High risk serotypes of the human papillomavirus (hpv) in patients With exofitic lesions in the oral cavity

Introduction: Oral squamous cell carcinoma has been associated with risk factors such as: tobacco consumption, alcohol and human papillomavirus, the authors determined the prevalence of high-risk serotypes of human papillomavirus infection in exofitic lesions of the oral cavity in a Cartagena hospital during the year 2014-2015. Material and Methods: an observational, descriptive, prospective and cross-sectional study was performed on 73 patients with verrucous lesions in the oral cavity, in which socio- demographic characteristics and the clinical and histopathological diagnosis were determined, and high-risk HPV was identified. The study complied with legal and ethical standards. The results were analyzed using descriptive statistics with the Stata v13.2 program. Results: The prevalence of HPV in the study population during the period 2014-2015 was 9.59% (n: 7). in none of the positive HPV cases in the histopathological study, any high-risk genotype was identified by the real-time multiplex PCR assay. HPV infection was more prevalent in patients in the third decade of life (29.5 years, DS ± 10.60), mean age was 62.8 years SD ± 17.74. The population came mainly from the rural area. The most common site was the labial mucosa. There was a relationship between smoking and the presence of HPV. Discussions: In the present study, no relationship of high risk HPV genotypes was found in the evaluated samples

High risk serotypes of the human papillomavirus (HPV) in patients with exofitic lesions in the oral cavity

Objetivo: Determinar la prevalencia de serotipos de alto riesgo del virus del papiloma humano en lesiones verrugosas de la cavidad bucal en un hospital de Cartagena durante el mes de julio de 2014 y julio de 2015.Metodología: Se realizó un estudio observacional, descriptivo y prospectivo en 73 pacientes. con lesiones verrugosas de la cavidad bucal, en las que se determinaron las características sociodemográficas, el diagnóstico clínico e histopatológico y se identificaron los genotipos 16 y 18 de alto riesgo de VPH del ADN, así como otros 12 genotipos de alto riesgo (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 y 68), mediante la prueba de PCR multiplex en tiempo real. El estudio cumplió con las normas legales y éticas. Los resultados se analizaron utilizando estadísticas descriptivas con el programa Stata v13.2.Resultados: La prevalencia de VPH en la muestra estudiada durante el período 2014-2015 fue del 9,59% (n: 7). En ninguno de los casos positivos para el VPH en el estudio histopatológico, se identificaron algunos genotipos de alto riesgo. Los serotipos de HPV fueron más prevalentes en pacientes en la tercera década de la vida (29.5 años, SD ± 10.60), la edad promedio fue de 62.8 años SD ± 17.74. La población provenía principalmente del área rural. El sitio más frecuente fue la mucosa labial. Un alto porcentaje de participantes (87.6%) reportó consumir tabaco.Conclusión: En el presente estudio no se encontraron genotipos de VPH de alto riesgo en las muestras evaluada

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele