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Book Review of Cocco, M. (2020).Una Cina “perfetta”. Roma:Carocci, 203 pp. Book Review by Giuseppe Palermo.

AIM: The objectives of this first‐in‐human study were to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, and maximum tolerated dose (MTD) of single ascending oral doses of RG7342, a positive allosteric modulator (PAM) of the metabotropic glutamate receptor 5 (mGlu5) for the treatment of schizophrenia, in healthy male subjects. METHODS: This was a single‐centre, randomized, double‐blind, adaptive study of 37 subjects receiving single ascending oral doses of RG7342 (ranging from 0.06–1.2 mg, n = 27) or placebo (n = 10). A modified continual reassessment method, with control for the probability of overdosing based on the occurrence of dose‐limiting events (DLEs), was applied to inform the subsequent dose decisions for RG7342. RESULTS: DLEs consisted of dizziness, nausea and vomiting, and the incidence and severity of these adverse events increased in a concentration‐dependent manner. RG7342 doses of 1.2 mg under fasting conditions, which reached a mean maximum plasma concentration (C(max)) of 10.2 ng ml(–1), were not tolerated (four out of six subjects experienced DLEs). RG7342 showed dose‐proportional pharmacokinetics, with rapid absorption and a biphasic decline, and a mean terminal half‐life estimated to be >1000 h. CONCLUSIONS: Single oral doses of RG7342 were generally tolerated up to 0.6 mg under fasting and 0.9 mg under fed conditions in healthy subjects. Bayesian adaptive methods describing the probability of DLEs were applied effectively to support dose escalation. MTDs (fasting, fed) were associated with a C(max) of 6.5 ng ml(–1). The development of RG7342 was discontinued owing to the potential challenges associated with a long half‐life in context of the observed adverse events.

In the last decades a growing interest has been dedicated to prevention, diagnosis and therapy of male genital pathologies, such as varicocele, infertility and erectile dysfunction in the population involved in sport activities. High incidence (up to 30%) of varicocele has been reported in a population of athletes and up to 60–80% in the subgroup of body-builders. The incidence of varicocele specifically increases with hours of training, in a linear model. Controversial data come from literature about the effects of physical activity on fertility, with prevalence of trials demonstrating worsening of seminal parameters. Furthermore, it has been demonstrated that physical stress in healthy male athletes can interfere with LH levels. Bicycling is one of the major risk factors for erectile dysfunction, with incidence of 13–24%. This is due to the prolonged compression of perineal arteries leading to reduced chronic penile perfusion. Bioengineering studies have been the basis for industry to produce specifically shaped saddles that significantly reduce and minimize compressive effects. Finally, high frequency of lower urinary tract symptoms (LUTS) in cyclists has been related to increased incidence of erectile dysfunction in comparison with normal population.

Nephron sparing surgery (NSS) with a minimal tumor-free margin is considered the cornerstone in the contemporary management of renal cell carcinoma (RCC) stage T1. The aim of this study is to review incidence, predictive risk factors, clinical significance and oncologic outcomes of positive surgical margins (PSM) in NSS. English articles published before March 2014 have been searched in Medline Databank.PSM are present in 0-7% of patients in all surgical approaches considered. Some predictive factors,such as tumor size, localization, and histology have been identified in the past. Other topics concerning surgical technique and approach are discussed.The majority of patients with PSM do not experience disease recurrence and PSM impact on overall survival and cancer-specific survival seems to be irrelevant. These results lead to more conservative clinical strategies. However, an active surveillance is mandatory for all patients with PSM and especially for those with high risk disease. Generalization of these results is limited by the low level of evidence of available studies. Further efforts are necessary to avoid PSM intraoperatively and to provide prospective information in order to standardize the postoperative management.

A novel featureless approach to the detection of masses and microcalcifications has been adopted, based on a Support Vector Machine (SVM) classifier. This method does not rely on any feature extraction task; on the contrary, the algorithm automatically learns to detect the lesions by the examples presented to it during the training phase. Our technique includes a pre-selection step, in which we select the intra-breast areas that will be analyzed. Those regions are then provided to an SVM classifier, trained to recognize suspect masses or microcalcifications. The CAD performance have been already assessed on digitized mammogram freely available on the net (DDSM USF and Nijmegen databases). In this paper we are going to test the CAD scheme on digital images coming from Giotto Image MD FFDM unit, a mammography system based on an amorphous Selenium detector. Images have a spatial resolution equal to 85 um and 13 bit gray-level resolution and have been collected at two different sites: Maggiore Hospital in Bologna (Italy) and Triemli Hospital in Zurich (Switzerland). Preliminary results are presented on a database gathered at these hospitals. The CAD system marked in the FFDM images 19 cancers out of 23, with a false-positive rate of 0.9 marks per image.

Argonautes (AGOs) are a highly conserved family of proteins found in most Eukaryotes, and involved in mechanisms of gene regulation, both at the transcriptional and post-transcriptional level. Among other functions, AGO proteins associate with microRNAs to mediate the post-transcriptional repression of protein-coding genes. In this process, AGOs associate with members of the trinucleotide repeat containing 6 protein (TNRC6) protein family to form the core of the RNA-induced silencing complex (RISC), the effector machinery that mediates microRNA function. However, the description of the exact composition of the RISC has been a challenging task due to the fact the AGO's interactome is dynamically regulated in a cell type- and condition-specific manner. Here, we summarize some of the most significant studies that have identified AGO complexes in mammalian cells, as well as the approaches used to characterize them. Finally, we discuss possible opportunities to exploit what we have learned on the properties of the RISC to develop novel anti-cancer therapies. Significance Statement The RNA-induced silencing complex (RISC) is the molecular machinery that mediates miRNA function in mammals. Studies over the past two decades have shed light on important biochemical and functional properties of this complex. However, still many aspects of this complex await further elucidation, mostly due to technical limitations that have hindered full characterization. Here, we summarize some of the most significant studies on the mammalian RISC, and discuss possible sources of biases in the approaches used to characterize it.

Background: To evaluate the difference at different steps of follow-up of the postoperative quality of life (QoL) in patients who had undergone radical cystectomy and ileal orthotopic neobladder derivation. Patients and Methods: A multicentric, cross-qualitative study was performed in 5 Italian centers of reference for the treatment of bladder cancer. One hundred seventy one patients who underwent radical cystectomy and creation of ileal orthotopic neobladder according to ‘Vescica Ileale Padovana' between 2006 and 2011 have been analyzed. The validated and dedicated questionnaires EORTC QLQ-C30, IOB-PRO and EORTC QLQ-BLM30 were used. Results: All data gathered were then processed, specifically means ± SD were included for comparison during 4 periods of follow-up (quartile): the first ranging from 1 to 18 months; the second ranging from 19 to 36 months; the third from 37 to 72 months and the fourth >72 months. Cancer-specific and health-related factors were analyzed separately, and the change was determined during follow-up. Conclusions: The global QoL, highlighted by validated cancer-specific and health-related questionnaires, is certainly on a satisfactory level. Thus, the education of the patient, the exploration of the pros and cons of an orthotopic neobladder and the active participation in treatment decision seem to be the keys to better improve the post-operative QoL during the follow-up period.

L’obiettivo del presente lavoro è stato quello di valutare la tipologia di lega metallica, il suo degrado e la tipologia di vernice dell’opera in ferro policroma “La Torre del Tempo” di E. Tadini. A tale scopo sono state effettuate delle misure di Microscopia Ottica, Diffrattometria a raggi X, Spettroscopia micro-Raman e Spettroscopia NMR. The goal of this study was to evaluate the type and the of conservation state of the metal alloy and the type of varnish of samples coming from “La Torre del Tempo” E. Tadini. The samples were characterized by Optical Microscopy, X-ray Diffractometry, micro-Raman Spectroscopy and NMR spectroscopy.

International audience; We present a project aimed at establishing a set of 12 spectro-photometric standards over a wide wavelength range from 320 to 2500 nm. Currently no such set of standard stars covering the near-IR is available. Our strategy is to extend the useful range of existing well-established optical flux standards into the near-IR by means of integral field spectroscopy with SINFONI at the VLT combined with state-of-the-art white dwarf stellar atmospheric models. As a solid reference, we use two primary HST standard white dwarfs. This ESO "Observatory Programme" has been collecting data since February 2007. The analysis of the data obtained in the first year of the project shows that a careful selection of the atmospheric windows used to measure fluxes and the stability of SINFONI make it possible to achieve an accuracy of 3- 6% depending on the wavelength band and stellar magnitude, well within our original goal of 10% accuracy. While this project was originally tailored to the needs of the wide wavelength range (320-2500 nm) of X-shooter on the VLT, it will also benefit any other near-IR spectrographs, providing a huge improvement over existing flux calibration methods.