Arsenic reduces the GATA3 expression associated with an increase in proliferation and migration of mammary epithelial cell line MCF-10A.

Arsenic is associated with the development of breast cancer. However, the molecular mechanisms of arsenic induction of breast cancer are not fully defined. Interaction with zinc finger (ZnF) motifs in proteins is one of the proposed mechanisms of arsenic toxicity. GATA3 is a transcription factor that regulates the transcription of genes associated with cell proliferation, cell differentiation and the epithelial-mesenchymal transition (EMT) in mammary luminal cells. Given that GATA3 possesses two ZnF motifs essential for the function of this protein and that arsenic could alter the function of GATA3 through interaction with these structural motifs, we evaluated the effect of sodium arsenite (NaAsO2) on GATA3 function and its relevance in the development of arsenic-induced breast cancer. Breast cell lines derived from normal mammary epithelium (MCF-10A), hormone receptor-positive and hormone receptor negative breast cancer cells (T-47D and MDA-MB-453, respectively) were used. We observed a reduction on GATA3 protein levels at non-cytotoxic concentrations of NaAsO2 in MCF-10A and T-47D, but not in MDA-MB-453 cells. This reduction was associated with an increase in cell proliferation and cell migration in MCF-10A, but not in T-47D or MDA-MB-453 cells. The evaluation of cell proliferation and EMT markers indicate that the reduction on GATA3 protein levels by arsenic, disrupts the function of this transcription factor. Our data indicate that GATA3 is a tumor suppressor in the normal mammary epithelium and that arsenic could act as an initiator of breast cancer by disrupting the function of GATA3.

The effects of sucrose and arsenic on muscular insulin signaling pathways differ between the gastrocnemius and quadriceps muscles.

Introduction: Insulin resistance in muscle can originate from a sedentary lifestyle, hypercaloric diets, or exposure to endocrine-disrupting pollutants such as arsenic. In skeletal muscle, insulin stimulates glucose uptake by translocating GLUT4 to the sarcolemma. This study aimed to evaluate the alterations induced by sucrose and arsenic exposure in vivo on the pathways involved in insulinstimulated GLUT4 translocation in the quadriceps and gastrocnemius muscles. Methods: Male Wistar rats were treated with 20% sucrose (S), 50 ppm sodium arsenite (A), or both (A+S) in drinking water for 8 weeks. We conducted an intraperitoneal insulin tolerance (ITT) test on the seventh week of treatment. The quadriceps and gastrocnemius muscles were obtained after overnight fasting or 30 min after intraperitoneal insulin injection. We assessed changes in GLUT4 translocation to the sarcolemma by cell fractionation and abundance of the proteins involved in GLUT4 translocation by Western blot. Results: Male rats consuming S and A+S gained more weight than control and Atreated animals. Rats consuming S, A, and A+S developed insulin resistance assessed through ITT. Neither treatments nor insulin stimulation in the quadriceps produced changes in GLUT4 levels in the sarcolemma and Akt phosphorylation. Conversely, A and A+S decreased protein expression of Tether containing UBX domain for GLUT4 (TUG), and A alone increased calpain-10 expression. All treatments reduced this muscle's protein levels of VAMP2. Conversely, S and A treatment increased basal GLUT4 levels in the sarcolemma of the gastrocnemius, while all treatments inhibited insulin-induced GLUT4 translocation. These effects correlated with lower basal levels of TUG and impaired insulin-stimulated TUG proteolysis. Moreover, animals treated with S had reduced calpain-10 protein levels in this muscle, while A and A+S inhibited insulin-induced Akt phosphorylation. Conclusion: Arsenic and sucrose induce systemic insulin resistance due to defects in GLUT4 translocation induced by insulin. These defects depend on which muscle is being analyzed, in the quadriceps there were defects in GLUT4 retention and docking while in the gastrocnemius the Akt pathway was impacted by arsenic and the proteolytic pathway was impaired by arsenic and sucrose.

Deep DNA sequencing of MGMT, TP53 and AGT in Mexican astrocytoma patients identifies an excess of genetic variants in women and a predictive biomarker.

PURPOSE: Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53. Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients. METHODS: We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT, MGMT and TP53, and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort). RESULTS: In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival. CONCLUSIONS: The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study.

Eficacia y seguridad de antipsicóticos y antidepresivos en el tratamiento de la anorexia nerviosa: revisión sistemática / Efficacy and Safety of Antipsychotics and Antidepressants in the Treatment of Anorexia Nervosa: a Systematic Review

RESUMEN Introducción: Las recomendaciones de las guías vigentes están basadas en evidencia de baja calidad. Se requiere su actualización periódica considerando la evidencia reciente. Objetivo: Sintetizar la mejor evidencia clínica disponible sobre eficacia y seguridad de antidepresivos y antipsicóticos de segunda generación en pacientes con anorexia nerviosa. Métodos: Revisión sistemática (CRD42020150577). Se buscaron en PubMed, SCOPUS, Ovid(Cochrane), EMBASE y LILACS los ensayos clínicos aleatorizados realizados en pacientes con anorexia nerviosa que evaluasen el uso de antipsicóticos de segunda generación o antidepresivos orales a cualquier dosis y por cualquier tiempo en el tratamiento ambulatorio y/u hospitalario tomando como resultados el peso (índice de masa corporal), las entidades psicopatológicas y la seguridad. Resultados: Se incluyeron 5 estudios, 4 catalogados como con alto riesgo de sesgo. La evidencia indica que los pacientes que reciben tratamiento con olanzapina o fluoxetina tienden a mantenerse por más tiempo dentro de los programas de tratamiento. La olanzapina mostró resultados favorables (un estudio) en cuanto al aumento de peso, pero no mostró los mismos resultados en psicopatología, donde la evidencia es contradictoria. Conclusiones: En concordancia con las revisiones anteriores, nuestro trabajo permite concluir que hay información contradictoria sobre la eficacia de los psicofármacos para la anorexia nerviosa. El trabajo futuro debe enfocarse en desarrollar ensayos clínicos de alta calidad metodológica.

ABSTRACT Introduction: The recommendations of the current guidelines are based on low quality evidence. Periodic updating is required, taking recent evidence into consideration. Objective: To synthesise the best available clinical evidence on the efficacy and safety of second-generation antidepressants and antipsychotics in patients with anorexia nervosa. Methods: Systematic review (CRD42020150577). We searched PubMed, SCOPUS, Ovid(Cochrane), EMBASE and LILACS for randomised clinical trials performed in patients with anorexia nervosa that evaluated the use of second-generation antipsychotics or oral antidepressants, at any dose and for any length of time, in outpatient and/or hospital treatment, taking weight (body mass index), psychopathological entities and safety as results. Results: Five studies were included, with four assessed as having a high risk of bias. The evidence indicates that patients receiving treatment with olanzapine or fluoxetine tend to stay in treatment programmes for longer. Olanzapine showed favourable results (one study) in terms of weight gain, but did not show the same results in psychopathology, where the evidence is contradictory. Conclusions: In accordance with previous reviews, our work allows us to conclude that there is contradictory information on the efficacy of psychotropic drugs in the treatment of anorexia nervosa. Future work should focus on developing clinical trials of high methodological quality.

The potential role of COVID-19 in the induction of DNA damage.

The coronavirus disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is challenging global health and economic systems. In some individuals, COVID-19 can cause a wide array of symptoms, affecting several organs, such as the lungs, heart, bowels, kidneys and brain, causing multiorgan failure, sepsis and death. These effects are related in part to direct viral infection of these organs, immunological deregulation, a hypercoagulatory state and the potential for development of cytokine storm syndrome. Since the appearance of COVID-19 is recent, the long-term effects on the health of recovered patients remain unknown. In this review, we focused on current evidence of the mechanisms of DNA damage mediated by coronaviruses. Data supports that these viruses can induce DNA damage, genomic instability, and cell cycle deregulation during their replication in mammalian cells. Since the induction of DNA damage and aberrant DNA repair mechanisms are related to the development of chronic diseases such as cancer, diabetes, neurodegenerative disorders, and atherosclerosis, it will be important to address similar effects and outcomes in recovered COVID-19 patients.

Is Arsenic Exposure a Risk Factor for Metabolic Syndrome? A Review of the Potential Mechanisms.

Exposure to arsenic in drinking water is a worldwide health problem. This pollutant is associated with increased risk of developing chronic diseases, including metabolic diseases. Metabolic syndrome (MS) is a complex pathology that results from the interaction between environmental and genetic factors. This condition increases the risk of developing type 2 diabetes, cardiovascular diseases, and cancer. The MS includes at least three of the following signs, central obesity, impaired fasting glucose, insulin resistance, dyslipidemias, and hypertension. Here, we summarize the existing evidence of the multiple mechanisms triggered by arsenic to developing the cardinal signs of MS, showing that this pollutant could contribute to the multifactorial origin of this pathology.

Association between Apoε4 allele and cardiometabolic and social risk factors with cognitive impairment in elderly population from Bogota / Associação entre o alelo Apoε4 fatores de risco cardiometabólicos e sociais com prejuízo cognitivo em idosos de Bogotá

ABSTRACT Being an ϵ4 carrier in the Apoϵ gene has been suggested as a modifying factor for the interaction between cardio-metabolic, social risk factors, and the development of cognitive impairment. Objective: The main objective of this study was to assess the existence of such interaction in a sample of Bogota's elderly population. Methods: A cross-sectional study was conducted with 1,263 subjects older than 50 years. Each participant was diagnosed by consensus, after neuropsychological and neuropsychiatric evaluations, under a diagnosis of normal cognition, mild cognitive impairment (MCI) according to Petersen's criteria, or dementia according to DSM-IV criteria. Apoϵ was typified and an analysis of MoCA test was performed in each group carrying or not ϵ4 allele. Results: Our study showed that 75% were women with a median age of 68 years (interquartile range 62-74 years) and a median schooling for 6 years (interquartile range 4-12 years). Dementia was related to low education level of ≤5 years OR=11.20 (95%CI 4.99-25.12), high blood pressure (HBP) OR=1.45 (95%CI 1.03-2.05), and age over 70 years OR=7.68 (95%CI 3.49-16.90), independently of being or not an ϵ4 allele carrier. Diabetic subjects with dementia carrying ϵ4 allele showed a tendency to exhibit lower scores on the MoCA test, when compared with noncarriers' diabetic subjects with dementia. Conclusions: The presence of ϵ4 allele does not modify the relationship between cognitive impairment and the different cardio-metabolic and social risk factors, except in diabetic subjects ϵ4 carriers with dementia who showed a tendency to exhibit lower scores of the MoCA test, when compared with noncarriers' diabetic subjects with dementia.

RESUMO Ser um portador ϵ4 no gene Apoϵ tem sido sugerido como um fator modificador da interação entre fatores cardiometabólicos, de risco social e o desenvolvimento de comprometimento cognitivo. Objetivo: O objetivo principal deste trabalho é avaliar a existência de tal interação em uma amostra da população idosa de Bogotá. Métodos: Um estudo transversal foi realizado com 1.263 indivíduos com mais de 50 anos. Cada participante foi diagnosticado por consenso após avaliações neuropsicológicas e neuropsiquiátricas, sob um diagnóstico de cognição normal, comprometimento cognitivo leve de acordo com os critérios de Petersen ou demência de acordo com os critérios do Manual Diagnóstico e Estatístico de Trastornos Mentais (DSM-IV). Apoϵ4 foi tipificada e uma análise do Montréal Cognitive Assessment Test (teste de MoCA) foi realizada em cada grupo portador ou não do alelo ϵ4. Resultados: Nosso estudo mostrou que 75% eram mulheres com idade mediana de 68 anos (intervalo interquartil 62 a 74 anos) e escolaridade mediana de seis anos (intervalo interquartil 4 a 12 anos). A demência estava relacionada ao baixo nível de escolaridade ≤5 anos Odds Ratio (OR)=11,20 (intervalo de confiança — IC95% 4,99-25,12), pressão alta OR=1,45 (IC95% 1,03-2,05) e idade acima de 70 anos OR=7,68 (IC95% 3,49-16,90), independentemente de ser ou não portador do alelo ϵ4. Indivíduos diabéticos com demência portadores do alelo ϵ4 mostraram tendência de exibir pontuações mais baixas no teste MoCA quando comparados com indivíduos diabéticos com demência não portadores do alelo ϵ4. Conclusões: A presença do alelo ϵ4 não modifica a relação entre o comprometimento cognitivo e os diferentes fatores de risco cardiometabólico e social, exceto em diabéticos portadores de ϵ4 com demência, que exibiram tendência a apresentar menores escores no teste MoCA quando comparados com indivíduos diabéticos com demência não portadores do alelo ϵ4.

Arsenic-protein interactions as a mechanism of arsenic toxicity.

Millions of people worldwide are exposed to arsenic, a metalloid listed as one of the top chemical pollutants of concern to human health. Epidemiological and experimental studies link arsenic exposure to the development of cancer and other diseases. Several mechanisms have been proposed to explain the effects induced by arsenic. Notably, arsenic and its metabolites interact with proteins by direct binding to individual cysteine residues, cysteine clusters, zinc finger motifs, and RING finger domains. Consequently, arsenic interactions with proteins disrupt the functions of proteins and may lead to the development and progression of diseases. In this review, we focus on current evidence in the literature that implicates the interaction of arsenic with proteins as a mechanism of arsenic toxicity. Data show that arsenic-protein interactions affect multiple cellular processes and alter epigenetic regulation, cause endocrine disruption, inhibit DNA damage repair mechanisms, and deregulate gene expression, among other adverse effects.

Modification of Proliferation and Apoptosis in Breast Cancer Cells by Exposure of Antioxidant Nanoparticles Due to Modulation of the Cellular Redox State Induced by Doxorubicin Exposure.

In this report, we investigated whether the use of chitosan-carrying-glutathione nanoparticles (CH-GSH NPs) can modify proliferation and apoptosis, and reduce cell damage induced by doxorubicin on breast cancer cells. Doxorubicin is a widely used antineoplasic agent for the treatment of various types of cancer. However, it is also a highly toxic drug because it induces oxidative stress. Thus, the use of antioxidant molecules has been considered to reduce the toxicity of doxorubicin. CH-GSH NPs were characterized in size, zeta potential, concentration, and shape. When breast cancer cells were treated with CH-GSH nanoparticles, they were localized in the cellular cytoplasm. Combined doxorubicin exposure with nanoparticles increased intracellular GSH levels. At the same time, decreasing levels of reactive oxygen species and malondialdehyde were observed and modified antioxidant enzyme activity. Levels of the Ki67 protein were evaluated as a marker of cell proliferation and the activity of the Casp-3 protein related to cell apoptosis was measured. Our data suggests that CH-GSH NPs can modify cell proliferation by decreasing Ki67 levels, induce apoptosis by increasing caspase-3 activity, and reduce the oxidative stress induced by doxorubicin in breast cancer cells by modulating molecules associated with the cellular redox state. CH-GSH NPs could be used to reduce the toxic effects of this antineoplastic. Considering these results, CH-GSH NPs represent a novel delivery system offering new opportunities in pharmacy, material science, and biomedicine.

Prenatal Particulate Matter (PM) Exposure and Natriuretic Peptides in Newborns from Mexico City.

(1) Background: The aim of this study was to assess associations between particulate matter (PM) exposure and natriuretic peptide concentrations in cord blood from newborns. (2) Methods: we conducted a cross-sectional study in Mexico City with 101 pregnant women from CIMIGEN Hospital. Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were measured in plasma from cord blood in 51 newborns by ELISA. We estimated PM exposure (PM2.5 and PM10) at first, second and third trimester of pregnancy. (3) Results: The median and interquartile range for ANP, BNP and CNP plasma concentrations were 66.71 (46.92-80.23), 98.23 (73.64-112.30) and 1129.11 (944.10-1452.02) pg/mL, respectively. PM2.5 and PM10 levels for the whole pregnancy period were 22.2 µg/m3 and 41.63 µg/m3, respectively. Employing multivariable linear regression models adjusted for maternal age, newborn sex, smoking before pregnancy, maternal occupation and newborns' length and height, we observed a 2.47 pg/mL (95%CI: -4.67, -0.27) decrease in BNP associated with PM2.5 exposure during second trimester. Adjusted for the same set of confounders, third trimester PM10 exposure was inversely associated with ANP concentrations (beta estimate: -0.90; 95% CI: -1.80, -0.03). Neither PM10 nor PM2.5 were associated with CNP at any trimester of pregnancy. (4) Conclusions: Prenatal exposure to particulate matter was associated with ANP and BNP decrease in newborns.

Ability of low contents of biosorbents to bind the food carcinogen aflatoxin B1in vitro.

In vitro experiments were conducted to evaluate the effectiveness of two new biosorbents (lettuce and field horsetail) in removing aflatoxin B1 (AFB1). Formosa firethorn was used as reference material. The adsorption of AFB1 (190 ng/mL) was investigated at two sorbent contents (0.5% and 0.1% w/v) and three pHs (2, 5, and 7). Batch experiments were performed at 40 °C for 2 h. Several methodologies were used to characterize the nature of the biosorbent-AFB1 interaction. In general, when using biosorbents at 0.5% w/v, AFB1 was well adsorbed by the three tested biomaterials (70 to 100%). Furthermore, with the lowest biosorbent content (0.1% w/v), significant AFB1 adsorption efficiencies were attained at pH 5 (33 to 50%). Nevertheless, at pH 7, lettuce showed the highest ability against AFB1 removal (95%). Further characterization of the AFB1-loaded biosorbents demonstrated that chemical and physical mechanisms were involved in the adsorption process.

Mifepristone Overcomes Tumor Resistance to Temozolomide Associated with DNA Damage Repair and Apoptosis in an Orthotopic Model of Glioblastoma.

The standard treatment for glioblastoma multiforme (GBM) is surgery followed by chemo/radiotherapy. A major limitation on patient improvement is the high resistance of tumors to drug treatment, likely responsible for their subsequent recurrence and rapid progression. Therefore, alternatives to the standard therapy are necessary. The aim of the present study was to evaluate whether mifepristone, an antihormonal agent, has a synergistic effect with temozolomide (used in standard therapy for gliomas). Whereas the mechanism of temozolomide involves damage to tumor DNA leading to apoptosis, tumor resistance is associated with DNA damage repair through the O6-methylguanine-DNA-methyltransferase (MGMT) enzyme. Temozolomide/mifepristone treatment, herein examined in Wistar rats after orthotopically implanting C6 glioma cells, markedly reduced proliferation. This was evidenced by a decreased level of the following parameters: a proliferation marker (Ki-67), a tumor growth marker (18F-fluorothymidine uptake, determined by PET/CT images), and the MGMT enzyme. Increased apoptosis was detected by the relative expression of related proteins, (e.g. Bcl-2 (B-cell lymphoma 2), Bax (bcl-2-like protein 4) and caspase-3). Thus, greater apoptosis of tumor cells caused by their diminished capacity to repair DNA probably contributed significantly to the enhanced activity of temozolomide. The results suggest that mifepristone could possibly act as a chemo-sensitizing agent for temozolomide during chemotherapy for GBM.

TNF promoter polymorphisms are associated with genetic susceptibility in COPD secondary to tobacco smoking and biomass burning.

Background: Smoking and smoke from biomass burning (BB) are the main environmental risk factors for COPD. Clinical differences have been described between COPD related to smoking and related to wood smoke, but no studies have shown genetic differences between patients exposed to these two risk factors. Methods: To investigate a possible association of tumor necrosis factor (TNF) promoter polymorphisms, we conducted a case-control study. A total of 1,322 subjects were included in four groups: patients with a diagnosis of COPD secondary to smoking (COPD-S, n=384), patients with COPD secondary to biomass burning (COPD-BB, n=168), smokers without COPD (SWOC, n=674), and biomass burning-exposed subjects (BBES n=96). Additionally, a group of 950 Mexican mestizos (MMs) was included as a population control. Three single nucleotide polymorphisms (SNPs) were selected in the TNF gene (rs1800629, rs361525, and rs1800750) and one SNP in the lymphotoxin alpha gene (rs909253). Results: Statistically significant differences were found with genotype GA of the rs1800629: COPD-S vs SWOC, (p<0.001, odds ratio [OR] =2.55, 95% CI=1.53-4.27); COPD-S vs COPD-BB (p,0.01). When performing the comparison of the less severe (G1: I + II) and the more severe (G2: III + IV) levels, differences were identified in G1 (p<0.05, OR=1.94, 95% CI=1.04-3.63) and G2 (p<0.001, OR=3.68, 95% CI=1.94-3.07) compared with SWOC. Regarding genotype GA of rs361525, it has been associated when comparing COPD-BB vs BBES (p=0.0079, OR=5.99, 95% CI=1.38-53.98). Conclusion: The heterozygous genotype GA of polymorphisms rs1800629 and rs361525 in the TNF promoter are associated with the risk of COPD.

Contabilidad, validez de criterio y discriminante del Montreal Cognitive Assessment (MoCA) test, en un grupo de adultos de Bogotá / Reliability, criterion and discriminant validity of the Montreal Cognitive Assessment Test (MoCA) in a group of adults from Bogotá

Resumen Introducción: el MoCA-test es un instrumento breve de tamizaje, sensible y específico, utilizado para la detección del deterioro cognitivo leve (DCL) y la demencia, con puntos de corte que varían según la población estudiada. Objetivo: evaluar la confiabilidad y validez discriminante del MoCA-test, en un grupo de adultos de Bogotá, con diferentes escolaridades. Material y Métodos: se aplicó el MoCA-test y el MMSE, a 1174 adultos mayores de 50 años de diferentes localidades de Bogotá. Los sujetos con MoCA-test < 26 y MMSE <24, fueron citados a una segunda evaluación aplicándoseles un protocolo amplio y fueron analizados por consenso, para determinar normalidad o deterioro cognitivo. Se determinó la consistencia interna (con coeficiente alpha de Cronbach), confiabilidad test-retest (con coeficiente de Lin), la validez de criterio (con coeficiente de Spearman) y validez discriminante (por medio de curvas ROC) del MoCA-Test. Resultados: la consistencia interna (alfa-Cronbach=0.851) y la confiabilidad test-retest (Lin=0.62) fueron aceptables. La validez de criterio respecto al MMSE, fue moderada (r=0.65). El MoCA mostró capacidad para discriminar entre diferentes grupos diagnósticos y sociodemográficos. El área bajo la curva fue 0.76 para DCL y 0,81 para demencia; el punto de corte para discriminar entre normalidad y DCL en el grupo en general fue 20/21 y entre DCL y demencia 17/18. Estos puntos variaron con el grado de escolaridad. Conclusión: el MoCA-test puede ser el instrumento de tamización en atención primaria, para detectar deterioro cognitivo en nuestra población adulta, considerando los puntos de corte propuestos según la escolaridad. (Acta Med Colomb 2016; 40: 221-228).

Abstract Introduction: the MoCA-Test is a brief, sensitive and specific screening tool used to detect mild cognitive impairment (MCI) and dementia, with cut-off points that vary according to the population studied. Objective: to evaluate the reliability and discriminant validity of the MoCA-test, in a group of adults from Bogotá, with different levels of schooling. Material and Methods: the MoCA-test and the MMSE were applied to 1174 adults over 50 years old from different locations in Bogotá. Subjects with MoCA-test <26 and MMSE <24, were referred to a second evaluation by applying a broad protocol and were analyzed by consensus, to determine normality or cognitive impairment. Internal consistency (with Cronbach's alpha coefficient), test-retest reliability (with Lin coefficient), criterion validity (with Spearman's coefficient) and discriminant validity (using ROC curves) of the MoCA-Test were determined. Results: internal consistency (alpha-Cronbach = 0.851) and test-retest reliability (Lin = 0.62) were acceptable. The criterion validity with respect to MMSE was moderate (r = 0.65). The MoCA-test showed the capacity to discriminate between different diagnostic and sociodemographic groups. The area under the curve was 0.76 for MCI and 0.81 for dementia; the cutoff point for discriminating between normality and MCI in the group in general was 20/21 and between MCI and dementia 17/18. These points varied with the level of schooling. Conclusion: the MoCA-test can be the screening tool in primary care in order to detect cognitive impairment in our adult population, considering the proposed cutoff points according to schooling. (Acta Med Colomb 2016; 40: 221-228).

Role of the inflammatory response in the hemorrhagic syndrome induced by the hemolymph of the caterpillar Lonomia achelous.

INTRODUCTION: Contact with the caterpillar of Lonomia achelous causes a hemorrhagic syndrome in humans prompted by two processes, an initial mild DIC that is later masked by overwhelming fibrinolytic activity. Although the venom affects both the hemostatic and inflammatory systems separately, it is not clear whether the hematological and hemostatic disturbances may in part be due to an indirect effect via inflammatory mediators. Here we report results on the crosstalk between these systems, particularly the effect of the pro-inflammatory cytokine TNF-α on hemostatic parameters. MATERIALS AND METHODS: the nitric oxide and TNF-α responses, as well as activation of the coagulation and fibrinolytic systems, were measured in macrophages and endothelial cells treated with Lonomia achelous hemolymph (LAH). The same responses were then determined, in a mouse model of LAH envenomation, after treatment with an anti-TNF-α antibody. RESULTS: Both macrophages and endothelial cells responded strongly to LAH in terms of pro-inflammatory mediator release and fibrinolytic activities as well as pro-coagulant activity (TF activity) in endothelial cells. Treatment with antibody against TNF-α decreased both TNF-α and NO3-/NO2- serum levels in the mice, after LAH injection. Blocking TNF-α also modified significantly the serum levels of plasminogen, fibrinogen and FXIII in mice, as well as decreased TF activity in endothelial cells. CONCLUSIONS: LAH may induce a hemostatic effect through endothelial and macrophage activation. These activated cell release hemostatic enzymes as well as pro-inflammatory mediators, principally TNF-α, that potentiate this release in an autocrine fashion, amplifying the fibrinolytic effect, which may in turn exacerbate the hemorrhagic manifestations. As far as we are aware, this is the first report of the relationship between the hemostatic system and the inflammatory responses in a hemorrhagic syndrome induce by animal secretions.

Deterioro cognitivo y factores de riesgo cardiovascular y metabólico en una muestra de adultos de Bogotá / Cardiovascular and metabolic risk factors, for cognitive impairment in adults from Bogotá

Introducción: la relación entre los factores de riesgo cardiovascular (FRCV) y los factores metabólicos con deterioro cognitivo (DC), definido como deterioro cognitivo leve (DCL) o demencia, es controversial. Objetivo: describir los FRCV y metabólicos relacionados con DC, en una muestra de adultos de Bogotá. Material y métodos: se diseñó un estudio de corte transversal y se evaluó el estado cognitivo en dos fases, en adultos mayores de 50 años, autónomos, no institucionalizados, aplicando pruebas neuropsicológicas y un protocolo de evaluación neuropsiquiátrica. Los FRCV y metabólicos fueron documentados por autoreporte, y se tomaron medidas antropométricas. Resultados: en 1.045 adultos estudiados, el promedio de edad fue de 68 años (DS 8.6), y de educación 8 años (DS 6.0), 76 % fueron mujeres, 56 % presentaba hipertensión arterial (HTA), 40 % dislipidemia, 37 % fueron fumadores, 37 % tenían sobrepeso, 28 % hipotiroidismo, 25 % obesidad, 17 % consumían alcohol y 16 % eran diabéticos. El DCL se asoció con escolaridad de primaria-incompleta OR:1.94 (95 % IC: 1.21- 3.14), primaria-completa OR:1.96 (95 % IC: 1.18- 3.25), bachillerato- incompleto OR:3.01 (95 % IC: 1.80-5.05), bachillerato-completo OR: 2.54 (95 % IC: 1.45- 4.45) y con edad entre 70 y 79 años OR:2.06 (95% IC: 1.32-3.23). La demencia se asoció con escolaridades de primaria-incompleta OR: 11.20 (95 % IC: 4.99- 25.12), primaria-completa OR: 7.91 (95 % IC: 3.44-18.16), bachillerato- incompleto OR: 2.87 (95 % IC: 1.17- 7.01) y con edades entre 70 -79 años OR: 2.82. (95 % IC: 1.37-5.80), o mayores de 80 años OR: 7.68 (95 % IC: 3.49- 16.90) y con sufrir HTA OR: 1.45 (95 % IC: 1.03-2.05). Conclusión: la baja escolaridad, una edad avanzada y sufrir HTA son en su orden los factores más importantes para el desarrollo de la demencia. Los adultos entre 70 y 79 años con bachillerato incompleto, tienen mayor riesgo de DCL.

Introduction: The relationship between some metabolic and cardiovascular risk factors (CVRF) and cognitive impairment (CI) defined as mild cognitive impairment (MCI) and dementia, is controversial. Objective: Describe the cardiovascular and metabolic risk factors that are associated with cognitive impairment in adults from Bogotá. Materials and methods: A cross-sectional study, where the state of cognitive functions (normal, MCI or dementia) was evaluated in two phases, in adults older than 50 years, autonomous, non-institutionalized, using neuropsychological tests and neuropsychiatric protocol. Its cardiovascular and metabolic risk by self-reported history and standardized anthropometric measurements were documented. Results: Of 1045 adults surveyed, the mean age of the group was 68 years(SD 8.6), and the mean education level was 8 years(SD 6.0), 76% were women, 56% had hypertension(HT), 40% dyslipidemia, 37% were smokers, 36% were overweight, 28% presented hypothyroidism, 25% were obese, 17% drank alcohol and 16% were diabetic. MCI was associated with incomplete high school education OR:3.01(95% CI 1.80-5.05) and aged between 70 and 79 years OR:2.06(95%CI 1.32-3.23). Dementia was associated with lower scholarity, incomplete-primary OR:11.20(95%CI 4.99-25.12), complete-primary OR 7.91(95% CI.3.44-18.16), incomplete-high school OR: 2.87(95% CI 1.17-7.01), age over 80 years OR:7.68(95%CI 3.49-16.90); and suffer hypertension OR:1.45(95%CI 1.03- 2.05) Conclusion: Low education, older age and hypertension are in order, the most important risk factors for the development of dementia in our population. Adults between 70 and 79 with incomplete high school have higher risk of MCI.

Acuerdo intra-interobservador en las pruebas Minimental State Examination (MMSE) y Montreal Cognitive Assessment (MoCA test) aplicados por personal en entrenamiento / Intra and interrater reliability of the Minimental State Exmination (MMSE) and Montréal Cognitive Assessment (MoCA test) applied by health personnel in training

Introducción: en el proceso del diagnóstico neuropsicológico, los instrumentos de tamizaje cognitivo, son una herramienta útil en la identificación de cambios mentales del sujeto, en momentos puntuales o a través del tiempo. Su uso se fundamenta en el análisis psicométrico. Objetivo: determinar el acuerdo inter e intra-observador en el MoCA test y el MMSE, aplicado por profesores y estudiantes en procesos de entrenamiento de tamización cognitiva. Materiales y métodos: a los estudiantes y profesores en entrenamiento en la puntuación del MoCA test y el MMSE, se les presentó un video en dos sesiones, con un intervalo de 5 meses, mostrando el desempeño de dos adultos mayores, respondiendo el MoCA test y el MMSE, previo consentimiento informado. Se compararon los puntajes dados en las dos sesiones por los sujetos en entrenamiento, con los de ellos mismos (intra-observador), usando el coeficiente de concordancia y correlación de Lin(rho) y con los del grupo restante (inter-observador) usando el coeficiente de correlación intra-clase (ICC). Resultados: participaron 46 evaluadores. Se encontró alta confiabilidad inter-observador para el MoCA (ICC=0.86), pero baja para el MMSE (ICC=0.24) y baja confiabilidad intra-observador tanto para el MoCA (rho paciente 1=0.012 y rho paciente 2=0.152) como para el MMSE (rho paciente 1=0.008 y rho paciente 2=0.012). Aunque los puntajes difirieron, las clasificaciones diagnósticas realizadas por los evaluadores fueron similares a las del patrón de oro. Conclusión: la correcta aplicación del test, requiere varios entrenamientos, y aunque hubo pocas diferencias entre los puntajes, los errores cuando se está cerca del punto de corte propuesto, aumentan el riesgo de sesgo.

Introduction: The instruments for screening cognitive functions, applied to subjects in clinical settings and research, are useful for determining if this person has any trouble in cognition or show changes in the time. The usefulness of these instruments is defined with the evaluation of their psychometrics properties. Objective: This study allows to determine the intra and inter-observer agreement, when the MoCA test and MMSE were applied by a group in training process Materials and methods: The study group who attended two training sessions, with an interval of 5 months, scored the MoCA test and MMSE, from two patients which were filmed responding the tests, previous informed consent signature. We compared how close were the scores of participants among themselves by concordance correlation coefficient of Lin (rho) and with those given from the others by intra-class correlation coefficients (ICC). Results: In total, 46 participants were included. Intra-rater reliability was high for MoCA test (ICC = 0.86), but it was poor for MMSE (ICC=0.24). Inter-rater was poor for MoCA test (rho patient 1= 0.012, rho patient 2= 0.152) and MMSE (rho patient 1 = 0.008, rho patient 2 = 0.012). Although the scores between participants and gold standard were different, the diagnoses were similar. Conclusion:The correct scoring of the test, requires several trainings to clinical and research groups, and although they can be found few differences between scores applied by non-expert personnel, if the scores mistakenly given, are close to the cut-of point proposed for each test, the bias increases.

Prueba piloto para la elaboración perfil epidemiológico de discapacidad en el municipio de Madrid (Cundinamarca) / Pilot test for the development of the health profile of disability in the Madrid Municipality (Cundinamarca) / Prova piloto para a elaboração do perfil epidemiológico de deficiência no município de Madrid (Cundinamarca)

A pesar de los esfuerzos para implementar estrategias que permitan determinar la frecuencia de discapacidad en Colombia, aún persisten problemáticas metodológicas y de recolección de la información. Lo anterior implica una necesidad creciente de implementar sistemas de vigilancia en salud pública en los que la discapacidad sea considerada como una condición de interés. En alianza con el Centro Ambulatorio Gustavo Escallón Cayzedo-Madrid Fundación Santa Fe de Bogotá (Cagec) y la Secretaría de Desarrollo Social del municipio de Madrid (Cundinamarca), se diseñó una guía metodológica y una ficha de recolección de información para la población con discapacidad, bajo los lineamientos de la Clasificación Internacional del Funcionamiento, de la Discapacidad y la Salud (CIF). Objetivo: Implementar una prueba piloto que permita fijar los criterios necesarios para la definición del perfil epidemiológico de discapacidad en el municipio de Madrid, Cundinamarca. Materiales y métodos: Se realizó un estudio descriptivo, articulado al proyecto de investigación Identificación de los factores relacionados con la inclusión social de las personas con discapacidad del municipio de Madrid (Cundinamarca), que permitió establecer los criterios para el uso de la ficha epidemiológica diseñada por el grupo investigador con el fin de determinar las características del perfil epidemiológico de discapacidad en el municipio. Resultados: 57 personas con discapacidad que asistieron a los servicios de rehabilitación del Cagecy de los programas sociales de la Secretaría de Desarrollo Social del municipio de Madrid, Cundinamarca, fueron vinculadas al estudio. Las variables que permiten describir el perfil epidemiológico de discapacidad incluyen la edad [promedio 39,9; desviación estándar (DE)13,9], escolaridad, empleo y estrato socioeconómico (entre 1 y 3). Conclusiones: A partir de los resultados del estudio, se evidencia la necesidad de implementar metodologías rigurosas para el registro y análisis de la información relacionada con discapacidad. La guía y el instrumento para la recolección de datos se ajustan a las consideraciones de la Organización Mundial de la Salud. Se requieren investigaciones adicionales para garantizar validez externa y representatividad desde perspectivas poblacionales.

Despite the efforts to implement strategies that allow to determine the frequency of disability in Colombia, still persists methodological issues and collection of information. The previous, involves an increasing need to implement systems of surveillance in public health in which disability is considered a condition of interest. In alliance with the Ambulatory Center Gustavo Escallón Cayzedo of the Foundation Santa Fe de Bogotá and the Office of Social Development of the municipality of Madrid (Cundinamarca), a methodological guide and an index card of collection of information for the population with disability were designed, under the contours of the International Classification of the Functioning, Disability and Health (ICF). Objective: To implement a pilot that will defined the necessary criteria for the definition of the epidemiological profile of disability in the municipality of Madrid, Cundinamarca. Materials and methods: a descriptive study was conducted, articulated to the project of investigation identification of the factors related with the social inclusion of the people with disability of the municipality of Madrid (Cundinamarca). This study allowed to establish the criteria for the use of the index epidemiological card designed by the researcher group with the goal to determine the characteristics of the epidemiological profile of disability in the municipality. Results: 57 people with disability that assisted to the services of rehabilitation of the Foundation Santa Fe de Bogotá and of the social programs of the Office of Social Development of the municipality of Madrid, Cundinamarca, were linked to the study. The variables that allow to describe the epidemiological profile of disability include: the age (average 39,9 S.D.13,9), schooling, employment and socioeconomic stratum (between 1 and 3). Conclusions: From the results of the study, it is evident the need to implement rigorous methodologies for the registration and analysis of the information related with disability. The guide and the instrument for the recollection of data is adjusted to the considerations of the World Health Organization. Further investigations are required to guarantee external validity and representativeness from populational perspectives.

A pesar dos esforços para implementar estratégias que permitam determinar a frequência de deficiência na Colômbia, ainda persistem problemáticas metodológicas e de recoleção da informação. O anterior implica uma necessidade crescente de implementar sistemas de vigilância em saúde pública nos que a deficiência seja considerada como uma condição de interesse. Em aliança com o Centro Ambulatório Gustavo Escallón Cayzedo (Madrid) Fundação Santa Fe de Bogotá (CAGEC) e a Secretaria de Desenvolvimento Social do município de Madrid (Cundinamarca), criou-se uma guia metodológica e uma ficha de recoleção de informação para a população com deficiência, sob os lineamentos da Classificação Internacional do Funcionamento da Deficiência e a Saúde (CIF). Objetivo: implementar uma prova piloto que permita definir os critérios necessários para a definição do perfil epidemiológico de deficiência no município de Madrid, Cundinamarca. Materiais e métodos: realizou-se um estudo descritivo, articulado ao projeto de pesquisa "Identificação dos fatores relacionados com a inclusão social das pessoas com deficiência do município de Madrid (Cundinamarca)", que permitiu estabelecer os critérios para o uso da ficha epidemiológica criada por o grupo pesquisador com o fim de determinar as características do perfil epidemiológico de deficiência no município. Resultados: 57 pessoas com deficiência que assistiram aos serviços de reabilitação do cagec e dos programas sociais da Secretaria de Desenvolvimento Social do município de Madrid, Cundinamarca, foram vinculadas ao estudo. As variáveis que permitem descrever o perfil epidemiológico de deficiência incluem a idade (média de 39,9 D.E.13, 9), escolaridade, emprego e estrato socioeconómico (entre 1 e 3). Conclusões: A partir dos resultados do estudo, evidencia-se a necessidade de implementar metodologias rigorosas para o registro e análise da informação relacionada com a deficiência. A guia e o instrumento para a recoleção de dados ajustam-se às considerações da Organização Mundial da Saúde. Requerem-se pesquisas adicionais para garantir validez externa e representatividade desde perspectivas populacionais.

Genotoxicity induced by Taenia solium and its reduction by immunization with calreticulin in a hamster model of taeniosis.

Genotoxicity induced by neurocysticercosis has been demonstrated in vitro and in vivo in humans. The adult stage of Taenia solium lodges in the small intestine and is the main risk factor to acquire neurocysticercosis, nevertheless its carcinogenic potential has not been evaluated. In this study, we determined the genotoxic effect of T. solium infection in the hamster model of taeniosis. In addition, we assessed the effect of oral immunization with recombinant T. solium calreticulin (rTsCRT) plus cholera toxin as adjuvant on micronuclei induction, as this protein has been shown to induce 33-44% protection in the hamster model of taeniosis. Blood samples were collected from the orbital venous plexus of noninfected and infected hamsters at different days postinfection, as well as from orally immunized animals, to evaluate the frequency of micronucleated reticulocytes as a measure of genotoxicity induced by parasite exposure and rTsCRT vaccination. Our results indicate that infection with T. solium caused time-dependent DNA damage in vivo and that rTsCRT immunization reduced the genotoxic damage induced by the presence of the tapeworms.

Immunological mechanisms involved in the protection against intestinal taeniosis elicited by oral immunization with Taenia solium calreticulin.

Oral immunization with functional recombinant Taenia solium calreticulin (rTsCRT) induces 37% reduction in tapeworm burden in the experimental model of intestinal taeniosis in hamsters. Furthermore, tapeworms recovered from vaccinated animals exhibit diminished length, being frequently found in more posterior parts of the small intestine. The aim of this study was to analyze the immunological mechanisms involved in protection in response to rTsCRT oral immunization. Hamsters were orally immunized with rTsCRT using cholera toxin (CT) as adjuvant, weekly for 4 weeks. Fifteen days after the last boost animals were challenged with four T. solium cysticerci. Reduction in the adult worm recovery and increased transcription of mRNA for IL-4 and IFN-γ in the mucosa of rTsCRT+CT immunized animals were observed. Immunization also induced goblet cell hyperplasia in the mucosa surrounding the implantation site of the parasite. Specific IgG and IgA antibodies in serum and fecal supernatants were detected after the second immunization, being more pronounced after challenge. Our data suggest that oral vaccination with rTsCRT+CT regulates a local expression of IL-4 and IFN-γ, stimulating secretion of IgA that, together with the increase of goblet cells and mucin production, could result in an unfavorable environment for T. solium promoting an impaired tapeworm development.