Identification of human intestinal parasites affecting an asymptomatic peri-urban Argentinian population using multi-parallel quantitative real-time polymerase chain reaction

Background: In resource-limited countries, stool microscopy is the diagnostic test of choice for intestinal parasites (soil-transmitted helminths and/or intestinal protozoa). However, sensitivity and specificity is low. Improved diagnosis of intestinal parasites is especially important for accurate measurements of prevalence and intensity of infections in endemic areas. Methods: The study was carried out in Orán, Argentina. A total of 99 stool samples from a local surveillance campaign were analyzed by concentration microscopy and McMaster egg counting technique compared to the analysis by multi-parallel quantitative real-time polymerase chain reaction (qPCR). This study compared the performance of qPCR assay and stool microscopy for 8 common intestinal parasites that infect humans including the helminths Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, and the protozoa Giardia lamblia, Cryptosporidium parvum/hominis, and Entamoeba histolytica, and investigated the prevalence of polyparasitism in an endemic area. Results: qPCR showed higher detection rates for all parasites as compared to stool microscopy except T. trichiura. Species-specific primers and probes were able to distinguish between A. duodenale (19.1 %) and N. americanus (36.4 %) infections. There were 48.6 % of subjects co-infected with both hookworms, and a significant increase in hookworm DNA for A. duodenale versus N. americanus (119.6 fg/μL: 0.63 fg/μL, P∈<∈0.001) respectively. qPCR outperformed microscopy by the largest margin in G. lamblia infections (63.6 % versus 8.1 %, P∈<∈0.05). Polyparasitism was detected more often by qPCR compared to microscopy (64.7 % versus 24.2 %, P∈<∈0.05). Conclusions: Multi-parallel qPCR is a quantitative molecular diagnostic method for common intestinal parasites in an endemic area that has improved diagnostic accuracy compared to stool microscopy. This first time use of multi-parallel qPCR in Argentina has demonstrated the high prevalence of intestinal parasites in a peri-urban area. These results will contribute to more accurate epidemiological survey, refined treatment strategies on a public scale, and better health outcomes in endemic settings.Fil: Cimino, Rubén Oscar. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jeun, Rebecca. Baylor College Of Medicine; Estados UnidosFil: Juarez, Marisa. Universidad Nacional de Salta; ArgentinaFil: Cajal, Pamela S.. Universidad Nacional de Salta; ArgentinaFil: Vargas Flores, Paola Andrea. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Echazú, Adriana. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bryan, Patricia E.. Baylor College Of Medicine; Estados UnidosFil: Nasser, Julio Rubén. Universidad Nacional de Salta; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mejia, Rojelio. Baylor College Of Medicine; Estados Unidos. Universidad Nacional de Salta; Argentin

Effect of Poor Access to Water and Sanitation As Risk Factors for Soil-Transmitted Helminth Infection: Selectiveness by the Infective Route

Background: Soil-transmitted helminth (STH) infections are a public health problem in resource-limited settings worldwide. Chronic STH infection impairs optimum learning and productivity, contributing to the perpetuation of the poverty-disease cycle. Regular massive drug administration (MDA) is the cardinal recommendation for its control; along with water, sanitation and hygiene (WASH) interventions. The impact of joint WASH interventions on STH infections has been reported; studies on the independent effect of WASH components are needed to contribute with the improvement of current recommendations for the control of STH. The aim of this study is to assess the association of lacking access to water and sanitation with STH infections, taking into account the differences in route of infection among species and the availability of adequate water and sanitation at home. Methods and Findings: Cross-sectional study, conducted in Salta province, Argentina. During a deworming program that enrolled 6957 individuals; 771 were randomly selected for stool/serum sampling for parasitological and serological diagnosis of STH. Bivariate stratified analysis was performed to explore significant correlations between risk factors and STH infections grouped by mechanism of entry as skin-penetrators (hookworms and Strongyloides stercoralis) vs. orally-ingested (Ascaris lumbricoides and Trichuris trichiura). After controlling for potential confounders, unimproved sanitation was significantly associated with increased odds of infection of skin-penetrators (adjusted odds ratio [aOR] = 3.9; 95% CI: 2.6–5.9). Unimproved drinking water was significantly associated with increased odds of infection of orally-ingested (aOR = 2.2; 95% CI: 1.3–3.7). Conclusions: Lack of safe water and proper sanitation pose a risk of STH infections that is distinct according to the route of entry to the human host used by each of the STH species. Interventions aimed to improve water and sanitation access should be highlighted in the recommendations for the control of STH.Fil: Echazú, Adriana. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bonanno, Daniela. Ministerio de Salud de la Nación. Dirección Nacional de Prevención de Enfermedades y Riesgos; ArgentinaFil: Juarez, Marisa. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Fundación Mundo Sano; ArgentinaFil: Cajal, Silvana P.. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; ArgentinaFil: Heredia, Viviana. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Caropresi, Silvia. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Cimino, Rubén Oscar. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caro, Nicolas. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; ArgentinaFil: Vargas Flores, Paola Andrea. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paredes, Gladys. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Estudio del impacto de la adopción de la NIIF 1 sobre los estados financieros la empresa MELKARTH Agentes Aduaneros, Pueblo Libre - 2019

El estudio se ha centrado en determinar la influencia de la adopción de la NIIF N°1 sobre los estados financieros de la empresa MELKARTH Agentes Aduaneros, ubicada en Pueblo Libre, 2019; para lo cual se enmarcó metodológicamente en una investigación con enfoque cuantitativo, de tipo básica y correlacional y con diseño no experimental de corte transversal. Aplicando un cuestionario como instrumento de recolección de información a un total de veintiún contadores participantes. Concluyendo que adoptar las NIIF N°1 dentro del manejo contable de las empresas dedicadas al rubro aduanero de Pueblo Libre influye positiva y significativamente sobre los estados financieros que presentan a los usuarios ratificado a través de p(sig) .000 y un coeficiente de correlación de .726. asimismo, se pudo precisar que la adopción de la NIIF N°1 influye positiva y significativamente sobre la información financiera y sobre las decisiones financieras básicas de dichas entidades, comprobado a través del p(sig) .000 para cada uno y un coeficiente de correlación .701 y .705 respectivamente.The study has focused on determining the influence of the adoption of IFRS No. 1 on the financial statements of companies MELKARTH, located in Pueblo Libre, 2019; For which it was methodologically framed in a research with a quantitative approach, of a basic and correlational type and with a non-experimental cross-sectional design. Applying a questionnaire as an instrument for collecting information to a total of twenty-one participating accountants. Concluding that adopting IFRS No. 1 within the accounting management of the companies dedicated to the customs area of Pueblo Libre has a positive and significant influence on the financial statements presented to users ratified through p (sig) .000 and a correlation coefficient of .726. Likewise, it was possible to specify that the adoption of IFRS No. 1 positively and significantly influences the financial information and the basic financial decisions of said entities, verified through the p (sig) .000 for each one and a correlation coefficient .701 and .705 respectively

Founder mutation in Lynch syndrome

El síndrome de Lynch es la más frecuente de las neoplasias colorrectales hereditarias. Se origina por mutaciones germinales deletéreas familia-específicas en los genes que codifican proteínas de reparación del ADN: MLH1 (homólogo humano de mutL), MSH2 y MSH6 (homólogo humano de mutS 2 y 6, respectivamente), PMS2 (homólogo humano de PMS1 2) y MUTYH (homólogo humano de la ADN-glycosilasa mutY). La mutación c.2252_2253delAA, p.Lys751Serfs*3 en el exón 19 del gen MLH1 segrega con un haplotipo descripto en la región norte de Italia y cuyo origen fue atribuido a un efecto fundador. Esta mutación co-segrega con características típicas del síndrome de Lynch, incluyendo afectación temprana y múltiples tumores primarios en el mismo individuo, una alta frecuencia de cáncer pancreático, elevada inestabilidad microsatelital y falta de expresión de PMS2. En el presente trabajo se comunica dicha mutación en una paciente argentina con adenocarcinoma endometroide de útero en cuya historia familiar existen antecedentes de cáncer de colon diagnosticado antes de los 50 años en familiares de primer grado, reuniendo los criterios de Ámsterdam I y síndrome de Lynch II. Los polimorfismos presentes en la paciente coinciden con el haplotipo descripto en una región del norte de Italia. El alto grado de patogenicidad asociada a esta mutación hace imprescindible el estudio de todos los integrantes de las familias con cáncer hereditario permitiendo el diagnóstico genético pre-sintomático, la instauración de tratamientos o conductas preventivas y su seguimientoLynch syndrome is the most frequent syndrome in hereditary colorectal cancer, a family-specific deleterious mutations in genes encoding DNA reparation proteins: MLH1 (mutL homolog 1), MSH2, MSH6 (mutS homolog 2 y 6, respectively), PMS2 (PMS1 homolog 2, mismatch repair system component) y MUTYH (mutY DNA glycosylase). The c.2252_2253delAA, p.Lys751Serfs*3 mutation in MLH1 gene segregates with a haplotype reported in the northern region of Italy and whose origin was attributed to a founder effect. This mutation co-segregates with typical characteristics of Lynch syndrome, including early age at onset and multiple primary tumors in the same individual, a high frequency of pancreatic cancer, high microsatellite instability and lack of PMS2 expression. This report describes a mutation in an Argentinian patient with endometrioid adenocarcinoma of uterus. Her first-degree relatives had a history of colon cancer diagnosed before 50 years, fulfilling the Amsterdam Criteria I and Lynch syndrome II. The high pathogenicity associated to this mutation makes necessary the study of all members from families with hereditary cancer, allowing pre-symptomatic genetic diagnosis, early assessment and the instauration of preventive treatments.Fil: Cajal, Andrea. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Piñero, Tamara Alejandra. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Verzura, Alicia. Hospital Italiano; ArgentinaFil: Santino, Juan Pablo. Hospital Italiano; ArgentinaFil: Solano, Angela Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Kalfayan, Pablo G.. Hospital Italiano; ArgentinaFil: Ferro, Fabiana Alejandra. Hospital Italiano; ArgentinaFil: Vaccaro, Carlos A.. Hospital Italiano; Argentin

Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma

Perfils epigenètics; Matriu extracel·lular; Cèl·lules immunesPerfiles epigenéticos; Matriz extracelular; Células inmunesEpigenetic profiles; Extracellular matrix; Immune cellsThe invasive tumor front (the tumor–host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. Herein we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression, and epigenetic profiles of classified aggressive primary uterine adenocarcinomas (24 patients) and leiomyosarcomas (11 patients). Sections of formalin-fixed samples before and after microdissection were scanned and studied. Reticular fiber architecture and immune cell infiltration were analyzed by automatized algorithms in colocalized regions of interest. Despite morphometric resemblance between reticular fibers and high presence of macrophages, we found some variance in other immune cell populations and distinctive gene expression and cell adhesion-related methylation signatures. Although no evident overall differences in immune response were detected at the gene expression and methylation level, impaired antimicrobial humoral response might be involved in uterine leiomyosarcoma spread. Similarities found at the invasive tumor front of uterine adenocarcinomas and leiomyosarcomas could facilitate the use of common biomarkers and therapies. Furthermore, molecular and architectural characterization of the invasive front of uterine malignancies may provide additional prognostic information beyond established prognostic factors.This research was supported by grants from the ISCIII and ERDF (PI17/01558 and PI20/01107), by the CIBERONC (contracts CB16/12/00484, CB16/12/0328, CB16/12/00363, CB16/12/00364, CB16/12/00481, and CB16/12/00231) and Grupos Coordinados Estables from the Asociación Española Contra el Cáncer (AECC). ÁD-L was funded by a contract “Juan Rodés” from the ISCIII (JR17/00016). The funders had no involvement in the research process nor in the preparation and submission of the article

miR-125b Acts as a Tumor Suppressor in Breast Tumorigenesis via Its Novel Direct Targets ENPEP, CK2-α, CCNJ, and MEGF9

MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. To explore the dysregulation of miRNAs in breast cancer, a genome-wide expression profiling of 939 miRNAs was performed in 50 breast cancer patients. A total of 35 miRNAs were aberrantly expressed between breast cancer tissue and adjacent normal breast tissue and several novel miRNAs were identified as potential oncogenes or tumor suppressor miRNAs in breast tumorigenesis. miR-125b exhibited the largest decrease in expression. Enforced miR-125b expression in mammary cells decreased cell proliferation by inducing G2/M cell cycle arrest and reduced anchorage-independent cell growth of cells of mammary origin. miR-125b was found to perform its tumor suppressor function via the direct targeting of the 3'-UTRs of ENPEP, CK2-alpha, CCNJ, and MEGF9 mRNAs. Silencing these miR-125b targets mimicked the biological effects of miR-125b overexpression, confirming that they are modulated by miR-125b. Analysis of ENPEP, CK2-alpha, CCNJ, and MEGF9 protein expression in breast cancer patients revealed that they were overexpressed in 56%, 40-56%, 20%, and 32% of the tumors, respectively. The expression of ENPEP and CK2-alpha was inversely correlated with miR-125b expression in breast tumors, indicating the relevance of these potential oncogenic proteins in breast cancer patients. Our results support a prognostic role for CK2-alpha, whose expression may help clinicians predict breast tumor aggressiveness. In particular, our results show that restoration of miR-125b expression or knockdown of ENPEP, CK2-alpha, CCNJ, or MEGF9 may provide novel approaches for the treatment of breast cancer

Tegumentary leishmaniasis and sand flies in a border area between Argentina and Bolivia

Background: Some sand flies are of medical importance because they are vectors of Leishmania parasites that are responsible for leishmaniasis. The aim of this study was to make a retrospective epidemiological analysis of tegumentary leishmaniasis (TL), to identify Leishmania spp. from patient isolates and to describe the diversity of sand flies from a border area between Bolivia and Argentina. Methods: TL cases included in the study were diagnosed in an endemic area of the north of Argentina from 1985 to 2017. The parasites isolated were characterized by the cytochrome B method. Sand flies were captured with Centers for Disease Control traps in Aguas Blancas and Media Luna-Algarrobito localities. Results: A total of 118 cases of TL were analysed. Eight isolates were characterized as Leishmania (Viannia) braziliensis. A total of 1291 sand flies were captured, including Nyssomyia neivai, Cortelezzii complex, Evandromyia sallesi, Migonemyia migonei and Micropygomyia quinquefer. Within the area, sand flies were found in the backyards of houses. Conclusions: In this region there exists the possibility of peridomestic transmission of TL in the neighbourhoods peripheral to the urban area and in rural environments as well as the risk of transmission to travellers that pass through the customs offices.Fil: Copa, Griselda Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Universidad Nacional de Salta. Facultad de Ciencias Naturales; ArgentinaFil: Almazán, María Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Universidad Nacional de Salta. Facultad de Ciencias Naturales; ArgentinaFil: Aramayo, Lorena Vanesa. Universidad Nacional de Salta; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; ArgentinaFil: Cajal, Silvana Pamela. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Juarez, Marisa. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Lauthier, Juan José. Kochi University. Kochi Medical School; JapónFil: Korenaga, Masataka. Kochi University. Kochi Medical School; JapónFil: Barroso, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Nasser, Julio Rubén. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Marco, Jorge Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Gil, José Fernando. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones en Energía no Convencional. Universidad Nacional de Salta. Facultad de Ciencias Exactas. Departamento de Física. Instituto de Investigaciones en Energía no Convencional; Argentin

Genetic and clinical characterization of a novel FH founder mutation in families with hereditary leiomyomatosis and renal cell cancer syndrome

Hereditary leiomyomatosis and renal cell cancer syndrome is a rare autosomal dominant hereditary syndrome. Previously, we published the largest cohort of FH mutation carriers in Spain and observed a highly recurrent missense heterozygous variant, FH(NM_000143.4):c.1118A > G p.(Asn373Ser), in 104 individuals from 31 apparently unrelated families. Here, we aimed to establish its founder effect and characterize the associated clinical phenotype. Results Haplotype analysis confirmed that families shared a common haplotype (32/38 markers) spanning 0.61-0.82 Mb, indicating this recurrent variant was inherited from a founder ancestor. Cutaneous and uterine leiomyomatosis were diagnosed in 64.6% (64/99) and 98% (50/51) of patients, respectively, and renal cell cancer was present in 10.4% (10/96). The pathogenic FH_c.1118A > G variant is a Spanish founder mutation that originated 12-26 generations ago. We estimate that the variant may have appeared between 1370 and 1720. Individuals carrying this founder mutation had similar frequency of renal cell cancer and a higher frequency of renal cysts and leiomyomas than those in other cohorts of this syndrome. Conclusions In the Spanish province of Alicante there is a high prevalence of HLRCC because of the founder mutation FH c.1118A > G; p.(Asn373Ser). The characterization of founder mutations provides accurate and specific information regarding their penetrance and expressivity. In individuals with suspected HLRCC from the province of Alicante, genetic testing by direct analysis of the founder FH c.1118A > G; p.(Asn373Ser) mutation may be a faster and more efficient diagnostic tool compared with complete gene sequencing