Gene expression networks regulated by human personality.

Genome-wide association studies of human personality have been carried out, but transcription of the whole genome has not been studied in relation to personality in humans. We collected genome-wide expression profiles of adults to characterize the regulation of expression and function in genes related to human personality. We devised an innovative multi-omic approach to network analysis to identify the key control elements and interactions in multi-modular networks. We identified sets of transcribed genes that were co-expressed in specific brain regions with genes known to be associated with personality. Then we identified the minimum networks for the co-localized genes using bioinformatic resources. Subjects were 459 adults from the Young Finns Study who completed the Temperament and Character Inventory and provided peripheral blood for genomic and transcriptomic analysis. We identified an extrinsic network of 45 regulatory genes from seed genes in brain regions involved in self-regulation of emotional reactivity to extracellular stimuli (e.g., self-regulation of anxiety) and an intrinsic network of 43 regulatory genes from seed genes in brain regions involved in self-regulation of interpretations of meaning (e.g., production of concepts and language). We discovered that interactions between the two networks were coordinated by a control hub of 3 miRNAs and 3 protein-coding genes shared by both. Interactions of the control hub with proteins and ncRNAs identified more than 100 genes that overlap directly with known personality-related genes and more than another 4000 genes that interact indirectly. We conclude that the six-gene hub is the crux of an integrative network that orchestrates information-transfer throughout a multi-modular system of over 4000 genes enriched in liquid-liquid-phase-separation (LLPS)-related RNAs, diverse transcription factors, and hominid-specific miRNAs and lncRNAs. Gene expression networks associated with human personality regulate neuronal plasticity, epigenesis, and adaptive functioning by the interactions of salience and meaning in self-awareness.

Temperament & Character account for brain functional connectivity at rest: A diathesis-stress model of functional dysregulation in psychosis.

The human brain's resting-state functional connectivity (rsFC) provides stable trait-like measures of differences in the perceptual, cognitive, emotional, and social functioning of individuals. The rsFC of the prefrontal cortex is hypothesized to mediate a person's rational self-government, as is also measured by personality, so we tested whether its connectivity networks account for vulnerability to psychosis and related personality configurations. Young adults were recruited as outpatients or controls from the same communities around psychiatric clinics. Healthy controls (n = 30) and clinically stable outpatients with bipolar disorder (n = 35) or schizophrenia (n = 27) were diagnosed by structured interviews, and then were assessed with standardized protocols of the Human Connectome Project. Data-driven clustering identified five groups of patients with distinct patterns of rsFC regardless of diagnosis. These groups were distinguished by rsFC networks that regulate specific biopsychosocial aspects of psychosis: sensory hypersensitivity, negative emotional balance, impaired attentional control, avolition, and social mistrust. The rsFc group differences were validated by independent measures of white matter microstructure, personality, and clinical features not used to identify the subjects. We confirmed that each connectivity group was organized by differential collaborative interactions among six prefrontal and eight other automatically-coactivated networks. The temperament and character traits of the members of these groups strongly accounted for the differences in rsFC between groups, indicating that configurations of rsFC are internal representations of personality organization. These representations involve weakly self-regulated emotional drives of fear, irrational desire, and mistrust, which predispose to psychopathology. However, stable outpatients with different diagnoses (bipolar or schizophrenic psychoses) were highly similar in rsFC and personality. This supports a diathesis-stress model in which different complex adaptive systems regulate predisposition (which is similar in stable outpatients despite diagnosis) and stress-induced clinical dysfunction (which differs by diagnosis).

Seroconversión posterior a la aplicación de vacuna Pfizer anticovid-19 en personal de la salud / Seroconversión rates following covid-19 Pfizer vaccine application among health personnel

Introducción: la pandemia por COVID-19 constituyó un problema de salud que requirió la realización de esfuerzos sin precedentes para la fabricación de vacunas en tiempo récord. Dada la emergencia no se podían llevar a cabo los protocolos establecidos que componen la fármacovigilancia, razón por la cual es importante realizar estudios locales que contribuyan al conocimiento y vigilancia clínica y farmacológica. Objetivos: evaluar los niveles de anticuerpos desarrollados en quienes recibieron la vacuna Pfizer, determinar los efectos secundarios más frecuentes y describir la mortalidad por todas las causas a un año en este grupo. Métodos: estudio prospectivo, de corte transversal de una cohorte de 105 pacientes, se realizó estadística descriptiva en el análisis univariado y bivariado para los niveles de anticuerpos, se describe la correlación de la edad con los niveles de anticuerpos y la mortalidad cruda de los pacientes a 1 año. Resultados: la edad media de los 105 pacientes fue 36,45 años (DE 10,11), con tendencia al aumento de los niveles de anticuerpos en la segunda toma y descenso en la tercera; se encontró una correlación negativa significativa entre edad y niveles de anticuerpos en la segunda toma. Conclusiones: en los sujetos más jóvenes se presentaron mayores títulos de anticuerpos que disminuyeron con el tiempo, la variabilidad en la titulación puede depender de varios factores como edad, género, imnunosupresores y comorbilidades. Es necesaria la medición para realizar una vacunación periódica e individualizarla. La mortalidad a un año fue de 0%.

Introduction: the COVID-19 pandemic prompted unprecedented efforts to manufacture vaccines in record time. Given the emergency, to conduct the established pharmacovigilance protocols was not possible, thus, the importance of carrying out local studies which contribute to gain understanding and clinical and pharmacological surveillance. Objectives: to evaluate antibody levels developed in subjects who received the Pfizer vaccine; to determine the most frequent side effects; and describe all-cause 1-year mortality in this group. Methods: a prospective, cross-sectional study in a cohort of 105 patients. Descriptive statistics were conducted by univariate and bivariate analyses of antibody levels. The correlation between age and antibody levels and the crude 1-year mortality rate among patients is described. Results: mean age was 36.45 years (SD 10.11), with a tendency for antibody levels to increase with the second dose and decrease with the third dose. A significant negative correlation was found between age and antibody levels in the second dose. Conclusions: younger subjects had higher antibody titers, which decreased over time. The variability of titer estimates may depend on several factors such as, age, gender, immunosuppressive therapies and comorbidities. Measurements are essential for periodic and individualized vaccination. One-year mortality rate was 0%.

Glomeruloesclerosis focal segmentaria de variante colapsante asociada a VIH. Reporte de caso / Focal segmental glomerulosclerosis of collapsing variant associated with HIV: Clinical case

Resumen La afectación del virus de la inmunodeficiencia humana (VIH) ha cambiado tras el inicio del tratamiento antirretroviral de gran actividad, ya que este ha generado una mayor supervivencia y un menor número de comorbilidades en los pacientes. Es común que en las personas con VIH el fracaso renal agudo esté asociado a sepsis, toxicidad por fármacos o afección directa por el propio virus. La nefropatía en pacientes con VIH es variada y puede estar asociada al uso de medicamentos o directamente al efecto del virus. La prevalencia de esta patología en este tipo de pacientes es <10% y se caracteriza por un colapso glomerular. Las células del parénquima renal expresan los receptores de quimiocinas CCR5 y CXCR4, que son esenciales para la entrada de cepas de VIH-1 en las células. El presente caso es particularmente interesante ya que la insuficiencia renal aguda en el marco de un síndrome nefrótico fue la primera manifestación en un paciente con VIH/sida.

Abstract : Human immunodeficiency virus infection has changed after the start of highly active antiretroviral treatment, generating greater survival and fewer patient comorbidities. In these patients, the finding of acute renal failure is common, which may be associated with sepsis, drug toxicity, or direct involvement by the virus itself. Nephropathy in patients with HIV infection is varied, where it can be associated with the use of medications or directly due to the effect of the virus (HIVAN). The prevalence is less than 10 % and is characterized by glomerular collapse. Renal parenchyma cells express the chemokine receptors CCR5 and CXCR4 that are essential for the entry of HIV-1 strains into cells. The present case is interesting, since acute renal failure in the framework of a nephrotic syndrome was the first manifestation of a patient with HIV / AIDS.

Three genetic-environmental networks for human personality.

Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are jointly organized and develop in an integrated manner. In three large independent genome-wide association studies from Finland, Germany, and Korea, we used a data-driven machine learning method to uncover joint phenotypic networks of temperament and character and also the genetic networks with which they are associated. We found three clusters of similar numbers of people with distinct combinations of temperament and character profiles. Their associated genetic and environmental networks were largely disjoint, and differentially related to distinct forms of learning and memory. Of the 972 genes that mapped to the three phenotypic networks, 72% were unique to a single network. The findings in the Finnish discovery sample were blindly and independently replicated in samples of Germans and Koreans. We conclude that temperament and character are integrated within three disjoint networks that regulate healthy longevity and dissociable systems of learning and memory by nearly disjoint sets of genetic and environmental influences.

Pandemia de COVID-19 y enfermedad renal: ¿Qué sabemos actualmente? / COVID-19pandemic and kidney disease: ¿What do we currently know?

Resumen Introducción: La enfermedad renal aguda es una patología relativamente frecuente en pacientes con infección por COVID-19, en especial en el grupo de pacientes que se encuentran críticamente enfermos; los pacientes con enfermedad renal crónica se consideran un grupo de riesgo durante la pandemia debido a la inmunosupresión asociada por lo cual es importante la detección de infección por SARS CoV-2 en estos pacientes además de quienes están en diálisis y pacientes con trasplante renal. Es de suma importancia la identificación de enfermedad renal al ingreso de pacientes con COVID-19 pues se ha demostrado que representa un indicador para valorar supervivencia y pronóstico; varios estudios han establecido que la falla renal aguda se relaciona directamente con peor pronóstico y mortalidad. Debido al impacto positivo en la supervivencia que significa el manejo oportuno de la falla renal en pacientes positivos para COVID-19. Objetivo: Presentar la información científica actual sobre la fisiopatología de falla renal en contexto de COVID-19, diagnóstico, tratamiento, estrategias de seguimiento de la función renal durante la hospitalización, manejo de unidades de diálisis, indicación de líquidos intravenosos y manejo de shock en pacientes con enfermedad renal. Métodos: Se realizó una revisión de la literatura utilizando las bases de datos PubMed, Google Scholar y Embase; los criterios de selección incluían artículos que registraran el abordaje general y específico de complicaciones en el contexto de enfermedad renal, no se usaron filtros en la búsqueda. Conclusión: La falla renal en el contexto de la infección por COVID-19 representa un aspecto importante a estudiar dentro del desarrollo de la enfermedad y requiere consideraciones especiales para su manejo.

Abstract Introduction: Acute kidney disease is relatively frequent in COVID-19 patients, especially in critically ill patients; chronic kidney disease patients are consider as a risk group during COVID-19 pandemic because of immunosuppression associated with their condition, that's why it is important to detect SARS CoV-2 in this group of patients as in dialysis patients and kidney transplant patients. It is important to identify kidney disease at admission of COVID-19 patients because it has been shown that AKI or kidney disease represent an indicator to value survival and prognosis; literature have established that acute kidney injury is related with worst prognosis and mortality. Because of positive impact in survival that means timely and early treatment and follow up of kidney disease in COVID-19 patients. Objective: To presents actual scientific information about acute kidney injury physiopathology in COVID-19 patients, diagnosis, treatment, follow up strategies during hospitalization, management of dialysis units, intravenous liquids indications and shock management in patients with kidney disease. Methods: A literature review was performed using PubMed, Google Scholar and Embase databases; the selection criteria include articles that record the general and specific approach to complications in the context of kidney disease, no filters are used in the search. Conclusion: Renal failure in the context of COVID-19 infection represents an important aspect to study during development of COVID-19 infection and requires special considerations for its correct management.

Uncovering Tumour Heterogeneity through PKR and nc886 Analysis in Metastatic Colon Cancer Patients Treated with 5-FU-Based Chemotherapy.

Colorectal cancer treatment has advanced over the past decade. The drug 5-fluorouracil is still used with a wide percentage of patients who do not respond. Therefore, a challenge is the identification of predictive biomarkers. The protein kinase R (PKR also called EIF2AK2) and its regulator, the non-coding pre-mir-nc886, have multiple effects on cells in response to numerous types of stress, including chemotherapy. In this work, we performed an ambispective study with 197 metastatic colon cancer patients with unresectable metastases to determine the relative expression levels of both nc886 and PKR by qPCR, as well as the location of PKR by immunohistochemistry in tumour samples and healthy tissues (plasma and colon epithelium). As primary end point, the expression levels were related to the objective response to first-line chemotherapy following the response evaluation criteria in solid tumours (RECIST) and, as the second end point, with survival at 18 and 36 months. Hierarchical agglomerative clustering was performed to accommodate the heterogeneity and complexity of oncological patients' data. High expression levels of nc886 were related to the response to treatment and allowed to identify clusters of patients. Although the PKR mRNA expression was not associated with chemotherapy response, the absence of PKR location in the nucleolus was correlated with first-line chemotherapy response. Moreover, a relationship between survival and the expression of both PKR and nc886 in healthy tissues was found. Therefore, this work evaluated the best way to analyse the potential biomarkers PKR and nc886 in order to establish clusters of patients depending on the cancer outcomes using algorithms for complex and heterogeneous data.

Estudio in vivo de la resistencia del P. falciparum a la cloroquina en Colombia: descripcion de la resistencia III / In vivo study of the resistance of Plasmodium falciparum to chloroquine in Colombia: description of type III resistance

En un grupo de 41 pacientes (16 ambulatorios y 25 hospitalizados) con infeccion por P. Falciparum se estudio la sensibilidad a la cloroquina a la dosis de 25 mg/kg, por la prueba estandar prolongada de la OMS y segun un protocolo previamente elaborado. La absorcion de la droga se midio por la prueba de Haskins en la orina . La cuantificacion de los parasitos se hizo diariamente la primera semana y luego tres veces por semana durante las tres semanas siguientes. Los pacientes cloroquino-resistentes recibieron tratamiento triconjugado a base de quinina 20 mg/kg/dia por 10 dias, primetamina 1 mg/kg/dia por 3 dias y sulfadiazina 40 mg/kg/dia por 5 dias. Se encontraron 35 casos cloroquino-resistentes (85%) asi: 22 resistencias I, 10 resistencias II y tres resistencias III. Los pacientes procedian de Uraba, Bajo Cauca, Magdalena Medio, Costa Atlantica y Choco; hubo un caso transfusional. Se presentan los datos de densidad parasitaria, antecedentes malaricos, adquisicion de la enfermedad, profilaxis y tratamientos previos. Se describen los aspectos clinicos de la malaria por P. Falciparum ...