Giant mesenteric lymphatic malformation presenting as small bowel volvulus

Abdominal pain with bilious emesis is an ominous clinical presentation with many possible causes. We describe a previously healthy 4-year-old boy who presented with these symptoms and ultrasound findings of fluid throughout most of the abdominal cavity. Computed tomography imaging revealed a large cystic mass (21-by-13 cm) associated with a small bowel obstruction due to volvulus. A laparoscopic exploration was undertaken, revealing a large mass arising from the small intestinal mesentery and causing a segmental volvulus of the small bowel. Conversion to mini-laparotomy allowed reduction of the volvulus and segmental resection of the small bowel associated with a giant mesenteric lymphatic malformation. This case describes a rare cause of intestinal volvulus due to a mesenteric lymphatic malformation

The Mechanism of Excessive Intestinal Inflammation in Necrotizing Enterocolitis: An Immature Innate Immune Response

Necrotizing enterocolitis (NEC) is a devastating neonatal intestinal inflammatory disease, occurring primarily in premature infants, causing significant morbidity and mortality. The pathogenesis of NEC is associated with an excessive inflammatory IL-8 response. In this study, we hypothesized that this excessive inflammatory response is related to an immature expression of innate immune response genes. To address this hypothesis, intestinal RNA expression analysis of innate immune response genes was performed after laser capture microdissection of resected ileal epithelium from fetuses, NEC patients and children and confirmed in ex vivo human intestinal xenografts. Changes in mRNA levels of toll-like receptors (TLR)-2 and -4, their signaling molecules and transcription factors (MyD88, TRAF-6 and NFκB1) and negative regulators (SIGIRR, IRAK-M, A-20 and TOLLIP) and the effector IL-8 were characterized by qRT-PCR. The expression of TLR2, TLR4, MyD88, TRAF-6, NFκB1 and IL-8 mRNA was increased while SIGIRR, IRAK-M, A-20 and TOLLIP mRNA were decreased in fetal vs. mature human enterocytes and further altered in NEC enterocytes. Similar changes in mRNA expression were observed in immature, but not mature, human intestinal xenografts. Confirmation of gene expression was also validated with selective protein measurements and with suggested evidence that immature TRL4 enterocyte surface expression was internalized in mature enterocytes. Cortisone, an intestinal maturation factor, treatment corrected the mRNA differences only in the immature intestinal xenograft. Using specific siRNA to attenuate expression of primary fetal enterocyte cultures, both TOLLIP and A-20 were confirmed to be important when knocked down by exhibiting the same excessive inflammatory response seen in the NEC intestine. We conclude that the excessive inflammatory response of the immature intestine, a hallmark of NEC, is due to a developmental immaturity in innate immune response genes

In vitro thymosin effect on T lymphocytes in alcoholic liver disease

The in vitro effect of thymosin fraction 5, a thymic gland extract, on thymus-dependent lymphocytes was studied in 12 patients with alcoholic hepatitis (AH) and in 18 patients with compensated alcoholic cirrhosis (CAC). The baseline number and proportion of spontaneous rosette-forming T lymphocytes were significantly reduced in AH as compared to the controls. No such decrease was seen in CAC. When the lymphocytes of patients with AH were incubated in the presence of thymosin fraction 5, the subsequent number and proportion of rosette-forming T lymphocytes showed a significant increase. There was no significant reponse to thymosin in CAC or in control subjects. There appears to be a subset of immature T lymphocytes in patients with AH that is responsive to exogenous thymic factors with subsequent activation of the capacity to form spontaneous rosettes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23618/1/0000581.pd

Peripheral nervous system: A promising source of neuronal progenitors for central nervous system repair

With a steadily aging population there is an increasing prevalence of neurological disorders. Given the lack of effective treatment strategies and a limited ability for the central nervous system (CNS) to regenerate endogenously, there is a critical need to better understand exogenous strategies for nervous system repair. Stem cell therapy offers a promising approach to promote the repair of neurologic tissue and function, however studies to date have been limited by various factors including challenges in harvesting donor cells from the CNS, ethical concerns regarding use of embryonic or fetal tissue, tumorigenic potential of induced pluripotent stem cells, and immune-mediated rejection of non-autologous cell sources. Here we review and propose two alternative sources of autologous cells derived from the peripheral nervous system (PNS) for CNS repair: enteric neuronal stem cells (ENSCs) and neural crest-derived Schwann cells found in subcutaneous adipose tissue (termed SAT-NSCs). ENSCs can be successfully isolated from the postnatal enteric nervous system, propagated in vitro, and transplanted successfully into models of CNS injury via both direct intracerebral injection and systemic tail vein injection. Similarly, SAT-NSCs can be readily isolated from both human and mouse adipose tissue and, although not yet utilized in models of CNS injury, have successfully been transplanted and restored function in models of colonic aganglionosis and gastroparesis. These unique sources of PNS-derived autologous cells offer an exciting option for stem cell therapies for the CNS as they have proven neurogenic potential and eliminate concerns around tumorigenic risk, ethical considerations, and immune-mediated rejection

Nonlinear Resonances in the Solar System

Orbital resonances are ubiquitous in the Solar system. They play a decisive role in the long term dynamics, and in some cases the physical evolution, of the planets and of their natural satellites, as well as the evolution of small bodies (including dust) in the planetary system. The few-body gravitational problem of hierarchical planetary-type systems allows for a complex range of dynamical timescales, from the fast orbital periods to the very slow orbit precession rates. The interaction of fast and slow degrees of freedom produces a rich diversity of resonance phenomena. Weak dissipative effects --- such as tides or radiation drag forces --- also produce unexpectedly rich dynamical behaviors. This paper provides a mostly qualitative discussion of simple dynamical models for the commonly encountered orbital resonance phenomena in the Solar system.Comment: Invited review for a special issue of Physica D on ``Modeling the Forces of Nature''. 13 pages, uuencoded compressed postscript file. 7 figures (available upon request from [email protected]

Palaeoenvironmental and diagenetic reconstruction of a closed-lacustrine carbonate system - the challenging marginal setting of the Miocene Ries Crater Lake (Germany)

Chemostratigraphic studies on lacustrine sedimentary sequences provide essential insights on past cyclic climatic events, on their repetition and prediction through time. Diagenetic overprint of primary features often hinders the use of such studies for palaeoenvironmental reconstruction. Here the potential of integrated geochemical and petrographic methods is evaluated to record freshwater to saline oscillations within the ancient marginal lacustrine carbonates of the Miocene Ries Crater Lake (Germany). This area is critical because it represents the transition from shoreline to proximal domains of a hydrologically closed system, affected by recurrent emergent events, representing the boundaries of successive sedimentary cycles. Chemostratigraphy targets shifts related to subaerial exposure and/or climatic fluctuations. Methods combine facies changes with δ13C–δ18O chemostratigraphy from matrix carbonates across five closely spaced, temporally equivalent stratigraphic sections. Isotope composition of ostracod shells, gastropods and cements is provided for comparison. Cathodoluminescence and back‐scatter electron microscopy were performed to discriminate primary (syn‐)depositional, from secondary diagenetic features. Meteoric diagenesis is expressed by substantial early dissolution and dark blue luminescent sparry cements carrying negative δ13C and δ18O. Sedimentary cycles are not correlated by isotope chemostratigraphy. Both matrix δ13C and δ18O range from ca −7·5 to +4·0‰ and show clear positive covariance (R = 0·97) whose nature differs from that of previous basin‐oriented studies on the lake: negative values are here unconnected to original freshwater lacustrine conditions but reflect extensive meteoric diagenesis, while positive values probably represent primary saline lake water chemistry. Noisy geochemical curves relate to heterogeneities in (primary) porosity, resulting in selective carbonate diagenesis. This study exemplifies that ancient lacustrine carbonates, despite extensive meteoric weathering, are able to retain key information for both palaeoenvironmental reconstruction and the understanding of diagenetic processes in relation to those primary conditions. Also, it emphasizes the limitation of chemostratigraphy in fossil carbonates, and specifically in settings that are sensitive for the preservation of primary environmental signals, such as lake margins prone to meteoric diagenesis

Multilevel structural equation models for longitudinal data where predictors are measured more frequently than outcomes: an application to the effects of stress on the cognitive function of nurses

Ecological momentary assessment is used to measure subjects' mood and behaviour repeatedly over time, leading to intensive longitudinal data. Variability in ecological momentary assessment schedules creates an analytical challenge because predictors are measured more frequently than responses. We consider this problem in a study of the effect of stress on the cognitive function of telephone helpline nurses, where stress is measured for each call and cognitive outcomes are measured at the end of a shift. We propose a flexible structural equation model which can handle multiple levels of clustering, measurement error, time trends and mixed variable types

Ednrb−/− mice with hirschsprung disease are missing Gad2-expressing enteric neurons in the ganglionated small intestine

Hirschsprung disease is most often characterized by aganglionosis limited to the distal colon and rectum, and mice lacking the Endothelin receptor type B (Ednrb) faithfully recapitulate this phenotype. However, despite the presence of enteric ganglia in the small intestine, both human patients and Ednrb−/− mice suffer from dysmotility and altered gastrointestinal function, thus raising the possibility of enteric nervous system (ENS) abnormalities proximal to the aganglionic region. We undertook the present study to determine whether abnormalities with the ENS in ganglionated regions may account for abnormal gastrointestinal function. We performed single-cell RNA sequencing on ENS cells from the small intestine of Ednrb−/− mice and compared the results to a published single-cell dataset. Our results identified a missing population of neurons marked by the enzyme Gad2, which catalyzes the production of γ-Aminobutyric acid (GABA), in the small intestine of Ednrb−/− animals. This result was confirmed by immunostaining enteric ganglia from Ednrb−/− mice and their wild-type littermates. These data show for the first time that ganglionated regions of the Hirschsprung gut lack a neuronal subpopulation, which may explain the persistent gastrointestinal dysfunction after surgical correction of Hirschsprung disease

Control of ULF wave accessibility to the inner magnetosphere by the convection of plasma density

During periods of storm activity and enhanced convection, the plasma density in theafternoon sector of the magnetosphere is highly dynamic due to the development of plasmasphericdrainage plume (PDP) structure. This significantly affects the local Alfvén speed and alters the propagationof ULF waves launched from the magnetopause. Therefore, it can be expected that the accessibility of ULFwave power for radiation belt energization is sensitively dependent on the recent history of magnetosphericconvection and the stage of development of the PDP. This is investigated using a 3-D model for ULF waveswithin the magnetosphere in which the plasma density distribution is evolved using an advection model forcold plasma, driven by a (VollandStern) convection electrostatic field (resulting in PDP structure). The wavemodel includes magnetic field day/night asymmetry and extends to a paraboloid dayside magnetopause,from which ULF waves are launched at various stages during the PDP development. We find that the plumestructure significantly alters the field line resonance location, and the turning point for MHD fast waves,introducing strong asymmetry in the ULF wave distribution across the noon meridian. Moreover, thedensity enhancement within the PDP creates a waveguide or local cavity for MHD fast waves, such thateigenmodes formed allow the penetration of ULF wave power to much lower L within the plume thanoutside, providing an avenue for electron energization

GLSMs for non-Kahler Geometries

We identify a simple mechanism by which H-flux satisfying the modified Bianchi identity arises in garden-variety (0,2) gauged linear sigma models. Taking suitable limits leads to effective gauged linear sigma models with Green-Schwarz anomaly cancellation. We test the quantum-consistency of a class of such effective theories by constructing an off-shell superconformal algebra, providing evidence that these models run to good CFTs in the deep IR.Comment: 37 pages, Minor updates for v