Análisis de relaciones fenotípicas mediante el uso de ontologías biomédicas: aplicaciones a enfermedades genéticas

A partir de la definición de los perfiles fenotípicos de cada gen y la construcción de una red de relaciones fenotípicas entre genes para estudiar las implicaciones funcionales de aquellos genes fenotípicamente similares. Esta red contiene nuevas relaciones entre genes causantes de la enfermedad, las cuales fueron útiles para explorar las bases moleculares de los procesos patológicos. Posteriormente, se desarrolló una herramienta (PhenUMA, www.phenuma.uma.es) que permite la consulta de genes y enfermedades para obtener sus relaciones fenotípicas y funcionales. Además, se hizo uso de herramientas de minería de textos para extraer de la bibliografía relaciones entre estos genes y enfermedades. El objetivo es incluir en PhenUMA relaciones procedentes de la bibliografía no presentes en las bases de datos públicas. Por último, se analizaron las relaciones genotipo-fenotipo en un conjunto heterogéneo de pacientes con síndromes genómicos procedente de DECIPHER. Se estudió la sintomatología común a los pacientes cuyas regiones afectadas son solapantes, para identificar regiones potencialmente patológicas. Esta información se usó para construir una red de pacientes. El análisis de esta red permitió identificar relaciones significativas entre características clínicas y variaciones estructurales. Además, se detectaron potenciales nuevos síndromes.El incremento en la eficiencia de las técnicas de alto rendimiento y el avance de los métodos de integración y análisis de información, han permitido estudiar las enfermedades integrando varios niveles de complejidad. El estudio de toda esta información ha proporcionado otra visión de enfermedades complejas y multifactoriales como el cáncer, la obesidad o la diabetes. El caso de las enfermedades raras es especialmente complejo debido a la heterogeneidad de las etiologías y la baja disponibilidad de muestras de pacientes y familias para el análisis molecular y fenotípico de estas patologías. La integración de datos masivos generados a partir de técnicas experimentales de alto rendimiento facilita el estudio de las enfermedades genéticas o de baja prevalencia. Trabajos como el desarrollado por Goh et al., 2007 resalta la importancia de estudiar la complejidad de las relaciones entre los genes asociados a enfermedades. Este estudio muestra que las enfermedades generalmente manifiestan diversos síntomas y que distintas patologías se pueden asociar a fenotipos patológicos similares; asociados a alteraciones en procesos biológicos relacionados funcionalmente. Si bien uno de los grandes problemas de la integración de información (pato)fenotípica radica en lo sujeta que está al lenguaje natural, herramientas como HPO facilitan esta integración. Para profundizar en las relaciones fenotípicas entre enfermedades, en esta tesis se trabaja en la hipótesis de que: El estudio de las enfermedades complejas a partir del perfil fenotípico que las describe y la integración de esta información en su contexto biomolecular permite identificar los mecanismos moleculares afectados en múltiples procesos patológicos. Para ello en primer lugar se analizaron las relaciones fenotípicas entre genes

Efectos del software JCLIC en la atención de los estudiantes del 2do. grado de educación primaria de la I.E José Abelardo Quiñones Gonzales, Los Olivos - 2013

La tesis titulada “Efectos del Software Jclic en la Atención de los Estudiantes del segundo grado de Primaria de la I.E José Abelardo Quiñones Gonzales, Los Olivos-2013” se originó de la preocupación ¿De qué manera el uso del software educativo Jclic mejora la atención en los niños y niñas del segundo grado de educación Primaria de la I.E José Abelardo Quiñones Gonzales? , la cual tuvo como objetivo establecer los efectos del uso del software Jclic como estrategia didáctica para mejorar la atención de los estudiantes. Esta investigación aplicada fue de enfoque cuantitativo con un diseño cuasi experimental, se tomó como muestra a toda la población conformada por 45 alumnos del segundo grado de Educación Primaria de la Institución Educativa José Abelardo Quiñones Gonzales, de la cual 23 alumnos del segundo grado “A” representa al grupo de control y 22 alumnos del segundo grado “B” al grupo experimental.Los instrumentos de recolección de datos fueron la prueba de atención A-2 que se aplicó en ambos grupos como pre test antes de iniciar las sesiones y como post test al finalizar las 10 sesiones de aprendizaje; los cuales se procesaron en el programa Excell ,utilizando la Prueba de ShapiroWilk para comprobar la normalidad de los datos para luego aplicar el estadístico t de Studen. Se concluyó, que el efecto de la aplicación del software Jclic fue positivo en los niños y niñas del segundo grado de la I.E José Abelardo Quiñones Gonzales ; de acuerdo al análisis estadístico existió una relación de dependencia entre las variables Jclic y la atención, logrando que los estudiantes ante diversos estímulos visuales por un tiempo determinado mejoren su atención

Clinical and Neuropsychological Correlates of Prefrailty Syndrome

Physical frailty is closely associated with cognitive impairment. We aim to investigate the neuropsychological profiles of prefrail and non-frail dementia-free community-dwelling older adults using a comprehensive neuropsychological evaluation, and to examine the association between specific frailty criteria and clinical and neuropsychological scores. Participants completed a comprehensive standardized neuropsychological evaluation (covering cognitive domains such as memory, executive functions, language and attention), and frailty assessment. Frailty was assessed according to biological criteria: unintentional weight loss, exhaustion, low physical activity, slowness, and weakness. The sample comprised 60 dementia-free community-dwelling adults, aged 65 years or older (range 65-89 years; 60.0% women). Forty-two participants were classified as robust (no frailty criteria present), and 18 as prefrail (1 or 2 frailty criteria present). We explored neurocognitive differences between the groups and examined the association between specific criteria of frailty phenotype and clinical and neuropsychological outcomes with bivariate tests and multivariate models. Prefrail participants showed poorer cognitive performance than non-frail participants in both memory and non-memory cognitive domains. However, delayed episodic memory was the only cognitive subdomain that remained significant after controlling for age, gender, and educational level. Gait speed was significantly associated with general cognitive performance, immediate memory, and processing speed, while grip strength was associated with visual episodic memory and visuoconstructive abilities. Both gait speed and grip strength were negatively associated with depressive scores. Our results suggest that prefrailty is associated with cognitive dysfunction. The fact that specific cognitive domains may be susceptible to subclinical states of physical frailty may have important clinical implications. Indeed, early detection of specific cognitive dysfunctions may allow opportunities for reversibility

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic lowgrade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

Generalidades de la Farmacovigilancia

Cuando nos referimos al termino farmacovigilancia describimos una acción para hablar de la prevención y riesgos de los medicamentos en los seres humanos y para evitar los gastos económicos con relación a los efectos adversos no esperados, también se refiere a las características de las mismas que se pueden presentar en el día a día, esto quiere decir que la farmacovigilancia es aquella encargada de evaluar, contar e identificar la prevención de todos los riesgos en el uso de cualquier medicamento, este seguimiento o evaluación que se le hace a los medicamentos es para que se garantice su seguridad y efectividad. El ente que se ocupa de estudiar detectar y prevenir los posibles efectos adversos de los medicamentos también es el encargado de detectar señales de alerta de estos posibles efectos adversos, en Colombia, estos responsables son las autoridades sanitarias que pueden ser estatales, comunitarias y autonómicas. El INVIMA (Instituto Nacional de Vigilancia de Medicamentos y Alimentos) además de dirigir, coordinar, controlar y evaluar las actividades relacionadas con la adquisición, almacenamiento, custodia, distribución e inventario de los elementos,es el encargado de la recolección de datos para realimentar un sistema de información sobre los efectos adversos de los medicamentos y así evitar riesgos futuros, gracias a ésta organización los errores encontrados en la comercialización y en la distribución de los medicamentos ha tenido una disminución favorable, y los responsables o encargados de la autorización comercial son el personal sanitario como los médicos, los farmacéuticos, los enfermeros y los odontólogos.When we refer to the term pharmacovigilance, it describes an action to talk about the prevention and risks of drugs in human beings, and to avoid economic expenses in relation to unexpected adverse effects, it also refers to the characteristics of the same that can occur on a day-to-day basis, this means that pharmacovigilance is responsible for evaluating, counting and identifying the prevention of all risks in the use of any medication, this monitoring or evaluation that is done to medications is for that its safety and effectiveness be guaranteed. The person in charge of detecting warning signs of these possible opposite effects, in Colombia, these responsible are the health authorities that can be state, community and autonomous. In addition to directing, coordinating, controlling and evaluating the activities related to the acquisition, storage, custody, distribution and inventory of the elements, INVIMA (national institute for the surveillance of medicines and food) is in charge of collecting data to feed back a information system on the adverse effects of drugs and thus avoid risks, thanks to this organization the errors found in the marketing and distribution of these have had a favorable decrease, and those responsible or in charge of commercial authorization and health personnel are the doctors, pharmacists, nurses and dentists

Analyses of chondrogenic induction of adipose mesenchymal stem cells by combined co-stimulation mediated by adenoviral gene transfer

INTRODUCTION: Adipose-derived stem cells (ASCs) have the potential to differentiate into cartilage under stimulation with some reported growth and transcriptional factors, which may constitute an alternative for cartilage replacement approaches. In this study, we analyzed the in vitro chondrogenesis of ASCs transduced with adenoviral vectors encoding insulin-like growth factor-1 (IGF-1), transforming growth factor beta-1 (TGF-β1), fibroblast growth factor-2 (FGF-2), and sex-determining region Y-box 9 (SOX9) either alone or in combinations. METHODS: Aggregate cultures of characterized ovine ASCs were transduced with 100 multiplicity of infections of Ad.IGF-1, Ad.TGF-β1, Ad.FGF-2, and Ad.SOX9 alone or in combination. These were harvested at various time points for detection of cartilage-specific genes expression by quantitative real-time PCR or after 14 and 28 days for histologic and biochemical analyses detecting proteoglycans, collagens (II, I and X), and total sulfated glycosaminoglycan and collagen content, respectively. RESULTS: Expression analyses showed that co-expression of IGF-1 and FGF-2 resulted in higher significant expression levels of aggrecan, biglycan, cartilage matrix, proteoglycan, and collagen II (all P ≤0.001 at 28 days). Aggregates co-transduced with Ad.IGF-1/Ad.FGF-2 showed a selective expression of proteoglycans and collagen II, with limited expression of collagens I and × demonstrated by histological analyses, and had significantly greater glycosaminoglycan and collagen production than the positive control (P ≤0.001). Western blot analyses for this combination also demonstrated increased expression of collagen II, while expression of collagens I and × was undetectable and limited, respectively. CONCLUSION: Combined overexpression of IGF-1/FGF-2 within ASCs enhances their chondrogenic differentiation inducing the expression of chondrogenic markers, suggesting that this combination is more beneficial than the other factors tested for the development of cell-based therapies for cartilage repair

Identification of viral infections in the prostate and evaluation of their association with cancer

<p>Abstract</p> <p>Background</p> <p>Several viruses with known oncogenic potential infect prostate tissue, among these are the polyomaviruses BKV, JCV, and SV40; human papillomaviruses (HPVs), and human cytomegalovirus (HCMV) infections. Recently, the Xenotropic Murine Leukemia Virus-related gammaretrovirus (XMRV) was identified in prostate tissue with a high prevalence observed in prostate cancer (PC) patients homozygous for the glutamine variant of the RNASEL protein (462Q/Q). Association studies with the R462Q allele and non-XMRV viruses have not been reported. We assessed associations between prostate cancer, prostate viral infections, and the RNASEL 462Q allele in Mexican cancer patients and controls.</p> <p>Methods</p> <p>130 subjects (55 prostate cancer cases and 75 controls) were enrolled in the study. DNA and RNA isolated from prostate tissues were screened for the presence of viral genomes. Genotyping of the RNASEL R462Q variant was performed by Taqman method.</p> <p>Results</p> <p>R/R, R/Q, and Q/Q frequencies for R462Q were 0.62, 0.38, and 0.0 for PC cases and 0.69, 0.24, and 0.07 for controls, respectively. HPV sequences were detected in 11 (20.0%) cases and 4 (5.3%) controls. XMRV and HCMV infections were detected in one and six control samples, respectively. The risk of PC was significantly increased (Odds Ratio = 3.98; 95% CI: 1.17-13.56, p = 0.027) by infection of the prostatic tissue with HPV. BKV, JCV, and SV40 sequences were not detected in any of the tissue samples examined.</p> <p>Conclusions</p> <p>We report a positive association between PC and HPV infection. The 462Q/Q RNASEL genotype was not represented in our PC cases; thus, its interaction with prostate viral infections and cancer could not be evaluated.</p

GENERALIZED URTICARIA AS A VASCULITIC MANIFESTATION IN A PATIENT WITH SARS-CoV-2 INFECTION: A CASE REPORT IN COLOMBIA

Skin manifestations have been reported in up to 20% of cases of SARS-CoV-2 infection, including morbilliform rash (22%), pernio-like acral lesions (18%), urticaria (16%), and macular erythema (13%). It is believed that in the case of SARS-CoV-2 infection, the mechanism involved is an inflammatory response that generates immune dysregulation, vascular congestion, vasculitis, vascular thrombosis, or neoangiogenesis. This case study, present the case of a patient with no previous history of urticarial reactions, autoimmune diseases, or exposure to medications who develops generalized urticaria lasting more than 24 hours and who was diagnosed with SARS-CoV-2 infection by RT-PCR with a nasopharyngeal swab. We suggest in this patient vasculitic urticaria as a manifestation of SARS-CoV-2 infection

Population based prostate cancer screening in north Mexico reveals a high prevalence of aggressive tumors in detected cases

Background: Prostate Cancer (PCa) is the second most frequent neoplasia in men worldwide. Previous reports suggest that the prevalence of PCa in Hispanic males is lower than in Africans (including communities with African ancestry) and Caucasians, but higher than in Asians. Despite these antecedents, there are few reports of open population screenings for PCa in Latin American communities. This article describes the results of three consecutive screenings in the urban population of Monterrey, Mexico. Methods: After receiving approval from our University Hospital's Internal Review Board (IRB), the screening was announced by radio, television, and press, and it was addressed to male subjects over 40 years old in general. Subjects who consented to participate were evaluated at the primary care clinics of the University Health Program at UANL, in the Metropolitan area of Monterrey. Blood samples were taken from each subject for prostate specific antigen (PSA) determination; they underwent a digital rectal examination (DRE), and were subsequently interviewed to obtain demographic and urologic data. Based on the PSA (>4.0 ng/ml) and DRE results, subjects were appointed for transrectal biopsy (TRB). Results: A total of 973 subjects were screened. Prostate biopsy was recommended to 125 men based on PSA values and DRE results, but it was performed in only 55 of them. 15 of these biopsied men were diagnosed with PCa, mostly with Gleason scores ≥ 7. Conclusion: Our results reflect a low prevalence of PCa in general, but a high occurrence of high grade lesions (Gleason ≥ 7) among patients that resulted positive for PCa. This observation remarks the importance of the PCa screening programs in our Mexican community and the need for strict follow-up campaigns

Population based prostate cancer screening in north Mexico reveals a high prevalence of aggressive tumors in detected cases

Background: Prostate Cancer (PCa) is the second most frequent neoplasia in men worldwide. Previous reports suggest that the prevalence of PCa in Hispanic males is lower than in Africans (including communities with African ancestry) and Caucasians, but higher than in Asians. Despite these antecedents, there are few reports of open population screenings for PCa in Latin American communities. This article describes the results of three consecutive screenings in the urban population of Monterrey, Mexico. Methods: After receiving approval from our University Hospital's Internal Review Board (IRB), the screening was announced by radio, television, and press, and it was addressed to male subjects over 40 years old in general. Subjects who consented to participate were evaluated at the primary care clinics of the University Health Program at UANL, in the Metropolitan area of Monterrey. Blood samples were taken from each subject for prostate specific antigen (PSA) determination; they underwent a digital rectal examination (DRE), and were subsequently interviewed to obtain demographic and urologic data. Based on the PSA (>4.0 ng/ml) and DRE results, subjects were appointed for transrectal biopsy (TRB). Results: A total of 973 subjects were screened. Prostate biopsy was recommended to 125 men based on PSA values and DRE results, but it was performed in only 55 of them. 15 of these biopsied men were diagnosed with PCa, mostly with Gleason scores ≥ 7. Conclusion: Our results reflect a low prevalence of PCa in general, but a high occurrence of high grade lesions (Gleason ≥ 7) among patients that resulted positive for PCa. This observation remarks the importance of the PCa screening programs in our Mexican community and the need for strict follow-up campaigns