CXCR4 and CXCL12 signaling regulates the development of extrinsic innervation to the colorectum.

The gastrointestinal tract is innervated by an intrinsic neuronal network, known as the enteric nervous system (ENS), and by extrinsic axons arising from peripheral ganglia. The nerve of Remak (NoR) is an avian-specific sacral neural crest-derived ganglionated structure that extends from the cloaca to the proximal midgut and, similar to the pelvic plexus, provides extrinsic innervation to the distal intestine. The molecular mechanisms controlling extrinsic nerve fiber growth into the gut is unknown. In vertebrates, CXCR4, a cell-surface receptor for the CXCL12 chemokine, regulates migration of neural crest cells and axon pathfinding. We have employed chimeric tissue recombinations and organ culture assays to study the role of CXCR4 and CXCL12 molecules in the development of colorectal innervation. CXCR4 is specifically expressed in nerve fibers arising from the NoR and pelvic plexus, while CXCL12 is localized to the hindgut mesenchyme and enteric ganglia. Overexpression of CXCL12 results in significantly enhanced axonal projections to the gut from the NoR, while CXCR4 inhibition disrupts nerve fiber extension, supporting a previously unreported role for CXCR4 and CXCL12 signaling in extrinsic innervation of the colorectum.

Novel insights into the modulation of the voltage-gated potassium channel KV1.3 activation gating by membrane ceramides.

Membrane lipids extensively modulate the activation gating of voltage-gated potassium channels (KV), however, much less is known about mechanisms of ceramide and glucosylceramide actions including which structural element is the main intramolecular target and whether there is any contribution of indirect, membrane biophysics-related mechanisms to their actions. We used two-electrode voltage-clamp fluorometry capable of recording currents and fluorescence signals to simultaneously monitor movements of the pore domain (PD) and the voltage sensor domain (VSD) of the KV1.3 ion channel after attaching an MTS-TAMRA fluorophore to a cysteine introduced into the extracellular S3-S4 loop of the VSD. We observed rightward shifts in the conductance-voltage (G-V) relationship, slower current activation kinetics and reduced current amplitudes in response to loading the membrane with C16-ceramide (Cer) or C16-glucosylceramide (GlcCer). When analyzing VSD movements, only Cer induced a rightward shift in the fluorescence signal-voltage (F-V) relationship and slowed fluorescence activation kinetics, whereas GlcCer exerted no such effects. These results point at a distinctive mechanism of action with Cer primarily targeting the VSD, while GlcCer only the PD of KV1.3. Using environment-sensitive probes and fluorescence-based approaches, we show that Cer and GlcCer similarly increase molecular order in the inner, hydrophobic regions of bilayers, however, Cer induces a robust molecular reorganization at the membrane-water interface. We propose that this unique ordering effect in the outermost membrane layer in which the main VSD rearrangement involving an outward sliding of the top of S4 occurs, can explain the VSD targeting mechanism of Cer, which is unavailable for GlcCer.

Avian ceca are indispensable for hindgut enteric nervous system development.

The enteric nervous system (ENS), which is derived from enteric neural crest cells (ENCCs), represents the neuronal innervation of the intestine. Compromised ENCC migration can lead to Hirschsprung disease, which is characterized by an aganglionic distal bowel. During the craniocaudal migration of ENCCs along the gut, we find that their proliferation is greatest as the ENCC wavefront passes through the ceca, a pair of pouches at the midgut-hindgut junction in avian intestine. Removal of the ceca leads to hindgut aganglionosis, suggesting that they are required for ENS development. Comparative transcriptome profiling of the cecal buds compared with the interceca region shows that the non-canonical Wnt signaling pathway is preferentially expressed within the ceca. Specifically, WNT11 is highly expressed, as confirmed by RNA in situ hybridization, leading us to hypothesize that cecal expression of WNT11 is important for ENCC colonization of the hindgut. Organ cultures using embryonic day 6 avian intestine show that WNT11 inhibits enteric neuronal differentiation. These results reveal an essential role for the ceca during hindgut ENS formation and highlight an important function for non-canonical Wnt signaling in regulating ENCC differentiation.

Fate of Chiral Symmetries in the Quark-Gluon Plasma from an Instanton-Based Random Matrix Model of QCD.

We propose a new way of understanding how chiral symmetry is realized in the high temperature phase of QCD. Based on the finding that a simple free instanton gas precisely describes the details of the lowest part of the spectrum of the lattice overlap Dirac operator, we propose an instanton-based random matrix model of QCD with dynamical quarks. Simulations of this model reveal that even for small quark mass the Dirac spectral density has a singularity at the origin, caused by a dilute gas of free instantons. Even though the interaction, mediated by light dynamical quarks, creates small instanton-anti-instanton molecules, those do not influence the singular part of the spectrum, and this singular part is shown to dominate Banks-Casher type sums in the chiral limit. By generalizing the Banks-Casher formula for the singular spectrum, we show that in the chiral limit the chiral condensate vanishes if there are at least two massless flavors. Our model also indicates a possible way of resolving a long-standing debate, as it suggests that for two massless quark flavors the U(1)_{A} symmetry is likely to remain broken up to arbitrarily high finite temperatures.

RET overactivation leads to concurrent Hirschsprung disease and intestinal ganglioneuromas.

Appropriately balanced RET signaling is of crucial importance during embryonic neural crest cell migration, proliferation and differentiation. RET deficiency, for example, leads to intestinal aganglionosis (Hirschsprung disease), whereas overactive RET can lead to multiple endocrine neoplasia (MEN) syndromes. Some RET mutations are associated with both intestinal aganglionosis and MEN-associated tumors. This seemingly paradoxical occurrence has led to speculation of a 'Janus mutation' in RET that causes overactivation or impairment of RET activity depending on the cellular context. Using an intestinal catenary culture system to test the effects of GDNF-mediated RET activation, we demonstrate the concurrent development of distal colonic aganglionosis and intestinal ganglioneuromas. Interestingly, the tumors induced by GDNF stimulation contain enteric neuronal progenitors capable of reconstituting an enteric nervous system when transplanted into a normal developmental environment. These results suggest that a Janus mutation may not be required to explain co-existing Hirschsprung disease and MEN-associated tumors, but rather that RET overstimulation alone is enough to cause both phenotypes. The results also suggest that reprogramming tumor cells toward non-pathological fates may represent a possible therapeutic avenue for MEN-associated neoplasms.

Essential Role of BMP4 Signaling in the Avian Ceca in Colorectal Enteric Nervous System Development.

The enteric nervous system (ENS) is principally derived from vagal neural crest cells that migrate caudally along the entire length of the gastrointestinal tract, giving rise to neurons and glial cells in two ganglionated plexuses. Incomplete migration of enteric neural crest-derived cells (ENCDC) leads to Hirschsprung disease, a congenital disorder characterized by the absence of enteric ganglia along variable lengths of the colorectum. Our previous work strongly supported the essential role of the avian ceca, present at the junction of the midgut and hindgut, in hindgut ENS development, since ablation of the cecal buds led to incomplete ENCDC colonization of the hindgut. In situ hybridization shows bone morphogenetic protein-4 (BMP4) is highly expressed in the cecal mesenchyme, leading us to hypothesize that cecal BMP4 is required for hindgut ENS development. To test this, we modulated BMP4 activity using embryonic intestinal organ culture techniques and retroviral infection. We show that overexpression or inhibition of BMP4 in the ceca disrupts hindgut ENS development, with GDNF playing an important regulatory role. Our results suggest that these two important signaling pathways are required for normal ENCDC migration and enteric ganglion formation in the developing hindgut ENS.

Systematic transcriptomic and phenotypic characterization of human and murine cardiac myocyte cell lines and primary cardiomyocytes reveals serious limitations and low resemblances to adult cardiac phenotype.

BACKGROUND: Cardiac cell lines and primary cells are widely used in cardiovascular research. Despite increasing number of publications using these models, comparative characterization of these cell lines has not been performed, therefore, their limitations are undetermined. We aimed to compare cardiac cell lines to primary cardiomyocytes and to mature cardiac tissues in a systematic manner. METHODS AND RESULTS: Cardiac cell lines (H9C2, AC16, HL-1) were differentiated with widely used protocols. Left ventricular tissue, neonatal primary cardiomyocytes, and human induced pluripotent stem cell-derived cardiomyocytes served as reference tissue or cells. RNA expression of cardiac markers (e.g. Tnnt2, Ryr2) was markedly lower in cell lines compared to references. Differentiation induced increase in cardiac- and decrease in embryonic markers however, the overall transcriptomic profile and annotation to relevant biological processes showed consistently less pronounced cardiac phenotype in all cell lines in comparison to the corresponding references. Immunocytochemistry confirmed low expressions of structural protein sarcomeric alpha-actinin, troponin I and caveolin-3 in cell lines. Susceptibility of cell lines to sI/R injury in terms of viability as well as mitochondrial polarization differed from the primary cells irrespective of their degree of differentiation. CONCLUSION: Expression patterns of cardiomyocyte markers and whole transcriptomic profile, as well as response to sI/R, and to hypertrophic stimuli indicate low-to-moderate similarity of cell lines to primary cells/cardiac tissues regardless their differentiation. Low resemblance of cell lines to mature adult cardiac tissue limits their potential use. Low translational value should be taken into account while choosing a particular cell line to model cardiomyocytes.

Characterization of technical skill progress in a standardized rabbit model for training in laparoscopic duodenal atresia repair.

BACKGROUND: Laboratory skills training is an essential step before conducting minimally invasive surgery in clinical practice. Our main aim was to develop an animal model for training in clinically highly challenging laparoscopic duodenal atresia repair that could be useful in establishing a minimum number of repetitions to indicate safe performance of similar interventions on humans. MATERIALS AND METHODS: A rabbit model of laparoscopic duodenum atresia surgery involving a diamond-shaped duodeno-duodenostomy was designed. This approach was tested in two groups of surgeons: in a beginner group without any previous clinical laparoscopic experience (but having undergone previous standardized dry-lab training, n = 8) and in an advanced group comprising pediatric surgery fellows with previous clinical experience of laparoscopy (n = 7). Each participant performed eight interventions. Surgical time, expert assessment using the Global Operative Assessment of Laparoscopic Skills (GOALS) score, anastomosis quality (leakage) and results from participant feedback questionnaires were analyzed. RESULTS: Participants in both groups successfully completed all eight surgeries. The surgical time gradually improved in both groups, but it was typically shorter in the advanced group than in the beginner group. The leakage rate was significantly lower in the advanced group in the first two interventions, and it reached its optimal level after five operations in both groups. The GOALS and participant feedback scores showed gradual increases, evident even after the fifth surgery. CONCLUSIONS: Our data confirm the feasibility of this advanced pediatric laparoscopic model. Surgical time, anastomosis quality, GOALS score and self-assessment parameters adequately quantify technical improvement among the participants. Anastomosis quality reaches its optimal value after the fifth operation even in novice, but uniformly trained surgeons. A minimum number of wet-lab operations can be determined before surgery can be safely conducted in a clinical setting, where the development of further non-technical skills is also required.

Assessing the Effects of Holling Type-II Treatment Rate on HIV-TB Co-infection.

In this paper, a HIV-TB co-infection model is explored which incorporates a non-linear treatment rate for TB. We begin with presenting a HIV-TB co-infection model and analyze both HIV and TB sub-models separately. The basic reproduction numbers corresponding to HIV-only, TB-only and the HIV-TB full model are computed. The disease-free equilibrium point of the HIV sub-model is shown to be locally as well as globally asymptotically stable when its corresponding reproduction number is less than unity. The HIV-only model exhibits a transcritical bifurcation. On the other hand, for the TB sub-model, the disease-free equilibrium point is locally asymptotically stable but may not be globally asymptotically stable. We have also analyzed the full HIV-TB co-infection model. Numerical simulations are performed to investigate the effect of treatment rate in the presence of resource limitation for TB infected individuals, which emphasize the fact that to reduce co-infection from the population programs to accelerate the treatment of TB should be implemented.

Opposing Effects of Chelidonine on Tyrosine and Serine Phosphorylation of STAT3 in Human Uveal Melanoma Cells.

STAT3 is a transcription factor that regulates various cellular processes with oncogenic potential, thereby promoting tumorigenesis when activated uncontrolled. STAT3 activation is mediated by its tyrosine phosphorylation, triggering dimerization and nuclear translocation. STAT3 also contains a serine phosphorylation site, with a postulated regulatory role in STAT3 activation and G2/M transition. Interleukin-6, a major activator of STAT3, is present in elevated concentrations in uveal melanomas, suggesting contribution of dysregulated STAT3 activation to their pathogenesis. Here, we studied the impact of chelidonine on STAT3 signaling in human uveal melanoma cells. Chelidonine, an alkaloid isolated from Chelidonium majus, disrupts microtubules, causes mitotic arrest and provokes cell death in numerous tumor cells. According to our flow cytometry and confocal microscopy data, chelidonine abrogated IL-6-induced activation and nuclear translocation, but amplified constitutive serine phosphorylation of STAT3. Both effects were restricted to a fraction of cells only, in an all-or-none fashion. A partial overlap could be observed between the affected subpopulations; however, no direct connection could be proven. This study is the first proof on a cell-by-cell basis for the opposing effects of a microtubule-targeting agent on the two types of STAT3 phosphorylation.

Live-Cell Imaging of Single Neurotrophin Receptor Molecules on Human Neurons in Alzheimer's Disease.

Neurotrophin receptors such as the tropomyosin receptor kinase A receptor (TrkA) and the low-affinity binding p75 neurotrophin receptor p75NTR play a critical role in neuronal survival and their functions are altered in Alzheimer's disease (AD). Changes in the dynamics of receptors on the plasma membrane are essential to receptor function. However, whether receptor dynamics are affected in different pathophysiological conditions is unexplored. Using live-cell single-molecule imaging, we examined the surface trafficking of TrkA and p75NTR molecules on live neurons that were derived from human-induced pluripotent stem cells (hiPSCs) of presenilin 1 (PSEN1) mutant familial AD (fAD) patients and non-demented control subjects. Our results show that the surface movement of TrkA and p75NTR and the activation of TrkA- and p75NTR-related phosphoinositide-3-kinase (PI3K)/serine/threonine-protein kinase (AKT) signaling pathways are altered in neurons that are derived from patients suffering from fAD compared to controls. These results provide evidence for altered surface movement of receptors in AD and highlight the importance of investigating receptor dynamics in disease conditions. Uncovering these mechanisms might enable novel therapies for AD.

Synaptic organization of cortico-cortical communication in primates.

In cortical circuitry, synaptic communication across areas is based on two types of axon terminals, small and large, with modulatory and driving roles, respectively. In contrast, it is not known whether similar synaptic specializations exist for intra-areal projections. Using anterograde tracing and three-dimensional reconstruction by electron microscopy (3D-EM), we asked whether large boutons form synapses in the circuit of somatosensory cortical areas 3b and 1. In contrast to observations in macaque visual cortex, light microscopy showed both small and large boutons not only in inter-areal pathways, but also in long-distance intrinsic connections. 3D-EM showed that correlation of surface and volume provides a powerful tool for classifying cortical endings. Principal component analysis supported this observation and highlighted the significance of the size of mitochondria as a distinguishing feature of bouton type. The larger mitochondrion and higher degree of perforated postsynaptic density associated with large rather than to small boutons support the driver-like function of large boutons. In contrast to bouton size and complexity, the size of the postsynaptic density appeared invariant across the bouton types. Comparative studies in human supported that size is a major distinguishing factor of bouton type in the cerebral cortex. In conclusion, the driver-like function of the large endings could facilitate fast dissemination of tactile information within the intrinsic and inter-areal circuitry of areas 3b and 1.

Amiodarone that has antibacterial effect against human pathogens may represent a novel catheter lock.

Infection is one of the most feared hospital-acquired complications. Infusion therapy is frequently administered through a central line. Infusions facilitating bacterial growth may be a source of central line-associated bloodstream infections. On the other hand, medications that kill bacteria may protect against this kind of infection and may be used as a catheter lock.In this study, we examined the impact of amiodarone on bacterial growth. Amiodarone is used for controlling cardiac arrhythmias and can be administered as an infusion for weeks. Standard microbiological methods have been used to study the growth of laboratory strains and clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and multidrug-resistant Acinetobacter baumannii in amiodarone. The minimum inhibitory concentration (MIC) of amiodarone was determined. Bacterial growth from in use amiodarone syringes and giving sets was also investigated.Most examined strains were killed within 1 min in amiodarone. The other strains were killed within 1 h. The MICs of amiodarone were <0.5-32 µg/mL.Amiodarone infusion is unlikely to be responsible for bloodstream infections as contaminating bacteria are killed within 1 h. Amiodarone may also protect against central line infections if used as a catheter lock.

Estradiol-Induced Epigenetically Mediated Mechanisms and Regulation of Gene Expression.

Gonadal hormone 17ß-estradiol (E2) and its receptors are key regulators of gene transcription by binding to estrogen responsive elements in the genome. Besides the classical genomic action, E2 regulates gene transcription via the modification of epigenetic marks on DNA and histone proteins. Depending on the reaction partner, liganded estrogen receptor (ER) promotes DNA methylation at the promoter or enhancer regions. In addition, ERs are important regulators of passive and active DNA demethylation. Furthermore, ERs cooperating with different histone modifying enzymes and chromatin remodeling complexes alter gene transcription. In this review, we survey the basic mechanisms and interactions between estrogen receptors and DNA methylation, demethylation and histone modification processes as well as chromatin remodeling complexes. The particular relevance of these mechanisms to physiological processes in memory formation, embryonic development, spermatogenesis and aging as well as in pathophysiological changes in carcinogenesis is also discussed.

Outcomes of laparoscopic incarcerated inguinal hernia repair in children.

AIM: Laparoscopic inguinal hernia repair (LIHR) is gaining widespread acceptance, but its role in the management of incarcerated cases is not well outlined. This review analyses the outcomes of laparoscopic repair of incarcerated inguinal hernia in children. PATIENTS AND METHODS: Literature was searched on PubMed® using terms 'laparoscopic', 'incarcerated', 'inguinal', 'hernia' and 'children'. Age, sex, side, sac content, operative technique, follow-up period, complication and recurrence rate were analysed. RESULTS: Fifteen articles with 689 paediatric incarcerated inguinal hernias were identified between 1998 and 2018. Median age of patients was 22.4 months (2 weeks-16 years; M:F = 2.2:1). Side was mentioned in n = 576: n = 398 (69.1%) right and n = 178 (30.9%) left. In n = 355 (51.5%) manual reduction and delayed surgery (MRDS), in n = 34 (4.9%) manual reduction in general anaesthesia (MRGA) followed by emergency LHR and in n = 300 (43.5%) intraoperative reduction (IOR) was necessary. Incarcerated contents were documented in n = 68: intestine n = 36 (52.9%), ovary n = 14 (20.6%), omentum n = 11 (16.2%), appendix n = 5 (7.4%) and Meckel's diverticulum n = 2 (2.9%). Among the n = 18 girls in IOR group, n = 14 (77.8%) had ovaries incarcerated. For LHR, the hook method was used in 376 (54.6%) and purse-string suture in 313 (45.4%), with two conversions in IOR group. Mean followup was 15 months (3-80 months), with one (0.15%) testicular atrophy, and 4 (0.58%) recurrences in MRDS and 1 (0.15%) in IOR. All five cases were closed with pursestring technique. Total recurrence rate was 0.73%; significantly higher (P = 0.014) with pursestring (n = 5, 1.6%) than with the hook (none). CONCLUSION: Hook and purse-string methods are equally popular in LHR for paediatric incarcerated hernias, with 50% hernia reductions possible at the time of surgery. Recurrence rate is low and comparable with non-incarcerated hernias; however, it is significantly higher in purse-string method than hook technique.

Homo- and Heteroassociations Drive Activation of ErbB3.

Dimerization or the formation of higher-order oligomers is required for the activation of ErbB receptor tyrosine kinases. The heregulin (HRG) receptor, ErbB3, must heterodimerize with other members of the family, preferentially ErbB2, to form a functional signal transducing complex. Here, we applied single molecule imaging capable of detecting long-lived and mobile associations to measure their stoichiometry and mobility and analyzed data from experiments globally, taking the different lateral mobility of monomeric and dimeric molecular species into account. Although ErbB3 was largely monomeric in the absence of stimulation and ErbB2 co-expression, a small fraction was present as constitutive homodimers exhibiting a ∼40% lower mobility than monomers. HRG stimulation increased the homodimeric fraction of ErbB3 significantly and reduced the mobility of homodimers fourfold compared to constitutive homodimers. Expression of ErbB2 elevated the homodimeric fraction of ErbB3 even in unstimulated cells and induced a ∼2-fold reduction in the lateral mobility of ErbB3 homodimers. The mobility of ErbB2 was significantly lower than that of ErbB3, and HRG induced a less pronounced decrease in the diffusion coefficient of all ErbB2 molecules and ErbB3/ErbB2 heterodimers than in the mobility of ErbB3. The slower diffusion of ErbB2 compared to ErbB3 was abolished by depolymerizing actin filaments, whereas ErbB2 expression induced a substantial rearrangement of microfilaments, implying a bidirectional interaction between ErbB2 and actin. HRG stimulation of cells co-expressing ErbB3 and ErbB2 led to the formation of ErbB3 homodimers and ErbB3/ErbB2 heterodimers in a competitive fashion. Although pertuzumab, an antibody binding to the dimerization arm of ErbB2, completely abolished the formation of constitutive and HRG-induced ErbB3/ErbB2 heterodimers, it only slightly blocked ErbB3 homodimerization. The results imply that a dynamic equilibrium exists between constitutive and ligand-induced homo- and heterodimers capable of shaping transmembrane signaling.

Surgical treatment of awn aspiration causing bronchopleural fistula and bronchiectasis: case reports.

BACKGROUND: Aspiration of grass inflorescences is an extremely rare phenomenon with potential diagnostic difficulties. Due to its special shape, each coughing and respiratory action helps its migration towards the periphery of lung, resulting late-onset, life-threatening complications. The diagnosis has some difficulties for the reason that soon after the aspiration initial symptoms, such as coughing, wheezing or vomiting disappear and bronchoscopy is mostly negative. At least serious complications such as tension pneumothorax, bronchopleurocutaneous fistula or even spontaneous percutan elimination may develope. CASE PRESENTATION: We present two cases of pleuropneumonia resulting from aspiration of the head of barley grass. Soon after the accidents initial symptoms diminished, inflammatory markers improved and bronchoscopy was unable to confirm the presence of awn. Despite of conservative treatment (antibiotics, physiotherapy, bronchodilators, expectorants, and inhalation) localized pulmonary inflammation developed after 1 and 9 months showed up on chest computed tomography. After ineffective conservative treatment, surgical resections became inevitable in order to remove chronically inflamed parts (lobectomy, segmentectomy) and foreign bodies. Both patients recovered and were discharged home after successful interventions. CONCLUSIONS: Due to its peculiar shape and behaviour, awn inhalation is a special and atypical form of aspiration, thus great care and awareness is needed in its treatment. Negative bronchoscopic result does not exclude the presence of bronchial grass head. Symptomless child with negative bronchoscopy and improved inflammatory markers should be followed up thoroughly to recognize late complications in time. Regular diagnostic steps (chest ultrasound/X-ray) should be performed to localize potential chronic lung inflammation. Chest computed tomography is a valuable diagnostic tool for identifying and localising the foreign body. In cases with localized inflammation and peripheric localisation, segmentectomy can be a successful and safe alternative of lobectomy.

Recurrence network analysis of exoplanetary observables.

Recent advancements of complex network representation among several disciplines motivated the investigation of exoplanetary dynamics by means of recurrence networks. We are able to recover different dynamical regimes by means of various network measures obtained from synthetic time series of a model planetary system. The framework of complex networks is also applied to real astronomical observations acquired by recent state-of-the-art surveys. The outcome of the analysis is consistent with earlier studies opening new directions to investigate planetary dynamics.

Intraganglionic macrophages: a new population of cells in the enteric ganglia.

The enteric nervous system shares embryological, morphological, neurochemical, and functional features with the central nervous system. In addition to neurons and glia, the CNS includes a third component, microglia, which are functionally and immunophenotypically similar to macrophages, but a similar cell type has not previously been identified in enteric ganglia. In this study we identify a population of macrophages in the enteric ganglia, intermingling with the neurons and glia. These intraganglionic macrophages (IMs) are highly ramified and express the hematopoietic marker CD45, major histocompatibility complex (MHC) class II antigen, and chB6, a marker specific for B cells and microglia in avians. These IMs do not express antigens typically associated with T cells or dendritic cells. The CD45+ /ChB6+ /MHCII+ signature supports a hematopoietic origin and this was confirmed using intestinal chimeras in GFP-transgenic chick embryos. The presence of green fluorescent protein positive (GFP+) /CD45+ cells in the intestinal graft ENS confirms that IMs residing within enteric ganglia have a hematopoietic origin. IMs are also found in the ganglia of CSF1RGFP chicken and CX3CR1GFP mice. Based on the expression pattern and location of IMs in avians and rodents, we conclude that they represent a novel non-neural crest-derived microglia-like cell population within the enteric ganglia.

Analysis of Complications After Button Battery Ingestion in Children.

AIM: Button battery ingestion (BBI) in children may cause severe complications. This analysis is a literature review of complications after pediatric BBI. METHODS: Literature was searched on PubMed (1995-2015) using the terms "button battery," "ingestion," and "children." End points were age, type and diameter of battery, complications, affected organ, and fatality. RESULTS: A total of 31 publications were analyzed. Patients from 4 months to 19 years old were included (n = 136,191, with n = 102,143 or 75% aged <6 y). In 6262, the diameter of the battery was documented. Batteries of 20 mm or greater in size were more prone to complications (n = 226). With regard to the anatomy, BBI caused complications mainly in the esophagus (n = 88, 38.94%). Sixty-one fatal outcomes were reported. CONCLUSIONS: Children younger than 6 years are the most prone to BBI, with lithium batteries of 20 mm or greater in size associated with complications. Complications have been estimated at 0.165%, with lethality of 0.04%. The esophagus is the most affected organ, but vascular involvement is often fatal.