Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells.

ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→︀A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration

Course and Lethality of SARS-CoV2 Epidemic in Nursing Homes after Vaccination in Florence, Italy

Evidence on the effectiveness of SARS-CoV-2 vaccines in nursing home (NHs) residents is limited. We examined the impact of the BNT162b2 mRNA SARS-CoV-2 vaccine on the course of the epidemic in NHs in the Florence Health District, Italy, before and after vaccination. Moreover, we assessed survival and hospitalization by vaccination status in SARS-CoV-2-positive cases occurring during the post-vaccination period. We calculated the weekly infection rates during the pre-vaccination (1 October–26 December 2020) and post-vaccination period (27 December 2020–31 March 2021). Cox analysis was used to analyze survival by vaccination status. The study involved 3730 residents (mean age 84, 69% female). Weekly infection rates fluctuated during the pre-vaccination period (1.8%–6.5%) and dropped to zero during the post-vaccination period. Nine unvaccinated (UN), 56 partially vaccinated (PV) and 35 fully vaccinated (FV) residents tested SARS-CoV-2+ during the post-vaccination period. FV showed significantly lower hospitalization and mortality rates than PV and UV (hospitalization: FV 3%, PV 14%, UV 33%; mortality: FV 6%, PV 18%, UV 56%). The death risk was 84% and 96% lower in PV (HR 0.157, 95%CI 0.049–0.491) and FV (HR 0.037, 95%CI 0.006–0.223) versus UV. SARS-CoV-2 vaccination was followed by a marked decline in infection rates and was associated with lower morbidity and mortality among infected NH residents

Human exposure in Italy to lead, cadmium and mercury through fish and seafood product consumption from Eastern Central Atlantic Fishing Area

The presence of cadmium (Cd), lead (Pb) and mercury (Hg) was investigated in fish and seafood products collected from the FAO Major Fishing Area 34, Eastern Central Atlantic. Samples were purchased from different retail outlets in Italy. Samples were selected so as to assess human exposure through diet. Metals were detected by Q-ICP-MS and Hg-AAS. All the metal concentrations detected were largely below the maximum levels (MLs) established by the European Union. The exposure assessment was undertaken by matching the concentration of Cd, Pb and total Hg in fish and other seafood products selected purposed according to Italian consumption data. The estimated weekly intakes (EWIs) for the evaluated elements related to the consumption of fish and other seafood products by the median of the Italian total population accounted for 14%, 2% and 14% of the standard tolerable weekly intake (TWI) for Cd and Hg as well as the provisional tolerable weekly intake (PTWI) for Pb, respectively

Efficacy of HPV Vaccination Regarding Vulvar and Vaginal Recurrences in Previously Treated Women: The Need for Further Evidence

Vulvar and vaginal cancers are relatively rare cancers, but their incidence is increasing worldwide. Overall, 78% of vaginal cancers and 25% of vulvar cancers are associated with Human papillomavirus (HPV) infection. Immunization could be an option for the management of these cases. We researched and assessed the evidence on the efficacy of HPV vaccination administered to women previously treated with surgery, radiotherapy, or chemotherapy with respect to the recurrence of vulvovaginal disease. From 2006 to November 2022, only one study evaluated the efficacy of HPV vaccination with respect to preventing vulvovaginal recurrences in treated women and showed that a quadrivalent HPV vaccine administered after the surgical treatment of vulvar high-grade squamous intraepithelial lesion (HSIL) can reduce vulvar recurrence of the disease. Therefore, the efficacy of HPV vaccination with respect to vulvovaginal recurrence is still an unexplored field. Further studies are needed to produce stronger evidence in order to appropriately support interventions to protect women’s health

Exposure to cadmium through Italian rice (Oryza sativa L.): Consumption and implications for human health

Cd bioaccumulation was investigated in the most consumed rice varieties (Oryza sativa L.) in Italy to assess the health risk related to consumption of the cereal for Italian population. In addition, the health implications concerning to consumption of rice-based foods was evaluated for Italian infants. Cadmium was detected by Q-ICP-MS. Method was validated in compliance with UNI CEI EN ISO/IEC 17025. Cd concentrations were found below the Maximum Levels (MLs) established at the European Union level for rice (0.092 mg kg−1for brown rice and 0.062 mg kg−1for white rice). The Cd Estimated Weekly Intakes (EWIs) through brown rice and white rice consumption by total population accounted approximately for 6% and 4% of the TWI set by the European Food Safety Authority (2.5 μg kg−1body weight), respectively. The Cd EWIs through rice consumption by different population groups obtained in this survey did not show notable differences with those related to the total population except for child group that showed the highest EWIs of Cd. As regards to the Cd EWIs quantified for infants of four, six and eight month old considering the rice-based infant food consumption accounted for 22%, 38%, and 36% of the EFSA TWI, respectively

Indicazioni ad interim sull’igiene degli alimenti durante l’epidemia da virus SARS-CoV-2. Versione del 19 aprile 2020

SARS-CoV-2 virus spreads by inter-human infection and there is currently no evidence of foodborne transmission or transmission from food business operators or from food packaging. Within the European legislation framework, food safety is ensured through a combined approach of prevention and control throughout the food chain, “for field to fork”. During the COVID-19 epidemic, however, the safeguard of food hygiene requires additional measures to reduce as much as possible the risk associated to the presence of potentially infected individuals in areas intended for food production or marketing. This report provides instructions and recommendations to ensure food and food packaging hygiene in the stages of food production, commercialization and consumption

Assessment of the Physiological Values and the Reference Histological Profile Related to Sex Steroids in Veal Calves

Among forbidden substances included in the European Union legislation, endogenous steroids constitute a challenge in the framework of veterinary Official Monitoring Plans. They can be naturally present in body fluids at variable levels depending on the species, sex and age of the animals. Considering the significant advances achieved in breeding conditions and in the selection of producing traits in meat cattle, the aim of this study was to verify by analytical method, in veal calves housed under controlled conditions, if the level of natural steroids hormones assumed as physiological are still actual. The second aim of the study was to verify if the normal histological pattern of growth promoters in target organs is influenced accordingly. Bovine male sex organs are currently analysed in the frame of the Italian histological plan to monitor illicit treatments trend, highlighting microscopic, induced alterations. The levels of 17β-estradiol and progesterone residues resulted under the Limit of Quantitation of the approved official methods and the level of testosterone resulted below the level stated in the Italian Ministerial Decree in force. Male target organs appeared within the limits of the standard histological features

Immunosuppression modifications based on an immune response assay: Results of a randomized, controlled trial

BACKGROUND: An immune function assay shows promise for identifying solid organ recipients at risk for infection or rejection. The following randomized prospective study was designed to assess the clinical benefits of adjusting immunosuppressive therapy in liver recipients based on immune function assay results. METHODS: Adult liver recipients were randomized to standard practice (control group; n = 102) or serial immune function testing (interventional group; n = 100) performed with a commercially available in vitro diagnostic assay (ImmuKnow; Viracor-IBT Laboratories, Lee's Summit, MO) before transplantation, immediately after surgery and at day 1, weeks 1 to 4, 6, and 8, and months 3 to 6, 9, and 12. The assay was repeated within 7 days of suspected/confirmed rejection/infection and within 1 week after event resolution. RESULTS: Based on immune function values, tacrolimus doses were reduced 25% when values were less than 130 ng/mL adenosine triphosphate (low immune cell response) and increased 25% when values were greater than 450 ng/mL adenosine triphosphate (strong immune cell response). The 1-year patient survival was significantly higher in the interventional arm (95% vs 82%; P < 0.01) and the incidence of infections longer than 14 days after transplantation was significantly lower among patients in the interventional arm (42.0% vs. 54.9%, P < 0.05). The difference in infection rates was because of lower bacterial (32% vs 46%; P < 0.05) and fungal infection (2% vs 11%; P < 0.05). Among recipients without adverse events, the study group had lower tacrolimus dosages and blood levels. CONCLUSIONS: Immune function testing provided additional data which helped optimize immunosuppression and improve patient outcomes