Valuacion del Control Interno en Politicas y Procedimientos en el area de redito de la Union de Cooperativas Agropecuarias y de Servicios "Agusto Cesar Sandino RL. (UCASACS,RL) en el Año 2013

El presente trabajo Monográfico fue elaborado con dedicación y esmero en búsqueda de resolver la problemática de la UNION DE COOPERATIVAS AGROPECUARIAS Y DE SERVICIOS “AUGUSTO C SANDINO”R.L, en su departamento de Crédito durante el periodo 2013; En el transcurso de nuestra investigación nos dimos cuenta de que los problemas correspondían a deficiencias de control interno altamente ligados con su políticas y procedimientos de crédito. Con el interés en el tema, investigamos las leyes vigentes que rigen a las cooperativas, estudiamos la teoría ligada al control interno según el informe COSO I, nos indagamos de sus procedimientos y estudiamos sus políticas de crédito, realizamos una evaluación metodológica conforme a los componentes del COSOI. Todo esto nos dio una base razonable para llegar a nuestras conclusiones y dar las recomendaciones pertinentes. Nuestro trabajo dio una pauta a la UCASACS R.L para mejorar en uno de sus departamentos y también servirá como prototipo en las organizaciones para que estas mejoren sus procesos contemplando la importancia que tienen los manuales y políticas de procedimientos y la incidencia que estos tienen sobre el control interno de toda institución

Cri-du-chat syndrome mimics Silver-Russell syndrome depending on the size of the deletion: a case report

BackgroundSilver-Russell Syndrome (SRS) is a rare growth-related genetic disorder mainly characterized by prenatal and postnatal growth failure. Although molecular causes are not clear in all cases, the most common mechanisms involved in SRS are loss of methylation on chromosome 11p15 (approximate to 50%) and maternal uniparental disomy for chromosome 7 (upd(7)mat) (approximate to 10%).Case presentationWe present a girl with clinical suspicion of SRS (intrauterine and postnatal growth retardation, prominent forehead, triangular face, mild psychomotor delay, transient neonatal hypoglycemia, mild hypotonia and single umbilical artery). Methylation and copy number variations at chromosomes 11 and 7 were studied by methylation-specific multiplex ligation-dependent probe amplification and as no alterations were found, molecular karyotyping was performed. A deletion at 5p15.33p15.2 was identified (arr[GRCh37] 5p15.33p15.2(25942-11644643)x1), similar to those found in patients with Cri-du-chat Syndrome (CdCS). CdCS is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-), whose main feature is a high-pitched mewing cry in infancy, accompanied by multiple congenital anomalies, intellectual disability, microcephaly and facial dysmorphism.ConclusionsThe absence of some CdCS features in the current patient could be due to the fact that in her case the critical regions responsible do not lie within the identified deletion. In fact, a literature review revealed a high degree of concordance between the clinical manifestations of the two syndromes.The costs of the publication and molecular analyses of this research were funded by grants from Instituto de Salud Carlos III (Institute of Health Carlos III) of the Spanish Ministry of Economy and Competitiveness, co-financed by the European Regional Development Fund (PI16/00073), the Department of Health of the Basque Government (GV2016111105; GV2017111040), and the University of the Basque Country UPV/EHU (PIF17/29)

Model for High-Throughput Screening of drug immunotoxicity - study of the antimicrobial G1 over peritoneal macrophages using flow cytometry

Modelos matematicos y citometriaQuantitative Structure-Activity (mt-QSAR) techniques may become an important tool for prediction of cytotoxicity and High-throughput Screening (HTS) of drugs to rationalize drug discovery process. In this work, we train and validate by the first time mt-QSAR model using TOPS-MODE approach to calculate drug molecular descriptors and Linear Discriminant Analysis (LDA) function. This model correctly classifies 8,258 out of 9,000 (Accuracy = 91.76%) multiplexing assay endpoints of 7903 drugs (including both train and validation series). Each endpoint correspond to one out of 1418 assays, 36 molecular and cellular targets, 46 standard type measures, in two possible organisms (human and mouse). After that, we determined experimentally, by the first time, the values of EC50 = 21.58 μg/mL and Cytotoxicity = 23.6 % for the anti-microbial / antiparasite drug G1 over Balb/C mouse peritoneal macrophages using flow cytometry. In addition, the model predicts for G1 only 7 positive endpoints out 1,251 cytotoxicity assays (0.56% of probability of cytotoxicity in multiple assays). The results obtained complement the toxicological studies of this important drug. This work adds a new tool to the existing pool of few methods useful for multi-target HTS of ChEMBL and other libraries of compounds towards drug discovery.Conacy

T-cell epitopes of the major peach allergen, Pru p 3: Identification and differential T-cell response of peach-allergic and non-allergic subjects

Lipid transfer proteins (LTPs), particularly peach Pru p 3, are the most relevant plant food allergens in the South of Europe, and, therefore, their allergic properties have been extensively studied. However, neither T-cell epitopes nor their effect on the patients’ T-cell response has been investigated in any member of the LTP panallergen family. The objective of the present study was to map the major T-cell epitopes of Pru p 3, as well as to evaluate their induced T-cell response in peach-allergic versus control subjects. Thus, peripheral blood mononuclear cells (PBMCs) from 18 peach-allergic patients and Pru p 3-specific T-cell lines (TCLs) from 9 of them were cultured with Pru p 3 and with a panel of 17 derived peptides (10-mer overlapping in 5 amino acids representing the full sequence of Pru p 3). Proliferation in 5-day assays was carried out via tritiated-thymidine incorporation, while IL4 and IFNγ production was assessed via sandwich enzyme-linked immunosorbent tests (ELISA) of TCL culture supernatants. The results were compared to those obtained from 10 non-peach allergic control volunteers. Two consecutive peptides showed the highest activation capacity. About 74% of PBMCs and TCLs recognized them, forming a single T-epitope: Pru p 365–80. Additionally, other specific T-cell epitopes were observed. Pru p 325–35 was detected by more than 60% of TCLs from peach-allergic patients, and Pru p 345–55 only activated PBMCs from control subjects. Interestingly, TCLs from patients were associated with a Th2-type, whereas control TCLs presented a Th1-type cytokine response. The major immunogenic T-cell epitope identified in Pru p 3, Pru p 365–80, is a good candidate to develop new vaccines for hypersensitivity reactions associated with LTP allergens from Rosaceae fruits

Methodological Strategies That Benefit Students With ADHD

El abordaje de las necesidades educativas especiales (NEE) dentro del aula es un gran desafío para los docentes en la actualidad, ya que al querer generar mayor inclusión dentro de la educación se hace un poco más dificil al momento de escoger estrategias que vayan acorde a cada necedidad específica de los estudiantes; especialmente en los estudiantes que presentan TDAH ya que al ser un trastorno del neurodesarrollo tan extenso, se presenta en una amplia gama de dimensiones que hace que cada niño presente una peculiaridad. En este último tiempo se ha tomado muy a consideración el implementar diferentes estrategias metodológicas para reforzar y motivar el aprendizaje y complementarlo. Por ello, el objetivo principal es analizar y desarrollar estrategias metodológicas efectivas que beneficien a estudiantes con Trastorno por Déficit de Atención e Hiperactividad (TDAH) en su proceso de aprendizaje, promoviendo un entorno educativo inclusivo y facilitando su participación activa en el séptimo de básica de la Unidad Educativa XXX. La metodología utilizada fue de tipo descriptiva y documental. Se aplicó a una muestra no probabilística de diez docentes los cuales respondieron una encuesta para poder medir la aplicación de diferentes estrategias metodológicas dentro del aula en los estudiantes con TDAH y evidenciar si los docentes los utilizan de una manera adecuada e inclusiva. Los resultados obtenidos fueron que las diferentes estrategias metodológicas son herramientas de gran utlidad para reforzar y motivar el aprendizaje de estudiantes con TDAH.Addressing special educational needs (SEN) within the classroom is a great challenge for teachers today, since wanting to generate greater inclusion within education makes it a little more difficult when choosing strategies that are in accordance with each specific need of the students; especially in students who have ADHD since it is such an extensive neurodevelopmental disorder, it occurs in a wide range of dimensions that makes each child present a peculiarity. In recent times, great consideration has been given to implementing different methodological strategies to reinforce and motivate learning and complement it. Therefore, the main objective is to analyze and develop effective methodological strategies that benefit students with Attention Deficit Hyperactivity Disorder (ADHD) in their learning process, promoting an inclusive educational environment and facilitating their active participation in the seventh grade of basic education. Educational Unit XXX. The methodology used was descriptive and documentary. It was applied to a non-probabilistic sample of ten teachers who responded to a survey to measure the application of different methodological strategies within the classroom in students with ADHD and to demonstrate whether teachers use them in an appropriate and inclusive way. The results obtained were that the different methodological strategies are very useful tools to reinforce and motivate the learning of students with ADHD

TRPV4 Channels Promote Pathological, but Not Physiological, Cardiac Remodeling through the Activation of Calcineurin/NFAT and TRPC6

TRPV4 channels, which respond to mechanical activation by permeating Ca2+ into the cell, may play a pivotal role in cardiac remodeling during cardiac overload. Our study aimed to investigate TRPV4 involvement in pathological and physiological remodeling through Ca2+-dependent signaling. TRPV4 expression was assessed in heart failure (HF) models, induced by isoproterenol infusion or transverse aortic constriction, and in exercise-induced adaptive remodeling models. The impact of genetic TRPV4 inhibition on HF was studied by echocardiography, histology, gene and protein analysis, arrhythmia inducibility, Ca2+ dynamics, calcineurin (CN) activity, and NFAT nuclear translocation. TRPV4 expression exclusively increased in HF models, strongly correlating with fibrosis. Isoproterenol-administered transgenic TRPV4-/- mice did not exhibit HF features. Cardiac fibroblasts (CFb) from TRPV4+/+ animals, compared to TRPV4-/-, displayed significant TRPV4 overexpression, elevated Ca2+ influx, and enhanced CN/NFATc3 pathway activation. TRPC6 expression paralleled that of TRPV4 in all models, with no increase in TRPV4-/- mice. In cultured CFb, the activation of TRPV4 by GSK1016790A increased TRPC6 expression, which led to enhanced CN/NFATc3 activation through synergistic action of both channels. In conclusion, TRPV4 channels contribute to pathological remodeling by promoting fibrosis and inducing TRPC6 upregulation through the activation of Ca2+-dependent CN/NFATc3 signaling. These results pose TRPV4 as a primary mediator of the pathological response

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease.This work was supported by grants from the Spanish MINECO-ISCIII (PI12/02591, PI12/00624) and FEDER (European Funds for Regional Development); the Centro en Red for Regenerative Medicine and Cellular Therapy from Castilla y León; the Spanish Health Thematic Network of Cooperative Research in Cancer (RTICC RD12/0056/0058 and RD12/0036/0003), and Spanish FIS (PS09/01897 and PS09/00843). AG-G received support from the Centro en Red for Regenerative Medicine and Cellular Therapy from Castilla y León and from the Spanish Society of Hematology and Hemotherapy (SEHH), and EDR from the Spanish Association for Cancer Research (AECC

Mapping of Genetic Abnormalities of Primary Tumours from Metastatic CRC by High-Resolution SNP Arrays

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: For years, the genetics of metastatic colorectal cancer (CRC) have been studied using a variety of techniques. However, most of the approaches employed so far have a relatively limited resolution which hampers detailed characterization of the common recurrent chromosomal breakpoints as well as the identification of small regions carrying genetic changes and the genes involved in them. [Methodology/Principal Findings]: Here we applied 500K SNP arrays to map the most common chromosomal lesions present at diagnosis in a series of 23 primary tumours from sporadic CRC patients who had developed liver metastasis. Overall our results confirm that the genetic profile of metastatic CRC is defined by imbalanced gains of chromosomes 7, 8q, 11q, 13q, 20q and X together with losses of the 1p, 8p, 17p and 18q chromosome regions. In addition, SNP-array studies allowed the identification of small (1.5 Mb) altered DNA sequences, many of which contain cancer genes known to be involved in CRC and the metastatic process. Detailed characterization of the breakpoint regions for the altered chromosomes showed four recurrent breakpoints at chromosomes 1p12, 8p12, 17p11.2 and 20p12.1; interestingly, the most frequently observed recurrent chromosomal breakpoint was localized at 17p11.2 and systematically targeted the FAM27L gene, whose role in CRC deserves further investigations. [Conclusions/Significance]: In summary, in the present study we provide a detailed map of the genetic abnormalities of primary tumours from metastatic CRC patients, which confirm and extend on previous observations as regards the identification of genes potentially involved in development of CRC and the metastatic process.This work has been partially supported by grants from the Consejeria de Sanidad, Junta de Castilla y Leon, Valladolid, Spain (SAN191/SA09/06 and SAN673/SA39/08), Fundacion Memoria de Don Samuel Solorzano Barruso, Salamanca, Spain, Caja de Burgos (Obra Social), Burgos, Spain, Grupo Excelencia de Castilla y Leon (GR37) and the RTICC from the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovacion, Madrid, Spain (RD06/0020/0035-FEDER). JM Sayagués, M Gonzalez, ME Sarasquete and MC Chillon are supported by grants (CP05/00321, FI08/00721, CA08/00212 and CA/07/00077, respectively) from the ISCIII, Ministerio de Ciencia e Innovación, Madrid, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Comparison of uniportal robotic-assisted thoracic surgery pulmonary anatomic resections with multiport robotic-assisted thoracic surgery: a multicenter study of the European experience

Background: Robotic-assisted thoracic surgery (RATS) has seen increasing interest in the last few years, with most procedures primarily being performed in the conventional multiport manner. Our team has developed a new approach that has the potential to convert surgeons from uniportal video-assisted thoracic surgery (VATS) or open surgery to robotic-assisted surgery, uniportal-RATS (U-RATS). We aimed to evaluate the outcomes of one single incision, uniportal robotic-assisted thoracic surgery (U-RATS) against standard multiport RATS (M-RATS) with regards to safety, feasibility, surgical technique, immediate oncological result, postoperative recovery, and 30-day follow-up morbidity and mortality. Methods: We performed a large retrospective multi-institutional review of our prospectively curated database, including 101 consecutive U-RATS procedures performed from September 2021 to October 2022, in the European centers that our main surgeon operates in. We compared these cases to 101 consecutive M-RATS cases done by our colleagues in Barcelona between 2019 to 2022. Results: Both patient groups were similar with respect to demographics, smoking status and tumor size, but were significantly younger in the U-RATS group [M-RATS =69 (range, 39-81) years; U-RATS =63 years (range, 19-82) years; P<0.0001]. Most patients in both operative groups underwent resection of a primary non-small cell lung cancer (NSCLC) [M-RATS 96/101 (95%); U-RATS =60/101 (59%); P<0.0001]. The main type of anatomic resection was lobectomy for the multiport group, and segmentectomy for the U-RATS group. In the M-RATS group, only one anatomical segmentectomy was performed, while the U-RATS group had twenty-four (24%) segmentectomies (P=0.0006). All M-RATS and U-RATS surgical specimens had negative resection margins (R0) and contained an equivalent median number of lymph nodes available for pathologic analysis [M-RATS =11 (range, 5-54); U-RATS =15 (range, 0-41); P=0.87]. Conversion rate to thoracotomy was zero in the U-RATS group and low in M-RATS [M-RATS =2/101 (2%); U-RATS =0/101; P=0.19]. Median operative time was also statistically different [M-RATS =150 (range, 60-300) minutes; U-RATS =136 (range, 30-308) minutes; P=0.0001]. Median length of stay was significantly lower in U-RATS group at four days [M-RATS =5 (range, 2-31) days; U-RATS =4 (range, 1-18) days; P<0.0001]. Rate of complications and 30-day mortality was low in both groups. Conclusions: U-RATS is feasible and safe for anatomic lung resections and comparable to the multiport conventional approach regarding surgical outcomes. Given the similarity of the technique to uniportal VATS, it presents the potential to convert minimally invasive thoracic surgeons to a robotic-assisted approach