Gene Editing and Genotoxicity: Targeting the Off-Targets

Gene editing technologies show great promise for application to human disease as a result of rapid developments in targeting tools notably based on ZFN, TALEN, and CRISPR-Cas systems. Precise modification of a DNA sequence is now possible in mature human somatic cells including stem and progenitor cells with increasing degrees of efficiency. At the same time new technologies are required to evaluate their safety and genotoxicity before widespread clinical application can be confidently implemented. A number of methodologies have now been developed in an attempt to predict expected and unexpected modifications occurring during gene editing. This review surveys the techniques currently available as state of the art, highlighting benefits and limitations, and discusses approaches that may achieve sufficient accuracy and predictability for application in clinical settings

The influence of the copper content in grape must on alcoholic fermentation kinetics and wine quality. A survey on the performance of 50 commercial Active Dry Yeasts

The effects of copper on the viability and fermentative activity of 50 active dry yeasts purchased on the northern Italian market were studied, and revealed that Copper excess may cause massive death of yeast cells, leading to a significant delay in the start and progress of alcoholic fermentation. A two-log units reduction in cell viability was observed when copper content of musts was around 20 mg∙L-1. Despite this, the difference noted in the kinetics after 20 days' fermentation was lower than that observed 48 hours after in the grape must. An excess of copper in must affected also the composition of the produced wines. The increase in acetic acid and in the sulphur dioxide concentration, observed in wines made using grape must with a high copper concentration, raises serious doubts both regarding the possibility of obtaining good wines from these raw materials and in relation to the progress of subsequent steps of winemaking, such as malolactic fermentation. While it is an important tool in preventing vine diseases, copper must be used very carefully to avoid serious troubles during wine fermentation, even if some yeasts seem more suited to ferment musts containing up to 20-30 mg∙L-1 copper.

Relapsing bronchiolitis obliterans organising pneumonia and chronic sarcoidosis in an atopic asthmatic patient

Asthma is thought to be a Th2 disease while sarcoidosis is considered a Th1 granulomatous disorder. Organising pneumonia is a histologic pattern of lung injury. When it has no recognisable cause it is defined as cryptogenic organising pneumonia. We herein report the case of a patient with recurrent and steroid sensitive organising pneumonia associated with chronic sarcoidosis in an atopic, moderate persistent asthmatic patient. Each disease has been documented with transbronchial biopsies and recurrence of organising pneumonia was suggested by clinical features and by follow up HRCT which shows distinctive signs even in associated disease. Steroids are the mainstay of therapy for these disorders and especially for the consolidated processes typical of organising pneumonia but prognostic indices for relapse and progression are lacking

A Pragmatics-based Model for Narrative Dialogue Generation

We describe a method and a proof of concept which allow the generation of rich and engaging dialogues between virtual characters from a formalised plot description. The structure of the dialogue generated borrows from inferential pragmatics, following the Geneva Model of discourse analysis, in order to provide realistic interaction between characters in the narrative. At a higher level, this discourse is organised following heuristics borrowed from narratology theory in order to elicit emotions linked to dramatic tension and thus favour narrative engagement. Besides enriching narrative generation systems embedded within simulation applications, our work also has the potential to be adapted to support engaging interactive dialogues between users and virtual conversational agents in narrative systems

Adenocarcinoma classification: patterns and prognosis

Lung cancer is the most frequent human malignancy and the principal cause of cancer-related death worldwide. Adenocarcinoma is now the main histologic type, accounting for almost half of all the cases. The 2015 World Health Organization has adopted the classification recently developed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification has incorporated up-to-date advances in radiological, molecular and oncological knowledge, providing univocal diagnostic criteria and terminology. For resection specimens, new entities have been defined such as adenocarcinoma in situ and minimally invasive adenocarcinoma to designate adenocarcinomas, mostly nonmucinous and ≤ 3 cm in size, with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm invasion, respectively. For invasive adenocarcinoma, the new classification has introduced histological subtyping according to the predominant pattern of growth of the neoplastic cells: lepidic (formerly non mucinous brochioloalveolar adenocarcinoma), acinar, papillary, micropapillary, and solid. Of note, micropapillary pattern is a brand new histologic subtype. In addition, four variants of invasive adenocarcinoma are recognized, namely invasive mucinous (formerly mucinous brochioloalveolar adenocarcinoma), colloid, fetal, and enteric. Importantly, three variants that were considered in the previous classification have been eliminated, specifically mucinous cystadenocarcinoma, signet ring cell, and clear cell adenocarcinoma. This review presents the changes introduced by the current histological classification of lung adenocarcinoma and its prognostic implications

Histopathology of vasculitis

The range of pathologies that are related to primitive vasculitis is broad, complex and not as typical as we would expect. Clinicians should be aware that several forms of primitive and systemic vasculitis, regardless of the size of the affected vessel, may exhibit identical histological alterations. This observation has important clinical implications as it means that cases of vasculitis do not correspond clinically and histologically. Thus, while histology remains the diagnostic gold standard, it can be used only as part of the most complete clinical assessment possible. Another point worth of the clinician’s attention is that vasculitis histology changes over time, as do disease evolution and activity, even without considering the masking effects of treatment and the possibility of sampling error due to the patchy occurrence of vasculitis. The purpose of this review is to identify the most common forms of vasculitis in clinical practice, and to provide guidance to the clinician on the pathology of the vessels