60 research outputs found
Caries Severity, Decayed First Permanent Molars and Associated Factors in 6-7 Years Old Schoolchildren Living in Palermo (Southern Italy).
To date, there are very few epidemiologic studies on caries disease in 6-7 year old children living in Sicily (Southern Italy). The first permanent molar (FPM) is the most commonly affected tooth in this target population, and a one-unit increase in the number of decayed FPMs is predictive of caries in other teeth and in adulthood. The primary aim of this research is to estimate the prevalence of caries in 6-7 year old schoolchildren living in Palermo and, as a secondary aim, to estimate the prevalence of affected FPMs. It was designed as a cluster cross-sectional survey on 995 children from 16 schools, selected based on their geographical location, in one of the eight city districts. Caries data were recorded using the International Caries Detection and Assessment System for each tooth surface. The relation between socio-economic status, behavioural determinants, and clinical information and the number of teeth with initial caries (IC), moderate caries (MC), or extensive caries (SC) was analysed through the ordinal logistic regression. Among the 995 schoolchildren, 662 (66.5%) had at least one lesion and 742 (74.6%) had FPMs. Of the latter, 238 (32.0%) were affected by IC, 86 (11.6%) were affected by MC, and only 3 (0.4%) were affected by SC. During multivariable analysis, there was evidence of an increased risk of MC and SC related to the deprivation of the district in which the children lived and went to school, as well as to the protective role of parental education and employment. The same significant determinants were found for IC and MC FPMs. The study showed the important role of socio-economic determinants, unhealthy behaviours, and social deprivation related to the increased risk of moderate and extensive caries in 6-7 year old schoolchildren. Investigating this target population is very important, as early development of caries in FPMs may have serious consequences in the prognostics of oral health in an adult
Vacancy generation in liquid phase epitaxy of Si
Concerted experiments and theoretical analysis are applied to conclusively demonstrate the vacancy generation during fast melting and regrowth of Si by laser irradiation. Experiments, based on the positron annihilation spectroscopy and designed to test the theoretical predictions, evidence a vacancy supersaturation after the laser process depending on the irradiation conditions. Stochastic atomistic simulations of the molten Si recrystallization show trapping of vacancies in the recrystallized region. Finally, continuum phase-field simulations of the full process, calibrated using the Monte Carlo results, show a defect evolution in close agreement with the experiments.Peer reviewe
Development of Si-based electrical biosensors: Simulations and first experimental results
In this work, we simulated and experimentally assessed the possibility to detect, through electrical transduction, hybridization of DNA molecules on MOS-like devices, having different dielectrics: SiO2, Si3N4 and SiO2/Si3N4/SiO2 (ONO). The electrical characterization was performed after the various functionalization steps, consisting of dielectric activation, silanization, DNA spotting and anchoring, and after the hybridization process, to test the devices effectiveness as DNA recognition biosensors. The experimental results were used to validate device simulations. The comparison shows the ability to determine a priori the DNA probe density needed to maximize the response. The results confirm that the structures analyzed are sensitive to the immobilization of DNA and its hybridization
Alternative sources of neurons and glia from somatic stem cells.
Stem cell populations have been shown to be extremely versatile: they can generate differentiated cells specific to the tissue in which they reside and descendents that are of different germ layer origin. This raises the possibility of obtaining neuronal cells from new biological source of the same adult human subjects. In this study, we found that epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) cooperated to induce the proliferation, self-renewal, and expansion of neural stem cell-like population isolated from several newborn and adult mouse tissues: muscle and hematopoietic tissues. This population, in both primary culture and secondary expanded clones, formed spheres of undifferentiated cells that were induced to differentiate into neurons, astrocytes, and oligodendrocytes. Brain engraftment of the somatic-derived neural stem cells generated neuronal phenotypes, demonstrating the great plasticity of these cells with potential clinical application
Intraarterial Injection of Muscle-Derived Cd34+Sca-1+ Stem Cells Restores Dystrophin in mdx Mice
Duchenne muscular dystrophy is a lethal recessive disease characterized by widespread muscle damage throughout the body. This increases the difficulty of cell or gene therapy based on direct injections into muscles. One way to circumvent this obstacle would be to use circulating cells capable of homing to the sites of lesions. Here, we showed that stem cell antigen 1 (Sca-1), CD34 double-positive cells purified from the muscle tissues of newborn mice are multipotent in vitro and can undergo both myogenic and multimyeloid differentiation. These muscle-derived stem cells were isolated from newborn mice expressing the LacZ gene under the control of the muscle-specific desmin or troponin I promoter and injected into arterial circulation of the hindlimb of mdx mice. The ability of these cells to interact and firmly adhere to endothelium in mdx muscles microcirculation was demonstrated by intravital microscopy after an intraarterial injection. Donor Sca-1, CD34 muscle-derived stem cells were able to migrate from the circulation into host muscle tissues. Histochemical analysis showed colocalization of LacZ and dystrophin expression in all muscles of the injected hindlimb in all of five out of five 8-wk-old treated mdx mice. Their participation in the formation of muscle fibers was significantly increased by muscle damage done 48 h after their intraarterial injection, as indicated by the presence of 12% β-galactosidase–positive fibers in muscle cross sections. Normal dystrophin transcripts detected enzymes in the muscles of the hind limb injected intraarterially by the mdx reverse transcription polymerase chain reaction method, which differentiates between normal and mdx message. Our results showed that the muscle-derived stem cells first attach to the capillaries of the muscles and then participate in regeneration after muscle damage
CBX2 shapes chromatin accessibility promoting AML via p38 MAPK signaling pathway
Abstract
Background: The dynamic epigenome and proteins specialized in the interpretation of epigenetic marks critically
contribute to leukemic pathogenesis but also offer alternative therapeutic avenues. Targeting newly discovered
chromatin readers involved in leukemogenesis may thus provide new anticancer strategies. Accumulating evidence
suggests that the PRC1 complex member CBX2 is overexpressed in solid tumors and promotes cancer cell survival.
However, its role in leukemia is still unclear.
Methods: We exploited reverse genetic approaches to investigate the role of CBX2 in human leukemic cell lines and
ex vivo samples. We also analyzed phenotypic effects following CBX2 silencing using cellular and molecular assays
and related functional mechanisms by ATAC-seq and RNA-seq. We then performed bioinformatic analysis of ChIPseq
data to explore the influence of histone modifications in CBX2-mediated open chromatin sites. Lastly, we used
molecular assays to determine the contribution of CBX2-regulated pathways to leukemic phenotype.
Results: We found CBX2 overexpressed in leukemia both in vitro and ex vivo samples compared to CD34+
cells.
Decreased CBX2 RNA levels prompted a robust reduction in cell proliferation and induction of apoptosis. Similarly,
sensitivity to CBX2 silencing was observed in primary acute myeloid leukemia samples. CBX2 suppression increased
genome-wide chromatin accessibility followed by alteration of leukemic cell transcriptional programs, resulting in
enrichment of cell death pathways and downregulation of survival genes. Intriguingly, CBX2 silencing induced epigenetic
reprogramming at p38 MAPK-associated regulatory sites with consequent deregulation of gene expression.
Conclusions: Our results identify CBX2 as a crucial player in leukemia progression and highlight a potential druggable CBX2-p38 MAPK network in AML
A Knowledge, Attitude, and Perception Study on Flu and COVID-19 Vaccination during the COVID-19 Pandemic: Multicentric Italian Survey Insights
In January 2020, Chinese health authorities identified a novel coronavirus strain never before isolated in humans. It quickly spread across the world, and was eventually declared a pandemic, leading to about 310 million confirmed cases and to 5,497,113 deaths (data as of 11 January 2022). Influenza viruses affect millions of people during cold seasons, with high impacts, in terms of mortality and morbidity. Patients with comorbidities are at a higher risk of acquiring severe problems due to COVID-19 and the flu-infections that could impact their underlying clinical conditions. In the present study, knowledge, attitudes, and opinions of the general population regarding COVID-19 and influenza immunization were evaluated. A multicenter, web-based, cross-sectional study was conducted between 10 February and 12 July 2020, during the first wave of SARS-CoV-2 infections among the general population in Italy. A sample of 4116 questionnaires was collected at the end of the study period. Overall, 17.5% of respondents stated that it was unlikely that they would accept a future COVID-19 vaccine (n = 720). Reasons behind vaccine refusal/indecision were mainly a lack of trust in the vaccine (41.1%), the fear of side effects (23.4%), or a lack of perception of susceptibility to the disease (17.1%). More than 50% (53.8%; n = 2214) of the sample participants were willing to receive flu vaccinations in the forthcoming vaccination campaign, but only 28.2% of cases had received it at least once in the previous five seasons. A higher knowledge score about SARS-CoV-2/COVID-19 and at least one flu vaccination during previous influenza seasons were significantly associated with the intention to be vaccinated against COVID-19 and influenza. The continuous study of factors, determining vaccination acceptance and hesitancy, is fundamental in the current context, in regard to improve vaccination confidence and adherence rates against vaccine preventable diseases
Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study
Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age.Methods: From the Italian LIPIGEN cohort, we selected 1188 (>= 18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation.Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives.Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age
Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations
: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice
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