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Abstract Introduction Vaccination is considered as one of the most promising strategies to overcome the COVID-19 pandemic. However, it could be associated with rare but serious complications. In the present study, we aimed to review the clinical course and etiology of post COVID-19 vaccination meningitis. Methods After a systematic search in PubMed, Scopus, and Web of Sciences online databases as well as Google Scholar, documents were screened and qualified. Then data extraction was performed and the most frequent underlying agent of meningitis was found based on the reported cases. Results Overall, 35 cases of post COVID-19 vaccination meningitis from 33 articles were included in the review. Among them, 12 cases had proven viral diagnosis and 23 of them were reported to be vaccine-induced. The most frequent viral pathogen among the cases was VZV. The most prevalent symptom was headache, and the most common time of appearance symptoms was one week after vaccination. Conclusion Overall, our study suggested meningitis as a critical but not devastating complication of COVID-19 vaccination. Almost all patients responded well to common agents used to manage viral or vaccine-induced meningitis. It is recommended to monitor patients with a history of chickenpox after COVID-19 vaccination regarding the development of meningitis.

Abstract Background Research in the neurosciences has highlighted the importance of intersubjective relationships in promoting neuromental development of the child. Children’s learning in early childhood occurs mainly in a dyadic context of an interaction with their parents: from this perspective, good dialogic parent–child communication is required to be promoted also through good educational practices. Dialogic Book-Sharing (DBS), a dialogic form of parent–child communication through the use of wordless picture books, provides a privileged ‘intersubjective’ space and is highly effective in promoting communication, language, attention, behavioural development and the parent–child relationship. DBS programme, successfully previously trialled in South Africa and the UK, will be applied for the first time in Italy for research purposes in Italian health, educational and maternal-child centres. Methods A multicentre randomised controlled trial is being conducted to evaluate DBS parenting intervention for children aged between 14 and 20 months. Parent–child dyads are randomly allocated to a book-sharing intervention group or to a wait-list control group. In the intervention, parents are trained in supportive book-sharing with their children by local staff of the centres. DBS intervention is carried out in small groups over a period of 4 weeks. Data are collected at baseline, post-intervention and at 6 months post-intervention with a questionnaire and video recording of parent–child interaction. Discussion DBS programme in early childhood could enhance the educational resources offered by Italian health, educational and maternal-child centres, in support of child’s development and parenting. DBS represents a strategic opportunity for bringing about positive effects, also in terms of prevention of socio-emotional and cognitive difficulties. As such it represents a promising response to the new social, health and educational needs of the post-COVID-19 pandemic era caused by the social isolation measures. Furthermore, the application of the DBS methodology is a way to promote the use of books, and thereby counteract the excessive use of technological devices already present in early childhood. Trial registration The trial is registered on the International Standard Randomised Controlled Trial Number database, registration number ISRCTN11755019 Registered on 2 November 2023. This is version 1 of the protocol for the trial.

Abstract Adolescence is characterized by emotional instability and risk-taking behaviours that can lead to, among other things, an increased risk of developing pathological video-gaming and gambling habits. The aim of this Study is to assess the prevalence and type of video gaming and gambling habits in adolescent students attending Italian upper-secondary schools. The cross-sectional study was conducted via an online survey using validated questionnaires. The primary outcome measures were the prevalence of past-year video gaming and gambling activities. The sample consisted of 502 adolescent students from first- and second-grade secondary schools. A total of 40.8% of participants were video gamers, 4.8% were gamblers, 17.8% were both video gamers and gamblers, and the remaining 36.6% were not players. Among participants who reported video gaming activity (n = 294), 68.0% were classified as nonproblem gamers, 24.5% as at-risk gamers, and 7.5% as disordered video gamers. Among the participants who reported gambling activity (n = 113), 85.8% were not problematic gamblers, 8.9% were at-risk gamblers, and 5.3% were pathological gamblers. Only 0.2% of all subjects met the criteria for both pathological gambling and pathological video game use. The findings indicate that video gaming and gambling are common leisure times among adolescent students. However, a small but significant minority of these adolescents met the criteria for either severe problem gaming or gambling or both.

Abstract Background Estimating the risk of intubation and mortality among COVID-19 patients can help clinicians triage these patients and allocate resources more efficiently. Thus, here we sought to identify the risk factors associated with intubation and intra-hospital mortality in a cohort of COVID-19 patients hospitalized due to hypoxemic acute respiratory failure (ARF). Results We included retrospectively a total of 187 patients admitted to the subintensive and intensive care units of the University Hospital “Maggiore della Carità” of Novara between March 1st and April 30th, 2020. Based on these patients’ demographic characteristics, early clinical and laboratory variables, and quantitative chest computerized tomography (CT) findings, we developed two random forest (RF) models able to predict intubation and intra-hospital mortality. Variables independently associated with intubation were C-reactive protein (p < 0.001), lactate dehydrogenase level (p = 0.018) and white blood cell count (p = 0.026), while variables independently associated with mortality were age (p < 0.001), other cardiovascular diseases (p = 0.029), C-reactive protein (p = 0.002), lactate dehydrogenase level (p = 0.018), and invasive mechanical ventilation (p = 0.001). On quantitative chest CT analysis, ground glass opacity, consolidation, and fibrosis resulted significantly associated with patient intubation and mortality. The major predictors for both models were the ratio between partial pressure of arterial oxygen and fraction of inspired oxygen, age, lactate dehydrogenase, C-reactive protein, glycemia, CT quantitative parameters, lymphocyte count, and symptom onset. Conclusions Altogether, our findings confirm previously reported demographic, clinical, hemato-chemical, and radiologic predictors of adverse outcome among COVID-19-associated hypoxemic ARF patients. The two newly developed RF models herein described show an overall good level of accuracy in predicting intra-hospital mortality and intubation in our study population. Thus, their future development and implementation may help not only identify patients at higher risk of deterioration more effectively but also rebalance the disproportion between resources and demand.

Abstract Background The cell adhesion molecule transmembrane and immunoglobulin (Ig) domain containing1 (TMIGD1) is a novel tumor suppressor that plays important roles in regulating cell–cell adhesion, cell proliferation and cell cycle. However, the mechanisms of TMIGD1 signaling are not yet fully elucidated. Results TMIGD1 binds to the ERM family proteins moesin and ezrin, and an evolutionarily conserved RRKK motif on the carboxyl terminus of TMIGD1 mediates the interaction of TMIGD1 with the N-terminal ERM domains of moesin and ezrin. TMIGD1 governs the apical localization of moesin and ezrin, as the loss of TMIGD1 in mice altered apical localization of moesin and ezrin in epithelial cells. In cell culture, TMIGD1 inhibited moesin-induced filopodia-like protrusions and cell migration. More importantly, TMIGD1 stimulated the Lysine (K40) acetylation of α-tubulin and promoted mitotic spindle organization and CRISPR/Cas9-mediated knockout of moesin impaired the TMIGD1-mediated acetylation of α-tubulin and filamentous (F)-actin organization. Conclusions TMIGD1 binds to moesin and ezrin, and regulates their cellular localization. Moesin plays critical roles in TMIGD1-dependent acetylation of α-tubulin, mitotic spindle organization and cell migration. Our findings offer a molecular framework for understanding the complex functional interplay between TMIGD1 and the ERM family proteins in the regulation of cell adhesion and mitotic spindle assembly, and have wide-ranging implications in physiological and pathological processes such as cancer progression.

Abstract Background Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer similar toxicity, in particular, genotoxicity. Nine CNT/F (MW #1–7 and CNF #1–2), commonly found in exposure assessment studies of U.S. facilities, were evaluated with reported diameters ranging from 6 to 150 nm. All materials were extensively characterized to include distributions of physical dimensions and prevalence of bundled agglomerates. Human bronchial epithelial cells were exposed to the nine CNT/F (0–24 μg/ml) to determine cell viability, inflammation, cellular oxidative stress, micronuclei formation, and DNA double-strand breakage. Computational modeling was used to understand various permutations of physicochemical characteristics and toxicity outcomes. Results Analyses of the CNT/F physicochemical characteristics illustrate that using detailed distributions of physical dimensions provided a more consistent grouping of CNT/F compared to using particle dimension means alone. In fact, analysis of binning of nominal tube physical dimensions alone produced a similar grouping as all characterization parameters together. All materials induced epithelial cell toxicity and micronuclei formation within the dose range tested. Cellular oxidative stress, DNA double strand breaks, and micronuclei formation consistently clustered together and with larger physical CNT/F dimensions and agglomerate characteristics but were distinct from inflammatory protein changes. Larger nominal tube diameters, greater lengths, and bundled agglomerate characteristics were associated with greater severity of effect. The portion of tubes with greater nominal length and larger diameters within a sample was not the majority in number, meaning a smaller percentage of tubes with these characteristics was sufficient to increase toxicity. Many of the traditional physicochemical characteristics including surface area, density, impurities, and dustiness did not cluster with the toxicity outcomes. Conclusion Distributions of physical dimensions provided more consistent grouping of CNT/F with respect to toxicity outcomes compared to means only. All CNT/F induced some level of genotoxicity in human epithelial cells. The severity of toxicity was dependent on the sample containing a proportion of tubes with greater nominal lengths and diameters.

Abstract Worldwide, 70% of the adult population has limited expression of lactase enzyme with a wide variation among different regions and countries. Lactase deficiency may lead to lactose intolerance (LI). Depending both on the amount of lactose ingested and on the lactase activity, people who suffer from lactose malabsorption might experience numerous gastrointestinal and extra-intestinal symptoms and manifestations. Treatment of LI mainly consists of reducing or eliminating lactose from the diet until the symptoms disappear as well as supplementing lactase, and inducing colon microbiome adaptation by probiotics. Cow’s milk is one of the major source of calcium and several other vitamins and minerals. Thus, a complete exclusion of dairy products may favor the development of bone diseases such as osteopenia and osteoporosis. Therefore, the dietetic approach has a crucial role in the management of LI patients. Additionally, the use of lactose and milk-derived products in non-dairy products (e.g., baked goods, breakfast cereals, drinks, and processed meat) has become widespread in the modern industry (the so-called “hidden lactose”). In this regard, a strict adherence to the lactose-free diet becomes challenging for LI patients, forced to continuous check of all products and food labels. In fact, lactose-free product labeling is still controversial. Considering that nowadays a specific cut-off value establishing “lactose-free” labeling policy is lacking and that there is no universal law regulating the production and commercialization of “delactosed” products, identification of specific safe and suitable products with a well-recognized lactose-free logo might help consumers. This narrative review aims to identify the dietary management for lactose intolerant people, avoiding symptoms and nutrients deficiencies, helped by the use of specific labelling to guide them to choose the safer product on the market.

Abstract Background Fetal programming during in utero life defines the set point of physiological and metabolic responses that lead into adulthood; events happening in “the first 1,000 days” (from conception to 2-years of age), play a role in the development of non-communicable diseases (NCDs). The infant gut microbiome is a highly dynamic organ, which is sensitive to maternal and environmental factors and is one of the elements driving intergenerational NCDs’ transmission. The A.MA.MI (Alimentazione MAmma e bambino nei primi MIlle giorni) project aims at investigating the correlation between several factors, from conception to the first year of life, and infant gut microbiome composition. We described the study design of the A.MA.MI study and presented some preliminary results. Methods A.MA.MI is a longitudinal, prospective, observational study conducted on a group of mother-infant pairs (n = 60) attending the Neonatal Unit, Fondazione IRCCS Policlinico San Matteo, Pavia (Italy). The study was planned to provide data collected at T0, T1, T2 and T3, respectively before discharge, 1,6 and 12 months after birth. Maternal and infant anthropometric measurements were assessed at each time. Other variables evaluated were: pre-pregnancy/gestational weight status (T0), maternal dietary habits/physical activity (T1-T3); infant medical history, type of feeding, antibiotics/probiotics/supplements use, environment exposures (e.g cigarette smoking, pets, environmental temperature) (T1-T3). Infant stool samples were planned to be collected at each time and analyzed using metagenomics 16S ribosomal RNA gene sequence-based methods. Results Birth mode (cesarean section vs. vaginal delivery) and maternal pre pregnancy BMI (BMI

Abstract Background The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT. Previously, MWCNT exposed to high temperature (MWCNT-HT) or synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their genotoxic and carcinogenic potential are not known. Our aim was to measure the genotoxicity of MWCNT-7 compared to these two physicochemically-altered MWCNTs in human lung epithelial cells (BEAS-2B & SAEC). Results Dose-dependent partitioning of individual nanotubes in the cell nuclei was observed for each MWCNT material and was greatest for MWCNT-7. Exposure to each MWCNT led to significantly increased mitotic aberrations with multi- and monopolar spindle morphologies and fragmented centrosomes. Quantitative analysis of the spindle pole demonstrated significantly increased centrosome fragmentation from 0.024–2.4 μg/mL of each MWCNT. Significant aneuploidy was measured in a dose-response from each MWCNT-7, HT, and ND; the highest dose of 24 μg/mL produced 67, 61, and 55%, respectively. Chromosome analysis demonstrated significantly increased centromere fragmentation and translocations from each MWCNT at each dose. Following 24 h of exposure to MWCNT-7, ND and/or HT in BEAS-2B a significant arrest in the G1/S phase in the cell cycle occurred, whereas the MWCNT-ND also induced a G2 arrest. Primary SAEC exposed for 24 h to each MWCNT elicited a significantly greater arrest in the G1 and G2 phases. However, SAEC arrested in the G1/S phase after 72 h of exposure. Lastly, a significant increase in clonal growth was observed one month after exposure to 0.024 μg/mL MWCNT-HT & ND. Conclusions Although MWCNT-HT & ND cause a lower incidence of genotoxicity, all three MWCNTs cause the same type of mitotic and chromosomal disruptions. Chromosomal fragmentation and translocations have not been observed with other nanomaterials. Because in vitro genotoxicity is correlated with in vivo genotoxic response, these studies in primary human lung cells may predict the genotoxic potency in exposed human populations.

Abstract Background Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos. Methods The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution. Results Mortality was significantly increased for ‘All Causes’ and ‘All Malignant Neoplasm (MN)’, in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%. Conclusions Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.

Abstract Background To evaluate the relationship between smoking and metabolic parameters in patients affected by type 1 diabetes (T1D). Patients and methods We enrolled 104 children and young adults (50 females and 54 males) with T1D (aged 16.4 ± 8.6 years). The subjects were divided into three groups according to their smoking habits: no smoking (NS), passive smoking (PS), active smoking (AS). The physical examination of the participants included nutritional status assessment by anthropometry and pubertal stage according to Marshall and Tanner as well as blood pressure measurement. In all patients, metabolic blood assays including fasting blood glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured. Insulin resistance was determined by glucose disposal rate (eGDR). Physical activity was also recorded. Results Significant differences in biochemical and functional parameters among the three groups were demonstrated, in particular for systolic (p = 0.002) and diastolic pressure (p = 0.02) and eGDR (p = 0.039). No differences in daily insulin dose (p = 0.75) and glycated hemoglobin (p = 0.39) were observed. AS group had significantly higher blood pressure (p

Abstract Background The cytoprotective nature of nitric oxide (NO) led to development of NO-aspirins in the hope of overcoming the gastric side-effects of aspirin. However, the NO moiety gives these hybrids potential for actions further to their aspirin-mediated anti-platelet and anti-inflammatory effects. Having previously shown that novel NO-aspirin hybrids containing a furoxan NO-releasing group have potent anti-platelet effects, here we investigate their anti-inflammatory properties. Here we examine their effects upon TNFα release from lipopolysaccharide (LPS)-stimulated human monocytes and monocyte-derived macrophages and investigate a potential mechanism of action through effects on LPS-stimulated nuclear factor-kappa B (NF-κB) activation. Methods Peripheral venous blood was drawn from the antecubital fossa of human volunteers. Mononuclear cells were isolated and cultured. The resultant differentiated macrophages were treated with pharmacologically relevant concentrations of either a furoxan-aspirin (B8, B7; 10 μM), their respective furazan NO-free counterparts (B16, B15; 10 μM), aspirin (10 μM), existing nitroaspirin (NCX4016; 10 μM), an NO donor (DEA/NO; 10 μM) or dexamethasone (1 μM), in the presence and absence of LPS (10 ng/ml; 4 h). Parallel experiments were conducted on undifferentiated fresh monocytes. Supernatants were assessed by specific ELISA for TNFα release and by lactate dehydrogenase (LDH) assay for cell necrosis. To assess NF-κB activation, the effects of the compounds on the loss of cytoplasmic inhibitor of NF-κB, IκBα (assessed by western blotting) and nuclear localisation (assessed by immunofluorescence) of the p65 subunit of NF-κB were determined. Results B8 significantly reduced TNFα release from LPS-treated macrophages to 36 ± 10% of the LPS control. B8 and B16 significantly inhibited monocyte TNFα release to 28 ± 5, and 49 ± 9% of control, respectively. The B8 effect was equivalent in magnitude to that of dexamethasone, but was not shared by 10 μM DEA/NO, B7, the furazans, aspirin or NCX4016. LDH assessment revealed none of the treatments caused significant cell lysis. LPS stimulated loss of cytoplasmic IκBα and nuclear translocation of the p65 NF-κB subunit was inhibited by the active NO-furoxans. Conclusion Here we show that furoxan-aspirin, B8, significantly reduces TNFα release from both monocytes and macrophages and suggest that inhibition of NF-κB activation is a likely mechanism for the effect. This anti-inflammatory action highlights a further therapeutic potential of drugs of this class.

Abstract Background Radioisotopes are introduced into the environment following nuclear power plant accidents or nuclear weapons tests. The immobility of these radioactive elements in uppermost soil layers represents a problem for human health, since they can easily be incorporated in the food chain. Preventing their assimilation by plants may be a first step towards the total recovery of contaminated areas. Methods The possibility of displacing radionuclides from the most superficial soil layers and their subsequent stabilisation at lower levels were investigated in laboratory trials. An experimental system reproducing the environmental conditions of contaminated areas was designed in plastic columns. A radiopolluted soil sample was treated with solutions containing ions normally used in fertilisation (NO3-, NH4+, PO4--- and K+). Results Contaminated soils treated with an acid solution of ions NO3-, PO4--- and K+, undergo a reduction of radioactivity up to 35%, after a series of washes which simulate one year's rainfall. The capacity of the deepest soil layers to immobilize the radionuclides percolated from the superficial layers was also confirmed. Conclusion The migration of radionuclides towards deeper soil layers, following chemical treatments, and their subsequent stabilization reduces bioavailability in the uppermost soil horizon, preventing at the same time their transfer into the water-bearing stratum.