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BACKGROUND: Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant (APOE3 Ch). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent. METHODS: We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants. RESULTS: Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease. In one of these participants, who underwent 18F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant. CONCLUSIONS: Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer's disease. (Funded by Good Ventures and others.).
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Enfermedad de Alzheimer , Apolipoproteína E3 , Presenilina-1 , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Edad de Inicio , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Apolipoproteína E3/genética , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Colombia , Familia , Genes Dominantes , Heterocigoto , Tomografía de Emisión de Positrones , Presenilina-1/genética , Estudios RetrospectivosRESUMEN
Introducción. La asociación entre SARS-CoV-2 y hepatopatías crónicas ha sido descrita mundial-mente con cohortes que reportan hasta un 11 % de pacientes hospitalizados con cirrosis hepática o trasplante hepático. Datos publicados reportan un aumento de la mortalidad en este grupo de pacientes. El objetivo de este estudio fue evaluar los desenlaces de mortalidad, necesidad de estan-cia en UCI y de ventilación mecánica, en pacientes hospitalizados por neumonía por SARS-CoV-2 e historia de hepatopatía crónica, con o sin antecedente de trasplante hepático. Metodología. Se realizó un estudio de cohorte observacional retrospectivo en un centro de referencia en trasplante hepático, con pacientes adultos hospitalizados por COVID-19 y antecedente de hepatopatía cróni-ca, trasplantados y no trasplantados. Resultados. Se incluyeron 100 pacientes, de ellos 42 pacien-tes (42 %) habían sido receptores de trasplante hepático. En el análisis al comparar trasplantados versus no trasplantados, se encontró mortalidad por cualquier causa 14 % versus 31 % (OR 0,37; IC95% 0,13-1,03), muerte por COVID-19 14 % versus 29 % (OR 0,52; IC95% 0,18-1,50), reque-rimiento de hospitalización en UCI 30 % versus 29 % (OR 1,48; IC95% 0,57-3,79) y ventilación mecánica 14 % versus 29 % (OR 1,53; IC95% 0,42-3,06), respectivamente. Conclusiones. Los resultados de este estudio sugieren que no hubo un incremento en el riesgo de mortalidad, necesi-dad de estancia en UCI o ventilación mecánica en los pacientes con antecedente de hepatopatía crónica, trasplantados y no trasplantados, que tenían neumonía por SARS-CoV-2.
Introduction. The association between SARS-CoV-2 and chronic liver disease has been described worldwide with cohorts reporting up to 11% of patients hospitalized with liver cirrhosis or liver transplantation. Published data has reported an increase in mortality in this group of patients. The objective of this study was to evaluate the outcomes of mortality, need for ICU stay and mechani-cal ventilation, in hospitalized transplanted and non-transplanted patients with history of chronic liver disease, who had SARS-CoV-2 pneumonia. Methodology. A retrospective cohort study was conducted in a liver transplant reference center with adult patients hospitalized for COVID-19 with a history of chronic liver disease either transplanted or not transplanted. A univariate analysis was performed to assess the outcomes of interest. Results. One hundred patients were included, of which 42 patients (42%) were liver transplant recipients. In the analysis comparing transplanted versus non-transplanted, mortality from any cause was 14% versus 31% (OR 0.37; 95% CI 0.13-1.03), death from COVID-19 14% versus 29% (OR 0.52; 95% CI 0.18-1.50), ICU hospitalization requirement 30% versus 29% (OR 1.48; 95% CI 0.57-3.79) and mechanical ventilation 14% versus 29% (OR 1.53; 95% CI 0.42-3.06), respectively. Conclusions. The results of this study suggest that there was no increased risk of mortality, need for ICU stay, or mechanical ventilation in transplanted and non-transplanted patients with a history of chronic liver disease who had SARS-CoV-2 pneumonia.
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Humanos , Adulto , Persona de Mediana Edad , AncianoRESUMEN
OBJECTIVE: To evaluate the outcomes of patients with sepsis-associated organ dysfunction and septic shock who receive fluid resuscitation with balanced and unbalanced solutions in a middle-income country. DESIGN: An observational, analytical cohort study with propensity score matching (PSM) in children admitted to a pediatric intensive care unit (PICU). Patients from one month to 17 years old who required fluid boluses due to hemodynamic instability were included. The primary outcome was the presence of acute kidney injury and the secondary outcomes were the need to begin continuous renal replacement therapy (CRRT), metabolic acidosis, PICU length of stay and mortality. MEASUREMENTS AND MAIN RESULTS: Out of the 1,074 admissions to the PICU during the study period, 99 patients had sepsis-associated organ dysfunction and septic shock. Propensity score matching was performed including each patient´s baseline characteristics. The median age was 9.9 months (IQR 4.9-22.2) with 55.5% of the patients being male. Acute kidney injury was seen less frequently in children who received a balanced solution than in those who received an unbalanced solution (20.3% vs 25.7% P = 0.006 ORa, 0.75; 95% CI, 0.65-0.87), adjusted for disease severity. In addition, the group that received balanced solutions had less need for CRRT (3.3 % vs 6.5%; P = 0.02 ORa 0.48; 95% CI, 0.36-0.64) and a shorter PICU stay (6 days IQR 4.4-20.2 vs 10.2 days IQR 4.7-26; P < 0.001) than the group with unbalanced solutions. We found no difference in the frequency of metabolic acidosis (P = 0.37), hyperchloremia (P = 0.11) and mortality (P = 0.25) between the 2 groups. CONCLUSION: In children with sepsis-associated organ dysfunction and septic shock, the use of unbalanced solutions for fluid resuscitation is associated with a higher frequency of acute kidney injury, a greater need for continuous renal support and a longer PICU stay compared to the use of balanced solutions, in a middle-income country.
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Acidosis , Lesión Renal Aguda , Sepsis , Choque Séptico , Acidosis/etiología , Acidosis/terapia , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/terapia , Niño , Estudios de Cohortes , Fluidoterapia , Humanos , Lactante , Masculino , Insuficiencia Multiorgánica/complicaciones , Resucitación , Estudios Retrospectivos , Sepsis/complicaciones , Sepsis/terapiaRESUMEN
PURPOSE: General surgeons, anesthesiologists, obstetricians and gynecologists (ob-gyns), and orthopedic surgeons are the vital disciplines to provide emergency surgery within a healthcare system. This paper aims to examine the relationship (if any) between multidimensional poverty (MDP) and GDP per-capita with the emergency surgery workforce density in Colombia. METHODS: We performed an ecological study, where the observation units were the 32 Colombian departments. The total numbers of general surgeons, anesthesiologists, ob-gyns, and orthopedic surgeons were obtained from the "Registro Unico Nacional de Talento Humano en Salud" (ReTHUS) registry. The 2020 population projections, the incidence of MDP and the GDP per capita were obtained from the Colombian National Administrative Department of Statistics. A spearman's correlation coefficient was calculated to measure the strength of the correlations between the surgical workforce density with MDP and GDP per-capita. RESULTS: There were significant moderate inverse linear correlations between the incidence of multidimensional poverty and workforce density. The correlation coefficients for the incidence of multidimensional poverty and the workforce density were - 0.5273, - 0.5620, - 0.4704, and - 0.4612 for surgeons, anesthesiologists, ob-gyns, and orthopedic surgeons, respectively. Conversely, the correlation coefficients for the GDP per-capita and the workforce density were 0.4045, 0.3822, 0.4404, and 0.3742 for surgeons, anesthesiologists, ob-gyns, and orthopedic surgeons, respectively. CONCLUSION: This study found that Colombian trauma and emergency surgery workforce density was inversely and directly correlated with multidimensional poverty and GDP per-capita levels, respectively. The relationship of these economic indicators with the surgical capacity deserves further investigation.
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Ginecología , Cirujanos , Colombia/epidemiología , Humanos , Pobreza , Recursos HumanosRESUMEN
Resumen El uso de técnicas no invasivas ni estresantes para determinar perfiles hormonales, como la medición de esteroides fecales, ha incrementado la comprensión de la fisiología reproductiva en animales silvestres. Debido a la escasa información con respecto a perfiles hormonales reproductivos del perezoso de dos dedos, Choloepus hoffmani, se realizó un estudio en hembras en cautiverio en el centro de rescate "Sloth Sanctuary" (Cahuita, Limón, Costa Rica) con el fin de determinar (i) la confiabilidad de la extracción de progesterona y estradiol en heces, y su cuantificación en el analizador AIA-360®, (ii) evaluar los parámetros sanguíneos en esta especie y (iii) establecer si existe una correlación entre los esteroides plasmáticos y fecales. El estudio se realizó en un periodo de tres meses, durante noviembre de 2013 a enero de 2014, con un total de 208 muestras de heces provenientes de cinco hembras sexualmente maduras, con peso promedio de 6.32 kg. El promedio de las concentraciones medianas en las heces de las cinco hembras fue 124.21 ng/g para progesterona y 1 708.95 pg/g de estradiol. En plasma, los valores de mediana fueron 1.26 ng/mL con un mínimo de 0.32 ng/mL y 12.84 ng/mL como valor máximo; los valores plasmáticos de estrógeno se encontraron por debajo del límite de detección del equipo (25 pg/mL). Aunque no se encontró una correlación estadísticamente significativa entre la progesterona plasmática y la fecal, nuestros datos sugieren que los eventos plasmáticos se reflejan en heces durante los dos días posteriores. Asimismo, los niveles de progesterona se mantuvieron elevados durante la primera mitad de noviembre, y posteriormente mostraron una reducción importante en todas las hembras. Nuestros resultados demuestran que las extracciones en heces y su medición en el AIA-360® permiten la detección y el seguimiento de variaciones hormonales en C. hoffmani, aunque no remplaza las mediciones plasmáticas para determinar valores absolutos.
Abstract In wild animal species, the use of non-invasive and non-stressful procedures to determine hormone profiles, such as fecal steroid measurements, has considerably increased the comprehension of their reproductive physiology. Since there is limited information related to the reproductive hormone profiles of the two-toed sloth, Choloepus hoffmani, a study was conducted in captive specimens at the "Sloth Sanctuary" (Cahuita, Limón, Costa Rica), in order to determine: (i) the reliability of the fecal progesterone and estrogen extraction and its quantification with an AIA-360® analyzer, (ii) assess blood parameters in this species and (iii) evaluate if there is a correlation between fecal and plasmatic steroids. The study was performed over a three-month period, from November, 2013 to January, 2014, with a total amount of 208 fecal samples collected from five sexually mature females weighing 6.32 kg in average. The average of the median concentrations of progesterone in feces of the five females was 124.21 ng/g, and 1 708.95 pg/g for estrogen. The average minimal and maximal values were 50.96 ng/g and 1 057.46 ng/g for progesterone and, 1 191.77 pg/g and 2 159.24 pg/g for estradiol. In plasma, progesterone median values were 1.26 ng/mL, showing a minimum of 0.32 ng/mL and 12.84 ng/mL as maximum values. The plasmatic estrogen levels were below the detection limit of the equipment (25 pg/mL). Although there was no strong statistical correlation between the fecal and plasmatic progesterone fluctuations, our data suggests that the plasmatic events are mostly reflected in feces two days afterwards. Also, the levels of progesterone were elevated during the first half of November and, subsequently, showed a successive and important reduction in all the females tested. Finally, our results demonstrated that fecal steroid extractions and their measurement in a AIA-360®, allowed the successful detection and represents an alternative non-invasive determination of hormone profiles in C. hoffmani. Rev. Biol. Trop. 66(1): 280-292. Epub 2018 March 01.
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Tyrosine kinase 2 (TYK2) is a member of the Janus kinases family implicated in the signal transduction of type I interferons and several interleukins. It has been described that genetic mutations within TYK2 lead to multiple deleterious effects in the immune response. In this work, we have analyzed three functional independent variants from the frequency spectrum on the TYK2 gene (common and low-frequency variants) suggested to reduce the function of the gene in mediating cytokine signaling and the susceptibility to infections by Trypanosoma cruzi and/or the development of Chagas cardiomyopathy in the Colombian population. A total of 1,323 individuals from a Colombian endemic region for Chagas disease were enrolled in the study. They were classified as seronegative (n = 445), seropositive asymptomatic (n = 336), and chronic Chagas Cardiomyopathy subjects (n = 542). DNA samples were genotyped using TaqMan probes. Our results showed no statistically significant differences between the allelic frequencies of the three analyzed variants when seropositive and seronegative individuals were compared, therefore these variants were not associated with susceptibility to Chagas disease. Moreover, when Chagas cardiomyopathy patients were compared to asymptomatic patients, no significant associations were found. Previous reports highlighted the association of this gene in immune-related disorders under an autoimmunity context, but not predisposing patients to infectious diseases, which is consistent with our findings. Therefore, according to our results, TYK2 gene variants do not seem to play an important role in Chagas disease susceptibility and/or chronic Chagas cardiomyopathy.
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Cardiomiopatías/genética , Enfermedad de Chagas/genética , Predisposición Genética a la Enfermedad , TYK2 Quinasa/genética , Adulto , Enfermedad de Chagas/epidemiología , Colombia/epidemiología , Femenino , Humanos , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
Justificación y objetivo: las esporas fúngicas aéreas son consideradas agentes etiológicos de la rinitis alérgica y el asma. El objetivo del presente estudio fue analizar la contaminación fúngica ambiental en tres centros de enseñanza primaria del cantón Central de la provincia de Heredia, midiendo la concentración de esporas fúngicas aéreas por metro cúbico. Métodos: se utilizó el equipo para muestreo volumétrico aéreo Burkard Personal Volumetric Air Sampler durante las épocas seca y lluviosa. Los conteos de esporas se relacionaron con los factores meteorológicos y las características estructurales de los centros educativos analizados. Resultados: se encontró un total de 1391,89 ± 119,70 esporas/m3 en marzo, 3194,45 ± 577,03 esporas/m3 en mayo, 3747,12 ± 568,05 esporas/m3 en octubre y 1009,99 ± 81,24 esporas/m3 en diciembre. En marzo, octubre y diciembre, aproximadamente el 91,0% de estas esporas pertenecían a cuatro grupos: Aspergillus/Penicillium, ascosporas, basidiosporas y Cladosporium. Sin embargo, en mayo el 78,46% de las esporas identificadas pertenecían al género Cladosporium. Al correlacionar la concentración de esporas fúngicas se encontró correlación negativa con la velocidad del viento (-0.418, p<0.05), correlación positiva con la precipitación pluvial (0,568, p<0,05), correlación positiva con el porcentaje de humedad relativa (0,504, p<0,05), y no se encontró correlación con los cambios de temperatura. Conclusión: la concentración de esporas fúngicas encontrada en las tres escuelas muestreadas es mayor al límite de 1000 esporas por metro cúbico, considerado saludable.
Background and aim: Fungal spores are considered etiological agents of allergic rhinitis and asthma; therefore, it is advised to monitor fungal levels within the classrooms. The aim of this paper was to study fungal aerial contamination in three public schools of Heredia by measuring the concentration of aerial fungal spores per cubic meter. Methods: We used the Burkard Personal Volumetric Air Sampler to collect and identify fungal spores during the dry and rainy season. The relationship between the fungal spore concentration, the meteorological factors and structural characteristics of the schools was determined. Results: A total of 1391.89 ± 119.70 spores/m3 was found in March, 3194.45 ± 577.03 spores/ m3 in May, 3747.12 ± 568.05 spores/m3 in October and 1009.99 ± 81.24 spores/m3 in December. Except for May, approximately 91.0 % of the spores identified belonged to four groups: Aspergillus/ Penicillium, ascospores, basidiospores and Cladosporium. In May, 78.46 % of the spores identified were Cladosporium. A negative correlation was found between spore concentration and wind velocity (-0.418; p<0.05), and a positive one with rain (0.568; p<0.05) and with humidity (0.504; p<0.05). No correlation was found with temperature changes. Conclusion: The three schools analysed presented fungal spore concentrations which exceeded the limit of 1000 spores per cubic meter which is considered as healthy.