Postmarketing nutrivigilance safety profile: A line of dietary food supplements containing red yeast rice for dyslipidemia

Introduction: In the absence of a European standardized postmarketing food supplement surveillance system (nutrivigilance), some member states and companies have developed their own approaches to monitoring potential adverse reactions to secure a high level of product safety. This paper describes the use of a nutrivigilance system in monitoring the incidence of spontaneously reported suspected adverse reactions associated with food supplements containing red yeast rice (RYR). Material and methods: We report the data from a widely used product marketed under the trademark Armolipid/Armolipid Plus. Postmarketing information was collected in a voluntary nutrivigilance system established by the manufacturing company (Meda Pharma SpA, a Viatris Company, Monza, Italy). From 1st October 2004 to 31st December 2019, this system captured cases of suspected adverse reactions spontaneously reported by consumers, healthcare professionals, health authorities, regardless of causality. Results: The total number of case reports received mentioning the RYR food supplement product line was 542, in which 855 adverse events (AEs) were reported. The total reporting rate of AEs was estimated to be 0.037% of 2,287,449 exposed consumers. Of the 542 cases, 21 (0.0009% of exposed consumers) included suspected serious adverse events (SAEs). After careful investigation, 6 cases (0.0003% of consumers exposed) and 6 AEs were assessed by the manufacturer as serious and potentially related to exposure to the above-mentioned RYR-based nutraceutical. Conclusions: This nutrivigilance-derived data analysis clearly demonstrates a low prevalence of suspected adverse events associated with the red yeast rice product line. Consumer safety of food supplements could be generally improved by raising awareness of the importance of following the indications and warnings detailed in a food supplement's labeling

The advantages of collimator optimization for intensity modulated radiation therapy

Purpose: The goal of this study was to improve dosimetry for pelvic, head and neck and other cancers with aspherical planning target volumes (PTV) using collimator optimization for intensity modulated radiation therapy (IMRT).Methods: A retroactive study on the effects of collimator optimization of 20 patients was done by comparing collimator angles from optimized plans in Eclipse version 11.0. Keeping all other parameters equal, plans were created with four collimator techniques: CA0, all fields have collimators set to 0°, CA­E, using the Eclipse collimator optimization, CAA­, minimizing the area of the jaws around the PTV, and CAX, minimizing the x-jaw gap. The minimum area and the minimum x-jaw angles were found by evaluating each field beam’s eye view of the PTV with ImageJ and finding the desired parameters with a custom script. The evaluation of the plans included the monitor units (MU), the maximum dose of the plan, the maximum dose to organs at risk (OAR), the conformity index (CI) and the number of split fields. Results: Compared to the CA0 plans, the monitor units decreased on average by 6% for the CAX with a p-value of 0.01 from an ANOVA test. The average maximum dose stayed within 1.1% between all four methods with the lowest being CAX. The maximum dose to the most at risk organ was best spared by the CAA, which decreased by 0.62% from the CA0. Minimizing the x-jaws significantly reduced the number of split field from 61 to 37.Conclusion: In every field tested the CAX optimization produced as good or superior results than the other three techniques. For aspherical PTVs, CAX on average reduced the number of split fields, the maximum dose, minimized the dose to the surrounding OAR, and reduced the MU all while achieving the same control of the PTV

Socially anxious mothers’ narratives to their children, and their relation to child representations and adjustment

Anxious mothers’ parenting, particularly transfer of threat information, has been considered important in their children’s risk for social anxiety disorder (SAnxD), and maternal narratives concerning potential social threat could elucidate this contribution. Maternal narratives to their pre-school 4-5 year-old children, via a picture book about starting school, were assessed in socially anxious (N=73), and non-anxious (N=63) mothers. Child representations of school were assessed via Doll Play (DP). After one school term, mothers (CBCL) and teachers (TRF) reported on child internalizing problems, and child SAnxD was assessed via maternal interview. Relations between these variables, infant behavioral inhibition, and attachment, were examined. Socially anxious mothers showed more negative (higher threat attribution), and less supportive (lower encouragement) narratives, than controls, and their children’s DP representations, SAnxD and CBCL scores were more adverse. High narrative threat predicted child SAnxD; lower encouragement predicted negative child CBCL scores and, particularly for behaviorally inhibited children, TRF scores and DP representations. In securely attached children, CBCL scores and risk for SAnxD were affected by maternal anxiety and threat attributions, respectively. Low encouragement mediated the effects of maternal anxiety on child DP representations, and CBCL scores. Maternal narratives are affected by social anxiety, and contribute to adverse child outcome

Further progress/developments, on surface/bulk treated Constantan wires, for anomalous heat generation by H2/D2 interaction

In the framework of those studies aimed to analyze anomalous effects (thermal and/or nuclear) due to the interaction among some specific materials (pure and/or alloys) and H2 (or D2), we focused, since 2011, on a specific alloy called Constantan (Cu55-Ni44-Mn1). We selected such material using our own considerations and intuitions and because, according to a scientific paper [1], it has the largest energy value for dissociation of H2 to 2H, i.e. about 3eV. Among others B. Ahern suggested that Ni-Cu-H can be used for heat generation. We improved the preparation procedure of such wire from simple thermal treatments (up to May 2012 [2])to more sophisticated ones, with more tight control of the multilayered (400-700) surface structures. Some of the results were presented at ICCF17, Aug. 2012 [3]. After [3], several groups asked to make their own experiments using such kind of wires ([phi]=200[mu]m, l=100cm) to cross-check (and possibly improve) our results. Some of such Researchers (group of M. Fleischmann Memorial Project; U. Mastromatteo) made public their (positive) results since Dec. 14, 2012 at Ministry of Aeronautics in Rome, Italy. In short, using an (home-made) apparatus integrated with an acquisition system (type PXi) by National Instruments, we made, since September 2012, not mentioning qualitative reconfirmation of previous results, further and unexpected progress and discoveries: a) We developed a new kind of procedure of measurement (about anomalous excess heat) under dynamic vacuum, to avoid the effect of different thermal conductivity, inside the gas cell, due to type of gas and pressure variation: the wire didn't lose, macroscopically, H even at T=600[degrees]C. b) We developed a new, very simple, type of surface coating (2 layers) that is nano-diamandoidslike; c) We observed, at least 2 times, the phenomenon of water splitting due to catalytic effect of surface treated Constantan. Such phenomenon is larger in comparison with what expected just by thermal splitting (wires temperature of about 300-500[degrees]C); d) We observed a very large variation (about a factor 100) of Resistive Thermal Coefficient (RTC) of the wire used (400 layers) as the amount of H (related to the macroscopic value of resistive ratio R/Ro, normalize to empty wire Ro) increased. As example, with "treated" virgin wire (w/o H2) the RTC was about 5*10-6 and increased to6*10-4 when the R/Ro reduced to 0.68; temperature range 20-300[degrees]C. The RTC is larger with D in respect to H. Experiments are in progress also at 77K. e) Overall results are affected by previous operating conditions

Improved understanding of self-sustained, sub-micrometric multi-composition surface Constantan wires interacting with H2 at high temperatures: experimental evidence of Anomalous Heat Effects

This article is an extension of what presented by our team at 17th International Conference on Cold Fusion, ICCF-17, in Daejon, Korea, in 2012 [1]. It documents the improvements on Constantan-related experiments, started in 2011, in order to study the feasibility of new Nickel based alloys that are able to absorb proper amounts of Hydrogen (H2) and/or Deuterium (D2) and that have, in principle, some possibility to generate anomalous thermal effects at temperatures >100°C. The interest in Ni comes in part because there is the possibility to use also H2 instead of expensive D2. Moreover, cross-comparison of results using H2 instead of D2 can be made and could help the understanding of the phenomena involved (atomic, nuclear, super-chemical origin?) due to the use of such isotopes. Keywords: calorimeter, LENR, Nickel based alloys, sub-micrometric surface

HLA-G 3'UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment

An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host's immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3'UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3'UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3'UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3'UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3'UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38-0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26-0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19-5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16-6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3'UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G

KRAS status and risk of venous thromboembolic events in patients with metastatic colorectal cancer: a case-control study.

No abstract availabl

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The SAFFO Study: Sex-Related Prognostic Role and Cut-Off Definition of Monocyte-to-Lymphocyte Ratio (MLR) in Metastatic Colorectal Cancer

Background: Emerging data suggest that gender-related immune system composition affects both immune response and efficacy of immunotherapy in cancer patients (pts). This study aimed to investigate the sex-related prognostic role of MLR in metastatic colorectal cancer (mCRC) pts. Methods: We analyzed a retrospective consecutive cohort of 490 mCRC patients treated from 2009 to 2018 at the Oncology Departments of Aviano and Pordenone (training set) and Udine (validation set), Italy. The prognostic impact of MLR on overall survival (OS) was evaluated with uni- and multivariable Cox regression models. The best cut-off value to predict survival was defined through ROC analyses. Results: Overall, we identified 288 males (59%) and 202 females (41%); 161 patients (33%) had a right-sided, 202 (42%) a left-sided primary, and 122 (25%) a rectal tumor. Interestingly, gender was associated with MLR (p = 0.004) and sidedness (p = 0.006). The obtained cut-off value for MLR in females and males was 0.27 and 0.49, respectively. According to univariate analysis of the training set, MLR (HR 9.07, p ≤ 0.001), MLR > 0.27 in females (HR 1.95, p = 0.003), and MLR > 0.49 in males (HR 2.65, p = 0.010) were associated with poorer OS, which was also confirmed in the validation set. In multivariate analysis, MLR > 0.27 in females (HR 2.77, p = 0.002), MLR > 0.49 in males (HR 5.39, p ≤ 0.001), BRAF mutation (HR 3.38, p ≤ 0.001), and peritoneal metastases (HR 2.50, p = 0.003) were still independently associated with worse OS. Conclusions: Males and females have a different immune response. Our study showed that high MLR, both in males and females, is an unfavorable Independent prognostic factor. Further prospective studies are needed to confirm these data