Congenital pancreatoblastoma: a case report

The literature describes 15 cases of congenital pancreatoblastoma (PB): 5 had prenatal diagnosis, none had metastases at diagnosis, 7 were associated with BeckwitheWiedemann syndrome (BWS). In 13 cases resection was radical, while in 2 there were macroscopic residues. Only one patient underwent chemotherapy after distant recurrence. All children are alive except one who died because of problems related to BWS. Our goal is to describe the approach adopted in an infant with congenital PB treated in our center. After a prenatal third semester diagnosis of abdominal anechoic lesion, the radiological investigations (ultrasound, MRI) performed at birth described a cystic lesion of unclear nature. We proceeded to laparoscopic exploration, transformed into open approach after the detection of a lesion located in the body of the pancreas; this lesion was resected, preserving the head and tail of pancreas. The histological diagnosis showed a completely excised PB. After excluding metastatic lesions, we decided to perform only careful follow-up without chemotherapy. The follow-up at 12 months is negative. Although PB is a malignant tumor that requires a multidisciplinary treatment, the congenital cases seem to have a less aggressive biological behavior. The treatment, therefore, in case of complete resection, could be only surgical, followed by a careful follow-up. These forms are often associated with congenital BWS, but in our case the patient did not have the typical characteristics of the syndrome

IMPACT OF TURBULENCE MODELING ON FLUID/SOLID HEAT TRANSFER INSIDE INDUSTRIAL AUTOCLAVES

This work is centred on the analysis of the impact of different turbulence modeling approaches on the fluid/solid heat exchange inside a commercial size autoclave. This project proposes itself to be a first step towards the optimization of the turbulent flow inside this kind of machinery to improve the curing treatment of Carbon-Fiber Reinforced Plastics (CFRP). The setup of the CFD simulations includes the presence of a metallic sample object inside the autoclave, where air will be recirculated with velocity, pressure and temperature typically adopted for this type of treatments. The analysis takes advantage of parallel CFD simulations, conducted by using the open-source software openFOAM v2106. Two turbulence models have been adopted: one is the well-known Reynolds-Average Navier-Stokes approach (RANS), which is currently used to model the turbulence inside this type of machinery. The second one is the Delayed Detached Eddy Simulations (DDES), which allows the full resolution of the majority of turbulent scales around the sample object. First, we propose the difference between the local heat flux distribution at the air/solid interface computed by using RANS and DDES, next we analyse the overall heat flux entering the sample object: the resolution of the turbulent scales does not influence the local heat flux only, but also the overall heat flux entering the object; an average increase of 35% is reported when the velocity fluctuations are neglected. Future steps of the research foresee the analysis of the heat flux and temperature distributions on the surface of realistic shapes and common-use CFRP. Afterwards, the autoclave design will be optimized by adding multiple inlets and aerodynamic devices to guarantee a more homogeneous heat flux distribution on the surface of realistic shapes of actual CFRP

Early Acquisition of Neural Crest Competence During hESCs Neuralization

Background: Neural crest stem cells (NCSCs) are a transient multipotent embryonic cell population that represents a defining characteristic of vertebrates. The neural crest (NC) gives rise to many derivatives including the neurons and glia of the sensory and autonomic ganglia of the peripheral nervous system, enteric neurons and glia, melanocytes, and the cartilaginous, bony and connective tissue of the craniofacial skeleton, cephalic neuroendocrine organs, and some heart vessels. Methodology/Principal Findings: We present evidence that neural crest (NC) competence can be acquired very early when human embryonic stem cells (hESCs) are selectively neuralized towards dorsal neuroepithelium in the absence of feeder cells in fully defined conditions. When hESC-derived neurospheres are plated on fibronectin, some cells emigrate onto the substrate. These early migratory Neural Crest Stem Cells (emNCSCs) uniformly upregulate Sox10 and vimentin, downregulate N-cadherin, and remodel F-actin, consistent with a transition from neuroepithelium to a mesenchymal NC cell. Over 13% of emNCSCs upregulate CD73, a marker of mesenchymal lineage characteristic of cephalic NC and connexin 43, found on early migratory NC cells. We demonstrated that emNCSCs give rise in vitro to all NC lineages, are multipotent on clonal level, and appropriately respond to developmental factors. We suggest that human emNCSC resemble cephalic NC described in model organisms. Ex vivo emNCSCs can differentiate into neurons in Ret.k- mouse embryonic gut tissue cultures and transplanted emNCSCs incorporate into NC-derived structures but not CNS tissues in chick embryos. Conclusions/Significance: These findings will provide a framework for further studying early human NC development including the epithelial to mesenchymal transition during NC delamination

Congenital pancreatoblastoma: a case report

The literature describes 15 cases of congenital pancreatoblastoma (PB): 5 had prenatal diagnosis, none had metastases at diagnosis, 7 were associated with BeckwitheWiedemann syndrome (BWS). In 13 cases resection was radical, while in 2 there were macroscopic residues. Only one patient underwent chemotherapy after distant recurrence. All children are alive except one who died because of problems related to BWS. Our goal is to describe the approach adopted in an infant with congenital PB treated in our center. After a prenatal third semester diagnosis of abdominal anechoic lesion, the radiological investigations (ultrasound, MRI) performed at birth described a cystic lesion of unclear nature. We proceeded to laparoscopic exploration, transformed into open approach after the detection of a lesion located in the body of the pancreas; this lesion was resected, preserving the head and tail of pancreas. The histological diagnosis showed a completely excised PB. After excluding metastatic lesions, we decided to perform only careful follow-up without chemotherapy. The follow-up at 12 months is negative. Although PB is a malignant tumor that requires a multidisciplinary treatment, the congenital cases seem to have a less aggressive biological behavior. The treatment, therefore, in case of complete resection, could be only surgical, followed by a careful follow-up. These forms are often associated with congenital BWS, but in our case the patient did not have the typical characteristics of the syndrome

Brain regions and functional interactions supporting early word recognition in the face of input variability

Perception and cognition in infants have been traditionally investigated using habituation paradigms, assuming that babies' memories in laboratory contexts are best constructed after numerous repetitions of the very same stimulus in the absence of interference. A crucial, yet open, question regards how babies deal with stimuli experienced in a fashion similar to everyday learning situations-namely, in the presence of interfering stimuli. To address this question, we used functional near-infrared spectroscopy to test 40 healthy newborns on their ability to encode words presented in concomitance with other words. The results evidenced a habituation-like hemodynamic response during encoding in the left-frontal region, which was associated with a progressive decrement of the functional connections between this region and the left-temporal, right-temporal, and right-parietal regions. In a recognition test phase, a characteristic neural signature of recognition recruited first the right-frontal region and subsequently the right-parietal ones. Connections originating from the right-temporal regions to these areas emerged when newborns listened to the familiar word in the test phase. These findings suggest a neural specialization at birth characterized by the lateralization of memory functions: the interplay between temporal and left-frontal regions during encoding and between temporo-parietal and right-frontal regions during recognition of speech sounds. Most critically, the results show that newborns are capable of retaining the sound of specific words despite hearing other stimuli during encoding. Thus, habituation designs that include various items may be as effective for studying early memory as repeated presentation of a single word.European Research Council under European Union 269502 CONICYT-Chile Program PIA/BASAL FB0003 "Progetto strategico NEURAT" from the University of Padua CONICYT-Chile Program PAI/Academia 7913002

Tumour-derived interleukin 1alpha (IL-1alpha) up-regulates the release of soluble intercellular adhesion molecule-1 (sICAM-1) by endothelial cells.

Levels of circulating soluble intercellular adhesion molecule-1 (sICAM-1) are elevated in patients affected by solid malignancies; however, the cellular sources generating high levels of sICAM-1 remain to be characterized. Using conditioned media (CM) from seven ICAM-1-positive or -negative neoplastic cells, we demonstrate that tumour-derived interleukin 1alpha (IL-1alpha) significantly (P < 0.05) up-regulates the release of sICAM-1 by human umbilical vein endothelial cells. The intensity of the effect correlated with the amounts of IL-1alpha detectable in CM. Levels of ICAM-1 mRNA were also up-regulated by tumour-secreted IL-1alpha. The up-regulation of the shedding of sICAM-1 and of its expression at protein and mRNA level were completely reversed by the addition of anti-IL-1alpha neutralizing antibodies. Consistent with the in vitro data, tumour endothelia were strongly stained for ICAM-1 compared with autologous normal tissue endothelia. Taken altogether, our observations reveal an IL-1alpha-mediated tumour-endothelium relationship sustaining the shedding of sICAM-1 by endothelial cells. This is a general phenomenon in solid malignancies that correlates with the ability of neoplastic cells to secrete IL-1alpha rather than with their expression of ICAM-1 and/or histological origin. sICAM-1 has been previously shown to inhibit LFA-1/ICAM-1-mediated cell-cell interactions; therefore, the ability of neoplastic cells to secrete IL-1alpha is likely to represent a mechanism for their escape from immune interaction

Expression and structural features of endoglin (CD105), a transforming growth factor beta1 and beta3 binding protein, in human melanoma.

Human endoglin (CD105) is a member of the transforming growth factor beta (TGF-beta) receptor family that binds TGF-beta1 and -beta3, but not TGF-beta2, on human endothelial cells. Immunohistochemical analyses demonstrated that CD105 is expressed on normal and neoplastic cells of the melanocytic lineage. The anti-CD105 MAb, MAEND3, stained 50, 25 and 34% of intradermal naevi, primary and metastatic melanomas investigated, respectively, and nine out of 12 melanoma cell lines. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that CD105 expressed by melanoma cells consists of a homodimeric protein with an apparent molecular weight of 180 and 95 kDa under non-reducing and reducing conditions. Cross-linking of 125I-labelled TGF-beta1 to melanoma cells, Mel 97, by disuccinimidyl suberate (DSS) demonstrated that CD105 expressed on pigmented cells binds TGF-beta1; the pattern of binding of TGF-beta1 to melanoma cells was found to be similar to that of human umbilical vein endothelial cells. The addition of exogenous, bioactive TGF-beta1 significantly (P<0.05) inhibited the growth of CD105-positive melanoma cells, Mel 97, but did not affect that of CD105-negative melanoma cells, F0-1. These data, altogether, demonstrate that CD105 is expressed on pigmented cells and might play a functionally relevant role in the biology of human melanoma cells by regulating their sensitivity to TGF-betas

Organizaciones saludables y eficiencia laboral

En la actualidad se analizan las organizaciones desde una perspectiva integral, siendo una de ellas la identificación como organización saludable (OS), que es aquella que organiza y desarrolla su estructura, cultura y procesos para lograr altos niveles de desempeño, promueve el bienestar de sus empleados, generando productos y servicios saludables y manteniendo relaciones apropiadas con el entorno organizacional y la comunidad. El cuidado del cliente y del entorno, la innovación, el aprendizaje continuo, el empoderamiento de los empleados promueven el logro de la salud organizacional a lo largo del tiempo. Cuatro factores contribuyen a la noción de OS: ambientales, físicos, mentales y sociales.De la presente investigación esperamos obtener resultados que nos acerquen a comprender las percepciones de los alumnos de posgrado en Ciencias de la Administración de la USAL, acerca de las variables que constituyen a una OS, antes y después de recibir capacitaciones, e identificar las diferencias entre las percepciones de los grupos analizados con antelación y con posterioridad a la capacitación en la Maestría de Coaching y Cambio Organizacional y en la Maestría de Dirección de Empresas, confrontando sus resultados con un grupo control de abogados, sin ninguna formación previa en esas temáticasLos resultados parciales determinan que uno de los elementos de menor importancia es la responsabilidad social empresaria, con la menor valoración siguiéndole la cultura organizacional. En relación con los factores que pueden contribuir al medio ambiente saludable, la satisfacción laboral y el bienestar en el trabajo, los tres grupos de encuestados han manifestado, en más del 70%, estar en completo desacuerdo con la afirmación “cuando las personas se escuchan entre sí pierden el tiempo”. Los dos últimos grupos de encuestados se encuentran en su mayoría, sumamente de acuerdo con la afirmación “al ver las cosas de un modo diferente, podemos obtener resultados que parecen imposibles”.Organizations are analyzed today through a comprehensive perspective, being one of them the capability to be identified as Healthy Organization. This organization grows and develops structure, culture and processes that are necessary to achieve higher levels of performance and promote thewellbeing of employees, and at the same time generates healthy products and services while keepingfriendly relationships with the environment and the community. Good care of the customerand the environment, innovation, continuing education, and employee empowerment encouragethe achievement of organizational health through time. Four factors are said to contribute to thenotion of Healthy Organizations: environmental, physical, mental and socialFrom this research we hope to obtain results that bring us closer to understanding the perceptionsof students graduate in management science from Universidad Salvador about variables thatconstitute an OS before and after receiving training, and identify the differences between the perceptionsof the groups analyzed in advance and after the training in the Master of Coaching andOrganizational Change and the Master of Business Administration, comparing their results with acontrol group of lawyers with no previous training in these topicsPartial results determine that one of the minor element, are corporate social responsibility followedby organizational culture. Regarding the factors that may contribute to healthy environment,job satisfaction and well-being at work, all three groups of respondents have declared in more than70%, be in complete disagreement with the statement “when people hear each lose time”. The lasttwo groups of respondents are mostly strongly agree with the statement “to see things differently,we obtain results that seem impossible”

Human ESC-Derived Neural Crest Model Reveals a Key Role for SOX2 in Sensory Neurogenesis

The transcription factor SOX2 is widely known to play a critical role in the central nervous system; however, its role in peripheral neurogenesis remains poorly understood. We recently developed an hESC-based model in which migratory cells undergo epithelial to mesenchymal transition (EMT) to acquire properties of neural crest (NC) cells. In this model, we found that migratory NC progenitors downregulate SOX2, but then start re-expressing SOX2 as they differentiate to form neurogenic dorsal root ganglion (DRG)-like clusters. SOX2 downregulation was sufficient to induce EMT and resulted in massive apoptosis when neuronal differentiation was induced. In vivo, downregulation of SOX2 in chick and mouse NC cells significantly reduced the numbers of neurons within DRG. We found that SOX2 binds directly to NGN1 and MASH1 promoters and is required for their expression. Our data suggest that SOX2 plays a key role for NGN1-dependent acquisition of neuronal fates in sensory ganglia

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO) : Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017. © 2019 The Author(s).Peer reviewe