Illegal Substance Use among Italian High School Students: Trends over 11 Years (1999–2009)

Purpose: To monitor changes in habits in drug use among Italian high school students. Methods: Cross-sectional European School Survey Project on Alcohol and Other Drugs (ESPAD) carried out in Italy annually for 11 years (1999-2009) with representative samples of youth attending high school. The sample size considered ranges from 15,752 to 41,365 students and response rate ranged from 85.5% to 98.6%. Data were analyzed to obtain measures of life-time prevalence (LT), use in the last year (LY), use in the last 30 days (LM), frequent use. Comparisons utilized difference in proportion tests. Tests for linear trends in proportion were performed using the Royston p trend test. Results: When the time-averaged value was considered, cannabis (30% LT) was the most, and heroin the least (2%) frequently used, with cocaine (5%), hallucinogens (2%) and stimulants (2%) in between. A clear gender gap is evident for all drugs, more obvious for hallucinogens (average M/F LY prevalence ratio 2, range 1.7-2.4, p,0.05), less for cannabis (average M/F LY prevalence ratio 1.3, range 1.2-1.5, p,0.05). Data shows a change in trend between 2005 and 2008; in 2006 the trend for cannabis use and availability dropped and the price rose, while from 2005 cocaine and stimulant use prevalence showed a substantial increase and the price went down. After 2008 use of all substances seems to have decreased. Conclusions: Drug use is widespread among students in Italy, with cannabis being the most and heroin the least prevalent. Girls are less vulnerable than boys to illegal drug use. In recent years, a decrease in heroin use is overbalanced by a marked rise in hallucinogen and stimulant use.-

Fingolimod: therapeutic mechanisms and ocular adverse effects.

Fingolimod is an oral immunomodulating drug used in the management of relapsing-remitting multiple sclerosis (RRMS). We aim to review the published literature on ocular manifestations of fingolimod therapy and their possible underlying mechanisms. The therapeutic effects of fingolimod are mediated via sphingosine receptors, which are found ubiquitously in various organs, including lymphoid cells, central nervous system, cardiac myocytes, and smooth muscle cells. Fingolimod-associated macular oedema (FAME) is the most common ocular side effect but retinal haemorrhages and retinal vein occlusion can occur. The visual consequences appear to be mild and, in cases of FAME, resolution is often attained with discontinuation of therapy. However, in cases of retinal vein occlusion, discontinuation of fingolimod alone may not be sufficient and intra-vitreal therapy may be required. We also propose a pragmatic service pathway for monitoring patients on fingolimod therapy, which includes stratifying them by risk and visual acuity

DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

<p>Abstract</p> <p>Background</p> <p>Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence.</p> <p>Methods</p> <p>A set of 4 genes, including <it>CDH1 </it>(E-cadherin), <it>SFN </it>(stratifin), <it>RARB </it>(retinoic acid receptor, beta) and <it>RASSF1A </it>(Ras association (RalGDS/AF-6) domain family 1), had their methylation patterns evaluated by MSP (Methylation-Specific Polymerase Chain Reaction) analysis in 49 fresh urinary bladder carcinoma tissues (including 14 cases paired with adjacent normal bladder epithelium, 3 squamous cell carcinomas and 2 adenocarcinomas) and 24 cell sediment samples from bladder washings of patients classified as cancer-free by cytological analysis (control group). A third set of samples included 39 archived tumor fragments and 23 matched washouts from 20 urinary bladder cancer patients in post-surgical monitoring. After genomic DNA isolation and sodium bisulfite modification, methylation patterns were determined and correlated with standard clinic-histopathological parameters.</p> <p>Results</p> <p><it>CDH1 </it>and <it>SFN </it>genes were methylated at high frequencies in bladder cancer as well as in paired normal adjacent tissue and exfoliated cells from cancer-free patients. Although no statistically significant differences were found between <it>RARB </it>and <it>RASSF1A </it>methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for <it>RARB </it>methylation (Fisher's Exact test (p < 0.0001; OR = 48.89) and, 58% and 17% (p < 0.05; OR = 0.29) for <it>RASSF1A </it>gene, respectively, in relation to the control group.</p> <p>Conclusion</p> <p>Indistinct DNA hypermethylation of <it>CDH1 </it>and <it>SFN </it>genes between tumoral and normal urinary bladder samples suggests that these epigenetic features are not suitable biomarkers for urinary bladder cancer. However, <it>RARB </it>and <it>RASSF1A </it>gene methylation appears to be an initial event in urinary bladder carcinogenesis and should be considered as defining a panel of differentially methylated genes in this neoplasia in order to maximize the diagnostic coverage of epigenetic markers, especially in studies aiming at early recurrence detection.</p

Malinvaud on Wicksell’s legacy to capital theory: some critical remarks

This critique of Malinvaud’s article of 2003 on Wicksell’s legacy to capital theory focuses in particular on three points raised there. The first regards the given amount of existing capital that appears in Wicksell’s theory and its connection with his alleged “missing equation”, the second the particular notion of the marginal product of capital adopted by Malinvaud and the meaning of its equality with the rate of interest, and the third the concept of the average period of production taken by Malinvaud from Hicks and its inverse relation to the rate of interest

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Antagonism in opioid peptides: The role of conformation

The availability of new, highly selective antagonists, in the field of opioid peptides and of other pain peptides, is important both for a better understanding of the interaction of the receptors with their ligands and for their practical relevance. The design of antagonists is not obvious even when the essential features of agonists are well known. In this review we have examined the main aspects of the problem using, as leading criteria two theoretical models of antagonism and the subdivision of opioid peptides into two functional domains. The main causes of antagonism have been integrated in two very general models: one, referred to as the participation model, attributes antagonism to the lack, with respect to the parent agonist, of an essential group, whereas another model, attributes antagonism to the misfit of the molecule inside the receptor. The second criterion is the division of the structure of peptide hormones, originally put forward by Robert Schwyzer, in two functional domains, the message domain, which is responsible of the larger part of the binding affinity of opioid agonists, and an address domain, which dictates most of the peptide specificity. The most significant achievements in the design of opioid antagonists are classified according to the relative importance of chemical constitution, conformation and chirality. © 2004 Bentham Science Publishers Ltd

Radiopharmacy and radiopharmaceuticals: 2007 update.

This issue contains research papers of selected highlights from the 13th European Symposium of Radiopharmacy and Radiopharmaceuticals, held in Lucca, Italy on 30 March-2 April 2006.Foreword

Microfluidics in radiopharmaceutical chemistry

The increased demand for molecular imaging tracers useful in assessing and monitoring diseases has stimulated research towards more efficient and flexible radiosynthetic routes, including newer technologies. The traditional vessel-based approach suffers from limitations concerning flexibility, reagent mass needed, hardware requirements, large number of connections and valves, repetitive cleaning procedures and overall big footprint to be shielded from radiation. For these reasons, several research groups have started to investigate the application of the fast growing field of microfluidic chemistry to radiosynthetic procedures. After the first report in 2004, many scientific papers have been published and demonstrated the potential for increased process yields, reduced reagent use, improved flexibility and general ease of setup. This review will address definitions occurring in microfluidics as well as analyze the different approaches under two macro-categories: microvessel and microchannel. In this perspective, several works will be collected, involving the use of positron emitting species (11C, 18F, 64Cu) and the fewer examples of gamma emitting radionuclides (99mTc, 125/131I). New directions in microfluidic research applied to PET radiochemistry, future developments and challenges are also discussed. © 2013 Elsevier Inc