Changes in the secretory profile of NSCLC-associated fibroblasts after ablative radiotherapy: potential impact on angiogenesis and tumor growth

In the context of radiotherapy, collateral effects of ablative ionizing radiation (AIR) on stromal components of tumors remains understudied. In this work, cancer-associated fibroblasts (CAFs) isolated from freshly resected human lung tumors were exposed to AIR (1x18Gy) and analyzed for their release of paracrine factors. Inflammatory mediators and regulators of angiogenesis and tumor growth were analyzed by multiplex protein assays in conditioned medium (CM) from irradiated and non-irradiated CAFs. Additionally, the profile of secreted proteins was examined by proteomics. In functional assays, effects of CAF-CM on proliferative and migratory capacity of lung tumor cells (H-520/H-522) and endothelial cells (HUVECs), and on the tube-forming capacity of endothelial cells was assessed. Our data show that exposure of CAFs to ablative doses of ionizing radiation results in a) down-regulated release of angiogenic factors SDF-1, angiopoietin and thrombospondin-2; b) up-regulated release of growth factor bFGF from most donors, and c) unaffected expression-levels of HGF and inflammatory mediators IL-6, IL-8, IL-1ƒÒ and TNF-£. Conditioned medium from irradiated and control CAFs did not affect differently the proliferative or migratory capacity of tumor cells (H-520/H-522), whereas migratory capacity of endothelial HUVEC cells was partially reduced in the presence of irradiated CAF conditioned medium. Overall we conclude that AIR mediates a transformation on the secretory profile of CAFs that could influence the behavior of other cells in the tumor tissue and hence guide to some extent therapeutic outcomes. The downstream consequences of the changes observed in this study merits further investigations

The Development of Reflective Thinking and its Influence on Patient Care Skills in Third Year Dental Students

This study examined if dental students could increase their level of reflective skills over time through composing reflective blogs during their introduction to patient care in their course, Clinical Practice of Dentistry I, and to document and analyze student perceptions of the use of reflective blogs, particularly pertaining to the clinical and metacognitive skills. The participants of this study included 69 third-year dental students. Reflective blogs were analyzed using a reflective rubric adapted from Wetmore, Boyd, Bowen & Patillio, 2010. Student perceptions regarding the use of reflective blogs were documented through a 14-question Likert-opinion survey and focus group interviews. Findings indicated reflective thought level increased significantly in all six reflective thought categories across the three assessed blogs. Overall, student perceptions of the use of reflective blogs were positive as based on a five-point Likert scale survey. They reported particularly high percentages for "I feel comfortable about reflecting on my clinical experiences" at ~ 90% Agree, "Reflective journals allow me to focus and think things over" at ~ 83% Agree, followed by "Reflective journals develop my ability to monitor and reflect on my own thinking processes"~ 74%. Both the qualitative and quantitative results of this study provide favorable evidence that reflective journaling is effective and in large measure is appreciated by students in their clinical phase of dental medical education

Large-scale secretome analyses unveil the superior immunosuppressive phenotype of umbilical cord stromal cells as compared to other adult mesenchymal stromal cells

Mesenchymal stromal cells (MSCs), given their regenerative potential, are being investigated as a potential therapeutic tool for cartilage lesions. MSCs express several bioactive molecules which act in a paracrine fashion to modulate the tissue microenvironment. Yet, little is known about the divergence of these signalling molecules in different MSC populations. The present study investigated secretomes of stromal cells harvested from Hoffa’s fat pad (HFPSCs), synovial membrane (SMSCs), umbilical cord (UCSCs) and cartilage (ACs) by quantitative liquid chromatography-mass spectrometry (LC-MS/MS) proteomics. Also, multiplex protein arrays and functional assays were performed to compare the constitutive immunomodulatory capabilities of different MSCs. Proteins involved in extracellular matrix degradation and inflammation, such as matrix metalloproteinases (MMPs), interleukin (IL)-17 and complement factors, were downregulated in UCSCs as compared to adult cell sources. Additionally, secretion of transforming growth factor (TGF)-β1 and prostaglandin E2 (PGE2) was enhanced in UCSC supernatants. UCSCs were superior in inhibiting peripheral blood mononuclear cell (PBMC) proliferation, migration and cytokine secretion as compared to adult stromal cells. SMSCs significantly suppressed the proliferation of PBMCs only if they were primed with pro-inflammatory cytokines. Although all cell types repressed human leukocyte antigen-DR isotype (HLA-DR) surface expression and cytokine release by activated macrophages, only UCSCs significantly blocked IL-6 and IL-12 production. Furthermore, UCSCs supernatants increased aggrecan gene expression in two-dimensional chondrocyte cultures. The data demonstrated that UCSCs displayed superior anti-inflammatory and immunosuppressive properties than stromal cells from adult tissues. This allogeneic cell source could potentially be considered as an adjuvant therapy for articular cartilage repair

Impacto del proceso de enseñanza endoscópica en la detección de adenomas colónicos

ResumenAntecedentesEl impacto que el proceso de entrenamiento endoscópico ejerce sobre la calidad de la colonoscopia en un medio hispanoamericano es escasa.ObjetivoDeterminar el efecto del entrenamiento en la técnica de colonoscopia sobre la detección de adenomas.Materiales y métodosEntre julio del 2012 y julio del 2013, 3 médicos recibieron entrenamiento en colonoscopia por parte de 4 endoscopistas experimentados; Las colonoscopias realizadas por endoscopistas en entrenamiento supervisados fueron comparadas con aquellas realizadas por endoscopistas experimentados.ResultadosSe incluyeron 318 colonoscopias realizadas por alguno de los 3 endoscopistas en entrenamiento bajo supervisión y 367 realizadas por alguno de los endoscopistas entrenados. El análisis univariado mostró una diferencia no significativa en la tasa de detección de adenomas (30.4 vs. 24.7%; p = 0.09). En el análisis multivariado, la tasa de detección de adenomas fue significativamente mayor en las colonoscopias realizadas por alguno de los 3 endoscopistas en entrenamiento (odds ratio = 1.72 [1.19-2.48]).ConclusiónEl involucramiento de endoscopistas en formación tiene un efecto positivo sobre la detección de adenomas.AbstractBackgroundThere has been little reported experience in the Latin American hospital setting in relation to the impact of the endoscopic training process on colonoscopy quality.AimsTo determine the effect that training in the technique of colonoscopy has on adenoma detection in an Argentinian teaching hospital.Material and methodWithin the time frame of July 2012 and July 2013, 3 physicians received training in colonoscopy from 4 experienced endoscopists. The colonoscopies performed by the supervised trainees were compared with those carried out by the experienced endoscopists.ResultsA total of 318 colonoscopies performed by any one of the 3 supervised trainees and 367 carried out by any one of the experienced endoscopists were included. The univariate analysis showed a non-significant difference in the detection rate of adenomas (30.4 vs. 24.7%, P=.09). In the multivariate analysis, the detection rate of adenomas was significantly higher in the colonoscopies performed by one of the 3 trainees (odds ratio = 1.72 [1.19-2.48]).ConclusionsThe supervised involvement of endoscopic trainees has a positive effect on adenoma detection

Reduced hippocampal subfield volumes and memory performance in preterm children with and without germinal matrix intraventricular hemorrhage.

Preterm newborns with germinal matrix-intraventricular hemorrhage (GM-IVH) are at a higher risk of evidencing neurodevelopmental alterations. Present study aimed to explore the long-term efects that GM-IVH have on hippocampal subfelds, and their correlates with memory. The sample consisted of 58 participants, including 36 preterm-born (16 with GM-IVH and 20 without neonatal brain injury), and 22 full-term children aged between 6 and 15 years old. All participants underwent a cognitive assessment and magnetic resonance imaging study. GM-IVH children evidenced lower scores in Full Intelligence Quotient and memory measures compared to their low-risk preterm and full-term peers. High-risk preterm children with GM-IVH evidenced signifcantly lower total hippocampal volumes bilaterally and hippocampal subfeld volumes compared to both low-risk preterm and full-term groups. Finally, signifcant positive correlations between memory and hippocampal subfeld volumes were only found in preterm participants together; memory and the right CA-feld correlation remained signifcant after Bonferroni correction was applied (p= .002). In conclusion, memory alterations and both global and regional volumetric reductions in the hippocampus were found to be specifcally related to a preterm sample with GM-IVH. Nevertheless, results also suggest that prematurity per se has a long-lasting impact on the association between the right CA-feld volume and memory during childhood

Tunable and precise two-bunch generation at FLASHForward

Beam-driven plasma-wakefield acceleration based on external injection has the potential to significantly reduce the size of future accelerators. Stability and quality of the acceleration process substantially depends on the incoming bunch parameters. Precise control of the current profile is essential for optimising energy-transfer efficiency and preserving energy spread. At the FLASHForward facility, driver--witness bunch pairs of adjustable bunch length and separation are generated by a set of collimators in a dispersive section, which enables fs-level control of the longitudinal bunch profile. The design of the collimator apparatus and its commissioning is presented.Comment: 7 pages, 5 figures, to be published in the proceedings of the 4th European Advanced Accelerator Concepts Workshop, 15-21 September 2019, La Biodola Bay, Isola d'Elba, Ital

Types of cover for the culture of Eisenia fetida (Oligochaeta, Lumbricidae). Incidence on distribution and density

La cobertura de un vermicultivo constituye una interfase de la que se espera contribuya a un control de malezas, brinde aislamiento térmico, facilite la infiltración del agua y el intercambio gaseoso, restrinja la evaporación, proteja de predadores y reduzca las fugas. Los materiales comúnmente usados para cubrir los vermicultivos suelen ser de naturaleza vegetal, sintética o bien mixta. Con el fin de establecer ventajas e inconvenientes derivados del uso de estas y simultáneamente proporcionar criterios objetivos para adoptar la cobertura más conveniente, se delimitaron parcelas con diferentes coberturas en dos lombricultivos experimentales bajo distintas estrategias de conducción (autosiembra y alimentación sucesiva). Se muestreó y evaluó la distribución y densidad de lombrices/Lecho para distinto tipos - combinaciones de materiales de cobertura (pastos secos, nylon y red semisombra doble del 80%). Se estableció que las cubiertas impermeables afectan negativamente a la capacidad de porte del sustrato, particularmente en profundidad, movilizando los animales subadultos y adultos hacia la superficie, reduciéndose, en algunos casos, la densidad a menos de la mitad de las lombrices que albergan coberturas permeables. Se recomienda la utilización de coberturas naturales en combinación con malla del tipo semisombra, simple, del 50%, o aún menos densas, desaconsejándose la utilización de nylon-polietileno.The cover of the vermiculture is an interface that is expected to contribute to weed control, offer thermal isolation, facilitate water infiltration and gas exchange, restrict evaporation, protect from predators and reduce animals escape. The materials commonly used for vermiculture may be vegetable, synthetic or mixed. With the purpose of assessing the advantages and disadvantages derived from the use of these materials, as well as establishing objective criteria for the adoption of the most convenient cover. Land plots with different covers were prepared in two experimental vermicultures run under different management strategies (self-inoculation and periodic feeding). The distribution and density of earthworms/Bed -2m - sampled and evaluated 2 for different types-combinations of cover materials (dry grass, nylon, 80% knitted shadecloth). It was established that impermeable covers affect the carrying capacity of the substratum, particularly in deep regions. Subadult and adult animals move towards the surface and density was reduced in some cases to less than half of the worms supported using permeable covers. We recommend the use of natural covers combined with simple, shadecloth (less than 80%), whereas the use of impermeable films is discouraged.Facultad de Ciencias Naturales y Muse

A high throughput screen for next-generation leads targeting malaria parasite transmission

Spread of parasite resistance to artemisinin threatens current frontline antimalarial therapies, highlighting the need for new drugs with alternative modes of action. Since only 0.2–1% of asexual parasites differentiate into sexual, transmission-competent forms, targeting this natural bottleneck provides a tangible route to interrupt disease transmission and mitigate resistance selection. Here we present a high-throughput screen of gametogenesis against a ~70,000 compound diversity library, identifying seventeen drug-like molecules that target transmission. Hit molecules possess varied activity profiles including male-specific, dual acting male–female and dual-asexual-sexual, with one promising N-((4-hydroxychroman-4-yl)methyl)-sulphonamide scaffold found to have sub-micromolar activity in vitro and in vivo efficacy. Development of leads with modes of action focussed on the sexual stages of malaria parasite development provide a previously unexplored base from which future therapeutics can be developed, capable of preventing parasite transmission through the population

Estudio para la mejora de la calidad del vino albariño

Premio de Investigación, Real Academia Galega de Ciencias, convocatoria 2009.[EN]Twenty-two clones from Albariño variety (Vitis vinifera L.), from an initial collection of 115 clones, were selected on the basis of their ampelographic, molecular and sanitary characteristics. These selected clones were studied from the agronomic and oenological point of view, and were also quantified for their levels of susceptibility to Powdery Mildew, Oidium and Botrytis. An ecotypic yeast was selected, its use has been patented and it is being exploited. Musts obtained from the previously selected Albariño clones were fermented with this yeast, essentially by increasing the content in volatile substances of interest (terpens: linalool and geraniol; norisoprenoids: α-ionone and β- damascenone), leading to wines with improved fermentative dynamic and sensorial attributes.[ES]En base a características ampelográficas, moleculares y sanitarias, se seleccionaron 22 clones de la variedad Albariño (Vitis vinifera L.), partiendo de 115 iniciales. Sobre los clones seleccionados se ha llevado a cabo un estudio agronómico y enológico, así como la cuantificación de los niveles de susceptibilidad a Mildiu, Oídio y Botrytis. Se ha seleccionado una levadura ecotípica, cuyo uso ha sido patentado y se encuentra en explotación. Con ella se fermentaron los mostos obtenidos a partir de los clones de Albariño previamente seleccionados, dando lugar a vinos con una dinámica fermentativa xPremio de Investigación, Real Academia Galega de Ciencias, convocatoria 2009 y unos atributos sensoriales mejorados, fundamentalmente en base al aumento del contenido en sustancias volátiles de interés (terpenos: linalool y geraniol; norisoprenoides: α-ionona y β- damascenona).La actividad realizada ha sido financiada, además de por la Bodega Terras Gauda S.A., por la Xunta de Galicia (PGIDIT04TAL035E), y por el propio CSIC (PIE 2004 7 0E 214).Peer reviewe

Whole-Brain Structural Connectivity in Dyskinetic Cerebral Palsy and Its Association With Motor and Cognitive Function

Dyskinetic cerebral palsy (CP) has long been associated with basal ganglia and thalamus lesions. Recent evidence further points at white matter (WM) damage. This study aims to identify altered WM pathways in dyskinetic CP from a standardized, connectome-based approach, and to assess structure-function relationship in WM pathways for clinical outcomes. Individual connectome maps of 25 subjects with dyskinetic CP and 24 healthy controls were obtained combining a structural parcellation scheme with whole-brain deterministic tractography. Graph theoretical metrics and the network-based statistic were applied to compare groups and to correlate WM state with motor and cognitive performance. Results showed a widespread reduction of WM volume in CP subjects compared to controls and a more localized decrease in degree (number of links per node) and fractional anisotropy (FA), comprising parieto-occipital regions and the hippocampus. However, supramarginal gyrus showed a significantly higher degree. At the network level, CP subjects showed a bilateral pathway with reduced FA, comprising sensorimotor, intraparietal and fronto-parietal connections. Gross and fine motor functions correlated with FA in a pathway comprising the sensorimotor system, but gross motor also correlated with prefrontal, temporal and occipital connections. Intelligence correlated with FA in a network with fronto-striatal and parieto-frontal connections, and visuoperception was related to right occipital connections. These findings demonstrate a disruption in structural brain connectivity in dyskinetic CP, revealing general involvement of posterior brain regions with relative preservation of prefrontal areas. We identified pathways in which WM integrity is related to clinical features, including but not limited to the sensorimotor system