New CXCR4 Antagonist Peptide R (Pep R) Improves Standard Therapy in Colorectal Cancer

he chemokine receptor CXCR4 is overexpressed and functional in colorectal cancer. To investigate the role of CXCR4 antagonism in potentiating colon cancer standard therapy, the new peptide CXCR4 antagonist Peptide R (Pep R) was employed. Human colon cancer HCT116 xenograft-bearing mice were treated with chemotherapeutic agents (CT) 5-Fluorouracil (5FU) and oxaliplatin (OX) or 5FU and radio chemotherapy (RT-CT) in the presence of Pep R. After two weeks, CT plus Pep R reduced by 4-fold the relative tumor volume (RTV) as compared to 2- and 1.6-fold reductions induced, respectively, by CT and Pep R. In vitro Pep R addition to CT/RT-CT impaired HCT116 cell growth and further reduced HCT116 and HT29 clonal capability. Thus, the hypothesis that Pep R could target the epithelial mesenchyme transition (EMT) process was evaluated. While CT decreased ECAD and increased ZEB-1 and CD90 expression, the addition of Pep R restored the pretreatment expression. In HCT116 and HT29 cells, CT/RT-CT induced a population of CD133+CXCR4+ cells, supposedly a stem-resistant cancer cell population, while Pep R reduced it. Taken together, the results showed that targeting CXCR4 ameliorates the effect of treatment in colon cancer through inhibition of cell growth and reversal of EMT treatment-induced markers, supporting further clinical studies

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

Prick by Prick Induced Anaphylaxis in a Patient with Peanuts and Lupine Allergy: Awareness of Risks and Role of Component Resolved Diagnosis

A case of anaphylaxis is reported in the course of a prick by prick with Lupinus albus and roasted peanut in a 20-year-old woman. We focused on some main topics. First of all it seems important to underscore the potential risks connected to the practice of the prick-by-prick with fresh foods in allergic patients, especially when testing cross-reactive substances, such as White Lupine, peanuts, or soy. It is important that clinicians who perform prick tests be aware of the risk related with in vivo tests in allergic patients. Second, we discuss the problem of the hidden allergens, such as White Lupine flour, or soy flour which are utilized to improve wheat flour because of their lower cost. Patients with a demonstrated allergy to peanuts should be assessed for lupine allergy and informed about the “hidden allergens” issue. Finally, we believe that component resolved diagnosis, the serum specific IgE against molecular components, that is normally considered a second-level diagnostic step has an important role even as a first line approach at least in some selected cases

Case Report Prick by Prick Induced Anaphylaxis in a Patient with Peanuts and Lupine Allergy: Awareness of Risks and Role of Component Resolved Diagnosis

A case of anaphylaxis is reported in the course of a prick by prick with Lupinus albus and roasted peanut in a 20-year-old woman. We focused on some main topics. First of all it seems important to underscore the potential risks connected to the practice of the prickby-prick with fresh foods in allergic patients, especially when testing cross-reactive substances, such as White Lupine, peanuts, or soy. It is important that clinicians who perform prick tests be aware of the risk related with in vivo tests in allergic patients. Second, we discuss the problem of the hidden allergens, such as White Lupine flour, or soy flour which are utilized to improve wheat flour because of their lower cost. Patients with a demonstrated allergy to peanuts should be assessed for lupine allergy and informed about the "hidden allergens" issue. Finally, we believe that component resolved diagnosis, the serum specific IgE against molecular components, that is normally considered a second-level diagnostic step has an important role even as a first line approach at least in some selected cases

When are serum specific IgE levels positive?

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Plasma Current, Shape, and Position Control in ITER

Invited paper on a Special Issue on Plasma Contro

Plasma Current, Shape and Position Control in ITER

Invited paper on a Special Issue on Plasma Contro

Susceptibility to vaccine-preventable diseases and vaccination adherence among healthcare workers in Italy: A cross-sectional survey at a regional acute-care university hospital and a systematic review.

Healthcare Workers (HCWs) have an increased risk both to acquire and to spread vaccine preventable diseases (VPDs) both to their colleagues and, especially, to vulnerable patients. The prevention of occupational hazards among HCWs is based on proper adoption of the standard and additional precautions, immunizations, and secondary preventive measures, such as post-exposure prophylaxis. Moreover, HCWs are often referred to as the most trusted source of vaccine-related information for their patients. In the present article, we report the findings of a cross-sectional study investigating the compliance to vaccinations among HCWs employed at the Obstetric Unit of a regional acute-care University Hospital in Northern Italy. Furthermore, a systematic review of the literature for some VPDs (i.e., HBV, measles, rubella, varicella and influenza) was performed, over a 17-year period, in order to update the socio-demographic and professional characteristics, the susceptibility status and the vaccination rates among HCWs in Italy