A modular magnetic anastomotic device for minimally invasive digestive anastomosis: proof of concept and preliminary data in the pig model

Background: The aim of our study was to assess the feasibility of minimally invasive digestive anastomosis using a modular flexible magnetic anastomotic device made up of a set of two flexible chains of magnetic elements. The assembly possesses a non-deployed linear configuration which allows it to be introduced through a dedicated small-sized applicator into the bowel where it takes the deployed form. A centering suture allows the mating between the two parts to be controlled in order to include the viscerotomy between the two magnetic rings and the connected viscera. Methods and procedures: Eight pigs were involved in a 2-week survival experimental study. In five colorectal anastomoses, the proximal device was inserted by a percutaneous endoscopic technique, and the colon was divided below the magnet. The distal magnet was delivered transanally to connect with the proximal magnet. In three jejunojejunostomies, the first magnetic chain was injected in its linear configuration through a small enterotomy. Once delivered, the device self-assembled into a ring shape. A second magnet was injected more distally through the same port. The centering sutures were tied together extracorporeally and, using a knot pusher, magnets were connected. Ex vivo strain testing to determine the compression force delivered by the magnetic device, burst pressure of the anastomosis, and histology were performed. Results : Mean operative time including endoscopy was 69.2±21.9min, and average time to full patency was 5days for colorectal anastomosis. Operative times for jejunojejunostomies were 125, 80, and 35min, respectively. The postoperative period was uneventful. Burst pressure of all anastomoses was ≥110mmHg. Mean strain force to detach the devices was 6.1±0.98 and 12.88±1.34N in colorectal and jejunojejunal connections, respectively. Pathology showed a mild-to-moderate inflammation score. Conclusions: The modular magnetic system showed enormous potential to create minimally invasive digestive anastomoses, and may represent an alternative to stapled anastomoses, being easy to deliver, effective, and low cost

Differential Cytokine Utilization and Tissue Tropism Results in Distinct Repopulation Kinetics of Naïve vs. Memory T Cells in Mice

Naïve and memory T cells co-exist in the peripheral T cell pool, but the cellular mechanisms that maintain the balance and homeostasis of these two populations remain mostly unclear. To address this question, here, we assessed homeostatic proliferation and repopulation kinetics of adoptively transferred naïve and memory T cells in lymphopenic host mice. We identified distinct kinetics of proliferation and tissue-distribution between naïve and memory donor T cells, which resulted in the occupancy of the peripheral T cell pool by mostly naïve-origin T cells in short term (<1 week), but, in a dramatic reversal, by mostly memory-origin T cells in long term (>4 weeks). To explain this finding, we assessed utilization of the homeostatic cytokines IL-7 and IL-15 by naïve and memory T cells. We found different efficiencies of IL-7 signaling between naïve and memory T cells, where memory T cells expressed larger amounts of IL-7Rα but were significantly less potent in activation of STAT5 that is downstream of IL-7 signaling. Nonetheless, memory T cells were superior in long-term repopulation of the peripheral T cell pool, presumably, because they preferentially migrated into non-lymphoid tissues upon adoptive transfer and additionally utilized tissue IL-15 for rapid expansion. Consequently, co-utilization of IL-7 and IL-15 provides memory T cells a long-term survival advantage. We consider this mechanism important, as it permits the memory T cell population to be maintained in face of constant influx of naïve T cells to the peripheral T cell pool and under competing conditions for survival cytokines

The First Very Long Baseline Interferometry Image of 44 GHz Methanol Maser with the KVN and VERA Array (KaVA)

We have carried out the first very long baseline interferometry (VLBI) imaging of 44 GHz class I methanol maser (7_{0}-6_{1}A^{+}) associated with a millimeter core MM2 in a massive star-forming region IRAS 18151-1208 with KaVA (KVN and VERA Array), which is a newly combined array of KVN (Korean VLBI Network) and VERA (VLBI Exploration of Radio Astrometry). We have succeeded in imaging compact maser features with a synthesized beam size of 2.7 milliarcseconds x 1.5 milliarcseconds (mas). These features are detected at a limited number of baselines within the length of shorter than approximately 650 km corresponding to 100 Mlambda in the uv-coverage. The central velocity and the velocity width of the 44 GHz methanol maser are consistent with those of the quiescent gas rather than the outflow traced by the SiO thermal line. The minimum component size among the maser features is ~ 5 mas x 2 mas, which corresponds to the linear size of ~ 15 AU x 6 AU assuming a distance of 3 kpc. The brightness temperatures of these features range from ~ 3.5 x 10^{8} to 1.0 x 10^{10} K, which are higher than estimated lower limit from a previous Very Large Array observation with the highest spatial resolution of ~ 50 mas. The 44 GHz class I methanol maser in IRAS 18151-1208 is found to be associated with the MM2 core, which is thought to be less evolved than another millimeter core MM1 associated with the 6.7 GHz class II methanol maser.Comment: 19 pages, 3 figure

Probe-based confocal laser endomicroscopy and fluorescence-based enhanced reality for real-time assessment of intestinal microcirculation in a porcine model of sigmoid ischemia

Background and aim: Surgeons currently rely on visual clues to estimate the presence of sufficient vascularity for safe anastomosis. We aimed to assess the accuracy of endoluminal confocal laser endomicroscopy (CLE) and laparoscopic fluorescence-based enhanced reality (FLER), using near-infrared imaging and fluorescence from injected Indocyanine Green, to identify the transition from ischemic to vascular areas in a porcine model of mesenteric ischemia. Methods: Six pigs underwent 1-h sigmoid segmental ischemia. The ischemic area was evaluated by clinical assessment and FLER to determine presumed viable margins. For each sigmoid colon, 5 regions of interest (ROIs) were identified: ischemic (ROI 1), presumed viable margins ROI 2a (distal) and 2b (proximal), and vascular areas 3a (distal) and 3b (proximal). After injection of fluorescein, CLE scanning of the mucosa from the ischemic area toward viable margins was performed. Capillary blood samples were obtained by puncturing the serosa at the ROIs, and capillary lactates were measured with the EDGE® analyzer. Results: Capillary lactates were significantly higher at ROI 1 (4.91mmol/L) when compared to resection margins (2.8mmol/L; mean difference: 2.11; p<0.05) identified by FLER. There was no significant difference in lactates between ROI1 and resection margins identified by clinical evaluation. In 50% of cases, ROI 2aCLINIC-2bCLINIC were considered to match (<1cm distance) with ROI 2aFLER-2bFLER. Confocal analysis revealed specific clues to identify the transition from ischemic to viable areas corresponding to those assessed by FLER in 11/12 cases versus 7/12 for those identified by clinical evaluation. Conclusions: In this experimental model, FLER and CLE were more accurate than clinical evaluation to delineate bowel vascularization

Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson\u27s disease modeling

Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson\u27s disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD