Oral Health in Migrants: An Observational Study on the Oral Health Status of a Migrant Cohort Coming from Middle-and Low-Income Countries

Introduction. The oral health conditions of migrants coming from middle-and low-income countries to developed countries have been shown to be poorer than those of the host population. Since the phenomenon of migration has continued to grow over the past five decades, the oral health status of migrant populations should be an issue of great concern. Objectives. The objective of our observational study was to analyse the periodontal health status and the prevalence of dental caries and lesions of the oral mucosa in a migrant cohort resident in Italy, assessing the association between the oral health status and the educational level of the included patients. Materials and Methods. Our research was conducted at the dental department of Policlinico Tor Vergata (Rome, Italy). A sample of 200 migrants coming from middle-and low-income countries, aged between 3 and 37, was included in our study. Each patient underwent a physical examination of the oral cavity, recording the DMFT/dmft index, Community Periodontal Index of Treatment Needs (CPI), and lesions of the oral mucosa. The one-way ANOVA test was used to establish the correlation between the oral health status and the educational level of the participants. Results. Many participants (62.5%) showed a DMFT/dmft Index ≥ 4; only 27% of the migrants had a DMFT/dmft Index lower than 4, and only 21 of them (10.5%) were recorded at 0. A CPI equal to 0 or 1 was observed in 131 patients (65.5%), while only 30 participants presented a CPI equal to or higher than 4 (15%), and 19.5% (39 patients) were assigned to code 2 and 3. Significant statistical differences were found in the CPI after adjusting data for the educational level of the included participants (p-value < 0.01). Conclusions. The data obtained in our research highlighted poor oral conditions among the analysed migrant population, recording a high prevalence of dental caries and inadequate oral hygiene habits

Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma

Ewing sarcoma (EWS), the second most common malignant bone tumor in children and adolescents, occurs abruptly without clear evidence of tumor history or progression. Previous association studies have identified some inherited variants associated with the risk of developing EWS but a common picture of the germline susceptibility to this tumor remains largely unclear. Here, we examine the association between thirty single nucleotide polymorphisms (SNPs) of the IGF2BP3, a gene that codes for an oncofetal RNA-binding protein demonstrated to be important for EWS patient's risk stratification, and five SNPs of SENCR, a long non-coding RNA shown to regulate IGF2BP3. An association between polymorphisms and EWS susceptibility was observed for three IGF2BP3 SNPs - rs112316332, rs13242065, rs12700421 - and for four SENCR SNPs - rs10893909, rs11221437, rs12420823, rs4526784 -. In addition, IGF2BP3 rs34033684 and SENCR rs10893909 variants increased the risk for female respect to male subgroup when carried together, while IGF2BP3 rs13242065 or rs76983703 variants reduced the probability of a disease later onset (> 14 years). Moreover, the absence of IGF2BP3 rs10488282 variant and the presence of rs199653 or rs35875486 variant were significantly associated with a worse survival in EWS patients with localized disease at diagnosis. Overall, our data provide the first evidence linking genetic variants of IGF2BP3 and its modulator SENCR to the risk of EWS development and to disease progression, thus supporting the concept that heritable factors can influence susceptibility to EWS and may help to predict patient prognosis

Berberine and Tinospora cordifolia exert a potential anticancer effect on colon cancer cells by acting on specific pathways

Berberine (BBR) is a natural active principle with potential antitumor activity. The compound targets multiple cell signaling pathways, including proliferation, differentiation, and epithelial-mesenchymal transition. The aim of this study was to elucidate the mechanisms behind the anticancer activity of BBR by comparing the effects of purified BBR with those of the extract of Tinospora cordifolia, a medicinal plant that produces this metabolite. The expression levels of a panel of 44 selected genes in human colon adenocarcinoma (HCA-7) cell line were quantified by real-time polymerase chain reaction (PCR). BBR treatment resulted in a time- and dose-dependent down regulation of 33 genes differently involved in cell cycle, differentiation, and epithelial-mesenchymal transition. The trend was confirmed across the two types of treatment, the two time points, and the different absolute dosage of BBR. These findings suggest that the presence of BBR in T. cordifolia extract significantly contributes to its antiproliferative activity

Von Hippel-Lindau–dependent polycythemia is endemic on the island of Ischia: identification of a novel cluster

AbstractChuvash polycythemia (MIM 263400) is an autosomal recessive disorder characterized by a high hemoglobin level, relatively high serum erythropoietin, and early death. It results from a Von Hippel-Lindau (VHL) gene mutation (C598T) that causes increased HIF-1α activity and erythrocyte production in the face of normoxia. This polycythemia is endemic in Chuvashia, whereas its worldwide frequency is very low. We investigated the incidence of the Chuvash-type VHL mutation in Campania (South Italy) and identified 14 affected subjects (5 families). Twelve live on the island of Ischia (Bay of Naples). From analysis of the mutated allele, we found that the disease was more frequent on Ischia (0.070) than in Chuvashia (0.057). The haplotype of all patients matched that identified in the Chuvash cluster, thereby supporting the single-founder hypothesis. We also found that nonaffected heterozygotes had increased HIF-1α activity, which might confer a biochemical advantage for mutation maintenance. In conclusion, we have identified the first large cluster of Chuvash erythrocytosis outside Chuvashia, which suggests that this familial polycythemia might be endemic in other regions of the world

Standard Model updates and new physics analysis with the Unitarity Triangle fit

We present here the update of the Unitarity Triangle (UT) analysis performed by the UTfit Collaboration within the Standard Model (SM) and beyond. Continuously updated flavour results contribute to improving the precision of several constraints and through the global fit of the CKM parameters and the SM predictions. We also extend the UT analysis to investigate new physics (NP) effects on $\Delta F=2$ processes. Finally, based on the NP constraints, we derive upper bounds on the coefficients of the most general $\Delta F=2$ effective Hamiltonian. These upper bounds can be translated into lower bounds on the scale of NP that contributes to these low-energy effective interactions.Comment: Proceedings of the 8th International Workshop on the CKM Unitarity Triangle (CKM 2014), Vienna, Austria, September 8-12, 201

Isolation and characterization of cancer stem cells in head and neck squamous cell carcinoma

The hypothesis that a small subset of cells with characteristics of staminality is essential for the cancer onset has been widely studied in many tumors, included head-neck cancer, the seventh most common cancer in humans (1). These cells represent a small oncogenic subpopulation, with a characteristic phenotype that confers them a greater resistance to chemotherapy and radiotherapy (2). In this study the expression profile of some genes that differentiates cancer stem cells (CSC) from tumor cell of origin (TC) has been evaluated using Real Time PCR. Three cell lines, PE46, PE15 and HEP2, obtained from head and neck squamous cell carcinoma, where placed in culture, in absence of serum and in the presence of specific growth factors, giving rise to a spheroid cell subpopulation, with characteristics belonging to CSC. CSC were isolated using a selective filtration procedure based on beads labeled with the anti-CD44, that recognize a specific antigen of CSC in head and neck cancer (1). Few genes potentially involved in the onset and progression of oral cancer, were eval- uated in Real Time PCR, in order to compare their expression in CSC respect TC. All the three cell lines showed a common expression profile among the stem cell markers, resulting in an overexpression of the CD44 and ALDH1A in the spheroid population. Many of the investigated tumor markers were highly over-expressed in CSC, like TNFα, a pro-inflammatory factor that inhibits precancerous cell death, TP63, which is associated with an increase in the malignant transformation and a poor prognosis, and S100A4, a pro-inflammatory mediator involved in epithelial-mesenchymal transition of cancer cells. These results suggest the potential role of CSC in the tumor invasiveness. The characterization of CSC may lead to an improvement in the diagnosis and cancer therapy, allowing implementing treatments able to destroy cells which are probably involved in the process of metastasis

Loss of function mutations in CCDC32 cause a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies

Despite the wide use of genomics to investigate the molecular basis of rare congenital malformations, a significant fraction of patients remains bereft of diagnosis. As part of our continuous effort to recruit and perform genomic and functional studies on such cohorts, we investigated the genetic and mechanistic cause of disease in two independent consanguineous families affected by overlapping craniofacial, cardiac, laterality, and neurodevelopmental anomalies. Using whole exome sequencing, we identified homozygous frameshift CCDC32 variants in three affected individuals. Functional analysis in a zebrafish model revealed that ccdc32 depletion recapitulates the human phenotypes. Because some of the patient phenotypes overlap defects common to ciliopathies, we asked if loss of CCDC32 might contribute to the dysfunction of this organelle. Consistent with this hypothesis, we show that ccdc32 is required for normal cilia formation in zebrafish embryos and mammalian cell culture, arguing that ciliary defects are at least partially involved in the pathomechanism of this disorder

The R521K polymorphism of EGFR influences the risk of colorectal cancer

In colorectal cancer (CRC) epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been found frequently over-expressed. New therapies directed against EGFR have been developed in many human cancers. Unexpectedly, EGFR alterations could be good prognostic indicators, like in lung cancer, where an EGFR variant in non-smoker female patients is associated with higher survival after surgery and increases the efficiency of therapy based on EGFR inhibitors. The role of the genetic polymorphisms of the EGFR family members in colorectal cancer development has not been completely explored. In our preliminary study, three missense polymorphisms mapping in EGFR family members have been investigated in the peripheral blood of a small Italian sample size of 70 patients and 72 controls to verify if they could be considered CRC susceptibility factors. For the first time, the evidence of genotype association was found for the R521K EGFR polymorphism: the protective effect for this variant allele has been found to reduce the risk for colon cancer onset

The 2004 UTfit Collaboration Report on the Status of the Unitarity Triangle in the Standard Model

Using the latest determinations of several theoretical and experimental parameters, we update the Unitarity Triangle analysis in the Standard Model. The basic experimental constraints come from the measurements of |V_ub/V_cb|, Delta M_d, the lower limit on Delta M_s, epsilon_k, and the measurement of the phase of the B_d - anti B_d mixing amplitude through the time-dependent CP asymmetry in B^0 to J/psi K^0 decays. In addition, we consider the direct determination of alpha, gamma, 2 beta + gamma and cos(2 beta) from the measurements of new CP-violating quantities, recently performed at the B factories. We also discuss the opportunities offered by improving the precision of the various physical quantities entering in the determination of the Unitarity Triangle parameters. The results and the plots presented in this paper can also be found at http://www.utfit.org, where they are continuously updated with the newest experimental and theoretical results.Comment: 32 pages, 17 figures. High resolution figures and updates can be found at http://www.utfit.org v2: misprints correcte

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p