The Italian Mandatory Notification System: An Important Public Health Tool For Continuous Monitoring Of Infectious Diseases.

Infectious diseases still register significant morbidity and mortality worldwide. Surveillance through a mandatory notification system allows the continuous analysis of the situation even at a local level and its importance has been highlighted by the recent COVID-19 pandemic. This paper aimed to outline the importance of the mandatory notification system as a Public Health tool in the continuous monitoring of infectious diseases. To this aim, we carried out a cross-sectional study examining the notifications reported in the Italian territory of Messina, Sicily, in the period 2001-2020. The institutional websites were examined and the notification data were used to obtain the incidences. Overall, a significant reduction of the incidence notification trend was observed. Chickenpox was by far the most notified infectious disease, followed by scabies, pediculosis, and brucellosis. Outbreaks of brucellosis, measles and hepatitis A occurred. All the diseases decreased over time, except syphilis, for which a significant increase was observed. Surveillance of infectious diseases through a mandatory notification system remains a bulwark of public health despite underreporting. Our study reflects the situation of a typical high-income area, although some unexpected criticisms are highlighted. Continuous information about correct behaviors through education campaigns are crucial in order to improve the situation. Keywords: mandatory notifications, infectious diseases, surveillance, public health Corresponding author: Alessio Facciolà, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Italy. Email: afacciola@unime.it.

Is the Antibacterial Activity of Multi-Walled Carbon Nanotubes (MWCNTs) Related to Antibiotic Resistance? An Assessment in Clinical Isolates.

Antimicrobial resistance has spread globally, compromising the treatment of common infections. This feature is particularly harmful for nosocomial pathogens that can survive on hospital surfaces. Research studies have been conducted to evaluate new materials that are able to counteract the microbial growth and the colonization of the hospital environment. In this context, nanotechnologies have showed encouraging applications. We investigated the antibacterial activity of multi-walled carbon nanotubes (MWCNTs), both pristine (p) and functionalized (f), at concentrations of 50 and 100 µg mL-1, against bacterial strains isolated from hospital-acquired infections, and this activity was correlated with the antibiotic susceptibility of the strains. The inhibiting effect of MWCNTs occurred for both types and doses tested. Moreover, f-MWCNTs exerted a greater inhibiting effect, with growth decreases greater than 10% at 24 h and 20% at 48 h compared to p-MWCNTs. Moreover, a lower inhibitory effect of MWCNTs, which was more lasting in Gram-positives resistant to cell wall antibiotics, or temporary in Gram-negatives resistant to nucleic acid and protein synthesis inhibitors, was observed, highlighting the strong relation between antibiotic resistance and MWCNT effect. In conclusion, an antimicrobial activity was observed especially for f-MWCNTs that could therefore be loaded with bioactive antimicrobial molecules. However, this potential application of CNTs presupposes the absence of toxicity and therefore total safety for patients.

In vitro assessment of neurotoxicity and neuroinflammation of homemade MWCNTs.

Multi walled carbon nanotubes (MWCNTs) activate pathways involved in cytotoxicity, genotoxicity and inflammation. Inhaled MWCNTs are translocated to extra pulmonary organs and their hydrophobicity allows them to cross the blood-brain barrier (BBB). Further exposure of central nervous system (CNS) occurs via olfactory neurons. Using differentiated SH-SY5Y, we studied the neurotoxicity and neuroinflammation of pristine and functionalised MWCNTs. ROS overproduction was dose- and time-dependent (P<0.01) and was related to mitochondrial impairment, DNA damage and decreased viability (P<0.05). Transcript levels of TNFα, IL-1ß and IL-6 increased, as confirmed by an ELISA test. Raman spectra were acquired to assess MWCNT-cells interactions. The almost superimposable pro-oxidant activity of both CNTs could be imputable to excessive lengths with regard to the pristine MWCNTs and to the eroded surface, causing increased reactivity, with regard to functionalised MWCNTs. Considering the ease with which lightweight MWCNTs aerosolize and the increased production, the results underlined the potential onset of neurodegenerative diseases, due to unintentional MWCNT exposure.

In vitro assessment of the indirect antioxidant activity of Sulforaphane in redox imbalance vanadium-induced.

Owing to sulforaphane presence, a dietary consumption of Brassicaceae prevents chronic diseases. This hormetic compound induces adaptive stress response at subtoxic doses, while doses that exceed the cellular defence are toxic. In HepG2, Caco-2 and Vero cells, we investigated the sulforaphane (SFN) (5 µM) role in counteracting redox imbalance induced by VOSO4 [V(IV)]. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test showed a dose-dependent viability reduction (r < -0.95; p < 0.01) (range 5-80 µM). At 5 µM, SFN enhancement of mitochondrial activity was confirmed by Δψm (p < 0.05) both in basal condition and in redox-stressed cells. Intracellular ROS, DNA and lysosomal oxidative damages underlined the indirect antioxidant SFN activity, confirmed by the increase of GSH. The SFN empowering effects on mitochondrial function were imputable to the presence of mitochondrial proteins among the Nrf2-responsive phase II proteins. Considering the link between oxidative stress and chronic diseases, a long-term dietary intake of Brassicaceae could be strongly advisable.

Mitochondrial dysfunction by pro-oxidant vanadium: ex vivo assessment of individual susceptibility.

The aim was to assess the individual susceptibility to mitochondrial impairment induced by ex vivo exposure to vanadium, an airborne pro-oxidant pollutant. In lymphocyte cultures V(IV)-treated of forty-five healthy subjects, we evaluated the mitochondrial transmembrane potential (Δψm) and the H2O2 in comparison to background values. As variables, we included both lifestyle factors and genetic polymorphisms (GSTM1 and GSTT1 variants, and C677T and A1298C variants of methylenetetrahydrofolate reductase MTHFR). H2O2 mitochondrial content increased significantly (P<0.05) after metal exposure while, in comparison to basal Δψm, both depolarisation and hyperpolarisation were recorded. This underlined the mitochondrial dysfunction vanadium-induced that worsens the redox imbalance by endogenous ROS overproduction. Only age was found to contribute significantly to the high inter-individual variability, as assessed by multivariate analysis. In older subjects, the H2O2/Δψm values underline the organelle impairment and, under V-exposure, Δψm values were inversely related to age (R=-0.591; P=0.012).

Toxicological assessment of multi-walled carbon nanotubes on A549 human lung epithelial cells.

An in vitro model resembling the respiratory epithelium was used to investigate the biological response to laboratory-made pristine and functionalised multi-walled carbon nanotubes (pMWCNT and MWCNT-COOH). Cell uptake was analysed by MWCNT-COOH, FITC labelled and the effect of internalisation was evaluated on the endocytic apparatus, mitochondrial compartment and DNA integrity. In the dose range 12.5-100µgml(-1), cytotoxicity and ROS generation were assayed, evaluating the role of iron (the catalyst used in MWCNTs synthesis). We observed a correlation between MWCNTs uptake and lysosomal dysfunction and an inverse relationship between these two parameters and cell viability (P<0.01). In particular, pristine-MWCNT caused a time- and dose-dependent ROS increase and higher levels of lipid hydroperoxides compared to the controls. Mitochondrial impairment was observed. Conversely to the functionalised MWCNT, higher micronuclei (MNi) frequency was detected in mono- and binucleate pMWCNT-treated cells, underlining an aneugenic effect due to mechanical damage. Based on the physical and chemical features of MWCNTs, several toxicological pathways could be activated in respiratory epithelium upon their inhalation. The biological impacts of nano-needles were imputable to their efficient and very fast uptake and to the resulting mechanical damages in cell compartments. Lysosomal dysfunction was able to trigger further toxic effects.

Ex vivo study for the assessment of behavioral factor and gene polymorphisms in individual susceptibility to oxidative DNA damage metals-induced.

Transition metals in fine particulate matter generated by combustion induce oxidative DNA damage and inflammation. However, there is remarkable inter-individual variability in susceptibility to these damages. To assess this variability, an ex vivo study was performed using lymphocytes of 47 Caucasian healthy subjects. Cell samples were exposed to a water solution of oil fly ash (OFA). This was formed by the distinctive transition metals vanadium, iron, and nickel. Oxidative DNA damage was evaluated by testing cell viability, intracellular ROS production and 8-oxo-dG. DNA fragmentation and DNA repair capacity were assessed by using the Alkaline-Halo assay. GSTM1, GSTT1, hOGG1, and C677T and A1298C MTHFR gene polymorphisms were tested. Demographic and behavioral factors, collected by questionnaire, were also considered. OFA induced damages showed: (a) a 20-fold variation in range among different subjects in ROS production, (b) a 7-fold variation in range of 8-oxo-dG, and (c) a 25-fold variation in range in DNA repair capacity. A significant increase in DNA damage was detected in GSTT1-deficent subjects compared with wild type genotype carriers. Increases in cytoplasmic ROS and decreases in DNA repair capacity (P<0.05) were observed in C677T and A1298C variants of MTHFR. A remarkable protective effect of high fruits and vegetable intake was observed for ROS production and DNA damage. Conversely, an adverse effect of meat intake was observed on ROS increase, DNA damage and repair capacity, probably due to the increased intake of bioavailable iron. Smoking decreased DNA repair capacity, while age increased OFA-induced DNA damage. The wide comparative analysis of the complex interactions network, between genetic and behavioral factors provides evidence of the remarkable role of several lifestyle factors. In comparison to genetic polymorphisms they seem to have a higher weight in determining individual susceptibility to the adverse effects of airborne pollutants as transition metals.