APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease.

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.).

Desenlaces clínicos en pacientes con hepatopatía crónica, con o sin antecedente de trasplante hepático, hospitalizados por neumonía por SARS-CoV-2 / Clinical outcomes in patients with chronic liver disease, with or without a history of liver transplantation, hospitalized for SARS-CoV-2 pneumonia

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.

VCAM1, HMOX1 and NOS3 differential endothelial expression may impact sickle cell anemia vasculopathy.

Endothelial dysfunction plays a major role in sickle cell anemia (SCA) systemic vasculopathy, with upregulation of adhesion molecules (e.g., VCAM-1), decreased nitric oxide bioavailability, and oxidative stress. We aimed to assess the modulation role of pro-inflammatory and pro-oxidative stimuli on endothelial VCAM1, NOS3, and HMOX1 expression. We also evaluated the effect of the main SCA therapeutic agent, hydroxyurea, on that modulation. Our results showed that two VCAM1 promoter haplotypes, we previously associated with pediatric cerebral vasculopathy and severe hemolysis in SCA, increased promoter activity in TNF-α-stimulated transfected EA.hy926 and HBEC cell lines, consistent with a higher VCAM1 expression in macro and microvascular settings. In non-transfected cells, we also observed TNF-α-induced VCAM1 overexpression as well as heme-induced overexpression of HMOX1 in both cell models. Heme did not affect VCAM1 nor NOS3 expression and the latter was also not affected by TNF-α stimulus. Hydroxyurea treatment lowered TNF-induced VCAM1 and NOS3 expression but did not affect heme-induced HMOX1 expression. These data further indicate that VCAM1 haplotypes we studied lead to higher VCAM1 expression affecting not only cerebral but also systemic vasculopathy risk. The differential endothelial expression of VCAM1, NOS3, and HMOX1 also confirms their genetic modulation role in SCA systemic vasculopathy.

Emergency surgery workforce and its inverse relationship with multidimensional poverty in Colombia.

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.

Association Between Unbalanced Solutions and Acute Kidney Injury During Fluid Resuscitation in Children With Sepsis.

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.

Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia.

We investigated biomarkers and genetic modulators of the cerebral vasculopathy (CV) subphenotype in pediatric sickle cell anemia (SCA) patients of sub-Saharan African ancestry. We found that one VCAM1 promoter haplotype (haplotype 7) and VCAM1 single nucleotide variant rs1409419_T were associated with stroke events, stroke risk, as measured by time-averaged mean of maximum velocity in the middle cerebral artery, and with high serum levels of the hemolysis biomarker lactate dehydrogenase. Furthermore, VCAM-1 ligand coding gene ITGA4 variants rs113276800_A and rs3770138_T showed a positive association with stroke events. An additional positive relationship between a genetic variant and stroke risk was observed for ENPP1 rs1044498_A. Conversely, NOS3 variants were negatively associated with silent cerebral infarct events (VNTR 4b_allele and haplotype V) and CV globally (haplotype VII). The -alpha3.7kb-thal deletion did not show association with CV. However, it was associated with higher red blood cell and neutrophil counts, and lower mean corpuscular volume, mean corpuscular hemoglobin and red cell distribution width. Our results underline the importance of genetic modulators of the CV sub-phenotype and their potential as SCA therapeutic targets. We also propose that a biomarker panel comprising biochemical, hematological, imaging and genetic data would be instrumental for CV prediction, and prevention.

Genetic modulators of fetal hemoglobin expression and ischemic stroke occurrence in African descendant children with sickle cell anemia.

Sickle cell anemia (SCA) is an autosomal recessive monogenic disease with significant clinical variability. Cerebrovascular disease, particularly ischemic stroke, is one of the most severe complications of SCA in children. This study aimed to investigate the influence of genetic variants on the levels of fetal hemoglobin (Hb F) and biochemical parameters related with chronic hemolysis, as well as on ischemic stroke risk, in ninety-one unrelated SCA patients, children of sub-Saharan progenitors. Our results show that a higher Hb F level has an inverse relationship with the occurrence of stroke, since the group of patients who suffered stroke presents a significantly lower mean Hb F level (5.34 ± 4.57% versus 9.36 ± 6.48%; p = 0.024). Furthermore, the co-inheritance of alpha-thalassemia improves the chronic hemolytic pattern, evidenced by a decreased reticulocyte count (8.61 ± 3.58% versus 12.85 ± 4.71%; p < 0.001). In addition, our findings have confirmed the importance of HBG2 and BCL11A loci in the regulation of Hb F expression in sub-Saharan African SCA patients, as rs7482144_A, rs11886868_C, and rs4671393_A alleles are significantly associated with a considerable increase in Hb F levels (p = 0.019, p = 0.026, and p = 0.028, respectively). Concerning KLF1, twelve different variants were identified, two of them novel. Seventy-three patients (80.2%) presented at least one variant in this gene. However, no correlation was observed between the presence of these variants and Hb F level, severity of hemolysis, or stroke occurrence, which is consistent with their in silico-predicted minor functional consequences. Thus, we conclude that the prevalence of functional KLF1 variants in a sub-Saharan African background does not seem to be relevant to SCA clinical modulation.

Analysis of the genetic component of systemic sclerosis in Iranian and Turkish populations through a genome-wide association study.

Objectives: SSc is an autoimmune disease characterized by alteration of the immune response, vasculopathy and fibrosis. Most genetic studies on SSc have been performed in European-ancestry populations. The aim of this study was to analyse the genetic component of SSc in Middle Eastern patients from Iran and Turkey through a genome-wide association study. Methods: This study analysed data from a total of 834 patients diagnosed with SSc and 1455 healthy controls from Iran and Turkey. DNA was genotyped using high-throughput genotyping platforms. The data generated were imputed using the Michigan Imputation Server, and the Haplotype Reference Consortium as a reference panel. A meta-analysis combining both case-control sets was conducted by the inverse variance method. Results: The highest peak of association belonged to the HLA region in both the Iranian and Turkish populations. Strong and independent associations between the classical alleles HLA-DRB1*11: 04 [P = 2.10 × 10-24, odds ratio (OR) = 3.14] and DPB1*13: 01 (P = 5.37 × 10-14, OR = 5.75) and SSc were observed in the Iranian population. HLA-DRB1*11: 04 (P = 4.90 × 10-11, OR = 2.93) was the only independent signal associated in the Turkish cohort. An omnibus test yielded HLA-DRB1 58 and HLA-DPB1 76 as relevant amino acid positions for this disease. Concerning the meta-analysis, we also identified two associations close to the genome-wide significance level outside the HLA region, corresponding to IRF5-TNPO3 rs17424921-C (P = 1.34 × 10-7, OR = 1.68) and NFKB1 rs4648133-C (P = 3.11 × 10-7, OR = 1.47). Conclusion: We identified significant associations in the HLA region and suggestive associations in IRF5-TNPO3 and NFKB1 loci in Iranian and Turkish patients affected by SSc through a genome-wide association study and an extensive HLA analysis.

Association of a rare variant of the TNFSF13B gene with susceptibility to Rheumatoid Arthritis and Systemic Lupus Erythematosus.

A rare variant (BAFF-var) of the tumor necrosis factor superfamily 13b (TNFSF13B) gene has been recently associated with multiple sclerosis (MS) and systemic lupus erythematosus (SLE). The aim of this study was to investigate the association between TNFSF13B BAFF-var and susceptibility to rheumatoid arthritis (RA) and replicate that association in SLE. 6,218 RA patients, 2,575 SLE patients and 4,403 healthy controls from three different countries were included in the study. TNFSF13B BAFF-var was genotyped using TaqMan allelic discrimination assay. PLINK software was used for statistical analyses. TNFSF13B BAFF-var was significantly associated with RA (p = 0.015, OR = 1.21, 95% CI = 1.03-1.41) in the Spanish cohort. A trend of association was observed in the Dutch (p = 0.115) and German (p = 0.228) RA cohorts. A meta-analysis of the three RA cohorts included in this study revealed a statistically significant association (p = 0.002, OR = 1.24, 95% CI = 1.10-1.38). In addition, TNFSF13B BAFF-var was significantly associated with SLE in the Spanish (p = 0.001, OR = 1.41, 95% CI = 1.14-1.74) and the German cohorts (p = 0.030, OR = 1.86, 95% CI = 1.05-3.28), with a statistically significant p-value obtained in the meta-analysis (p = 0.0002, OR = 1.46, 95% CI = 1.09-2.32). The results obtained confirm the known association of TNFSF13B BAFF-var with SLE and, for the first time, demonstrate that this variant contributes to susceptibility to RA.

Parámetros sanguíneos y perfil de hormonas reproductivas de hembras de Choloepus hoffmanni en cautiverio / Blood parameters and reproductive hormone profile of female Choloepus hoffmanni in captivity

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.

Comprehensive analysis of three TYK2 gene variants in the susceptibility to Chagas disease infection and cardiomyopathy.

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.

Hemorheological alterations in sickle cell anemia and their clinical consequences - The role of genetic modulators.

Sickle cell anemia (SCA) is an autosomal recessive disease caused by the HBB:c.20A>T mutation that leads to hemoglobin S synthesis. The disease presents with high clinical heterogeneity characterized by chronic hemolysis, recurrent episodes of vaso-oclusion and infection. This work aimed to characterize by in silico studies some genetic modulators of severe hemolysis and stroke risk in children with SCA, and understand their consequences at the hemorheological level.Association studies were performed between hemolysis biomarkers as well as the degree of cerebral vasculopathy and the inheritance of several polymorphic regions in genes related with vascular cell adhesion and vascular tonus in pediatric SCA patients. In silico tools (e.g. MatInspector) were applied to investigate the main variant consequences.Variants in vascular adhesion molecule-1 (VCAM1) gene promoter and endothelial nitric oxide synthase (NOS3) gene were significantly associated with higher degree of hemolysis and stroke events. They potentially modify transcription factor binding sites (e.g. VCAM1 rs1409419_T allele may lead to an EVI1 gain) or disturb the corresponding protein structure/function. Our findings emphasize the relevance of genetic variation in modulating the disease severity due to their effect on gene expression or modification of protein biological activities related with sickled erythrocyte/endothelial interactions and consequent hemorheological abnormalities.

Contaminación fúngica ambiental en tres centros de enseñanza primaria del cantón central de la provincia de Heredia, Costa Rica / Aerial fungal contamination in three primary schools of the province of Heredia, Costa Rica

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.

Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility.

OBJECTIVE: The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc). PATIENTS AND METHODS: The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays. RESULTS: We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (pc=6.6E-4 and pc=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (pc=1.7E-03 and pc=8E-4, respectively). CONCLUSIONS: These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.

New azasterols against Trypanosoma brucei: role of 24-sterol methyltransferase in inhibitor action.

A series of azasterol derivatives, designed as potential inhibitors of the Delta(24)-sterol methyltransferase enzyme (24-SMT), were synthesized and evaluated for their activities against parasitic protozoa. Values in the nanomolar range were obtained for 50% effective dose against the Trypanosoma brucei subsp. rhodesiense bloodstream form cultured in vitro. In order to investigate the mode of action, Trypanosoma brucei subsp. brucei 24-SMT was cloned and overexpressed and compounds were assayed for inhibitory activity. None of the inhibitors tested appeared to be active against the enzyme. Sterol composition analysis showed that only cholestane type sterols are present in membranes of bloodstream forms while ergosterol is a major component of procyclic sterol extracts. Interestingly, Northern blot analysis showed the presence of 24-SMT mRNA in both the procyclic and the bloodstream forms of the parasite, although levels of mRNA were threefold lower in the latter. Likewise, Western blot analysis and activity determinations evidenced the existence of active enzyme in both forms of the parasite. We conclude that the designed compounds act at sites other than 24-SMT in Trypanosoma brucei.