Telepractice in School-Age Children Who Stutter: A Controlled Before and After Study to Evaluate the Efficacy Of MIDA-SP.

The COVID-19 pandemic necessitated a general reorganization of rehabilitation services in Italy. The lockdown in Italy led to the use of telepractice for the delivery of speech therapy, including stuttering. The aim of the present work was to evaluate the effectiveness of the Multidimensional, Integrated, Differentiated, Art-Mediated Stuttering Program (MIDA-SP; Tomaiuoli et al., 2012), delivered online for school-age children who stutter. A non-randomized controlled pre- and post-treatment study included an experimental group (11 children) receiving a telepractice adaptation of MIDA-SP and a historical control group (11 children) receiving in-person MIDA-SP. Both groups had been assessed with the Stuttering Severity Instrument - Fourth Edition (SSI-4) and Overall Assessment of the Speaker's Experience of Stuttering (OASES-S) pre- and post-treatment. No statistically significant differences were found between the two modes of delivery. These findings suggest that MIDA-SP treatment delivered via telepractice is effective for school-age children who stutter.

Biological effects of combustion-derived particles from different biomass sources on human bronchial epithelial cells.

Combustion-derived particles (CDPs), in particular from traffic, are regarded as a central contributor for adverse health effects linked to air pollution. Recently, also biomass burning has been recognized as an important source for CDPs. Here, the effects of CDPs (PM10) originating from burning of pellet, charcoal and wood on key processes associated to lung carcinogenesis were explored. Human bronchial epithelial cells (HBEC3-KT) were exposed to 2.5 µg/cm2 of CDPs for 24 h and biological effects were examined in terms of cytotoxicity, inflammation, epithelial to mesenchymal transition (EMT)-related effects, DNA damage and genotoxicity. Reduced cell migration, inflammation and modulation of various PM-associated genes were observed mainly after exposure to wood and pellet. In contrast, only particles from pellet burning induced alteration in cell proliferation and DNA damage, which resulted in cell cycle alterations. Charcoal instead, appeared in general less effective in inducing pro-carcinogenic effects. These results illustrate differences in the toxicological profile due to the CDPs source. The different chemical compounds adsorbed on CDPs seemed to be central for particle properties, leading to an activation of various cellular signaling pathways involved in early steps of cancer progression.

Combustion-derived particles from biomass sources differently promote epithelial-to-mesenchymal transition on A549 cells.

Combustion-derived particles (CDPs), due to the presence in their composition of several toxic and carcinogenic chemical compounds, such as polycyclic aromatic hydrocarbons (PAHs) and metals, are linked to several respiratory diseases, including lung cancer. Epithelial-to-mesenchymal transition (EMT) is a crucial step in lung cancer progression, involving several morphological and phenotypical changes. The study aims to investigate how exposure to CDPs from different biomass sources might be involved in cancer development, focusing mainly on the effects linked to EMT and invasion on human A549 lung cells. Biomass combustion-derived particles (BCDPs) were collected from a stove fuelled with pellet, charcoal or wood, respectively. A time course and dose response evaluation on cell viability and pro-inflammatory response was performed to select the optimal conditions for EMT-related studies. A significant release of IL-8 was found after 72 h of exposure to 2.5 µg/cm2 BCDPs. The EMT activation was then examined by evaluating the expression of some typical markers, such as E-cadherin and N-cadherin, and the possible enhanced migration and invasiveness. Sub-acute exposure revealed that BCDPs differentially modulated cell viability, migration and invasion, as well as the expression of proteins linked to EMT. Results showed a reduction in the epithelial marker E-cadherin and a parallel increase in the mesenchymal markers N-cadherin, mainly after exposure to charcoal and wood. Migration and invasion were also increased. In conclusion, our results suggest that BCDPs with a higher content of organic compounds (e.g. PAHs) in their chemical composition might play a crucial role in inducing pro-carcinogenic effects on epithelial cells.

Daily submicron particle doses received by populations living in different low- and middle-income countries.

In the present study, the daily dose in terms of particle surface area received by citizens living in different low- and middle-income countries, characterized by different lifestyles, habits, and climates, was evaluated. The level of exposure to submicron particles and the dose received by the populations of Accra (Ghana), Cairo (Egypt), Florianopolis (Brazil), and Nur-Sultan (Kazakhstan) were analyzed. A direct exposure assessment approach was adopted to measure the submicron particle concentration levels of volunteers at a personal scale during their daily activities. Non-smoking adult volunteers performing non-industrial jobs were considered. Exposure data were combined with time-activity pattern data (characteristic of each population) and the inhalation rates to estimate the daily dose in terms of particle surface area. The received dose of the populations under investigation varied from 450 mm2 (Florianopolis, Brazil) to 1300 mm2 (Cairo, Egypt). This work highlights the different contributions of the microenvironments to the daily dose with respect to high-income western populations. It was evident that the contribution of the Cooking & Eating microenvironment to the total exposure (which was previously proven to be one of the main exposure routes for western populations) was only 8%-14% for low- and middle-income populations. In contrast, significant contributions were estimated for Outdoor day and Transport microenvironments (up to 20% for Cairo, Egypt) and the Sleeping & Resting microenvironment (up to 28% for Accra, Ghana), highlighting the effects of different site-specific lifestyles (e.g. time-activity patterns), habits, socioeconomic conditions, climates, and outdoor air quality.

Seasonal Variation in the Biological Effects of PM2.5 from Greater Cairo.

Greater Cairo (Egypt) is a megalopolis where the studies of the air pollution events are of extremely high relevance, for the geographical-climatological aspects, the anthropogenic emissions and the health impact. While preliminary studies on the particulate matter (PM) chemical composition in Greater Cairo have been performed, no data are yet available on the PM's toxicity. In this work, the in vitro toxicity of the fine PM (PM2.5) sampled in an urban area of Greater Cairo during 2017-2018 was studied. The PM2.5 samples collected during spring, summer, autumn and winter were preliminary characterized to determine the concentrations of ionic species, elements and organic PM (Polycyclic Aromatic Hydrocarbons, PAHs). After particle extraction from filters, the cytotoxic and pro-inflammatory effects were evaluated in human lung A549 cells. The results showed that particles collected during the colder seasons mainly induced the xenobiotic metabolizing system and the consequent antioxidant and pro-inflammatory cytokine release responses. Biological events positively correlated to PAHs and metals representative of a combustion-derived pollution. PM2.5 from the warmer seasons displayed a direct effect on cell cycle progression, suggesting possible genotoxic effects. In conclusion, a correlation between the biological effects and PM2.5 physico-chemical properties in the area of study might be useful for planning future strategies aiming to improve air quality and lower health hazards.

Intracerebral Injection of Extracellular Vesicles from Mesenchymal Stem Cells Exerts Reduced Aß Plaque Burden in Early Stages of a Preclinical Model of Alzheimer's Disease.

Bone marrow Mesenchymal Stem Cells (BM-MSCs), due to their strong protective and anti-inflammatory abilities, have been widely investigated in the context of several diseases for their possible therapeutic role, based on the release of a highly proactive secretome composed of soluble factors and Extracellular Vesicles (EVs). BM-MSC-EVs, in particular, convey many of the beneficial features of parental cells, including direct and indirect ß-amyloid degrading-activities, immunoregulatory and neurotrophic abilities. Therefore, EVs represent an extremely attractive tool for therapeutic purposes in neurodegenerative diseases, including Alzheimer's disease (AD). We examined the therapeutic potential of BM-MSC-EVs injected intracerebrally into the neocortex of APPswe/PS1dE9 AD mice at 3 and 5 months of age, a time window in which the cognitive behavioral phenotype is not yet detectable or has just started to appear. We demonstrate that BM-MSC-EVs are effective at reducing the Aß plaque burden and the amount of dystrophic neurites in both the cortex and hippocampus. The presence of Neprilysin on BM-MSC-EVs, opens the possibility of a direct ß-amyloid degrading action. Our results indicate a potential role for BM-MSC-EVs already in the early stages of AD, suggesting the possibility of intervening before overt clinical manifestations.

In vitro pulmonary and vascular effects induced by different diesel exhaust particles.

Diesel exhaust particles (DEP) are responsible for both respiratory and cardiovascular effects. However many questions are still unravelled and the mechanisms behind the health effects induced by the exposure to ultrafine particles (UFP) need further investigations. Furthermore, different emission sources can lead to diverse biological responses. In this perspective, here we have compared the effects of three DEPs, two standard reference materials (SRM 1650b and 2975) and one DEP directly sampled from a EuroIV vehicle without Diesel Particulate Filter (DPF). For the biological investigations, different in vitro lung models involving both epithelial and vascular endothelial cells, were used. Cell viability, oxidative stress, inflammation, DNA damage and endothelial activation markers were investigated at sub-cytotoxic DEP doses. The data obtained have shown that only DEP EuroIV, which had the major content of polycyclic aromatic hydrocarbons (PAHs) and metals, was able to induce oxidative stress, inflammation and consequent endothelial activation, as demonstrated by the expression of adhesion molecules (ICAM-1 and VCAM-1) and the release of inflammatory markers (IL-8) from endothelial cells. Standard reference materials were not effective under our experimental conditions. These data suggest that oxidative stress, endothelial activation and systemic inflammatory cytokines release are crucial events after DEP exposure and that the source of DEP emission, responsible of the particle chemical fingerprint, may have a key role in the resulting adverse biological outcomes.

In vitro lung toxicity of indoor PM10 from a stove fueled with different biomasses.

Biomass combustion significantly contributes to indoor and outdoor air pollution and to the adverse health effects observed in the exposed populations. Besides, the contribution to toxicity of the particles derived from combustion of different biomass sources (pellet, wood, charcoal), as well as their biological mode of action, are still poorly understood. In the present study, we investigate the toxicological properties of PM10 particles emitted indoor from a stove fueled with different biomasses. PM10 was sampled by gravimetric methods and particles were chemically analyzed for Polycyclic Aromatic Hydrocarbons (PAHs) and elemental content. Human lung A549 cells were exposed for 24 h to 1-10 µg/cm2 PM and different biological endpoints were evaluated to comparatively estimate the cytotoxic, genotoxic and pro-inflammatory effects of the different PMs. Pellet PM decreased cell viability, inducing necrosis, while charcoal and wood ones mainly induced apoptosis. Oxidative stress-related response and cytochrome P450 enzymes activation were observed after exposure to all the biomasses tested. Furthermore, after pellet exposure, DNA lesions and cell cycle arrest were also observed. The severe genotoxic and pro-necrotic effects observed after pellet exposure were likely the consequence of the high metal content. By administering the chelating agent TPEN, the genotoxic effects were indeed rescued. The higher content in PAHs measured in wood and charcoal PMs was likely the reason of the enhanced expression of metabolizing and oxidative stress-related enzymes, like CYP1B1 and HO-1, and the consequent increase in apoptotic cell death. These data suggest that combustion particles from different biomass sources may impact on lung cells according to different pathways, finally producing different toxicities. This is strictly related to the PM chemical composition, which reflects the quality of the combustion and the fuel in particular. Further studies are needed to clarify the role of particle dimension and the molecular mechanisms behind the harmful effects observed.

The role of IL-6 released from pulmonary epithelial cells in diesel UFP-induced endothelial activation.

Diesel exhaust particles (DEP) and their ultrafine fraction (UFP) are known to induce cardiovascular effects in exposed subjects. The mechanisms leading to these outcomes are still under investigation, but the activation of respiratory endothelium is likely to be involved. Particles translocation through the air-blood barrier and the release of mediators from the exposed epithelium have been suggested to participate in the process. Here we used a conditioned media in vitro model to investigate the role of epithelial-released mediators in the endothelial cells activation. Diesel UFP were sampled from a Euro 4 vehicle run over a chassis dyno and lung epithelial BEAS-2B cells were exposed for 20 h (dose 5 µg/cm2). The exposure media were collected and used for endothelial HPMEC-ST1.6R cells treatment for 24 h. The processes related to oxidative stress and inflammation were investigated in the epithelial cells, accordingly to the present knowledge on DEP toxicity. The release of IL-6 and VEGF was significantly augmented in diesel exposed cells. In endothelial cells, VCAM-1 and ICAM-1 adhesion molecules levels were increased after exposure to the conditioned media. By interfering with IL-6 binding to its endothelial receptor, we demonstrate the role of this interleukin in inducing the endothelial response.

Cognitive profiles in bilingual children born to immigrant parents and Italian monolingual native children with specific learning disorders.

PURPOSE: The aim of this study is to compare the Wechsler Intelligence Scale for Children® - fourth edition IV (WISC IV) intellectual profile of two groups of children with specific learning disorder, a group of bilingual children and a group of monolingual Italian children, in order to identify possible significant differences between them. PATIENTS AND METHODS: A group of 48 bilingual children and a group of 48 Italian monolingual children were included in this study. A preliminary comparison showed the homogeneity of the two groups regarding learning disorder typology and sociodemographic characteristics (age at WISC IV assessment, sex and years of education in Italy) with the exception of socioeconomic status. Socioeconomic status was then used as a covariate in the analysis. RESULTS: Even if the two groups were comparable in specific learning disorder severity and, in particular, in the text comprehension performance, our findings showed that the WISC IV performances of the bilingual group were significantly worse than the Italian group in Full Scale Intelligence Quotient (P=0.03), in General Ability Index (P=0.03), in Working Memory Index (P=0.009) and in some subtests and clusters requiring advanced linguistic abilities. CONCLUSION: These results support the hypothesis of a weakness in metalinguistic abilities in bilingual children with specific learning disorders than monolinguals. If confirmed, this result must be considered in the rehabilitation treatment.

C-type natriuretic peptide is closely associated to obesity in Caucasian adolescents.

CNP is a natural regulator of adipogenesis playing a role in the development of obesity in childhood. Aim of the study was to evaluate CNP plasma levels in normal-weight (N), overweight (OW) and obese adolescents (O). Eighty two subjects (age:12.8±2.4, years) without cardiac dysfunction were enrolled and CNP plasma levels were measured by RIA. NT-proBNP, MR-proANP, AGEs, reactive hyperemia index (RHI) and standard clinical chemistry parameters were also measured. O and OW adolescents had higher values of BMI and fat mass than N. CNP levels were significantly lower in OW:4.79[3.29-21.15] and O:3.81[1.55-13.4] than in N:13.21[7.6-37.8]; p<0.0001N vs O, p=0.0003N vs OW). LogCNP values correlated significantly and inversely with BMI z-score, FM%, TF% and circulating levels of CRP, insulin, total cholesterol, LDL, and triglycerides, in addition to an inverse relationship with skin AGEs and a direct correlation with RHI. LogCNP was also inversely associated with LogNT-proBNP and LogMR-proANP values. Using ROC analysis the risk of obesity resulted significantly (p≪0.0001) associated with CNP values (AUC=0.9724). These results suggest that CNP may play a more important role than BNP and ANP related peptides, as risk marker of obesity, in addition to its involvement in adipogenesis and endothelial dysfunction.