The El Niño-Southern Oscillation (ENSO) Modoki signal in the stratosphere

El Niño-Southern Oscillation (ENSO) is known to be the largest source of interannual variability in the tropical troposphere. However, the variability in the tropical Pacific since 1979 seems to be associated not only with "canonical" ENSO events but also with a variation thereof known as ENSO Modoki, which is characterized by warm anomalies in the central Pacific, west from those occurring during a typical ENSO. This works analyzes the signal of ENSO Modoki in the stratosphere and compares it to canonical ENSO by using the chemistry-climate Whole Atmosphere Community Climate Model (WACCM3.5). The results reveal a significant warming in the Southern Hemisphere polar stratosphere during boreal winter months, which propagates downward in early spring; this is absent during canonical warm ENSO events. On the other hand, in the Northern Hemisphere stratosphere, the anomalous warming typical of canonical El Niño episodes during boreal winter is not statistically significant during El Niño Modoki events. These differences are related in WACCM3.5 to changes in tropical convection and tropospheric teleconnections associated with each type of event. In particular, an enhancement and westward displacement of the anomalous convective area during El Niño Modoki episodes is related to an intensification of the Pacific South American teleconnection pattern and a weakening of the Aleutian Low. During cold ENSO Modoki events a significant anomalous cooling is present in the model simulations

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

Alteraciones neuropsicológicas y daño cerebral en la infancia y adolescencia asociados al nacimiento prematuro

Prematurity is defined by the World Health Organization (WHO, 1977) as a delivery occurring before 37 completed weeks of gestation. White matter (WM) abnormalities and periventricular leukomalacia (PVL) are the most prominent pathologies in the preterm neonate. Compared with their term-peers, children born preterm have lower intelligence quotient (IQ) scores, although within the normal range. Moreover, domain-specific measures of neuropsychological abilities such as executive functions, visuoperceptual and linguistic skills are often impaired. Preterm children with PVL have a similar profile, with lower IQ scores and poorer executive functions, mental calculation and visuoperceptual skills than controls. Cerebral structural gray matter (GM) abnormalities that might contribute to the poor performance of preterm samples are localized in the frontal, parietal, temporal and occipital lobes. The cerebellum and deep gray matter structures such as the caudate nuclei, the thalami and the hippocampus are also altered. Over the past few years, magnetic resonance imaging and neuropathological studies have shown that, in addition to the classical WM injury seen in preterm samples with PVL, cortical and subcortical GM injury may also contribute to the impaired cognitive performance.La prematuridad es definida por la Organización Mundial de la Salud (OMS, 1977) como el parto que ocurre antes de las 37 semanas de gestación. La alteración de la sustancia blanca (SB) es la principal característica de daño cerebral y la leucomalacia periventricular (LPV) es el hallazgo patológico más común en estudios de resonancia magnética Los niños nacidos prematuros comparados con los niños nacidos a término presentan un cociente de inteligencia (CI) con puntuaciones menores pero dentro de la normalidad. Las funciones neuropsicológicas específicas más afectadas son las ejecutivas, visuo-perceptivas y lingüísticas. Los niños prematuros con LPV, también muestran puntuaciones más bajas en el CI, en las funciones ejecutivas, en el cálculo mental y en las capacidades visuoperceptivas. Las alteraciones cerebrales estructurales de sustancia gris (SG) que pueden contribuir a una peor ejecución cognitiva en estas muestras de prematuros implican regiones en los lóbulos cerebrales temporal, parietal, frontal y occipital. Además, el cerebelo y diversos núcleos grises subcorticales tales como el núcleo caudado, el tálamo y el hipocampo están también afectados. En los últimos años, los estudios de resonancia magnética y neuropatológicos, están demostrando que además de la alteración clásica de SB, los niños prematuros con LPV presentan daño en la SG tanto cortical como subcortical a los cuales se les atribuye una implicación directa en la peor ejecución cognitiva

Alteraciones neuropsicológicas y daño cerebral en la infancia y adolescencia asociados al nacimiento prematuro

Prematurity is defined by the World Health Organization (WHO, 1977) as a delivery occurring before 37 completed weeks of gestation. White matter (WM) abnormalities and periventricular leukomalacia (PVL) are the most prominent pathologies in the preterm neonate. Compared with their term-peers, children born preterm have lower intelligence quotient (IQ) scores, although within the normal range. Moreover, domain-specific measures of neuropsychological abilities such as executive functions, visuoperceptual and linguistic skills are often impaired. Preterm children with PVL have a similar profile, with lower IQ scores and poorer executive functions, mental calculation and visuoperceptual skills than controls. Cerebral structural gray matter (GM) abnormalities that might contribute to the poor performance of preterm samples are localized in the frontal, parietal, temporal and occipital lobes. The cerebellum and deep gray matter structures such as the caudate nuclei, the thalami and the hippocampus are also altered. Over the past few years, magnetic resonance imaging and neuropathological studies have shown that, in addition to the classical WM injury seen in preterm samples with PVL, cortical and subcortical GM injury may also contribute to the impaired cognitive performance.  La prematuridad es definida por la Organización Mundial de la Salud (OMS, 1977) como el parto que ocurre antes de las 37 semanas de gestación. La alteración de la sustancia blanca (SB) es la principal característica de daño cerebral y la leucomalacia periventricular (LPV) es el hallazgo patológico más común en estudios de resonancia magnética Los niños nacidos prematuros comparados con los niños nacidos a término presentan un cociente de inteligencia (CI) con puntuaciones menores pero dentro de la normalidad. Las funciones neuropsicológicas específicas más afectadas son las ejecutivas visuo-perceptivas y lingüísticas. Los niños prematuros con LPV, también muestran puntuaciones más bajas en el CI, en las funciones ejecutivas, en el cálculo mental y en las capacidades visuoperceptivas. Las alteraciones cerebrales estructurales de sustancia gris (SG) que pueden contribuir a una peor ejecución cognitiva en estas muestras de prematuros implican regiones en los lóbulos cerebrales temporal, parietal, frontal y occipital. Además, el cerebelo y diversos núcleos grises subcorticales tales como el núcleo caudado, el tálamo y el hipocampo están también afectados. En los últimos años, los estudios de resonancia magnética y neuropatológicos, están demostrando que además de la alteración clásica de SB, los niños prematuros con LPV presentan daño en la SG tanto cortical como subcortical a los cuales se les atribuye una implicación directa en la peor ejecución cognitiva

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

Cortical thickness and behavior abnormalities in children born preterm

Abstract Aim To identify long-term effects of preterm birth and of periventricular leukomalacia (PVL) on cortical thickness (CTh). To study the relationship between CTh and cognitive-behavioral abnormalities. Methods We performed brain magnetic resonance imaging on 22 preterm children with PVL, 14 preterm children with no evidence of PVL and 22 full-term peers. T1-weighted images were analyzed with FreeSurfer software. All participants underwent cognitive and behavioral assessments by means of the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) and the Child Behavior Checklist (CBCL). Results We did not find global CTh differences between the groups. However, a thinner cortex was found in left postcentral, supramarginal, and caudal middle rostral gyri in preterm children with no evidence of PVL than in the full-term controls, while PVL preterm children showed thicker cortex in right pericalcarine and left rostral middle frontal areas than in preterm children with no evidence of PVL. In the PVL group, internalizing and externalizing scores correlated mainly with CTh in frontal areas. Attentional scores were found to be higher in PVL and correlated with CTh increments in right frontal areas. Interpretation The preterm group with no evidence of PVL, when compared with full-term children, showed evidence of a different pattern of regional thinning in the cortical gray matter. In turn, PVL preterm children exhibited atypical increases in CTh that may underlie their prevalent behavioral problems

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

White matter integrity in dyskinetic cerebral palsy: Relationship with intelligence quotient and executive function

Background: Dyskinetic cerebral palsy (CP) is one of the most disabling motor types of CP and has been classically associated with injury to the basal ganglia and thalamus. Although cognitive dysfunction is common in CP, there is a paucity of published quantitative analyses investigating the relationship between white matter (WM) microstructure and cognition in this CP type. Aims: This study aims (1) to compare brain WM microstructure between people with dyskinetic CP and healthy controls, (2) to identify brain regions where WM microstructure is related to intelligence and (3) to identify brain regions where WM microstructure is related to executive function in people with dyskinetic CP and (4) to identify brain regions where the correlations are different between controls and people with CP in IQ and executive functions. Patients and methods: Thirty-three participants with dyskinetic CP (mean +/- SD age: 24.42 +/- 12.61, 15 female) were age and sex matched with 33 controls. Participants underwent a comprehensive neuropsychological battery to assess intelligence quotient (IQ) and four executive function domains (attentional control, cognitive flexibility, goal setting and information processing). Diffusion weighted MRI scans were acquired at 3T. Voxel-based whole brain groupwise analyses were used to compare fractional anisotropy (FA) and of the CP group to the matched controls using a general lineal model. Further general linear models were used to identify regions where white matter FA correlated with IQ and each of the executive function domains. Results: White matter FA was significantly reduced in the CP group in all cerebral lobes, predominantly in regions connected with the parietal and to a lesser extent the temporal lobes. There was no significant correlation between IQ or any of the four executive function domains and WM microstructure in the control group. In participants with CP, lower IQ was associated with lower FA in all cerebral lobes, predominantly in locations that also showed reduced FA compared to controls. Attentional control, goal setting and information processing did not correlate with WM microstructure in the CP group. Cognitive flexibility was associated with FA in regions known to contain connections with the frontal lobe (such as the superior longitudinal fasciculus and cingulum) as well as regions not known to contain tracts directly connected with the frontal lobe (such as the posterior corona radiata, posterior thalamic radiation, retrolenticular part of internal capsule, tapetum, body and splenium of corpus callosum). Conclusion: The widespread loss in the integrity of WM tissue is mainly located in the parietal lobe and related to IQ in dyskinetic CP. Unexpectedly, executive functions are only related with WM microstructure in regions containing fronto-cortical and posterior cortico-subcortical pathways, and not being specifically related to the state of fronto-striatal pathways which might be due to brain reorganization. Further studies of this nature may improve our understanding of the neurobiological bases of cognitive impairments after early brain insult

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