The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9.

Siglec-9 is a sialic-acid-binding lectin expressed predominantly on myeloid cells. Aberrant glycosylation occurs in essentially all types of cancers and results in increased sialylation. Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression. Moreover, MUC1-ST induced macrophages to display a tumor-associated macrophage (TAM)-like phenotype, with increased expression of the checkpoint ligand PD-L1. Binding of MUC1-ST to Siglec-9 did not activate the phosphatases SHP-1 or SHP-2 but, unexpectedly, induced calcium flux that led to activation of the kinases MEK-ERK. This work defines a critical role for aberrantly glycosylated MUC1 and identifies an activating pathway that follows engagement of Siglec-9.

Disturbed flow increases endothelial inflammation and permeability via a Frizzled-4-ß-catenin-dependent pathway.

Multidirectional or disturbed flow promotes endothelial dysfunction and is associated with early atherogenesis. Here we investigated the role of Wnt signalling in flow-mediated endothelial dysfunction. The expression of Frizzled-4 was higher in cultured human aortic endothelial cells (ECs) exposed to disturbed flow compared to that seen for undisturbed flow, obtained using an orbital shaker. Increased expression was also detected in regions of the porcine aortic arch exposed to disturbed flow. The increased Frizzled-4 expression in cultured ECs was abrogated following knockdown of R-spondin-3. Disturbed flow also increased the nuclear localisation and activation of ß-catenin, an effect that was dependent on Frizzled-4 and R-spondin-3. Inhibition of ß-catenin using the small-molecule inhibitor iCRT5 or knockdown of Frizzled-4 or R-spondin-3 resulted in reduced expression of pro-inflammatory genes in ECs exposed to disturbed flow, as did inhibition of WNT5A signalling. Inhibition of the canonical Wnt pathway had no effect. Inhibition of ß-catenin also reduced endothelial paracellular permeability; this was associated with altered junctional and focal adhesion organisation and cytoskeletal remodelling. These data suggest the presence of an atypical Frizzled-4-ß-catenin pathway that promotes endothelial dysfunction in response to disturbed flow.

Isolation of Human Milk Difucosyl Nona- and Decasaccharides by Ultrahigh-Temperature Preparative PGC-HPLC and Identification of Novel Difucosylated Heptaose and Octaose Backbones by Negative-Ion ESI-MSn.

Despite their many important physiological functions, past work on the diverse sequences of human milk oligosaccharides (HMOs) has been focused mainly on the highly abundant HMOs with a relatively low degree of polymerization (DP) due to the lack of efficient methods for separation/purification and high-sensitivity sequencing of large-sized HMOs with DP ≥ 10. Here we established an ultrahigh-temperature preparative HPLC based on a porous graphitized carbon column at up to 145 °C to overcome the anomeric α/ß splitting problem and developed further the negative-ion ESI-CID-MS/MS into multistage MSn using a combined product-ion scanning of singly charged molecular ion and doubly charged fragment ion of the branching Gal and adjacent GlcNAc residues. The separation and sequencing method allows efficient separation of a neutral fraction with DP ≥ 10 into 70 components, among which 17 isomeric difucosylated nona- and decasaccharides were further purified and sequenced. As a result, novel branched difucosyl heptaose and octaose backbones were unambiguously identified in addition to the conventional linear and branched octaose backbones. The novel structures of difucosylated DF-novo-heptaose, DF-novo-LNO I, and DF-novo-LNnO I were corroborated by NMR. The various fucose-containing Lewis epitopes identified on different backbones were confirmed by oligosaccharide microarray analysis.

CarbArrayART: a new software tool for carbohydrate microarray data storage, processing, presentation, and reporting.

Glycan microarrays are essential tools in glycobiology and are being widely used for assignment of glycan ligands in diverse glycan recognition systems. We have developed a new software, called Carbohydrate microArray Analysis and Reporting Tool (CarbArrayART), to address the need for a distributable application for glycan microarray data management. The main features of CarbArrayART include: (i) Storage of quantified array data from different array layouts with scan data and array-specific metadata, such as lists of arrayed glycans, array geometry, information on glycan-binding samples, and experimental protocols. (ii) Presentation of microarray data as charts, tables, and heatmaps derived from the average fluorescence intensity values that are calculated based on the imaging scan data and array geometry, as well as filtering and sorting functions according to monosaccharide content and glycan sequences. (iii) Data export for reporting in Word, PDF, and Excel formats, together with metadata that are compliant with the guidelines of MIRAGE (Minimum Information Required for A Glycomics Experiment). CarbArrayART is designed for routine use in recording, storage, and management of any slide-based glycan microarray experiment. In conjunction with the MIRAGE guidelines, CarbArrayART addresses issues that are critical for glycobiology, namely, clarity of data for evaluation of reproducibility and validity.

O-linked mucin-type glycosylation regulates the transcriptional programme downstream of EGFR.

Aberrant mucin-type O-linked glycosylation is a common occurrence in cancer where the upregulation of sialyltransferases is often seen leading to the early termination of O-glycan chains. Mucin-type O-linked glycosylation is not limited to mucins and occurs on many cell surface glycoproteins including EGFR, where the number of sites can be limited. Upon EGF ligation, EGFR induces a signaling cascade and may also translocate to the nucleus where it directly regulates gene transcription, a process modulated by Galectin-3 and MUC1 in some cancers. Here, we show that upon EGF binding, breast cancer cells carrying different O-glycans respond by transcribing different gene expression signatures. MMP10, the principal gene upregulated when cells carrying sialylated core 1 glycans were stimulated with EGF, is also upregulated in ER-positive breast carcinoma reported to express high levels of ST3Gal1 and hence mainly core 1 sialylated O-glycans. In contrast, isogenic cells engineered to carry core 2 glycans upregulate CX3CL1 and FGFBP1 and these genes are upregulated in ER-negative breast carcinomas, also known to express longer core 2 O-glycans. Changes in O-glycosylation did not significantly alter signal transduction downstream of EGFR in core 1 or core 2 O-glycan expressing cells. However, striking changes were observed in the formation of an EGFR/galectin-3/MUC1/ß-catenin complex at the cell surface that is present in cells carrying short core 1-based O-glycans but absent in core 2 carrying cells.

Maternal and perinatal outcomes in external cephalic version: prognostic factors for the success of the technique.

Background We aimed to analyze the success rate of external cephalic version (ECV) for breech presentations performed in our center between March 2011 and March 2016. We evaluated factors related to a successful ECV, delivery mode, complications and newborn status after ECV. Methods Analysis of assembled data of 327 consecutive ECVs in the third trimester was done. Results The total success rate was 56.6%. After a successful ECV, 85.9% of the fetuses were delivered vaginally. Logistic regression analysis of background factors leading to a successful ECV showed that tocolysis with ritodrine and anterior placenta were each significantly correlated with the rate of successful version. No severe complications were registered during the ECVs, and all babies had normal Apgar scores at delivery. Conclusion These findings suggest that attempting an ECV in breech presentations, once or even twice, seems to be an appropriate management given that a successful ECV decreases the rate of cesarean section in this group of patients and by doing so, it might also decrease the risk of cesarean sections in future pregnancies.

An RNAi screen of Rho signalling networks identifies RhoH as a regulator of Rac1 in prostate cancer cell migration.

BACKGROUND: Cell migration is essential for development and tissue repair, but it also contributes to disease. Rho GTPases regulate cell migration, but a comprehensive analysis of how each Rho signalling component affects migration has not been carried out. RESULTS: Through an RNA interference screen, and using a prostate cancer cell line, we find that approximately 25% of Rho network components alter migration. Some genes enhance migration while others decrease basal and/or hepatocyte growth factor-stimulated migration. Surprisingly, we identify RhoH as a screen hit. RhoH expression is normally restricted to haematopoietic cells, but we find it is expressed in multiple epithelial cancer cell lines. High RhoH expression in samples from prostate cancer patients correlates with earlier relapse. RhoH depletion reduces cell speed and persistence and decreases migratory polarity. Rac1 activity normally localizes to the front of migrating cells at areas of dynamic membrane movement, but in RhoH-depleted cells active Rac1 is localised around the whole cell periphery and associated with membrane regions that are not extending or retracting. RhoH interacts with Rac1 and with several p21-activated kinases (PAKs), which are Rac effectors. Similar to RhoH depletion, PAK2 depletion increases cell spread area and reduces cell migration. In addition, RhoH depletion reduces lamellipodium extension induced by PAK2 overexpression. CONCLUSIONS: We describe a novel role for RhoH in prostate cancer cell migration. We propose that RhoH promotes cell migration by coupling Rac1 activity and PAK2 to membrane protrusion. Our results also suggest that RhoH expression levels correlate with prostate cancer progression.

O-linked mucin-type glycosylation in breast cancer.

Changes in mucin-type O-linked glycosylation are seen in over 90% of breast cancers where increased sialylation is often observed and a change from branched glycans to linear glycans is often seen. There are many mechanisms involved including increased/altered expression of glycosyltransferases and relocalisation to the endoplasmic reticulum of the enzymes responsible for the addition of the first sugar, N-acetyl-d-galactosamine. It is now becoming clear that these changes can contribute to tumour growth and progression by modulating the micro-environment through glycan-sensing lectins expressed on immune cells, by modulating interactions with tumour surface receptors and by binding to selectins. The understanding of how changes in mucin-type O-linked glycosylation influence tumour growth and progression reveals new potential targets for therapeutic intervention in the treatment of breast cancer.

Pregnancy outcomes in patients with portal cavernoma: A case series study.

OBJECTIVE: Non-cirrhotic portal vein cavernoma (PVC) is a cause of portal hypertension (PH) frequently affecting women of childbearing age. Cavernous transformation of the portal vein is frequently associated with prothrombotic disorders and often entails multiple hemodynamic changes, porto-collateral shunt development and thrombopenia, all of which can affect the course of pregnancy. Our aim was to evaluate the risk of PH-related complications and pregnancy outcomes in patients with PVC. METHODS: Retrospective case series study of patients with PVC undergoing pregnancy in a tertiary care hospital. RESULTS: Eight pregnancies fulfilled the eligibility criteria. All patients had a predisposing factor for PVC. One episode of variceal bleeding was reported at week 28. Six cesarean sections were scheduled to avoid labor while two urgent surgeries were indicated due to fetal distress and intrauterine growth restriction (IUGR). In all but one case, anticoagulation was prescribed after delivery. No hemorrhagic or thrombotic complications were reported. There were four cases of IUGR with no case of miscarriage or stillbirth. CONCLUSION: Pregnancy in patients with PVC has an overall favorable outcome albeit a higher risk of PH-derived complications, and IUGR may be expected. Hence, PVC must not be considered a contraindication for pregnancy although larger prospective studies are necessary.

Status of breast cancer in Latin American: Results of the breast cancer revealed initiative.

The Breast Cancer Revealed initiative was designed and conducted to know the status of breast cancer at each point of breast cancer care, through i) prevention, ii) detection, iii) diagnosis, iv) treatment, and iv) the capacity of our health systems. The expert panel from 11 Latin American countries identified several strategies and proposed high impact priorities, including implementation of prevention policies, improve primary healthcare capacity for breast cancer screening, have adequate infrastructure to make effective and timely diagnoses, have a multidisciplinary team in the treatment process, access to a variety of treatments for all types of patients, have a coordinated and articulated system from primary care to specialized hospital. In a region with limited resources, prioritization in high-impact strategies for breast cancer control could lead to improved clinical outcomes and quality of life for our patients.

Recommendations for streamlining precision medicine in breast cancer care in Latin America.

BACKGROUND: The incidence of breast cancer (BC) in LMICs has increased by more than 20% within the last decade. In areas such as Latin America (LA), addressing BC at national levels evoke discussions surrounding fragmented care, limited resources, and regulatory barriers. Precision Medicine (PM), specifically companion diagnostics (CDx), links disease diagnosis and treatment for better patient outcomes. Thus, its application may aid in overcoming these barriers. RECENT FINDINGS: A panel of LA experts in fields related to BC and PM were provided with a series of relevant questions to address prior to a multi-day conference. Within this conference, each narrative was edited by the entire group, through numerous rounds of discussion until a consensus was achieved. The panel proposes specific, realistic recommendations for implementing CDx in BC in LA and other LMIC regions. In these recommendations, the authors strived to address all barriers to the widespread use and access mentioned previously within this manuscript. CONCLUSION: This manuscript provides a review of the current state of CDx for BC in LA. Of most importance, the panel proposes practical and actionable recommendations for the implementation of CDx throughout the Region in order to identify the right patient at the right time for the right treatment.

Proteome-wide prediction of bacterial carbohydrate-binding proteins as a tool for understanding commensal and pathogen colonisation of the vaginal microbiome.

Bacteria use carbohydrate-binding proteins (CBPs), such as lectins and carbohydrate-binding modules (CBMs), to anchor to specific sugars on host surfaces. CBPs in the gut microbiome are well studied, but their roles in the vagina microbiome and involvement in sexually transmitted infections, cervical cancer and preterm birth are largely unknown. We established a classification system for lectins and designed Hidden Markov Model (HMM) profiles for data mining of bacterial genomes, resulting in identification of >100,000 predicted bacterial lectins available at unilectin.eu/bacteria. Genome screening of 90 isolates from 21 vaginal bacterial species shows that those associated with infection and inflammation produce a larger CBPs repertoire, thus enabling them to potentially bind a wider array of glycans in the vagina. Both the number of predicted bacterial CBPs and their specificities correlated with pathogenicity. This study provides new insights into potential mechanisms of colonisation by commensals and potential pathogens of the reproductive tract that underpin health and disease states.

Maternal and perinatal outcomes in pregnancy-associated melanoma. Report of two cases and a systematic literature review.

OBJETIVES: Melanoma is one of the most frequent malignancies during gestation. However, oncological and perinatal management is still challenging. Our first objective is to describe the cases of pregnancy-associated melanoma (PAM) diagnosed in our centre between January-2004 and May-2015. Secondly, to perform a systematic review of the published articles analysing the maternal-perinatal outcomes of patients diagnosed with PAM. DESIGN, POPULATION AND METHODS: Obstetrical, oncological and perinatal variables were recorded in the case series. For the systematic review we include all published articles assessing the obstetric and neonatal outcomes in PAM cases in Pubmed, Web of Knowledge and Cochrane Library. The search was restricted to articles published in English, between January-2004 and May-2015. Study characteristics, oncological and maternal-perinatal variables were recorded in the systematic review. RESULTS: Two patients were found: the first case presents a newly diagnosed metastatic melanoma at 26-weeks of gestation with fatal maternal and neonatal outcome. The second case presents a patient with metastatic melanoma who got pregnant during her treatment. For the systematic review we found 25 articles, providing data from 489 patients. Maternal-perinatal outcomes, including termination of pregnancy rates, vary depending on the country, gestational age and tumour stage at diagnosis. PAM is usually detected at advanced stages, even with metastasis affecting the placenta and the foetus. CONCLUSIONS: When diagnosed at early stages, melanoma does not seem to alter the evolution of gestation, whereas patients with advanced stages of melanoma frequently deliver prematurely, by caesarean section, with lower neonatal weight, higher neonatal morbidity and mortality rates.

[ADHERENCE TO THE MEDITERRANEAN DIET AND HYDRATION IN SPANISH AND MOROCCAN POPULATIONS]. / SEGUIMIENTO DE LA DIETA MEDITERRÁNEA E HIDRATACIÓN DE LA POBLACIÓN ESPAÑOLA Y MARROQUÍ.

INTRODUCTION: southern European, Middle Eastern, and North African countries bordering the Mediterranean share dietary habits characterized by moderation and a variety of foods, notably fruit and vegetables. These customs are becoming modified due to social and economic changes. An adequate intake of water and other drinks is essential for a healthy diet. OBJECTIVE: to study adherence to the Mediterranean Diet (MD) and bottled water/beverage consumption in two Mediterranean populations. METHODS: adults from North-Western Morocco and Southern Spain (n = 400) completed a semi-quantitative food frequency questionnaire. The bottled waters they reported were then purchased locally (17 brands in Morocco, 30 in Southern Spain) for ionic-exchange chromatography study. RESULTS: cation values (mg/L) ranged from 140.16 to 439 for C, 53.15 to 87.5 for Mg, 1169.78 to 257.2 for Na, and 50.26 to 26.5 mg/L for K, i.e. waters with medium mineralization levels. No cation supplied > 7% of the recommended dietary allowance (RDA) in either population. MD adherence was higher in the Spanish (6.28 ± 1.38) versus Moroccan (4.42 ± 1.52) population. There is a substantial intake of water through the MD due to its elevated fruit/vegetable content. Consumption of bottled water, infusions, and juices was higher in the Moroccan population; consumption of beer and other alcoholic drinks was higher in the Spanish population. The total liquid consumption was higher in the Moroccan population. The drinks intake profile permits classification of the populations, with odds ratios ranging from 1.6 to 11.01 for a higher intake of juices, soft drinks, tea, bottled water, and total liquids in the Moroccan versus Spanish population.

Introducción: la dieta mediterránea (DM) comprende la ribera europea, africana y asiática del mar Mediterráneo. Características de la DM son variedad de alimentos y sobriedad. Junto a los nutrientes, es esencial la ingesta de agua y bebidas. Objetivo: estudiar la DM y la contribución del agua y las bebidas a la hidratación de dos poblaciones de la ribera mediterránea. Métodos: adultos procedentes del noroeste de Marruecos y sur de España (n = 400), completaron un cuestionario semi-cuantitativo de frecuencia de consumo de alimentos. Se analizó agua envasada consumida por la población y comprada en el mercado local (17 marcas/ tipos en Marruecos y 30 en el sur de España). Resultados: por cromatografía de intercambio iónico se analizaron diversas sales. El rango fue: Ca entre 140,16 y 439 mg/L; Mg entre 53,15 y 87,5 mg/L; Na entre 1169,78 y 257,2 mg/L y K 50,26 y 26,5 mg/L, valores tanto para muestras españolas como marroquís. Son aguas de mineralización media y su ingesta de minerales no contribuye más del 7% a la RDA de las poblaciones estudiadas. El seguimiento de la DM es superior en la población española (6,28 ± 1,38) que en la marroquí (4,42 ± 1,52). El perfil de ingesta de bebidas permite clasificar a la población al encontrar valores OR que van desde 1,6 a 11,01 para mayor ingesta de zumo, refrescos, te, agua envasada y total de ingesta de líquidos para la población marroquí frente a la española. Conclusión: el consumo de aguas envasadas no supone un suplemento mineral de interés en estas poblaciones.

A new case of successful outcome of pregnancy in a carrier of homozygous type II (L99F) antithrombin deficiency.

Inherited antithrombin deficiency is associated with an increased risk of venous thromboembolism. There is no consensus about pregnancy management in antithrombin deficiency patients because there are very few cases published in the literature. We report a successful pregnancy in a 32-year-old female carrier of a homozygous type II (L99F) antithrombin deficiency who developed a spontaneous deep vein thrombosis at the age of 27 years.

Estudio observacional sobre el grado de conocimiento de los pacientes acerca del tratamiento con acenocumarol / Observational study on patients' degree of knowledge about the treatment with acenocoumarol

Introducción: El tratamiento con anticoagulantes orales derivados de cumarinas como el acenocumarol es bastante complejo pues, además de presentar un estrecho margen terapéutico, pueden interaccionar con numerosos fármacos, alimentos o productos de herbolario, favoreciendo la aparición de reacciones adversas y comprometiendo la seguridad del paciente anticoagulado. Objetivos: El objetivo de este trabajo ha sido evaluar la relación entre el grado de conocimiento del paciente en tratamiento con acenocumarol y la aparición de efectos adversos derivados del mismo. Métodos: Se realizó un estudio observacional descriptivo en 30 pacientes de 3 oficinas de farmacia y un centro de atención primaria de la Comunidad de Madrid. Para ello, se elaboró un cuestionario basado en el de Zeolla y cols. (2016), validado en EE.UU. para pacientes en tratamiento con warfarina y adaptado a nuestra zona geográfica y al tratamiento con acenocumarol. Resultados: Del 67% de los pacientes encuestados que afirmaron haber solicitado y obtenido consejo sobre el tratamiento con acenocumarol, sólo el 56% adquirió un grado de conocimiento adecuado y únicamente el 29% demostró conocer los medicamentos y productos de herbolario/dietéticos que debe evitar el paciente anticoagulado. Además, se observó que dicho grado de conocimiento era significativamente mayor en los pacientes que no habían presentado efectos adversos asociados al tratamiento anticoagulante con anterioridad. Conclusiones: Un adecuado grado de conocimiento acerca del tratamiento con acenocumarol y las posibles interacciones del mismo con otros medicamentos que no requieren prescripción médica o productos de herbolario/dietéticos reduce significativamente el riesgo de presentar efectos adversos asociados al tratamiento anticoagulante

Introduction: Treatment with oral anticoagulants derived from coumarins such as acenocoumarol is quite complex since, apart from having a narrow therapeutic margin, they can interact with numerous drugs, food or herbal products, favoring the appearance of adverse reactions and compromising the safety of the anticoagulated patient. Objectives: The main objective of this study was to evaluate the relationship between the patient’s degree of knowledge about the treatment with acenocumarol and the appearance of adverse effects derived from it. Methods: A descriptive observational study was performed in 30 patients from 3 pharmacy offices and a primary care center in the Comunidad de Madrid. For this, we adapted to our geographical area and treatment with acenocumarol a questionnaire based on the one from Zeolla et al. (2016), validated in the USA for patients on warfarin therapy. Results: Among the 67% of patients surveyed who claimed to have sought and obtained advice on acenocoumarol treatment, only 56% acquired adequate knowledge and only 29% demonstrated to be awared of the drugs and herbal/dietary products that should be avoided by anticoagulated patients. In addition, it was observed that the degree of knowledge was significantly higher in patients who had not presented adverse effects associated with anticoagulant treatment. Conclusions: An adequate knowledge about the treatment with acenocoumarol and the fact of knowing which medications that do not need prescription, herbal and dietary products have to be avoided, reduces the risk of adverse effects associated with such treatment

Marco de referencia de la aplicación de manufactura esbelta en la industria / A framework for the implementation of lean manufacturing in the industry

RESUMEN: 21. Actualmente las empresas que aplican las herramientas de Manufactura Esbelta cometen el error de implementarlas de manera aislada para cubrir las necesidades de mejora a un corto plazo, por lo que obtienen beneficios limitados. Se presenta una revisión de litera tura relacionada con la implementación de herramientas de Manufactura Esbelta en la Industria, tales como Takt Time, 5's, Ocho desperdicios "mudas", Control Visual, Células de Manufactura, a prueba de errores (Poka-Yoke), Nivelación de la producción (Heijunka), Automatización inteligente (Jidoka), Mejora continua (Kaizen), Kanban, Cambios rápidos de modelo (SMED), Mantenimiento total de la producción (TPM), Justo a tiempo (JIT) y Mapeo del flujo de valor (VSM), analizando su aplicación tanto individual como en conjunto. Se visualiza que las 5'S, el VSM, Kaizen, Kanban y TPM son las más utilizadas en el ramo Manufacturero con un 9,46%, 8.1%, 6,75%, 5,4% y 4,05% respectivamente, y SMED con un 4,05% y JET con un 6,76% en el sector Automotriz; caso contrario, las Células de Manufactura, Heijunka y Andon son las menos utilizadas (en 1,35%).

ABSTRACT: 26. Currently the industries that apply Len Manufacturing tools commit the mistake of implement them in insolation to meet short-term improvement needs, so that, they obtain limited benefits. A literature review present is related with the implementation of Lean Manufacturing tools in the industry, such as Takt Time, 5's, Eight wastes "mudas", Visual Control, Manufacturing Cells, mistake proof ing (Poka-Yoke), Leveling production (Heijunka), Intelligent automa tion (Jidoka), Continuous improvement (Kaizen), Kanban, Quick changeover of model (SMED), Total productive maintenance (TPM), Just in time (JIT) and Value stream map (VSM), analyzing their application both individual and in assemblage. It is visualized that the 5's, the VSM, Kaizen, Kanban and TPM are the most utilized tools in the Manufacturing branch with 9.46%, 8.1%, 6.75%, 5.4% and 4.05% respectively, and SMED with 4.05% and JIT with 6.76% in the Automotive sector, otherwise, the Manufacturing Cells, Heijunka and Andon are the least used in 1.35%.

Intravenous immunoglobulin treatment increased live birth rate in a Spanish cohort of women with recurrent reproductive failure and expanded CD56(+) cells.

PROBLEM: Natural killer (NK, CD3(-)CD56(+)/CD16(+)) and NKT-like cells (CD3(+)CD56(+)/CD16(+)) activity is considered among the key factors for reproductive success. In the absence of immunological screening, beneficial effects of intravenous immunoglobulin (IVIG) in preventing recurrent reproductive failure (RRF) have not been reported. Here, we analyse the IVIG influence on pregnancy success in women with RRF and circulating NK or/and NKT-like cells expansion. METHOD OF STUDY: One hundred fifty-seven women with previous recurrent miscarriage and/or recurrent implantation failure after in vitro fertilization were consecutively studied. Sixty-four patients with CD56(+) cell expansion, no apparent underlying disease and who maintained their desire to conceive were selected. Forty of them received IVIG during pregnancy. RESULTS: Overall, the clinical pregnancy rate for the women under IVIG therapy was 92.5% and the live birth rate was 82.5%. Significantly lower pregnancy and live birth rates (25% and 12.5%, respectively) were observed for the patients with recurrent pregnancy loss and NK/NKT-like cells expansion without IVIG. After three cycles of IVIG, NK cell percentages decreased significantly and these values persisted throughout gestation. CONCLUSION: Intravenous immunoglobulin therapy for women with RRF and NK or NKT-like cell expansion was a safe and beneficial therapeutic strategy that associated with high clinical pregnancy and live birth rates.

Hodgkin's lymphoma presenting as dominant gastric lesion in immunocompetent patients: report of 5 cases with EBV analysis.

Primary Hodgkin's lymphoma (HL) of the stomach is an extremely rare entity. Most cases of gastric involvement by HL are observed in the setting of disseminated disease. The nonspecific nature of the symptoms and endoscopic findings, which include a large malignant-looking ulcer and mass or wall thickening, together with the considerable histological overlap between HLs and some non-HLs or undifferentiated carcinoma, make the surgical resection diagnosis extremely difficult. An accurate diagnosis is important as treatment and outcome differ significantly for these neoplasms. In small endoscopic gastric biopsies and even in postoperative specimens, the precise histological diagnosis of HL is particularly challenging. Here, the authors report 5 cases of 2 women and 3 men aged 22 to 68, with gastric involvement by classic HLs-3 primary gastric HLs and 2 as part of widespread disease. All 5 patients presented with digestive symptoms. At endoscopy, the lesions presented as ulcerated and elevated lesions, with or without mucosal thickening. Four patients were misdiagnosed in the preoperative biopsy or in the gastrectomy specimen. Association with Epstein-Barr virus (EBV) was detected in 4 cases, with a predominance of subtype A EBV. These cases illustrate the significant difficulties, both clinical and pathological, in achieving the diagnosis of HL involving the stomach in immunocompetent patients.

Modelos de ecuaciones estructurales: Características, fases, construcción, aplicación y resultados / Structural equation modeling: Features, phases, construction, implementation and results

Se exponen las características y fases de los modelos de ecuaciones estructurales, así como las etapas de construcción, siendo estas la especificación, identificación, estimación de parámetros, evaluación del ajuste, reespecificación del modelo y la interpretación de resultados. Se presenta el análisis factorial exploratorio y confirmatorio como parte para la construcción de un modelo. Se detallan algunos paquetes computacionales como el LISREL, AMOS y SPSS. A modo de ejemplificar los modelos de ecuaciones estructurales, se realiza un estudio en la población docente de tiempo completo del departamento de ingeniería Industrial y Manufactura de una universidad pública de Ciudad Juárez, Chihuahua, México. Se estudia el impacto de los factores socioculturales y ergoambientales en la satisfacción laboral, obteniendo un modelo resultante en el que se detallan las variables más y menos significativas. No se rechazan las cuatro hipótesis cuyos valores son 0,06, 0,06, 0,071, 0,074, respectivamente.

The characteristics and phases of structural equation modeling and construction phases, and these are the specification, identification, parameter estimation, assessment of adjustment, re-specification of the model and the interpretation of results are shown. The exploratory and confirmatory factor analysis as part for the construction of a model is presented. Some software packages like LISREL, AMOS and SPSS are detailed. By way of illustrating the structural equation modeling, a study was performed on the population of full-time faculty of the Department of Industrial Engineering and Manufacturing of a public university in Ciudad juarez, Chihuahua, Mexico. The impact of sociocultural and ergoambientales factors in getting a job satisfaction resulting model in which more and less significant variables detailed studied. The four scenarios whose values are 0,06, 0,06, 0,071, 0,074 respectively can not refuse.