistant HT-29 cell lines, with potential interest to treat colon carcinoma. Heterocombretastatins 9a,b inhibit tubulin polymerization similarly to CA-4 by having a binding to colchicine site five times stronger

Novel terphenyls and 3,5-diaryl isoxazole derivatives endowed with growth supporting and antiapoptotic properties.

A new study on terphenyl and diaryl-isoxazole and -isoxazoline derivatives, maintaining a common 3-adamantyl-4-hydroxyphenyl moiety, has been conducted to find compounds with growth supporting and antiapoptotic properties. Unexpectedly, diphenyisoxazole derivatives bearing a nitro group replacing the carboxylic function have been found with the highest cell protective activity within the series, in complete and in serum-free conditions. Inhibition of apoptosis induced by daunorubicin has also been observed for the most active compound

Audit on the appropriateness of integrated COPD management: The "aLT-BPCO" project

Background: Non communicable chronic diseases (including respiratory ones) are the leading cause of death and disability. To cope with them we need to redesign the health system, improving primary prevention, screening, and outpatient services, while fully integrating different branches of the health service. The Italian Ministry of Health published extended guidelines on integrated COPD management (COPD-GL) in 2010. In 2011 a condensed version was produced. These documents define appropriateness of management regarding both the specialist and the health service. Methods: An internal audit on how clinical practice conforms to COPD-GL standards was implemented in one Italian region involving 29 respiratory units (RU) (65.8% of the total regional RU): data were collected from the clinical database at time zero and after 6 months. In the meantime, specialists of RU underwent education on COPD-GL. Results: At time zero, significant gaps between current practice and recommendations emerged both in medical practice (mean agreement 25%) and in the health organization (48%). At month 6 the gaps were reduced more in clinical practice (60.7%) than in organization (54.7%). Conclusions: It is easier to resolve the gaps in specialist clinical practice than the organizational gaps, changing which is the politicians' task. Correcting specialists' inappropriateness may be worthless if this is not accompanied by improvement of the organizational obstacles. The search for appropriateness should not be limited only to specialists or to a strict control of drug prescription but should include all the organizational aspects. Implementation of COPD-GL calls for actions on the part of both specialists and the health system