Isolation of Microascus sp. and Cephalotheca sp. from Bats in Argentina.

Bats worldwide play significant roles in ecosystem functions, encompassing pollination, seed dispersal, and pest control while concurrently serving as diseases reservoirs. As part of a comprehensive wildlife health surveillance effort, bats were systematically sampled within two national protected areas in Argentina. During this study 67 bats were examined and samples were collected from eight Molossus spp. individuals exhibiting conspicuous yellowish or white lesions on their noses. All samples were cultured on Sabouraud dextrose agar and lactrimel agar for fungal growth evaluation. Fungal isolates were identified using morphologic and molecular taxonomic techniques, leading to the detection of Microascus sp. in three Molossus rufus from Ibera National Park and Cephalotheca sp. in five Molossus molossus from Marsh Deer National Park. No fungal growth was identified in samples collected from the healthy hairs of the bats displaying lesions on their noses. The two fungi, which have not previously been isolated from bats, should be considered potentially pathogenic, evidenced by diseased hairs in the affected individuals.

Multigene germline testing usefulness instead of BRCA1/2 single screening in triple negative breast cancer cases.

Triple negative breast cancer is considered as the worst aggressive subtype with poor prognosis. Recent studies suggest a hereditary component is involved in TNBC development, especially in young patients. However, genetic spectrum remains unclear. Our purpose was to evaluate the usefulness of multigene panel testing in triple negative patients compared to overall breast cancer cases as well as contributing to elucidate which genes are most implicated in triple negative subtype development. Two breast cancer cohorts, comprising 100 triple negative breast cancer patients and 100 patients with other breast cancer subtypes, were analyzed by Next-Generation Sequencing using an On-Demand panel which included 35 predisposition cancer genes associated with inherited cancer susceptibility. The percentage of germline pathogenic variant carriers was higher in the triple negative cohort. ATM, PALB2, BRIP1 and TP53 were the most non-BRCA mutated genes. Moreover, triple negative breast cancer patients without family history related who were identified as carriers were diagnosed at significantly earlier age. As conclusion, our study reinforces the usefulness of multigene panel testing in breast cancer cases but specifically in those with triple negative subtype regardless family history.

Identification of a new Sarcocystis sp. in marsh deer (Blastocerus dichotomus) from wetlands of Argentina.

The marsh deer (Blastocerus dichotomus) is the largest South American native deer species and is listed as "Vulnerable" by IUCN due to the population reduction. As part of a conservation and disease surveillance program, muscle samples from 14 marsh deer found dead in 2016 and 2017 in northeast Argentina were obtained at necropsy. Samples from each animal were processed as pooled muscles (heart, diaphragm, tongue and hindlimb) by homogenization and direct microscopical observation to detect intracellular Sarcocystis spp. cysts. Sarcocysts were observed in six samples, and several cysts recovered from two samples were processed by transmission electron microscopy. The cysts were thin-walled and showed a cyst-wall ultrastructure with ribbon-like protrusions similar to other species using cervids as intermediate host and canids as definitive hosts. Genomic DNA from individual sarcocysts from three marsh deer were successfully amplified by PCR of 18S rRNA and COI gene fragments and further sequenced. Sequence comparison revealed a 99.3-100% identity among them and only 93.7-96.6% and 88.8-89.7% identity at 18S rRNA and COI markers, respectively, with other Sarcocystis spp. Despite morphological similarities, the high sequence divergence at 18S rRNA and COI fragments allowed the assumption that Sarcocystis sp. from marsh deer is a different species from others using cervids as intermediate hosts. Therefore, we propose the name Sarcocystis blastoceris n. sp. for the species infecting marsh deer.

Vertical transmission and pathological findings in the mother, the placenta and the offspring, during first and last thirds of gestation in a mouse model of congenital toxoplasmosis.

We performed a study of congenital toxoplasmosis of the first and third gestation periods in mice, and determined its effects on the embryos/fetuses, the placentae and the maternal organs. We infected pregnant BALB/c mice by i.v. injection of 2.5--10.0 × 106 tachyzoites of the ME49 T. gondii strain and euthanized them 72 h later. The tissues were analyzed by histopathology, immunohistochemistry and parasite-specific qPCR. Infections with the lowest dose induced remarkably different changes in the two thirds: a) all doses diminished the number of products/litter, the lowest dose only by 14%; but most embryos still visible were degenerated in the case of the first period, while the fetuses of the last third were perfectly preserved; b) the transmission rate in the first third was relatively high, but with a very low parasite burden; c) with the lowest dose, strong vascular changes (congestion, thrombosis and hemorrhage) predominated in the placentas of the first period, while they were absent in the last third; d) necrosis caused by T. gondii to maternal organs was much stronger during the last gestation period than in the first. Our results suggest that the vascular alterations at the placenta of the first third of pregnancy prevent embryo from large parasite burden, but provoke its death by starvation. In the last gestation period, there was poor control of parasite dissemination to the placenta and the fetus, but there was greater capacity of the product to defend itself from T. gondii.

Validación externa y reproducibilidad del cuestionario PUMA para el diagnóstico de EPOC en una población latinoamericana: validación externa del cuestionario PUMA / External validation and reproducibility of the PUMA questionnaire for the diagnosis of COPD in a Latin American population: external validation of the PUMA questionnaire

Resumen El uso de escalas de predicción clínica puede incrementar la detección temprana de enfermedad pulmonar obstructiva crónica (EPOC). Su rendimiento en población latinoamericana ha sido pobremente estudiado. Nuestro objetivo fue determinar la validez y reproducibilidad del cuestionario PUMA, como herramienta de tamización en atención primaria en población colombiana, mediante un estudio tipo corte transversal; donde se establecieron las características operativas del cuestionario, área bajo la curva de características operativas del receptor (ACOR) y el mejor punto de corte para esta población. 1.980 sujetos fueron incluidos en el análisis. La prevalencia de EPOC correspondió a 18,9%. La capacidad discriminatoria del cuestionario fue de 0,69 (IC95%: 0,66-0,72), para un punto de corte óptimo mayor de 5, con una sensibilidad del 60%, especificidad 66% y un valor predictivo negativo de 88%. La escala PUMA para tamizaje de pacientes en riesgo de EPOC tiene una capacidad discriminatoria moderada y una excelente reproducibilidad en la población estudiada.

The use of clinical prediction scales may increase the early detection of chronic obstructive pulmonary disease (COPD). The performance characteristics of these scales in the Latin American population is poorly studied. We aimed to evaluate validity and reproducibility of PUMA questionnaire as a screening tool in primary care in a Colombian population. A cross-sectional study was performed. Operational characteristics of the questionnaire, the area under the received operator curve (AUROC), and the best cut-off point of the score were calculated. 1,980 individuals were included in this analysis. Prevalence of COPD was 18.9%. AUROC of the questionary was 0.69 (CI95%: 0.66-0.72), with an optimal cut-off point greater than 5 (sensitivity 60%, specificity 66%); predictive negative value was 88%. PUMA's scale for the screening of patients at risk of COPD has a moderate accuracy and an excellent reproducibility in the studied population.

Dutasteride combined with androgen receptor antagonists inhibit glioblastoma U87 cell metabolism, proliferation, and invasion capacity: Androgen regulation.

Glioblastoma (GB) is the most common and aggressive primary brain tumor in adult humans. Therapeutic resistance and tumor recurrence after surgical resection contributes to a poor prognosis for glioblastoma patients. Men are known to be more likely than women to develop an aggressive form of GB. Although the reasons for this disparity remain poorly understood, differences in sex steroids have emerged as a leading explanation. Studies indicate that GB-derived cells express androgen receptors (ARs) and synthesize androgens, suggesting that androgens may have a role in the tumor pathogenesis. Thus, our objective was to investigate the effects of the 5α-reductase enzyme inhibitor dutasteride, the AR antagonists cyproterone and flutamide, and combinations of these drugs on the metabolism, proliferation, and invasion capacity of GB-derived U87 cells. We also examined the effects of three natural androgens testosterone, androstenedione and dihydrotestosterone (T, A4, and DHT) on these cells. Cell metabolism was investigated by MTT assay, proliferation was assessed by the bromodeoxyuridine (BrdU) incorporation assay, and invasion was assessed by Boyden chamber assay. The results revealed that T and especially DHT, but not A4, increased U87 cell metabolism and proliferation. Following these findings, we examined the effect of adding dutasteride, cyproterone, or flutamide to the culture media and found that they all significantly decreased cell metabolism and proliferation. Dutasteride also significantly reduced cell invasion. Moreover, any combination of these drugs enhanced their inhibitory effects; the combination of dutasteride to flutamide was most effective at decreasing GB cell proliferation. Our results suggest that administering a combination of AR antagonists and enzyme blockers may be a more effective alternative treatment for GB.

A participatory surveillance of marsh deer (Blastocerus dichotomus) morbidity and mortality in Argentina: first results.

BACKGROUND: In an era of unprecedented socio-ecological changes, managing wildlife health demands high-quality data collection and the engagement of local communities. Blastocerus dichotomus, the largest South American deer, is Vulnerable to extinction mainly due to habitat loss. Diseases have been recognised as a potential threat, and winter mortality has been historically described in marsh deer populations from Argentina. Field difficulties have, however, prevented in-depth studies of their health status. RESULTS: Between May 2014 and April 2017, we investigated marsh deer morbidity and mortality in the two largest populations in Argentina. We collected data by means of a passive surveillance system that involved a network of researchers, field partners (veterinarians, park rangers, and local community), and decision makers. We sampled marsh deer during as well as outside mortality events. A total of 44 marsh deer with different body condition scores were evaluated. We obtained haematology and biochemistry values from animals with good body condition score. Marsh deer with poor body condition had a high burden of the ticks Amblyomma triste and Rhipicephalus microplus. Vector-borne agents such as Theileria cervi, Trypanosoma theileri, Trypanosoma evansi, Ehrlichia chaffeensis, Anaplasma platys, Anaplasma odocoilei, Anaplasma marginale, and Candidatus Anaplasma boleense were also found. Haemonchus spp., Ostertagia spp., and Trichostrongylus spp. were the most frequent gastrointestinal parasites in deer with poor body condition. A Multiple Correspondence Analysis reinforced a possible association of winter period with lower body score condition, high tick loads, infection with E. chaffeensis, and presence of harmful gastrointestinal parasites. CONCLUSIONS: Our approach allowed the establishment of a participatory surveillance network of marsh deer morbidity and mortality in Argentina. We report and analyse the first data obtained opportunistically within the framework of this network, providing information on the infectious and parasitic agents in marsh deer populations. The occurrence of Fasciola hepatica and Leptospira interrogans serovar pyrogenes is reported for the first time in wild marsh deer from Argentina. Our data will be useful to improve the interpretation of future mortality events. The field implementation of a surveillance network is key to a holistic approach to wildlife diseases.

Evidence of Ehrlichia chaffeensis in Argentina through molecular detection in marsh deer (Blastocerus dichotomus).

Vector-borne pathogens are responsible for serious emerging diseases and have been widely described in wildlife. Ehrlichia chaffeensis causes the zoonotic "monocytic ehrlichiosis" in humans, is transmitted by the tick Amblyomma americanum and its reservoir host is the white-tailed deer (Odocoileus virginianus) in North America. Little is known about the native reservoir and the tick vectors involved in the transmission cycle in South America. We report here the detection of E. chaffeensis in a study on marsh deer (Blastocerus dichotomus) mortality in Argentina, in different time periods between 2007 and 2016. Four deer, from two distinct populations, were positive for E. chaffeensis through molecular methods. Additionally, the variable-length PCR target (VLPT) region of positive samples was genotyped. Our results provide the first evidence of E. chaffeensis in autochthonous Cervidae from Argentina, contributing to uncover the distribution of this tick-borne infection in South America.

Prevalencia y características de uveítis como manifestación extraarticular en Espondiloartritis Axial / Prevalence and characteristics of uveitis as an extra-articular manifestation in Axial Spondyloarthritis

Introducción: La Uveítis Anterior Aguda (UAA) es la manifestación extraarticular más frecuente en la Espondiloartritis axial (EsPax), con una prevalencia global de 32,7%. El objetivo de este estudio fue determinar la prevalencia de UAA en una cohorte Argentina de pacientes con EsPax, describir sus características clínicas, frecuencia de episodios, respuesta al tratamiento y pronóstico a largo plazo, así como su asociación con características generales de la enfermedad. Material y métodos: Se realizó un estudio de corte transversal. Se incluyeron pacientes con diagnóstico de EsPax (criterios ASAS 2009) de la cohorte ESPAXIA (Estudio de Espondiloartritis Axial IREP Argentina). Se consignaron datos sociodemográficos, características de la enfermedad y tratamientos recibidos; números de episodios de uveítis, año de aparición, características del mismo, tratamiento realizado y complicaciones. Se registró rigidez matinal, medidas de movilidad axial por Bath Ankylosing Spondylitis Metrological Index (BASMI), número de articulaciones tumefactas, sitios de entesitis por medio de Maastricht AS Enthesitis Score (MASES), eritrosedimentación (ERS), proteína C reactiva (PCR) y presencia de HLA-B27. Se empleó Escala Visual Numérica (EVN) para evaluar el dolor, dolor nocturno, actividad de la enfermedad según el paciente y el médico. Se administraron autocuestionarios: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) y Ankylosing Spondylitis Quality of Life (ASQoL). Se calculó Simplified Ankylosing Spondylitis Disease Activity Score con ERS y PCR (SASDAS ERS/PCR). Análisis estadístico: Estadística descriptiva. Test T de Student, test de Chi² y análisis de regresión logística múltiple. Se consideró significativo un valor de p<0,05. Resultados: Se incluyeron 231 pacientes con EsPax, 174 de sexo masculino (75,3%) con una mediana de edad de 46 años (RIC 36-57) y mediana de tiempo de evolución de la enfermedad de 20,5 años (RIC 10,5-30,5). Sesenta pacientes (26%) presentaron al menos un episodio de uveítis, siendo la primera manifestación de la enfermedad en 22 (37,9%) de ellos. La UAA fue la forma más frecuente, observándose en 59 pacientes (98,3%). El promedio de episodios de UAA fue 4,78 (DS 5,64). Las recurrencias fueron unilaterales en 48,8% de los casos. El tratamiento recibido fue local en 42 (79,2%) de los pacientes. Doce pacientes (22,2%) presentaron secuelas luego del primer episodio, siendo la disminución de la agudeza visual y cataratas las más frecuentes (16,7% y 5,6%, respectivamente). Las variables asociadas independientemente con UAA fueron mayor tiempo de evolución de la enfermedad (24,91±14,2 años vs 20,7±13,2 años, p=0,038) y positividad de HLA-B27, (69% vs 47,4%, p=0,006). Conclusión: La prevalencia de uveítis en nuestra cohorte fue del 26%. Fue significativamente más frecuente en pacientes HLA-B27 (+) y con mayor tiempo de evolución de la enfermedad.

Background: Acute Anterior Uveitis (AAU) is the most frequent extra-articular manifestation in axial Spondyloarthritis (axSpA), with an overall prevalence of 32.7%. The aim of this study was to determine the prevalence of AAU in an Argentinian cohort of patients with axSpA and to describe their clinical characteristics, frequency of episodes, response to treatment and long-term prognosis, as well as their association with general disease characteristics. Methods: A cross-sectional study was carried out. We included patients with axSpA according to ASAS 2009 criteria from ESPAXIA cohort (Estudio de Espondiloartritis Axial IREP Argentina). Sociodemographic data, characteristics of the disease, and treatments received; numbers of episodes of uveitis, incidence date, and its characteristics, treatment and complications were consigned. Morning stiffness, axial mobility (BASMI), enthesitis (MASES), ESR, CRP and HLA-B27 were registered. Pain, night pain, patient and physician global assessment were evaluated by Numerical Visual Scale (NVA). BASDAI, BASFI and ASQoL self-questionnaires were administered. Statistical analysis: Descriptive statistics. Student's T-test, Chi² test and multiple logistic regression analysis. A p value <0.05 was considered significant. Results: Two hundred and thirty one patients with axSpA were included, 174 male (75.3%) with a median age of 46 years (IQR 36-57) and median disease duration of 20.5 years (IQR 10.5-30.5). Sixty patients (26%) had at least one episode of uveitis, being the first manifestation of the disease in 22 (37.9%) of them. Acute anterior uveitis was the most frequent form, and it was observed in 59 patients (98.3%). The mean number of episodes was 4.78 (SD 5.64). Recurrences were unilateral in 48.8% of cases. They received local therapy in 42 (79.2%) of the patients. Twelve patients (22.2%) presented a complication after the first episode, being the decrease in visual acuity and cataracts, the most frequent ones (16.7% and 5.6%, respectively). The presence of uveitis was significantly associated with longer disease duration (24.9 years vs 20.7 years, p=0.038) and with the positivity for HLA-B27, (69% vs 47.4%, p=0.006) and these variables were maintained in the multivariate analysis, after adjusting for other variables. Conclusion: The prevalence of uveitis in our cohort was 26%. It was significantly more frequent in patients HLA-B27 (+) and with longer disease duration.

Foot and ankle deformities in children with Down syndrome.

PURPOSE: Foot and ankle deformities are common orthopaedic disorders in children with Down syndrome. However, radiographic measurements of the foot and ankle have not been previously reported. The aim of this study is to describe the foot and ankle deformity in children with Down syndrome. METHODS: Children who had foot and ankle radiographs in the standing weight-bearing position were selected. Three groups of patients were identified. The relationship of radiographic measurements with age, body mass index and pain is discussed. In all, 41 children (79 feet) had foot radiographs and 60 children (117 ankles) had ankle radiographs, with 15 children overlapping between Groups I and II. RESULTS: In Group I, hallux valgus deformity was seen before ten years of age and hallux valgus angle increased afterwards. Metatarsus adductus angle showed a significant increase (p = 0.006) with obesity and was higher in patients who had foot pain (p = 0.05). In Group II, none of the ankle measurements showed a significant difference with age or body mass index percentiles. Tibiotalar angle (TTA) and medial distal tibial angle (MDTA) were higher in patients who had ankle pain. In Group III, correlation analysis was performed between the different measurements with the strongest correlations found between TTA and MDTA. CONCLUSION: In children with Down syndrome, radiographic evaluation of the foot and ankle reveals higher prevalence of deformities than clinical examination. However, foot and ankle radiographs are needed only for symptomatic children with pain and gait changes. LEVEL OF EVIDENCE: Level IV - Prognostic Study.

Estudio piloto de validación y adaptación de un cuestionario para evaluar el impacto de la espondiloartritis axial en la sexualidad de los pacientes / A validation and adaptation pilot study of a questionnaire to evaluate the impact of axial spondyloarthritis in the sexuality of patients

Introducción: El Qualisex es un cuestionario desarrollado y validado para evaluar la sexualidad en pacientes con artritis reumatoidea. Hasta el momento, según nuestro conocimiento, no se ha desarrollado un cuestionario que evalúe específicamente la sexualidad en pacientes que padecen Espondiloartritis axial (EsPax). Por este motivo, nuestro objetivo fue validar y adaptar el cuestionario Qualisex en pacientes con EsPax y evaluar el impacto de su enfermedad en la sexualidad. Material y métodos: Estudio de corte transversal. Se incluyeron pacientes ≥21 años de edad con diagnóstico de EsPax según criterios ASAS '09, en forma consecutiva. Se consignaron datos sociodemográficos, tiempo de evolución de la enfermedad, síntomas relacionados con la enfermedad, comorbilidades y tratamiento recibido. Se evaluó la salud sexual de los pacientes utilizando el cuestionario Qualisex. El mismo consta de 10 preguntas con respuestas categorizadas en una escala de 11 puntos (0-10); el resultado surge del promedio de las mismas y su rango es de 0-10, las puntuaciones más altas indican un mayor impacto en la sexualidad. La versión original del Qualisex fue traducida y adaptada para EsPax. Para el análisis estadístico, se utilizó estadística descriptiva, test de Mann-Whitney y test de Chi² y test exacto de Fisher. Regresión lineal. Correlación de Spearman. Coeficiente de correlación intraclase (CCI) para evaluar la reproducibilidad del cuestionario. Resultados: Se invitó a participar a 61 pacientes, 11 de los cuales se negaron. 50 pacientes fueron incluidos, 40 (80%) eran de sexo masculino, con una edad mediana de 47 años (RIC 21-72), y un tiempo mediano de evolución de 13 años (RIC 1-46). La mediana de Qualisex fue de 2,5 (RIC 1,1-4,2), el tiempo mediano para completar el cuestionario fue de 2,1 minutos (RIC 1,7-3,1). La reproducibilidad fue excelente con un CCI de 0,99 (IC 95% 0,65-1). Se hallaron algunas preguntas redundantes con correlación intraítem mayor a 0,8. El Qualisex presentó buena correlación con las medidas de evaluación de la enfermedad: ASQoL (Rho: 0,52, p=0,001), BASDAI (Rho: 0,57, p<0,0001), BASFI (Rho: 0,53, p=0,001), PsAQoL (Rho: 0,69, p=0,01). El Qualisex fue significativamente mayor en el sexo femenino (5,4 en mujeres vs 2,5 en varones, p=0,02), en los desocupados (4,7 en desocupados vs 2,3 ocupados, p=0,01), en pacientes con mayor actividad de la enfermedad evaluado por BASDAI >4 (4,2 pacientes activos vs 1,6 en pacientes inactivos, p=0,01) y menor en los pacientes en tratamiento biológico (TB) (1,9 con TB vs 3,8 sin TB, p=0,01). En el análisis multivariado, sexo femenino, mayor tiempo de evolución de la enfermedad y mayor actividad de la enfermedad se mantuvieron independientemente asociadas a mayor impacto en la sexualidad. Conclusión: El Qualisex adaptado a EsPax es un cuestionario válido y confiable, aunque presenta algunas preguntas redundantes. Los pacientes con EsPax de sexo femenino, con mayor tiempo de evolución y mayor actividad de la enfermedad presentaron peor calidad de vida sexual.

Introduction: The Qualisex is a questionnaire developed and validated to evaluate sexuality in patients with Rheumatoid Arthritis. According to our knowledge, a questionnaire that specifically assesses sexuality in patients with axial spondyloarthritis (AxSpA) has not been developed. For this reason, our objective was to validate and adapt the Qualisex questionnaire in patients with AxSpA and evaluate the impact of their disease on sexuality. Material and methods: Cross-sectional study. We included patients ≥21 years of age with a diagnosis of AxSpA according to ASAS '09 criteria. Sociodemographic data were recorded, time of evolution of the disease, symptoms related to the disease, comorbidities and treatment received. The sexual health of the patients was evaluated using the Qualisex questionnaire. It consists of 10 questions with answers categorized on a scale of 11 points (0-10). Qualisex's score is the mean of the results for the 10 questions, the highest scores indicate a greater impact on sexuality. The original version of the Qualisex was translated and adapted for AxSpA. For the statistical analysis, descriptive statistics, Mann-Whitney test and Chi² test and Fisher's exact test were used. Linear regression. Spearman correlation. Intraclass correlation coefficient (ICC) was used to evaluate the reproducibility of the questionnaire. Results: 61 patients were invited to participate, 11 of whom refused. 50 patients were included, 40 (80%) were male, with a median age of 47 years (IR 21-72), and a median time of evolution of 13 years (IR 1-46). The median of Qualisex was 2.5 (IR 1.1-4.2), the median time to complete the questionnaire was 2.1 minutes (IR 1.7-3.1). Reproducibility was excellent with a ICC of 0.99 (95% CI 0.65-1). Some redundant questions were found. The Qualisex presented good correlation with the evaluation measures of the disease: ASQoL (Rho: 0.52, p=0.001), BASDAI (Rho: 0.57, p<0.0001), BASFI (Rho: 0.53, p=0.001), PsAQoL (Rho: 0.69, p=0.01). The Qualisex was significantly higher in the female sex (5.4 in women vs 2.5 in males, p=0.02), in the unemployed (4.7 in unemployed vs 2.3 occupied, p=0.01), in patients with greater activity of the disease evaluated by BASDAI >4 (4.2 active patients vs 1.6 in inactive patients, p=0.01) and lower in patients on biological treatment (BT) (1.9 with BT vs 3.8 without BT, p=0.01). In the multivariate analysis, female sex, longer time of evolution of the disease and greater activity of the disease were independently associated with greater impact on sexuality. Conclusion: The Qualisex adapted to AxSpA is a valid and reliable questionnaire, although it presents some redundant questions. The patients with AxSpA of female sex, with longer time of evolution and greater activity of the disease presented worse quality of sexual life.

Arthroscopic knee anatomy in young achondroplasia patients.

PURPOSE: Achondroplasia is the most common form of skeletal dysplasia, affecting more than 250 000 individuals worldwide. In these patients, the developing knee undergoes multiple anatomical changes. The purpose of this study was to characterise the intra-articular knee anatomy in children with achondroplasia who underwent knee arthroscopy. METHODS: Records of achondroplasia patients who underwent knee arthroscopy between 2009 and 2014 were reviewed. Demographic data, operative reports, follow-up notes, MRI and arthroscopy images were reviewed. Bony, cartilaginous and ligamentous changes were noted. The trochlea sulcus angle was measured from intra-operative arthroscopic images. RESULTS: A total of 12 knee arthroscopies in nine patients were performed. The mean age at surgery was 16.9 years (12 to 22). In all patients, the indication for surgery was knee pain and/or mechanical symptoms that were refractory to non-operative treatment. Three anatomical variations involving the distal femur were found in all knees: a deep femoral trochlea; a high A-shaped intercondylar notch; and a vertically oriented anterior cruciate ligament. The average trochlea sulcus angle measured 123°. Pathology included: synovial plica (one knee); chondral lesions (three knees); discoid lateral meniscus (11 knees); and meniscal tears (six knees). All patients were pain-free and returned to normal activity at final follow-up. CONCLUSION: Children with achondroplasia have characteristic distal femur anatomy noted during knee arthroscopy. These variations should be considered normal during knee arthroscopy in these patients. Arthroscopic findings confirmed previous MRI findings within this specific population with the addition of a deep trochlear groove which was not previously reported.

A DNA methylation map of human cancer at single base-pair resolution.

Although single base-pair resolution DNA methylation landscapes for embryonic and different somatic cell types provided important insights into epigenetic dynamics and cell-type specificity, such comprehensive profiling is incomplete across human cancer types. This prompted us to perform genome-wide DNA methylation profiling of 22 samples derived from normal tissues and associated neoplasms, including primary tumors and cancer cell lines. Unlike their invariant normal counterparts, cancer samples exhibited highly variable CpG methylation levels in a large proportion of the genome, involving progressive changes during tumor evolution. The whole-genome sequencing results from selected samples were replicated in a large cohort of 1112 primary tumors of various cancer types using genome-scale DNA methylation analysis. Specifically, we determined DNA hypermethylation of promoters and enhancers regulating tumor-suppressor genes, with potential cancer-driving effects. DNA hypermethylation events showed evidence of positive selection, mutual exclusivity and tissue specificity, suggesting their active participation in neoplastic transformation. Our data highlight the extensive changes in DNA methylation that occur in cancer onset, progression and dissemination.

Tratamiento actual y nuevas terapias contra la infección crónica por el virus de la hepatitis B / Current treatment and new therapies against chronic hepatitis B virus infection

Resumen La infección crónica por el virus de la hepatitis B (VHB) es un grave problema de salud pública a nivel mundial. Sus consecuencias llegan a ser mortales y el tratamiento actual no ofrece curación sino control de la enfermedad. Las principales limitantes para una cura son la dificultad para destruir el ADN circular covalente cerrado (ADNccc) del virus en el núcleo celular y la presencia de material genético viral integrado en el ADN de la célula hospedera. No obstante, hay múltiples frentes de investigación enfocados en encontrar una cura definitiva al potenciar la respuesta inmune del hospedero o al actuar directamente contra el virus y su ciclo de replicación. En este artículo se exponen los principales avances que se han realizado en este campo.

Abstract Chronic hepatitis B virus infections are a serious public health problem worldwide. Its consequences can be deadly, and current treatment offers only control of the disease rather than a cure. The main limiting factors for a cure are the difficulty of destroying the cDNA of the virus in the cell nucleus and the presence of viral genetic material integrated into the DNA of the host cell. Multiple fronts of research focus on finding a definitive cure by enhancing the immune response of the host or by acting directly against the virus and its replication cycle. This article presents the main advances that have been made in this field.

Validation of an Argentine version of Lupus Quality of Life questionnaire.

OBJECTIVE: To determine reproducibility and validity of an Argentine version of the Lupus Quality of Life questionnaire (LupusQoL) and to determine cut-off values in the questionnaire. MATERIALS AND METHODS: One hundred and forty-seven systemic lupus erythematosus patients (American College of Rheumatology 1982/1997) were assessed from April 2014 to July 2014. Demographic and socioeconomic variables were collected, as well as SELENA/SLEDAI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index Score, comorbidities and treatment data. Patients completed LupusQoL-Argentine version and European Quality of Life Questionnaire (EuroQoL-5D). Internal consistency and reliability were examined. Convergent validity with EuroQoL-5D was assessed through analysis of latent classes, which established homogeneous categories from the responses of each domain of LupusQoL and for the total. RESULTS: Out of 147 patients, 93.2% were female, mean age 36.4 ± 11.1 years, mean disease duration 2.7 ± 9 years, mean SELENA/SLEDAI 2.7 ± 3 points. The cut-off point that defined good or bad quality of life was 0.739 for EuroQoL 5D and 63 for LupusQoL. Cut-off values for each LupusQoL domain were also defined, creating two classes in each of them. There was moderate to high concordance to classify quality of life (Kappa = 0.74, 95% confidence interval = 0.54, 0.95). CONCLUSION: The Argentine version of LupusQoL is a valid, reliable and reproducible instrument to assess quality of life. In this study, cut-off points that allow the classification of patients regarding whether they have good or bad quality of life are established for the first time.

Thermally stable and efficient polymer solar cells based on a novel donor-acceptor copolymer.

We report high photovoltaic performance of a novel donor-acceptor (D-A) conjugated polymer poly[2,6[4,8-bis(2-ethyl-hexyl)benzo[1,2-b;4,5-b']dithiophene-co-2,5-thiophene-co-4,7[5,6-bis-octyloxy-benzo[1,2,5]thiadiazole]-co-2,5-thiophene] (PBDTTBTZT) in bulk heterojunctions with [6,6]-phenyl-C71-butyric acid methyl ester (PC70BM). A power conversion efficiency (PCE) of more than 7% is obtained for optimized charge-extracting electrodes. Upon application of thermal stress via annealing, a superior thermal stability is demonstrated as compared to poly[N-9″-hepta-decanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (PCDTBT).

First finding of Trypanosoma cruzi II in vampire bats from a district free of domestic vector-borne transmission in Northeastern Argentina.

Establishing the putative links between sylvatic and domestic transmission cycles of Trypanosoma cruzi, the etiological agent of Chagas disease, is of public health relevance. We conducted three surveys to assess T. cruzi infection in wild mammals from a rural and a preserved area in Misiones Province, Northeastern Argentina, which had recently been declared free of vector- and blood-borne transmission of human T. cruzi infection. A total of 200 wild mammals were examined by xenodiagnosis (XD) and/or polymerase chain reaction (PCR) amplification of the hyper-variable region of kinetoplast DNA minicircles of T. cruzi (kDNA-PCR). The overall prevalence of T. cruzi infection was 8%. Nine (16%) of 57 Didelphis albiventris opossums and two (7%) of 29 Desmodus rotundus vampire bats were positive by both XD and kDNA-PCR. Additionally, one D. rotundus positive for T. cruzi by kDNA-PCR tested positive by satellite-DNA-PCR (SAT-DNA-PCR). The T. cruzi-infected bats were captured indoors and in the yard of a vacant dwelling. All D. albiventris were infected with TcI and both XD-positive D. rotundus by TcII. Fifty-five opossum cubs within the marsupium were negative by XD. The mean infectiousness to the vector was 62% in D. albiventris and 50% in D. rotundus. Mice experimentally infected with a parasite isolate from a vampire bat displayed lesions typically caused by T. cruzi. Our study documents the presence of the genotype TcII in a sylvatic host for the first time in Argentina, and the occurrence of two transmission cycles of T. cruzi in a district free of domestic vector-borne transmission.

Vacunación y eventos supuestamente atribuibles a vacunación o inmunización en estudiantes universitarios / Vaccination and events considered attributable to vaccination or immunization in university students / Vacinação e eventos supostamente atribuíveis à vacinação ou imunização em estudantes universitários

La vacunación es la intervención que mayor impacto ha tenido en la salud después de la potabilización del agua. Las vacunas no \r\nestán exentas de efectos adversos. Los eventos supuestamente atribuibles a vacunación o inmunización son: todo cuadro clínico \r\nque aparece luego de la administración de una vacuna y que eventualmente puede atribuirse a esta. En la Universidad Nacional \r\nde San Luis se realizó un Operativo de Vacunación en mayo del 2014. El objetivo fue determinar: vacunas administradas, eventos \r\nsupuestamente atribuibles a vacunación o inmunización presentados, datos sociodemográficos y conocimiento sobre la notifi\r\n-\r\ncación de eventos supuestamente atribuibles a vacunación o inmunización. Se realizó una encuesta a 84 personas vacunadas \r\nseleccionadas al azar de un total de 285; se incluyeron datos de edad, sexo, vacunas, número, tipo y síntomas de los eventos \r\nsupuestamente atribuibles a vacunación o inmunización, tratamiento recibido y motivos de la no notificación. Los síntomas se clasificaron como: generales y locales; letales, graves, moderados, leves; y por necesidad de tratamiento o no. Resultados: edad: \r\n18-45 años; sexo: femenino 72, masculino 12; vacunas: antigripal (48%), hepatitis B (24%), triple bacteriana acelular (15%), sarampión \r\nrubéola (7%) y doble bacteriana adultos (6%). Eventos supuestamente atribuibles a vacunación o inmunización (39): leves (38) y \r\nmoderado (1). Síntomas: dolor, hinchazón, induración, malestar general y fiebre. Motivos para no notificar: desconocimiento de \r\nla existencia de la notificación (4), dónde y cómo realizar la notificación (7) y pensar que los eventos supuestamente atribuibles a \r\nvacunación o inmunización esperables no se deben notificar (28). Existen porcentajes elevados de eventos supuestamente atri\r\n-\r\nbuibles a vacunación o inmunización leves y de desconocimiento del sistema de notificación. Es fundamental conocer y vigilar \r\nlos eventos supuestamente atribuibles a vacunación o inmunización de cada vacuna y promover su notificación para garantizar \r\nla seguridad de vacunas y pacientes.

Vaccination is the intervention with the greatest impact on \r\nthe health of the world's population after water purification. \r\nVaccines are not exempt of side effects. Events attributed to \r\nvaccination or immunizations are clinical events that appear after \r\nadministration of a vaccine that could eventually be suspected \r\nof being caused by the vaccine. A vaccination study took place \r\nat the Universidad Nacional de San Luis in May 2014. The objec\r\n-\r\ntive was to determine the following: administered vaccines, \r\nevents attributed to vaccination or immunization, socio-de\r\n-\r\nmographic data, and knowledge regarding the reporting of \r\nevents attributed to vaccination or immunization. A sample \r\nto 84 vaccinated individuals was randomly selected from \r\na total of 285. A survey, including types and symptoms of \r\nevents attributed to vaccination or immunization, age, sex, \r\nvaccines, treatment received and reasons for non-reporting, \r\nwas performed. The symptoms were classified as: general and \r\nlocal; lethal, serious, moderate, mild; and needing treatment or \r\nnot. Results: age range: 18-45 years; gender: female 72, male \r\n12; vaccines: influenza (48%), hepatitis B (24%), triple acellular \r\nbacterial (15%), double viral (7%), and bacterial double (6%). \r\nEvents attributed to vaccination or immunization (39): mild (38), \r\nmoderate (1). Symptoms: pain, swelling, induration, malaise and \r\nfever. Reasons for not reporting: unawareness of the reporting \r\noption (4), where and how to make the report (7), thinking that \r\nthe expected events attributed to vaccination or immuniza\r\n-\r\ntion must not be reported (28). There is a high percentage of \r\nmild events thought attributable to vaccination or immuniza\r\n-\r\ntion, and a significant lack of reporting system knowledge. It is \r\nvery important to know and monitor adverse effects of each \r\nvaccine and to promote their reporting to ensure the safety of \r\nthe vaccine and that of patients.

A vacinação é a intervenção que tem tido um maior impacto \r\nsobre a saúde depois da tornar potável da água. As vacinas \r\nnão são isentas de efeitos adversos. Os eventos, supostamente \r\ndevido à vacinação ou imunização, são todos os quadros \r\nclínicos que aparecem após a administração de uma vacina \r\nque poderiam, eventualmente, ser atribuídos a esta. Na Univer\r\n-\r\nsidad Nacional de San Luis se realizou uma campanha de \r\nvacinação em maio de 2014. O objetivo foi determinar: vacinas \r\nadministradas, eventos apresentados supostamente devidos à \r\nvacinação ou imunização, dados sociodemográficos e conhe\r\n-\r\ncimento em matéria de notificação de eventos supostamente \r\natribuíveis à vacinação ou imunização. Foi realizada uma \r\npesquisa com 84 indivíduos vacinados, selecionados aleatoria\r\n-\r\nmente a partir de um total de 285, onde se incluíram idade, \r\nsexo, vacinas, tratamento recebido e as razões da não notifi\r\n-\r\ncação, tipos e sintomas dos eventos supostamente atribuíveis \r\nà vacinação ou imunização, tratamento recebido e motivos da \r\nnão notificação. Os sintomas foram classificados como: geral e \r\nlocal; letal, sério, moderado, leve e, precisam de tratamento ou \r\nnão. Resultados: idade: 18-45 anos; sexo: feminino 72, masculino \r\n12; vacinas: influenza (48%), hepatite B (24%), tríplice bacteriana \r\nacelular (15%), dupla viral (7%), dupla bacteriana (6%). Eventos \r\nsupostamente devidos à vacinação ou imunização (39): leves \r\n(38), moderado (1). Sintomas: dor, inchaço, induração, mal-estar \r\ne febre. Razões para não serem notificadas: a ignorância da exis\r\n-\r\ntência da notificação (4), onde e como proceder à notificação \r\n(7), pensar que os eventos esperados supostamente devidos à \r\nvacinação ou imunização não devem ser notificados (28). Existe \r\numa elevada percentagem de eventos supostamente devidos \r\nà vacinação ou imunização leves e de desconhecimento do \r\nsistema de notificação. É importante conhecer e monitorar os \r\nefeitos adversos de cada vacina e promover a sua notificação, \r\npara garantir a segurança das vacinas e dos pacientes

Pregnancy rate in dairy cows treated with progesterone for six days during estrus synchronization with PGF2α.

The present study evaluated the effect of progesterone supplementation during a double PGF2α injection synchronization protocol on pregnancy per artificial insemination (P/AI) and on the incidence of twin births. Seven hundred and eighty three dairy cows were synchronized with two injections of PGF2α 14 days apart, starting on day 35 postpartum for their first postpartum insemination. Six days before the second PGF2α injection, cows were treated either with a progesterone-releasing intravaginal device (PRID-Delta) and an intramuscular injection of 500mg of progesterone (n=387) or served as control (n=396) and did not receive progesterone treatment. Cows were inseminated 12h after being detected in estrus. Pregnancy was diagnosed 40-45 days later by transrectal palpation. Progesterone administration improved (P<0.05) the percentage of cows detected in estrus in multiparous [(192/255) 75% vs (161/267) 60%], but not in primiparous cows [93/132 (70%) vs 90/129 (70%)]. Progesterone treatment increased P/AI in multiparous [53/192 (28%) vs 27/161 (17%)] but not in primiparous cows [25/93 (27%) vs 29/90 (32%)]. The incidence of twin births tended to be lower (P=0.09) in cows treated with progesterone [1/74 (1%)] than in the control group [4/53 (7%)]. It is concluded that progesterone administration during estrus synchronization with two PGF2α injections in dairy cows improves estral response and increases P/AI in multiparous, but not in primiparous cows, and tended to decrease the incidence of twin births.