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- Assessing the impact of TiO2 nanomaterials on intestinal cells: New evidence for epithelial translocation and potential pro-inflammatory effectsPublication . Rolo, Dora; Pereira, Joana F.S.; Gonçalves, Lídia; Bettencourt, Ana; Jordan, Peter; Silva, Maria João; Matos, Paulo; Louro, HenriquetaUnderstanding the potential impact of nanomaterials (NMs) on human health requires further investigation into the organ-specific nano-bio interplay at the cellular and molecular levels. We showed increased chromosomal damage in intestinal cells exposed to some of in vitro digested Titanium dioxide (TiO2) NMs. The present study aimed to explore possible mechanisms linked to the uptake, epithelial barrier integrity, cellular trafficking, as well as activation of pro-inflammatory pathways, after exposure to three TiO2-NMs (NM-102, NM-103, and NM-105). Using confocal microscopy, we show that all NMs, digested or not, were able to enter different types of intestinal cells. At the physiologically relevant concentration of 14 μg/mL, the digested TiO2-NMs did not compromise the transepithelial resistance, nor the levels of epithelial markers E-cadherin and Zonula occludens protein 1 (ZO-1), of polarized enterocyte monolayers. Nonetheless, all NMs were internalized by intestinal cells and, while NM-102 was retained in lysosomes, NM-103 and NM-105 were able to transverse the epithelial barrier through transcytosis. Moreover, 24 h exposure of 14 and 1.4 μg/mL digested NM-105, promoted interleukin IL-1β expression in activated M1 macrophages, indicating a potential pro-inflammatory action in the gut. Taken together, our findings shed light on the cell-specific nano-bio interplay of TiO2-NMs in the context of the intestinal tract and highlight transcytosis as a potential gateway for their systemic distribution. The potential proinflammatory action of digested NM-105 emphasizes the importance of pursuing research into the potential impact of NMs on human health and contribute to the weight of evidence to limit their use in food.
- Incidental nanoparticle characterisation in industrial settings to support risk assessment modellingPublication . Moreno-Martín, Veronica; López, Maria; Bou, David; Fraga, Sónia; Teixeira, João Paulo; López-Lilao, Ana; Sanfélix, Vicenta; Monfort, Eliseo; Viana, MarResearch on nanoparticle (NP) release and potential exposure can be assessed through experimental field campaigns, laboratory simulations, and prediction models. However, risk assessment models are typically designed for manufactured NP (MNP) and have not been adapted for incidental NP (INP) properties. A notable research gap is identifying NP sources and their chemical, physical, and toxicological properties, especially in real-world settings. This work aims to provide insights into the release and physico-chemical properties of INP while contributing to improving models for INP release. INP release was evaluated through a case study in a ceramic tile firing facility, where aerosol (10 nm - 10 μm) properties were determined. The Control Banding (CB) Nanotool model was applied to test outputs based on provided input parameters. Results: demonstrate the constant generation and release of INP during tile firing, with NP concentrations up to 68711/cm³ and mean diameters of 37 nm, with 95% smaller than 100 nm. Particle morphology was mostly spherical, suggesting nucleation from precursor gases as the main formation mechanism. INP chemical composition was driven by primary ceramic components, while trace elements like Ni and Ti exhibited sizedependent patterns. In vitro cell viability tests indicated low to medium cytotoxicity of PM2 aerosols, decreasing human alveolar epithelial cell viability in a concentration-dependent manner. Applying the risk model with varying input parameters revealed that the risk level (RL) based on severity scores decreased when aerosol size distribution data were used, illustrating the model’s sensitivity to input variables. We conclude on the need for comprehensive experimental datasets to support risk assessment models and achieve effective risk management strategies in real-world scenarios.
- Relative effectiveness of the second booster COVID-19 vaccines against laboratory confirmed SARS-CoV-2 infection in healthcare workers: VEBIS HCW VE cohort study (1 October 2022-2 May 2023)Publication . Savulescu, Camelia; Prats-Uribe, Albert; Brolin, Kim; Uusküla, Anneli; Bergin, Colm; Fleming, Catherine; Zvirbulis, Viesturs; Zavadska, Dace; Szułdrzyński, Konstanty; Gaio, Vânia; Popescu, Corneliu Petru; Craiu, Mihai; Cisneros, Maria; Latorre-Millán, Miriam; Lohur, Liis; McGrath, Jonathan; Ferguson, Lauren; Abolina, Ilze; Gravele, Dagne; Machado, Ausenda; Florescu, Simin Aysel; Lazar, Mihaela; Subirats, Pilar; Clusa Cuesta, Laura; Sui, Jacklyn; Kenny, Claire; Krievins, Dainis; Barzdina, Elza Anna; Melo, Aryse; Kosa, Alma Gabriela; Miron, Victor Daniel; Muñoz-Almagro, Carmen; Milagro, Ana María; Bacci, Sabrina; Kramarz, Piotr; Nardone, Anthony; VEBIS HCW Study GroupIntroduction: Repeated COVID-19 booster vaccination was recommended in healthcare workers (HCWs) to maintain protection. We measured the relative vaccine effectiveness (rVE) of the second booster dose of COVID-19 vaccine compared to the first booster, against laboratory-confirmed SARS-CoV-2 infection in HCWs. Methods: In a prospective cohort study among HCWs from 12 European hospitals, we collected nasopharyngeal or saliva samples at enrolment and during weekly/fortnightly follow-up between October 2022 and May 2023. We estimated rVE of the second versus first COVID-19 vaccine booster dose against SARS-CoV-2 infection, overall, by time since second booster and restricted to the bivalent vaccines only. Using Cox regression, we calculated the rVE as (1-hazard ratio)*100, adjusting for hospital, age, sex, prior SARS-CoV-2 infection and at least one underlying condition. Results: Among the 979 included HCWs eligible for a second booster vaccination, 392 (40 %) received it and 192 (20 %) presented an infection during the study period. The rVE of the second versus first booster dose was -5 % (95 %CI: -46; 25) overall, 3 % (-46; 36) in the 7-89 days after receiving the second booster dose. The rVE was 11 % (-43; 45) when restricted to the use of bivalent vaccines only. Conclusion: The bivalent COVID-19 could have reduced the risk of SARS-CoV-2 infection among HCWs by 11 %. However, we note the limitation of imprecise rVE estimates due to the proportion of monovalent vaccine used in the study, the small sample size and the study being conducted during the predominant circulation of XBB.1.5 sub-lineage. COVID-19 vaccine effectiveness studies in HCWs can provide important evidence to inform the optimal timing and the use of updated COVID-19 vaccines.
- Prevalence of T. rubrum and T. interdigitale Exhibiting High MICs to Terbinafine in Clinical Samples Analyzed in the Portuguese Mycology Reference LaboratoryPublication . Schirmer, Helena; Henriques, Camila; Simões, Helena; Veríssimo, Cristina; Sabino, RaquelCutaneous fungal infections represent a significant burden worldwide with a high impact on public health. Accurate identification of dermatophyte species causing these infections is vital for an appropriate treatment. Terbinafine is the primary agent against Trichophyton species due to its clinical efficacy; however, cases of elevated minimum inhibitory concentration (MIC) have been reported, raising clinical and epidemiological concerns. Herein, we aimed to detect Trichophyton rubrum and Trichophyton interdigitale isolates collected from clinical samples with terbinafine-high MICs (TRB-hMIC). A total of 168 isolates, recovered from 2017 to 2023, were identified as T. rubrum complex (140/83.4%) or T. interdigitale (28/16.7%) and further screened regarding their terbinafine susceptibility. Four isolates with capacity to grow in terbinafine media were detected by screening, and these and a further sixteen random isolates were submitted to the broth microdilution method. This methodology confirmed the four (2.4%) isolates as TRB-hMIC. One T. rubrum and three T. interdigitale showed a minimum inhibitory concentration (MIC) higher than 1 mg/L. Partial sequencing of the SQLE gene identified point mutations in T. rubrum (Phe397Iso) and in one T. interdigitale (Phe397Leu) isolate. Notably, in the other two T. interdigitale isolates with TRB-hMIC, no point mutations in the SQLE gene were identified. In conclusion, TRB-hMIC isolates (T. rubrum and T. interdigitale) were identified in clinical samples analyzed in Portugal, as antifungal susceptibility testing is a crucial routine for identifying treatment failures and also for epidemiological purposes aiming to monitor the dynamics of terbinafine resistance.