The diagnostic model of early stage of oral malignant lesion based on single nucleotide polymorphisms

El objetivo de este trabajo fue evaluar los caracteres genotípicos (polimorfismos del codón 72 pp53, 751 de XPD y 241 de XRCC3) en pacientes con cáncer oral (CO) a fin de desarrollar un modelo estadístico de predicción de riesgo. Se realizó un estudio transversal caso-control de pacientes adultos, de ambos géneros, atendidos por demanda espontanea. Se excluyeron de este, pacientes con corticoterapias o quimioterapias, enfermedades sistémicas, alcoholismo crónico, consumo de drogas y cánceres de otras localizaciones. A fin de identificar factores pronósticos se construyeron modelos a través de métodos de clasificación como regresión logística y árboles de clasificación/regresión. Encontramos asociación entre el grupo Control (CON)y el genotipo GG. Entre los genotipos CG y CC y CO. En relación a XPDLys751Gln, encontramos asociación entre cáncer oral y los genotipos AA y AC. Con respecto a XRCC3Thr241Met, hallamos asociación significativa entre CO y este polimorfismo. Como conclusión podemos decir que los polimorfismos juegan diferentes roles en el desarrollo del cáncer en diferentes poblaciones sumados a otros factores como el alcohol, el consumo de tabaco, el riesgo de VPH, etc. Este trabajo muestra nuestros resultados preliminares que deberán ser confirmados en estudios que incluyan mayor número de pacientes que pertenezcan a diferentes regionesFil: Galíndez Costa, María Fernanda. Universidad Nacional de Córdoba. Facultad de Odontología. Departamento de Patología Bucal; Argentina.Fil: Carrica, Victoriano Andrés. Universidad Nacional de Córdoba. Facultad de Odontología. Departamento de Patología Bucal; Argentina.Fil: González Segura, Ignacio. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra Biología Celular A; Argentina.Fil: Panico, René Luis. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Estomatología A; Argentina.Fil: Barra, José Luis. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento Química Biológica; Argentina.Fil: Barra, José Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica; ArgentinaFil: Zárate, Ana María. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra Biología Celular A; Argentina.Fil: Brunotto, Mabel. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra Biología Celular A; Argentina.Otras Ciencias de la Salu

An unexpected finding in a labial swelling

An 18-year-old male was referred to our institution with a labial swelling of 45 days of evolution located on the upper lip. The patient was healthy, without systemic diseases or mental disabilities. No relevant family medical history was recorded during anamnesis. The patient mentioned that the lesion began as a painful small inflammation of the lip that increased in size. The patient consulted a general physician, who ordered laboratory tests to rule out syphilis diagnosis. Subsequently, the patient was treated with amoxicillin for 1 month with no improvement of the lesion. Labial discomfort became more intense, presenting episodes of pus discharge and suppuration of a whitish fluid. Clinical examination revealed a mobile, nonfluctuant, slightly firm mass, which measured 1.5 cm in greatest diameter, covered by a surface with normal mucosa (Figure 1). Extraoral examination revealed no facial swelling, asymmetry, or regional lymphadenopathy. Laboratory tests were requested and revealed normal values. Surgical intervention under local anesthesia was performed to arrive at the final diagnosis.Fil: Panico, René Luis. Universidad Nacional de Córdoba. Facultad de Odontología. Oral Medicine Department; ArgentinaFil: Panico, Ignacio. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud. Dentistry School; ArgentinaFil: Leonardi, Nicolás. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud. Oral Medicine Department, Dentistry School; ArgentinaFil: Garola, Federico. Universidad Nacional de Córdoba. Facultad de Odontología. Oral Medicine Department; ArgentinaFil: Gilligan, Gerardo. Universidad Nacional de Córdoba. Facultad de Odontología. Oral Medicine Department; Argentin

Austerità o politiche coordinate ed espansive? Le difficili scelte delle autorità europee

The paper deals with the debt crisis in the euro zone. The literature presents two interpretations of these events. The first attributes the responsibility of the crisis to the political authorities of the countries under attack. They let the citizens live beyond the standard allowed by the economy. This interpretation supports the use of austerity policies to solve the crisis. The second interpretation argues that the political authorities of all the European Union are responsible for the crisis. They kept alive an institutional organization of the coordination process between monetary and fiscal policies, which was known to be faulty. The paper presents theoretical and empirical arguments in favour of the second interpretation. It argues that austerity fails to stabilise the public debt and contends that a coordination process based on effective enforcement and on a European Fiscal Agency can achieve better results by favouring the adoption of coordinated and expansive fiscal policies

UHRF1 epigenetically orchestrates smooth muscle cell plasticity in arterial disease

Adult vascular smooth muscle cells (VSMCs) possess the peculiar ability to de-differentiate in response to extracellular cues, such as vascular damage and inflammation. De-differentiated VSMCs are proliferative, migratory, and have decreased contractile capacity. VSMC dedifferentiation contributes not only to vascular repair, but also to cardiovascular pathologies, such as intimal hyperplasia/restenosis in coronary artery or peripheral vascular diseases and arterial aneurysm. We here demonstrate the role of ubiquitin-like, containing PHD and RING finger domains, 1 (UHRF1) as an epigenetic master regulator of VSMC plasticity. The expression of UHRF1 correlates with the development of a wide array of vascular pathologies associated also with modulation of non-coding RNAs, such as microRNAs. Importantly, miR-145, a pivotal gene regulating VSMC plasticity, which is reduced in vascular diseases, was found to control Uhrf1 mRNA translation. In turn, UHRF1 triggers VSMC proliferation by directly repressing the promoters of cell cycle inhibitor genes, such as p21 and p27, and of key pro-differentiation genes via the methylation of DNA and histones. Local vascular viral delivery of Uhrf1 shRNAs or Uhrf1 VSMC-specific deletion prevented intimal hyperplasia in mouse carotid artery and decreased vessel damage in a mouse model of aortic aneurysm.Our study demonstrates the fundamental role of Uhrf1 in regulating VSMC phenotype by promoting proliferation and de-differentiation. UHRF1 targeting may hold therapeutic potential in vascular pathologies, modulating also the VSMC component

UHRF1 epigenetically orchestrates smooth muscle cell plasticity in arterial disease

Adult vascular smooth muscle cells (VSMCs) dedifferentiate in response to extracellular cues such as vascular damage and inflammation. Dedifferentiated VSMCs are proliferative, migratory, less contractile, and can contribute to vascular repair as well as to cardiovascular pathologies such as intimal hyperplasia/restenosis in coronary artery and arterial aneurysm. We here demonstrate the role of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) as an epigenetic master regulator of VSMC plasticity. UHRF1 expression correlated with the development of vascular pathologies associated with modulation of noncoding RNAs, such as microRNAs. miR-145 - pivotal in regulating VSMC plasticity, which is reduced in vascular diseases - was found to control Uhrf1 mRNA translation. In turn, UHRF1 triggered VSMC proliferation, directly repressing promoters of cell-cycle inhibitor genes (including p21 and p27) and key prodifferentiation genes via the methylation of DNA and histones. Local vascular viral delivery of Uhrf1 shRNAs or Uhrf1 VSMC-specific deletion prevented intimal hyperplasia in mouse carotid artery and decreased vessel damage in a mouse model of aortic aneurysm. Our study demonstrates the fundamental role of Uhrf1 in regulating VSMC phenotype by promoting proliferation and dedifferentiation. UHRF1 targeting may hold therapeutic potential in vascular pathologies.Adult vascular smooth muscle cells (VSMCs) dedifferentiate in response to extracellular cues such as vascular damage and inflammation. Dedifferentiated VSMCs are proliferative, migratory, less contractile, and can contribute to vascular repair as well as to cardiovascular pathologies such as intimal hyperplasia/restenosis in coronary artery and arterial aneurysm. We here demonstrate the role of ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) as an epigenetic master regulator of VSMC plasticity. UHRF1 expression correlated with the development of vascular pathologies associated with modulation of noncoding RNAs, such as microRNAs. miR-145-pivotal in regulating VSMC plasticity, which is reduced in vascular diseases-was found to control Uhrf1 mRNA translation. In turn, UHRF1 triggered VSMC proliferation, directly repressing promoters of cell-cycle inhibitor genes (including p21 and p27) and key prodifferentiation genes via the methylation of DNA and histones. Local vascular viral delivery of Uhrf1 shRNAs or Uhrf1 VSMC-specific deletion prevented intimal hyperplasia in mouse carotid artery and decreased vessel damage in a mouse model of aortic aneurysm. Our study demonstrates the fundamental role of Uhrf1 in regulating VSMC phenotype by promoting proliferation and dedifferentiation. UHRF1 targeting may hold therapeutic potential in vascular pathologies

Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies

Several prospective studies have shown a moderate positive association between increasing circulating insulin-like growth factor-I (IGF-I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF-I’s major binding protein, IGFBP-3, showed major discrepancies between studies. We investigated the association of colorectal cancer risk with serum IGF-I, total and intact IGFBP-3, in a case-control study nested within the EPIC cohort (1,121 cases of colorectal cancer and 1,121 matched controls). Conditional logistic regression was used to adjust for possible confounders. Our present study results were combined in a meta-analysis with those from 9 previous prospective studies to examine the overall evidence for a relationship of prediagnostic serum IGF-I with colorectal cancer risk. In the EPIC study, serum concentrations of IGF-I and IGFBP-3 showed no associations with risk of colorectal cancer overall. Only in subgroup analyses did our study show moderate positive associations of IGF-I levels with risk, either among younger participants only (and only for colon cancer) or among participants whose milk intakes were in the lowest tertile of the population distribution (RR for an increase of 100 ng/ml = 1.43 [95% CI = 1.13-1.93]). Nevertheless, in the meta-analysis a modest positive association remained between serum IGF-I and colorectal cancer risk overall (RR = 1.07 [1.01-1.14] for 1 standard deviation increase in IGF-I). Overall, data from our present study and previous prospective studies combined indicate a relatively modest association of colorectal cancer risk with serum IGF-I