Subcutaneous Trastuzumab (scT) and metronomic oral Vinorelbine (mVRL) combination in HER2 + ve advanced breast cancer (ABC) patients (pts): a pilot evaluation of toxicity. Preliminary results of the VICTOR-4 study

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GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed

A common mutation in the Insulin Receptor Substrate -1 gene is a genetic marker for the insulin resistance syndrome in patients with coronary artery disease

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Traceability of different apple varieties by multivariate analysis of isotope ratio mass spectrometry data

RATIONALE: The awareness of customers of the origin of foods has become an important issue. The growing demand for foods that are healthy, safe and of high quality has increased the need for traceability and clear labelling. Thus, this study investigates the capability of C and N stable isotope ratios to determine the geographical origin of several apple varieties grown in northern Italy. METHODS: Four apple varieties (Cripps Pink, Gala, Golden Delicious, Granny Smith) have been sampled in orchards located in the Districts of Bolzano, Ferrara, Verona and Udine (northern Italy). Carbon (δ13C) and nitrogen (δ15N) isotope values of the whole apple fruits and three sub-fractions (peel, pulp and seed) have been determined simultaneously by isotope ratio mass spectrometry. RESULTS: The δ13C and δ15N values of apples and apple sub-fractions, such as peel, seed and pulp, were significantly affected by the geographical origin and the fruit variety. The four varieties could be distinguished to a certain extent only within each district. A 99% correct identification of the samples according to their origin was, however, achieved by cross validation with the ’leave-one-out’ method. CONCLUSIONS: This study proves the potential of stable isotopes to discriminate the geographical origin of apples grown in orchards located only a few hundreds of kilometres apart. Stable isotopes were also able to discriminate different apple varieties, although only within small geographical areas

Selective Amine Recognition Driven by Host\u2013Guest Proton Transfer and Salt Bridge Formation

The stepwise synthesis of ionizable p-tert-butylcalix[5]arenes 1a\ub7H and 1b\ub7H, featuring a fixed cone cavity endowed with a carboxyl moiety at the narrow rim, is described. Single-crystal X-ray analyses have shown that in the solid state 1a\ub7H and 1b\ub7H adopt a cone-out conformation with the carboxylic OH group pointing in, toward the bottom of the aromatic cavity, as a result of a three- or two-center hydrogen-bonding pattern between the carboxyl group and the phenolic oxygen atom(s). The affinity of amines for calix[5]arene derivatives 1a\ub7H and 1b\ub7H was probed by 1H NMR spectroscopy and single-crystal X-ray diffraction studies. These carboxylcalix[5]arenes are shown to selectively recognize linear primary amines - over branched, secondary, and tertiary amines - by a two-step process involving a proton transfer from the carboxyl to the amino group to provide the corresponding alkylammonium ion, followed by binding of the latter inside the cavity of the ionized calixarene. Proton transfer occurs only with linear primary amines, that is, when the best size and shape fit between host and substrate is achieved, while the other amines remain in their noncompeting unprotonated form. The role of the solvent in the ionization/complexation process is discussed. Structural studies on the n-BuNH2 complexes with 1a\ub7H and 1b\ub7H provide evidence that binding of the in situ formed n-BuNH3 + substrate to the cavity of the ionized macrocycle is ultimately secured, in the case of 1a\ub7H, by the formation of an unprecedented salt-bridge interaction

The G972R variant of the Insulin Receptor Substrate-1 (IRS-1) gene, body fat distribution and insulin-resistance

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Quality of life in patients with Charcot-Marie-Tooth disease

The authors evaluated quality of life in Charcot-Marie-Tooth disease by administering the Medical Outcome Study Short Form-36 (SF-36) questionnaire to 121 Italian patients. Patients scored lower on all of the SF-36 scales compared with Italian normative data. Scores were lower in nonworking vs working patients, women vs men, and older vs younger patients, but not between patients with demyelinating vs axonal forms or between patients who had undergone orthopedic foot surgery vs those who had not