Brain Aging Among Racially and Ethnically Diverse Middle-Aged and Older Adults.

Importance: Neuroimaging studies have documented racial and ethnic disparities in brain health in old age. It remains unclear whether these disparities are apparent in midlife. Objective: To assess racial and ethnic disparities in magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration in midlife and late life. Design, Setting, and Participants: Data from 2 community-based cohort studies, Washington Heights-Inwood Columbia Aging Project (WHICAP) and the Offspring Study of Racial and Ethnic Disparities in Alzheimer Disease (Offspring), were used. Enrollment took place from March 2011 and June 2017, in WHICAP and Offspring, respectively, to January 2021. Of the 822 Offspring and 1254 WHICAP participants approached for MRI scanning, 285 and 176 refused participation in MRI scanning, 36 and 76 were excluded for contraindications/ineligibility, and 4 and 32 were excluded for missing key variables, respectively. Main Outcomes and Measures: Cortical thickness in Alzheimer disease-related regions, white matter hyperintensity (WMH) volume. Results: The final sample included 1467 participants. Offspring participants (497 [33.9%]) had a mean (SD) age of 55 (10.7) years, had a mean (SD) of 13 (3.5) years of education, and included 117 Black individuals (23.5%), 348 Latinx individuals (70%), 32 White individuals (6.4%), and 324 women (65.2%). WHICAP participants (970 [66.1%]) had a mean (SD) age of 75 (6.5) years, had a mean (SD) of 12 (4.7) years of education, and included 338 Black individuals (34.8%), 389 Latinx individuals (40.1%), 243 White individuals (25.1%), and 589 women (65.2%). Racial and ethnic disparities in cerebrovascular disease were observed in both midlife (Black-White: B = 0.357; 95% CI, 0.708-0.007; P = .046) and late life (Black-Latinx: B = 0.149, 95% CI, 0.068-0.231; P < .001; Black-White: B = 0.166; 95% CI, 0.254-0.077; P < .001), while disparities in cortical thickness were evident in late life only (Black-Latinx: B = -0.037; 95% CI, -0.055 to -0.019; P < .001; Black-White: B = -0.064; 95% CI -0.044 to -0.084; P < .001). Overall, Black-White disparities were larger than Latinx-White disparities for cortical thickness and WMH volume. Brain aging, or the association of age with MRI measures, was greater in late life compared with midlife for Latinx (cortical thickness: B = 0.006; 95% CI, 0.004-0.008; P < .001; WMH volume: B = -0.010; 95% CI, -0.018 to -0.001; P = .03) and White (cortical thickness: B = 0.005; 95% CI, 0.002-0.008; P = .001; WMH volume: B = -0.021; 95% CI -0.043 to 0.002; P = .07) participants but not Black participants (cortical thickness: B = 0.001; 95% CI, -0.002 to 0.004; P =.64; WMH volume: B = 0.003; 95% CI, -0.010 to 0.017; P = .61), who evidenced a similarly strong association between age and MRI measures in midlife and late life. Conclusions and Relevance: In this study, racial and ethnic disparities in small vessel cerebrovascular disease were apparent in midlife. In Latinx and White adults, brain aging was more pronounced in late life than midlife, whereas Black adults showed accelerated pattern of brain aging beginning in midlife.

Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40.

Many bacterial and fungal pathogens cause disease across mucosal surfaces, and to a lesser extent through skin surfaces. Pathogens that potentially cause disease vaginally across epithelial cells include Staphylococcus aureus, group A and B streptococci, Escherichia coli, Neisseria gonorrhoeae, and Candida albicans. We have previously shown that staphylococcal and streptococcal superantigens induce inflammatory chemokines from vaginal epithelial cells through the immune costimulatory molecule CD40 through use of a CRISPR cas9 knockout mutant and complemented epithelial cell line. In this study, we show that the potential vaginal pathogens S. aureus, group A and B streptococci, E. coli, an Enterococcus faecalis strain, and C. albicans in part use CD40 to stimulate interleukin-8 (IL-8) production from human vaginal epithelial cells. In contrast, N. gonorrhoeae does not appear to use CD40 to signal IL-8 production. Normal flora Lactobacillus crispatus and an Enterococcus faecalis strain that produces reutericyclin do not induce IL-8. These data indicate that many potential pathogens, but no normal commensals, induce IL-8 to help disrupt the human vaginal epithelial barrier through CD40, thus providing a potential therapeutic target for drug development. IMPORTANCE Most bacterial and fungal pathogens cause disease across mucosal, and to a lesser extent, skin barriers with the help of induced chemokines from epithelial cells. In this study, we showed that potential vaginal pathogens Staphylococcus aureus, group A and B streptococci, some Enterococcus faecalis strains, Escherichia coli, and Candida albicans use the immune costimulatory molecule CD40 to induce the chemokine interleukin-8 production. In contrast, Neisseria gonorrhoeae does not use CD40 to stimulate interleukin-8. Normal flora lactobacilli and at least one E. faecalis strain do not induce interleukin-8.

Differential Clinical Features in Colombian Patients With Rolandic Epilepsy and Suggestion of Unlikely Association With GRIN2A, RBFOX1, or RBFOX3 Gene Variants.

PURPOSE: Our purpose was to describe the phenotypic features and test for association of genes GRIN2A, RBFOX1 and RBFOX3 with rolandic epilepsy in patients from Colombia. METHODS: Thirty patients were enrolled. A structured interview was applied. In addition, saliva samples were collected from the patients and their parents. One polymorphism in each of GRIN2A, RBFOX1 and RBFOX3 genes was tested. RESULTS: The average age at onset was 5.3 years. Almost half the sample presented prolonged seizures (>5 minutes); although the majority of the patients presented their seizures only while asleep, over a quarter presented them only while awake. The most frequent comorbidity was the presence of symptoms compatible with attention-deficit hyperactivity disorder (ADHD). Personal history of febrile seizures and parasomnias were equally frequent (20%). Family history of any type of epilepsy was reported in 80% of the patients, followed by migraine (73.3%) and poor academic performance (63.3%). About half the sample reported sleepwalking in parents or sibs. Most patients had received pharmacologic treatment. We found no association of rolandic epilepsy with the single nucleotide polymorphisms tested. CONCLUSIONS: Our rolandic epilepsy cohort presents clinical features clearly different from other cohorts. For instance, age at onset is much earlier in our set of patients, and personal and family history of febrile seizures as well as parasomnias are highly prevalent in our sample. No association of rolandic epilepsy with variants at the 3 genes tested was found. This lack of association may reflect the high genetic heterogeneity of the epilepsies.

Leucemia linfocítica crónica y deleción del gen TP53: reporte de un caso y revisión de la literatura / Chronic lymphocytic Leukemia and deletion of the TP53 gene: Case report and literature review

RESUMEN Las alteraciones genéticas en el gen TP53 están presentes entre el 5 al 8 % de los pacientes de leucemia linfocítica crónica (LLC) en el momento del diagnóstico. Estos casos se relacionan con un mal pronóstico debido a su resistencia al tratamiento estándar. Presentamos el caso de un paciente masculino de 52 años diagnosticado con LLC, expresión del marcador CD38 y una deleción en el gen TP53 (17p13.1). Tras la evaluación posterior del tratamiento, se observó enfermedad mínima residual lo que llevó a un trasplante haploidéntico de progenitores hematopoyéticos. Debido al alto riesgo de recaída, su edad y la ausencia de comorbilidades, era la única opción curativa hasta la fecha para la LLC. El objetivo de este trabajo es realizar una revisión de la literatura que sirva como base para analizar el caso clínico presentado, en el marco de las implicaciones clínicas, pronóstico y respuesta al tratamiento en los individuos con LLC que presentan alteraciones en el gen TP53.

SUMMARY Genetic alterations in the TP53 gene are present in 5 to 8% of chronic lymphocytic leukemia (CLL) cases at the time of diagnosis. These cases are typically associated with poor prognosis due to their resistance against standard CLL treatment. In our report a 52-yearold male patient was diagnosed with CLL, CD38 expression and a deletion in the TP53 gene (17p13.1). Upon evaluation post-treatment, minimal residual disease (MDR) was observed, and a haploidentical stem cell transplant was performed. Because of the high risk of relapse, his age, and the absence of comorbidities it was the only curative option to date for CLL. The purpose of this article is to complete a literature review that will give a basis to analyze the clinical case presented, within the framework of the clinical implications, prognosis, and response to treatment in patients with CLL who present with aberrations of the TP53 gene.

El "efecto fin de semana" en pacientes que asisten a urgencias por hemorragia digestiva superior no varicosa. La experiencia en un hospital de alta complejidad / The "Weekend Effect" in patients admitted to the Emergency Unit with non-variceal upper gastrointestinal bleeding. A high-complexity hospital experience

Resumen Introducción y objetivos: el "efecto fin de semana" se define como un incremento en la mortalidad en pacientes que ingresan a centros asistenciales durante el fin de semana o días festivos. Este estudio se realizó para evaluar el posible "efecto fin de semana" en pacientes con hemorragia digestiva superior (HDS) con base en una experiencia de 3 años en un hospital de alta complejidad en Latinoamérica. Materiales y métodos: estudio observacional descriptivo realizado entre 2016 y 2018. Se describieron las características demográficas, factores de riesgo, síntomas de ingreso, hallazgos endoscópicos y diferentes intervenciones médicas. Además, se compararon los tiempos de realización de endoscopia, estancia hospitalaria y mortalidad entre los pacientes admitidos durante el fin de semana frente a días entre semana. Resultados: el análisis incluyó 274 pacientes en fines de semana y festivos (39,1 %) frente a pacientes en días entre semana (60,9 %). La mediana de edad fue de 68,5 años (rango intercuartílico [RIC]: 53-79), el 56,6 % fueron hombres. Las manifestaciones más comunes fueron melenas y hematemesis. La úlcera péptica fue el diagnóstico endoscópico más común (48,7 %). Los tiempos de estancia hospitalaria (7,38 ± 8,7 frente a 7,38 ± 7,1; p = 0,234) y mortalidad (1,9 % frente a 4,2 %; p = 0,274) fueron similares en ambos grupos. Se realizó una mayor cantidad de endoscopias después de las 24 horas en pacientes ingresados el fin de semana (19,6 % frente a 9,6 %; p = 0,041). Conclusiones: en esta cohorte no se presentó el "efecto fin de semana", no se observan diferencias en relación con la estancia hospitalaria, ni con la mortalidad en pacientes ingresados por HDS.

Abstract Introduction and Objectives: The "Weekend Effect" refers to an increase in mortality of patients admitted to health care centers on weekends or holidays. This study was performed to assess the impact of weekend admissions in patients with upper gastrointestinal bleeding (UGIB) based on a three year-experience in a high-complexity hospital in Latin America. Materials and Methods: A descriptive observational study was performed between 2016 and 2018. Data on demographic characteristics, risk factors, symptoms, endoscopic findings, and medical treatment was described. Moreover, the time to perform an endoscopy, the length of hospital stay, and the mortality level among patients admitted on weekends were compared with the same factors during the week. Results: The analysis included 274 patients admitted during the weekend and holidays (39.1%) versus patients admitted during the week (60.9%). The median age was 68.5 years old (interquartile range [IQR]: 53-79), and 56.6% were men. The most common conditions were tarry stools and hematemesis. Peptic ulcer was the most common endoscopic diagnosis (48.7%). Similar results were found in the length of hospital stay (7,38 ± 8,7 versus 7,38 ± 7,1; p = 0,234) and mortality groups (1,9 % versus 4,2 %; p = 0,274). A higher number of endoscopies 24 hours after the patient was admitted was performed (19,6 % versus 9,6 %; p = 0,041). Conclusions: The "Weekend Effect" was not present in the analyzed group, and there are no significant differences related to the length of hospital stay or the mortality of patients diagnosed with UGIB.

Cisticercosis en Boyacá, Colombia: estudio de seroprevalencia / Cisticercosis in Boyacá, Colombia: seroprevalence study

Introducción. La cisticercosis humana es una infección producida por la forma larval de la Taenia solium, quepresenta múltiples manifestaciones clínicas de acuerdo a los órganos y tejidos que afecte, la neurocisticercosis(NC) es la forma más grave. En Colombia se desconoce la prevalencia de la cisticercosis en la población general.Objetivo. Estimar la prevalencia de la cisticercosis en el departamento de Boyacá en población general, a travésde pruebas serológicas.Materiales y Métodos. La metodología utilizada, teniendo en cuenta que se trata de una encuesta departamentalcon proyección nacional, se basó en tres fases, una primera correspondiente a su diseño estadístico y planteamiento metodológico, una segunda etapa dada por la ejecución en campo para obtener información a través de instrumentosde recolección de datos, toma de muestras de sangre y procesamiento de las mismas en el Laboratorio de Parasitología del Instituto Nacional de Salud mediante la técnica de Elisa y una última fase de consolidación, análisisy divulgación de los resultados. El diseño muestral fue probabilístico, trietápico, de conglomerados y estratificado. Resultados. La prevalencia general de anticuerpos anti-cisticerco en el departamento de Boyacá fue de 4,02%.Entre hábitos de aseo no realizar el lavado de manos después de ir al sanitario configura un riesgo muy importante(RP=4,63 I.C 95% 4,50 – 4,76 p <0,05) junto con otros hábitos como la eliminación de excretas al aire libre o enletrina sin pozo (RP=1,27 I.C 1,24 – 1,31) p <0,05.Conclusiones. Se logró conocer la seroprevalencia de la cisticercosis determinada en población general deldepartamento de Boyacá y algunos factores epidemiológicos determinantes de esta patología, todo ello puedeestablecerse como una línea base para dar inicio al proceso de la vigilancia epidemiológica, control y prevenciónde esta patología.

Introduction. Human cysticercosis is an infection caused by the larval form of Taenia solium, which has many clinicalmanifestations according to the organs and tissues affected, being the neurocysticercosis (NC) the most severe form. In Colombia, the prevalence of cysticercosis is unknown in the general population and habits exist in our population. Objective. To estimate the prevalence of the cysticercosis in Boyaca Department in general population through serologicaltests. Materials and Methods. The methodology used, taking into account that this is a survey at the departmental level with national projection was based on three phases, an initial design for statistical and methodological approach, a second stage performance given by its field to obtain information through data collection instruments, blood sampling and processing them in the Laboratory of Parasitology, National Institute of Health by ELISA and a final phase of consolidation, analysis and dissemination of results. The sample design was probabilistic, three-stage, stratified cluster. Results. The overall prevalence of anti-cysticercus antibodies in the department of Boyacá was 4.02%. Hygiene habitswere a group of factors which are found not to hand washing after using the bathroom set up a very significant risk (RP = 4.63 CI 4.50 to 4.76) p <0.05 with other habits, such as excreta or in outdoor pit latrine without (RP = 1.27 CI 1.24 to 1.31) p <0.05. Conclusions. Understanding was reached on the status of cysticercosis seroprevalence determined by the general populationof the department of Boyacá and some determinants of this disease, constituting a baseline you can start the process of epidemiological surveillance, control and prevention of this disease in this department.

Actualización de la fisiología gástrica / Update gastric physiology

La fisiología gástrica constituye una compleja y dinámica interacción entre estructuras anatómicas, sus secreciones, el ambiente circundante y los factores exígenos aportados por el individuo. Este trabajo pretende hacer una breve revisión actualizada sobre fisiología de la secreción y la motilidad gástricas. Se expondrá la función de las principales células de la mucosa gástrica, sus secreciones y aquellas sustancias, hormonas y neurotransmisores que las estimulan, modulan o inhiben, haciendo especial énfasis en los mecanismos de prducción del acido gástrico. Además, se tratar  específicamente el tema de la mortalidad gástrica con idéntica metodología...