A synthetic and spectroscopic investigation of the asymmetric α-lithiation-trapping of six-membered N-Boc heterocycles using Alexakis diamines

The asymmetric lithiation-trapping of six-membered N-Boc heterocycles using s-BuLi and two different Alexakis diamines is reported. These readily available ligands outperform the current ‘best-in-class’ sparteine-type diamines in the lithiation and benzophenone trapping of N-Boc piperazines and the lithiation-cyclisation-trapping of N-Boc-4-chloropiperidine. In situ IR spectroscopy has been used to optimise lithiation times and to discover previously unknown subtleties regarding the lithiation step

Development and Implementation of the AIDA International Registry for Patients With Undifferentiated Systemic AutoInflammatory Diseases

Objective: This paper points out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients affected by Undifferentiated Systemic AutoInflammatory Diseases (USAIDs). Methods: This is an electronic registry employed for real-world data collection about demographics, clinical, laboratory, instrumental and socioeconomic data of USAIDs patients. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is designed to obtain standardized information for real-life research. The instrument is endowed with flexibility, and it could change over time according to the scientific acquisitions and potentially communicate with other similar tools; this platform ensures security, data quality and data governance. Results: The focus of the AIDA project is connecting physicians and researchers from all over the world to shed a new light on heterogeneous rare diseases. Since its birth, 110 centers from 23 countries and 4 continents have joined the AIDA project. Fifty-four centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 179 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry is collecting baseline and follow-up data using 3,769 fields organized into 23 instruments, which include demographics, history, symptoms, trigger/risk factors, therapies, and healthcare information access for USAIDs patients. Conclusions: The development of the AIDA International Registry for USAIDs patients will facilitate the online collection of real standardized data, connecting a worldwide group of researchers: the Registry constitutes an international multicentre observational groundwork aimed at increasing the patient cohort of USAIDs in order to improve our knowledge of this peculiar cluster of autoinflammatory diseases

Broncalt®, class II medical device, in patients with acute upper airways disease: A survey in clinical practice

Inflammation is a common pathogenic mechanism involved in many otorhinolaryngological (ORL) disorders. Broncalt® is a class II Medical Device containing: Thermal water (Medesano, PR, Italy), hyaluronic acid, and grapefruit seed extract. It has been reported that it exerted a safe and effective anti-inflammatory, washing, and antimicrobial activity by virtue of these components. Therefore, the aim of the current survey, conducted in clinical practice of 84 Italian ORL centers, was to evaluate its safety and efficacy in the treatment of patients with acute upper airways disease. The 3,533 (1,797 males, mean age 43.5 years) patients were evaluated at baseline (T0) and after a 2-week treatment (T1) with or without Broncalt®. Signs and symptoms severity were measured by visual analogue scale. Broncalt® significantly and safely diminished the clinical features in all sub-groups (p<0.001 for all). Interestingly, Broncalt® significantly induced a faster symptom relief already within 3 days after the start of the treatment. In conclusion, Broncalt® is a class II Medical Device able to exert a safe and effective activity in patients with acute ORL disorders. (www.actabiomedica.it)

Broncalt®, class ii medical device, in patients with chronic relapsed upper airways disease: A survey in clinical practice

Chronic respiratory otorhinolaryngological (ORL) diseases may exacerbate. Broncalt® is a class II Medical Device containing: thermal water (Medesano, PR, Italy), hyaluronic acid, and grapefruit seed extract. It could exert a safe and effective anti-inflammatory, washing, and antimicrobial activity. The current survey, conducted in clinical practice of 84 Italian ORL centers, evaluated its safety and efficacy in the treatment of patients with exacerbated chronic upper airways disease. The 459 (254 males, mean age 44.7 years) patients were evaluated at baseline (T0) and after a 2-week treatment (T1), treated or not-treated with Broncalt®. Signs and symptoms severity were measured by visual analogue scale. Broncalt® significantly, quickly, and safely diminished the clinical features in all sub-groups (p<0.001 for all). In conclusion, Broncalt® is a class II Medical Device able to exert a safe, quick, and effective activity in patients with relapsed chronic ORL disorders. (www.actabiomedica.it)

“High” temperature asymmetric lithiation of N-Boc heterocycles: synthesis of tetra-substituted pyrrolidines

This thesis describes the study of new methodologies for the asymmetric synthesis of N-Boc heterocycles using lithiation chemistry, with the main focus on N-Boc pyrrolidine. The “high” temperature asymmetric lithiation-trapping of five-membered heterocycles N-Boc pyrrolidine and N-Boc imidazolidine and six-membered heterocycles N-Boc piperidine and N-Boc piperazine is described in Chapter Two. It was found that lithiated N-Boc pyrrolidine is configurationally stable for 1 hour at 40 °C and 30 °C giving high ers (90:10 er). With N-Boc imidazolidine, yields above 50% can be achieved using THF as solvent and are supported by VT 1H NMR spectroscopy studies as well as ReactIR™ spectroscopy studies. In Chapter Three, attempts towards the elucidation of the instability of α-amino sulfoxides are described. The synthetic strategies planned to clarify the possible mechanism causing the elimination of the sulfoxide group were unsuccessful and ultimately, we were unable to understand which process was at the basis of the elimination. As part of these studies, the development of the asymmetric lithiation-trapping of 4-phenyl N-Boc pyrrolidine is also described. Chapter Four describes the development of the asymmetric synthesis of α,α' tri- and tetra-substituted pyrrolidines. The use of ReactIR™ spectroscopy experiments was fundamental for the studies into the interconversion of N-Boc rotamers and to achieve good yields of the trapped products. An interesting match/mismatch mechanism for the formation of tri-substituted pyrrolidines is shown, which can give ers of >99:1 er. Finally, the synthesis of several new tetra-substituted pyrrolidines in 70:30-91:9 dr is presented

Prognostic Significance of Immunohistochemical Phenotypes in Patients Treated for High-Grade Cervical Intraepithelial Neoplasia

Strong evidence exists that the host’s immune system plays a crucial role for the development of human papillomavirus-related cervical premalignant and malignant lesions. In particular, effective cell-mediated immunity (CMI) promotes spontaneous infection clearance and cancer precursors regression in healthy subjects, while immunosuppressed individuals are more likely to experience infection persistence, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer. In this study, the prognostic significance of immunohistochemical profiling of CD4+ T-cells, CD8+ T-cells, dendritic cells (CD11c+), T-bet+, and GATA-3+ transcription factors has been studied in surgical specimens of 34 consecutive women affected by high-grade cervical intraepithelial neoplasia (CIN2-3) submitted to cervical conization. Results have been correlated with the clinical outcomes at 24 months after treatment and statistically analyzed. Higher rates of CD4+ T-cells, CD11c+ dendritic cells, and T-bet+ transcription factor positivity showed a strong statistically significative correlation with favourable clinical outcomes (P≤0.0001). These data reinforce the evidence of the relevance of the host’s immune status in the natural history of HPV-related cervical disease and add a prognostic significance of the cervical immunological profile in terms of predicting significant lower recurrence rates

Carbon Dots Dispersed on Graphene/SiO2/Si: A Morphological Study

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimLow-dimensional carbon materials occupy a relevant role in the field of nanotechnology. Herein, the authors report a study conducted by atomic force microscopy and Raman spectroscopy on the deposition of carbon dots onto graphene surfaces. The study aims at understanding if and how the morphology and the microstructure of chemical vapor deposited graphene on Si/SiO2 may change due to the interaction with the carbon dots. Potential alteration in the graphene's electrical properties might be detrimental for optoelectronic applications. The deposition of carbon dots dispersed in water and ethanol solvents are explored to investigate the effect of solvents with different fluidic properties. The obtained results indicate that the carbon dots do not alter the quality of graphene.N