Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluación de conocimientos y prácticas sobre la leishmaniasis tegumentaria en un área endémica de Venezuela

Introduccion. La leishmaniasis es un grave problema de salud publica en muchas partes de America. Las poblaciones expuestas a la leishmaniasis carecen de informacion de la enfermedad, razon por la cual es necesario realizar intervenciones y evaluaciones educativas que contribuyan a que el control tenga un mayor impacto. Objetivo. Determinar el nivel de conocimientos y practicas sobre la leishmaniasis tegumentaria y la fauna de flebotomos en las comunidades endemicas de Bolero Alto y Bajo del municipio Pinto Salina del Estado Merida, Venezuela, entre septiembre de 2006 y julio de 2007. Materiales y metodos. Se elaboro una encuesta en la cual se incluyeron aspectos epidemiologicos, de prevencion y de control de la leishmaniasis. Se aplicaron a personas mayores de siete anos en viviendas seleccionadas aleatoriamente. Tambien se realizaron capturas intradomiciliarias y peridomiciliarias de flebotominos vectores. Resultados. Mas del 68% de los individuos de las comunidades poseia un nivel de conocimientos considerado como insuficiente; los aspectos de mayor desconocimiento fueron en relacion con la transmision y la prevencion. Se detectaron siete especies de Lutzomyia de importancia epidemiologica: L youngi, L. ovallesi, L. gomezi, L. walkeri, L. panamensis, L. punctigeniculata y L. venezuelensis. Las especies predominantes para ambas comunidades fueron L. youngi con mas del 55% y L. ovallesi con mas del 24% del total de especimenes capturados. Conclusion. Se determino un bajo nivel de conocimientos sobre la leishmaniasis en los pobladores de las comunidades endemicas estudiadas, lo cual se debe tener en cuenta en el desarrollo de alternativas educativas de impacto en el control complementario de la enfermedad. Las mismas deben dirigirse a cubrir las deficiencias de conocimientos mas acentuadas en la poblacion, enfocadas a evitar las picaduras del insecto vector.
Identification of a sustained neurogenic zone at the dorsal surface of the adult mouse hippocampus and its regulation by the chemokine SDF‐1

We identified a previously unknown neurogenic region at the dorsal surface of the hippocampus; (the “subhippocampal zone,” SHZ) in the adult brain. Using a reporter mouse in which SHZ cells and their progeny could be traced through the expression of EGFP under the control of the CXCR4 chemokine receptor promoter we observed the presence of a pool of EGFP expressing cells migrating in direction of the dentate gyrus (DG), which is maintained throughout adulthood. This population appeared to originate from the SHZ where cells entered a caudal migratory stream (aCMS) that included the fimbria, the meninges and the DG. Deletion of CXCR4 from neural stem cells (NSCs) or neuroinflammation resulted in the appearance of neurons in the DG, which were the result of migration of NSCs from the SHZ. Some of these neurons were ectopically placed. Our observations indicate that the SHZ is a neurogenic zone in the adult brain through migration of NSCs in the aCMS. Regulation of CXCR4 signaling in these cells may be involved in repair of the DG and may also give rise to ectopic granule cells in the DG in the context of neuropathology. © 2015 Wiley Periodicals, Inc.
Effects of spaced learning in the water maze on development of dentate granule cells generated in adult mice

New dentate granule cells (GCs) are generated in the hippocampus throughout life. These adult‐born neurons are required for spatial learning in the Morris water maze (MWM). In rats, spatial learning shapes the network by regulating their number and dendritic development. Here, we explored whether such modulatory effects exist in mice. New GCs were tagged using thymidine analogs or a GFP‐expressing retrovirus. Animals were exposed to a reference memory protocol for 10–14 days (spaced training) at different times after newborn cells labeling. Cell proliferation, cell survival, cell death, neuronal phenotype, and dendritic and spine development were examined using immunohistochemistry. Surprisingly, spatial learning did not modify any of the parameters under scrutiny including cell number and dendritic morphology. These results suggest that although new GCs are required in mice for spatial learning in the MWM, they are, at least for the developmental intervals analyzed here, refractory to behavioral stimuli generated in the course of learning in the MWM. © 2015 Wiley Periodicals, Inc.
Further understanding of the immunopathology of multiple sclerosis: impact on future treatments

ABSTRACT Introduction: The understanding of the immunopathogenesis of multiple sclerosis (MS) has expanded with more research into T-cell subtypes, cytokine contributors, B-cell participation, mitochondrial dysfunction, and more. Treatment options have rapidly expanded with three relatively recent oral therapy alternatives entering the arena. Areas covered: In the following review, we discuss current mechanisms of immune dysregulation in MS, how they relate to current treatments, and the impact these findings will have on the future of therapy. Expert commentary: The efficacy of these medications and understanding their mechanisms of actions validates the immunopathogenic mechanisms thought to underlie MS. Further research has exposed new targets, while new promising therapies have shed light on new aspects into the pathophysiology of MS.
Greater loss of object than spatial mnemonic discrimination in aged adults

Previous studies across species have established that the aging process adversely affects certain memory‐related brain regions earlier than others. Behavioral tasks targeted at the function of vulnerable regions can provide noninvasive methods for assessing the integrity of particular components of memory throughout the lifespan. The present study modified a previous task designed to separately but concurrently test detailed memory for object identity and spatial location. Memory for objects or items is thought to rely on perirhinal and lateral entorhinal cortices, among the first targets of Alzheimer's related neurodegeneration. In line with prior work, we split an aged adult sample into “impaired” and “unimpaired” groups on the basis of a standardized word‐learning task. The “impaired” group showed widespread difficulty with memory discrimination, whereas the “unimpaired” group showed difficulty with object, but not spatial memory discrimination. These findings support the hypothesized greater age‐related impacts on memory for objects or items in older adults, perhaps even with healthy aging. © 2015 Wiley Periodicals, Inc.
Abnormal hippocampal structure and function in clinical anxiety and comorbid depression

Given the high prevalence rates of comorbidity of anxiety and depressive disorders, identifying a common neural pathway to both disorders is important not only for better diagnosis and treatment, but also for a more complete conceptualization of each disease. Hippocampal abnormalities have been implicated in anxiety and depression, separately; however, it remains unknown whether these abnormalities are also implicated in their comorbidity. Here we address this question by testing 32 adults with generalized anxiety disorder (15 GAD only and 17 comorbid MDD) and 25 healthy controls (HC) using multimodal MRI (structure, diffusion and functional) and automated hippocampal segmentation. We demonstrate that (i) abnormal microstructure of the CA1 and CA2‐3 is associated with GAD/MDD comorbidity and (ii) decreased anterior hippocampal reactivity in response to repetition of the threat cue is associated with GAD (with or without MDD comorbidity). In addition, mediation‐structural equation modeling (SEM) reveals that our hippocampal and dimensional symptom data are best explained by a model describing a significant influence of abnormal hippocampal microstructure on both anxiety and depression—mediated through its impact on abnormal hippocampal threat processing. Collectively, our findings show a strong association between changes in hippocampal microstructure and threat processing, which together may present a common neural pathway to comorbidity of anxiety and depression. © 2016 Wiley Periodicals, Inc.
Use of Tissue Microarray and Automated Quantitative Analysis for Screening and Validation of Potential Biomarkers in Mantle Cell Lymphoma

BackgroundCancer biomarker studies using the combination of tissue microarray and automated quantitative assessment of immunofluorescence (TMA-AQUA) have been successfully performed for various types of human carcinoma, but its performance characteristics have yet to be evaluated in human lymphoma. MethodsA pilot TMA was constructed containing duplicate 1.5 mm cores from 15 cases of mantle cell lymphoma (MCL), 3 cases of low-grade B-cell lymphoma, and 3 cases of benign lymphoid tissue. Protein expression of c-Myc, Cdc2, Cyclin D1, Ki-67, Mcm2, and p27 by immunofluorescence and chromagenic staining were evaluated by AQUA and visual scoring, respectively. Gene expression of cMYC, CDC2, and CCND1 was determined by quantitative nuclease protection assay. ResultsProtein expression between duplicate cores determined by AQUA showed excellent correlation for all markers [correlation coefficient (R)=0.79 to 0.94] and Cyclin D1 expression was significantly higher in MCL cases compared with non-MCL cases (P=0.00019). Overall correlation of AQUA with scoring of chromagenic staining by 2 pathologists was good for all markers (R=0.56 to 0.90), except Cdc2 (R=0.25). Localization of expression to cytoplasmic and/or nuclear compartments was comparable with chromagenic staining patterns for all markers except Ki-67 and Mcm2, where a significant difference between nuclear and cytoplasmic expression could not be appreciated by AQUA, despite clear nuclear localization by chromagenic staining. Correlation of gene expression with protein expression was variable for CDC2, cMYC, and CCND1 (R=0.32, 0.35, and 0.69). ConclusionsTMA-AQUA has the potential to be successfully used as a high-throughput protein biomarker screening platform for MCL; however, appropriate target protein selection and antibody performance validation are factors that need to be considered.
Cytotoxic Properties of Adamantyl Isothiocyanate and Potential In vivo Metabolite Adamantyl‐N‐Acetylcystein in Gynecological Cancer Cells

This study determined the in vitro potential of novel compounds adamantyl‐N‐acetylcystein and adamantyl isothiocyanate to treat gynecological cancers. Adamantyl‐N‐acetylcystein is postulated to be an in vivo metabolite of adamantyl isothiocyanate as dietary isothiocyanates are converted to N‐acetylcysteine‐conjugates. A viability assay suggested that adamantyl isothiocyanate and adamantyl‐N‐acetylcystein are cytotoxic to cancer cells including gynecological cell lines. A NCI60 cancer cell assay revealed that growth‐inhibition and cytotoxicity of adamantyl‐N‐acetylcystein were cell line, but not tissue type‐specific. Cell cycle studies revealed that adamantyl‐N‐acetylcystein and adamantyl isothiocyanate arrest SKOV‐3 ovarian cancer cells in G2/M phase. By TUNEL, immunoblotting, and viability studies employing caspase and p38 mitogen‐activated protein kinase inhibitors, we proved that reduction in SKOV‐3 viability is a consequence of DNA fragmentation and apoptosis. Cytotoxic action of adamantyl‐N‐acetylcystein in SKOV‐3 and endometrial cancer (ECC‐1, RL95‐2, AN3CA, and KLE) cells required excess generation of reactive oxygen species which could be blocked by antioxidant co‐treatment. Adamantyl‐N‐acetylcystein treatment led to modified expression or activation of apoptotic and oncogenic proteins such as JNK/SAPK, AKT, XIAP, and EGF‐R for SKOV‐3 and JNK/SAPK and ERK1/2 for ECC‐1 cells. We suggest the further development of adamantyl‐N‐acetylcystein by sensitizing cells to the drug using signaling inhibitors or redox‐modulating agents and by evaluating the drug efficacy in ovarian and endometrial in‐vivo tumor models.
Insulin-like Growth Factor Receptor-1 (IGF-1R) Expression in Normal Breast, Proliferative Breast Lesions, and Breast Carcinoma

Insulin-like growth factor receptor 1 (IGF-1R) is a receptor protein tyrosine kinase that is activated by ligand (IGF-1) binding and promotes mitogenic, metastatic, and antiapoptotic phenotypes of breast cancer. There is a dearth of studies analyzing IGF-1R expression by immunohistochemistry in breast carcinoma. This biomarker analysis will be important for pharmacologic interventions that target the IGF system. IGF-1R expression pattern was first analyzed in normal breast tissue and a variety of breast lesions (71 diagnoses from 35 patients), followed by analysis in 191 consecutive invasive breast carcinomas. Furthermore, 86 carcinomas treated with neoadjuvant chemotherapy were also analyzed. The carcinomas were classified using immunohistochemical surrogate (to molecular classes) markers—estrogen receptors (ER), progesterone receptors, and human epidermal growth factor receptor 2. IGF-1R is expressed at moderate level in normal breast tissue which was considered as normal expression. Overexpression and lower expression were defined as higher than normal or lower than normal expression, respectively. Among the benign and noninvasive breast lesions, IGF-1R expression was slightly increased in lesions that are hormonally driven (such as atypical ductal hyperplasia and columnar cells changes) whereas it was significantly reduced in ER-negative lesions (such as apocrine metaplasia). Similarly, in 191 consecutive breast carcinomas, IGF-1R overexpression was predominantly seen in ER-positive (+) tumors. The tumor group that consistently showed reduced expression was the ERBB2 group (ER negative/progesterone receptors negative/human epidermal growth factor receptor 2 positive). The expression was somewhat heterogeneous in the triple-negative group. IGF-1R expression was not predictive of pathologic complete response or tumor volume reduction in ER-negative tumors, but reduced IGF-1R was associated with pathologic complete response and significant tumor volume reduction in ER+ tumors. Therapies targeting IGF-1R will be useful in majority of ER+ and a subset of triple-negative tumors that express IGF-1R. The consistent presence of IGF-1R in ER+ tumors may explain the lower response rate to neoadjuvant chemotherapy in luminal tumors.
A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals?

The advent of high‐resolution magnetic resonance imaging (MRI) has enabled in vivo research in a variety of populations and diseases on the structure and function of hippocampal subfields and subdivisions of the parahippocampal gyrus. Because of the many extant and highly discrepant segmentation protocols, comparing results across studies is difficult. To overcome this barrier, the Hippocampal Subfields Group was formed as an international collaboration with the aim of developing a harmonized protocol for manual segmentation of hippocampal and parahippocampal subregions on high‐resolution MRI. In this commentary we discuss the goals for this protocol and the associated key challenges involved in its development. These include differences among existing anatomical reference materials, striking the right balance between reliability of measurements and anatomical validity, and the development of a versatile protocol that can be adopted for the study of populations varying in age and health. The commentary outlines these key challenges, as well as the proposed solution of each, with concrete examples from our working plan. Finally, with two examples, we illustrate how the harmonized protocol, once completed, is expected to impact the field by producing measurements that are quantitatively comparable across labs and by facilitating the synthesis of findings across different studies. © 2016 Wiley Periodicals, Inc.
Ataxia telangiectasia syndrome: moonlighting ATM

ABSTRACT Introduction: Ataxia-telangiectasia (A-T) a multisystem disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. Identification of the gene defective in this syndrome, ataxia-telangiectasia mutated gene (ATM), and further characterization of the disorder together with a greater insight into the function of the ATM protein have expanded our knowledge about the molecular pathogenesis of this disease. Area covered: In this review, we have attempted to summarize the different roles of ATM signaling that have provided new insights into the diverse clinical phenotypes exhibited by A-T patients. Expert commentary: ATM, in addition to DNA repair response, is involved in many cytoplasmic roles that explain diverse phenotypes of A-T patients. It seems accumulation of DNA damage, persistent DNA damage response signaling, and chronic oxidative stress are the main players in the pathogenesis of this disease.
Developing inter-disciplinary and inter-agency networks: reflections on a "community of practice" approach

Purpose – People with a dual diagnosis or other multiple and complex needs often require support from a range of services and agencies. Social policy has focused on achieving an integrated response from practitioners; however, service responses to this group frequently remain fragmented. Practitioners supporting these clients are likely to need knowledge drawn from multiple disciplines and awareness of complex and changing services. Research suggests the value of professional networks for knowledge transfer. The purpose of this paper is to describe one's approach to supporting integration and facilitating knowledge exchange through the development of “communities of practice”. Design/methodology/approach – The paper describes a “communities of practice” model, as implemented by researchers from King's College London and Revolving Doors Agency through their Communities of Practice Development Programme. It outlines potential benefits of the model – identified through focus groups and survey responses of me.
Lymphangiogenesis and Podoplanin Expression in Oral Squamous Cell Carcinoma and the Associated Lymph Nodes

The objective of this study was to evaluate lymphangiogenesis in oral squamous cell carcinoma and in the associated lymph nodes and podoplanin expression in neoplastic cells at the invasive front. In addition, the association of the above parameters with lymph node metastasis was also investigated. We used immunohistochemistry to examine primary tumors and lymph nodes, regardless of metastasis. Lymphatic vessel density (LVD) and microvessel density (MVD) were assessed by antibodies D2-40 and CD105, respectively, in intratumoral and peritumoral areas and in lymph node regions. Vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 expression was evaluated in tumor cells and D2-40 (podoplanin) expression in parenchymal cells found at the invasive front. The majority of cases with nodal involvement presented a high peritumoral LVD. In addition, a strong association of LVD with size and site of primary tumors could also be identified. MVD was statistically associated with metastasis, and a significant association between the lymphangiogenic factors and the density of vessels in the intratumoral region was also seen. The well-differentiated tumors did not express podoplanin. LVD and MVD were higher in metastatic lymph nodes than in nonmetastatic lymph nodes. The enhanced vascular network in metastatic lymph nodes reinforces the previous reports of lymphangiogenesis occurrence in lymph nodes. Moreover, the expression of podoplanin by more undifferentiated tumor cells suggests that this protein could be an indicator of tumor aggressiveness.
Home glucose monitoring in patients aged over 40 years with diabetes mellitus

The effectiveness of home glucose monltoring (HGM) was assessed In patients over the age of 40 years with dlabetes. Results were obtalned from 158 patients who were seen consecutlvely in the clinic. Of Insulin-treated patients, 78.0% performed self-monitorlng of blood glucose (SMBG), whlist 76.3% of non-insulin-treated patients performed urlne testing alone at home. Only 5.6% of patients failed to undertake any HGM and these were all non-insulin-treated patients. Insulin-treated patients performing SMBG did not have an improved HbA1 compared with those doing urine tests alone (SMBG 10.3±1.8%, Urine 9.9±1.8%). only 26.6% of patients performing SMBG felt confident to change their own insulin regimens. Patients performing urine tests seemed generally more satisfied with their HGM (91. 5%) than those performing urine blood tests (63.0% p<6;0.01). In summary, virtually all patients performed some form of HGM, the majority being those on insulin who were attempting SMBG. With SMBG there was no improvement in glycaemic control, few patients changed their own insulin and many patlents would have preferred urine testing alone. Patients should be carefulty selected for use of SMBG.
The impact of aortic arch geometry on flow dynamics using a simplified approach with magnetic resonance velocity mapping.

BACKGROUND We sought to determine, in vivo, the impact of aortic arch geometry on flow dynamics, which affects overall cardiovascular energetics and has implications for organ perfusion and Doppler flow calculations. METHODS Twenty-seven patients (13 with left and 14 with right aortic arches) underwent magnetic resonance phase-encoded velocity mapping in the ascending and descending aorta. The cross-sectional area were divided into 4 equal quadrants aligned along the long axis of the aorta for analysis. Significance P < . 05. RESULTS In the ascending aorta, there was a significantly higher total flow throughout the cardiac cycle in the posterior and leftward quadrant of right aortic arch than left aortic arch (P = .007) that was compensated for by significantly lower flow in anterior and rightward quadrant of right aortic arch than left aortic arch (P = .02). In the right aortic arch, maximum velocity (100 +/- 14 cm/second) occurred in 7/9 patients in the right half while in left aortic arch, maximum velocity (107 +/- 20 cm/second) occurred in 13/15 in the left half. In the descending aorta, whether left aortic arch or right aortic arch, the posterior half appeared to have greater flow than the anterior half. CONCLUSION Right aortic arch geometry impacts flow dynamics in the ascending aorta whereas it is not altered in the descending aorta, where flow is predominantly in the posterior half. The sidedness of the aortic arch determined the location of maximum velocity. Alternatively, this also may suggest that hemodynamics could have played a role in the development of right aortic arch in certain individuals.
Comparison of different methods for determination of the duodenal and ileal flows of endogenous nitrogen and amino acids in growing goats

The objective of the present study was to compare the isotope dilution, the difference and the amino acid profile (AAP) methods for the quantification of duodenal and ileal flows of endogenous nitrogen (N) and amino acids (AA) in growing goats. Nine growing goats were fed the same diet containing maize stover, ground corn and soybean meal. The duodenal flow of endogenous N determined by the isotope dilution method was significantly (p < 0.01) higher than that determined by the difference and AAP methods, while there was no difference between the difference and the AAP methods. The duodenal flows of individual endogenous AA determined by the isotope dilution method exceed those determined by the difference and the AAP method by 10 to 106%. The endogenous flow at the ileum determined by the isotope dilution method was not significantly different to those determined by the water-soluble method, but tended to be lower for N and all amino acids. It is concluded that the difference method and AAP method underestimate the duodenal flow of endogenous N and AA compared to the isotope dilution method.