Ascaris suum infection in juvenile pigs elicits a local Th2 response in a setting of ongoing Th1 expansion

Ascaris spp. undergo extensive migration within the body before establishing patent infections in the small intestinal tract of humans and pigs. However, whether larval migration is critical for inducing efficient type 2 responses remains poorly understood. Therefore, we investigated systemic versus local adaptive immune responses along the hepato-tracheal migration of Ascaris suum during primary, single infections in conventionally raised pigs. Neither the initial invasion of gut tissue nor migration through the liver resulted in discernable Th2 cell responses. In contrast, lung-stage larvae elicited a Th2-biased pulmonary response, which declined after the larvae had left the lungs. In the small intestine, we observed an accumulation of Th2 cells upon the arrival of fourth-stage larvae (L4) to the small intestinal lumen. In parallel, we noticed robust and increasing Th1 responses in circulation, migration-affected organs, and draining lymph nodes. Phenotypic analysis of CD4+ T cells specifically recognizing A. suum antigens in the circulation and lung tissue of infected pigs confirmed that the majority of Ascaris -specific T cells produced IL-4 (Th2) and, to a much lesser extent, IL-4/IFN-g (Th2/1 hybrids) or IFN-g alone (Th1). These data demonstrate that lung-stage but not the early liver-stage larvae lead to a locally restricted Th2 response. Significant Th2 cell accumulation in the small intestine occurs only when L4 complete the body migration. In addition, Th2 immunity seems to be hampered by the concurrent, nonspecific Th1 bias in growing pigs. Together, the late onset of Th2 immunity at the site of infection and the Th1-biased systemic immunity likely enable the establishment of intestinal infections by sufficiently large L4 stages and pre-adult worms, some of which resist expulsion mechanisms

Satellite communications systems and technology. Executive Summary

NASA and the National Science Foundation (NSF) commissioned a panel of US experts to study the international status of satellite communications systems and technology. The study covers emerging systems concepts, applications, services, and the attendant technologies. The panel members travelled to Europe, Japan, and Russia to gather information first-hand. They visited 17 sites in Europe, 20 sites in Japan, and four in Russia. These included major manufacturers, government organizations, service providers, and associated R&D facilities. The panel's report was reviewed by the sites visited, by the panel, and by representatives of US industry. The report details the information collected and compares it to US activities

Information and communication technology

NASA and the National Science Foundation (NSF) commissioned a panel of U.S. experts to study the international status of satellite communications systems and technology. The study covers emerging systems concepts, applications, services, and the attendant technologies. The panel members traveled to Europe, Japan, and Russia to gather information firsthand. They visited 17 sites in Europe, 20 in Japan, and 4 in Russia. These included major manufacturers, government organizations, service providers, and associated research and development facilities. The panel's report was reviewed by the sites visited, by the panel, and by representatives of U.S. industry. The report details the information collected and compares it to U.S. activities

VACTERL association etiology: The impact of de novo and rare copy number variations

Copy number variations (CNVs), either DNA gains or losses, have been found at common regions throughout the human genome. Most CNVs neither have a pathogenic significance nor result in disease-related phenotypes but, instead, reflect the normal population variance. However, larger CNVs, which often arise de novo, are frequently associated with human disease. A genetic contribution has long been suspected in VACTERL (Vertebral, Anal, Cardiac, TracheoEsophageal fistula, Renal and Limb anomalies) association. The anomalies observed in this association overlap with several monogenetic conditions associated with mutations in specific genes, e.g. Townes Brocks (SALL1), Feingold syndrome (MYCN) or Fanconi anemia. So far VACTERL association has typically been considered a diagnosis of exclusion. Identifying recurrent or de novo genomic variations in individuals with VACTERL association could make it easier to distinguish VACTERL association from other syndromes and could provide insight into disease mechanisms. Sporadically, de novo CNVs associated with VACTERL are described in literature. In addition to this literature review of genomic variation in published VACTERL association patients, we describe CNVs present in 68 VACTERL association patients collected in our institution. De novo variations (>30 kb) are absent in our VACTERL association cohort. However, we identified recurrent rare CNVs which, although inherited, could point to mechanisms or biological processes contributing to this constellation of developmental defects

Randomized Trial of Ciclosporin with 2-h Monitoring vs. Tacrolimus with Trough Monitoring in Liver Transplantation:DELTA Study

Background and Aims: Previous trials comparing cyclosporine and tacrolimus after liver transplantation (LT) showed conflicting results. Most used trough monitoring for cyclosporine (C0), leading to less accurate dosing than with 2-h monitoring (C2). Only one larger trial compared C2 with tacrolimus based on trough level (T0) after LT, with similar treated biopsy-proven acute rejection (tBPAR) and graft loss, while a smaller trial had less tBPAR with C2 compared to T0. Therefore, it is still unclear which calcineurin inhibitor is preferred after LT. We aimed to demonstrate superior efficacy (tBPAR), tolerability, and safety of C2 or T0 after first LT. Methods: Patients after first LT were randomized to C2 or T0. tBPAR, patient-and graft survival, safety and tolerability were the main endpoints, with analysis by Fisher test, Kaplan–Meier survival analysis and log-rank test. Results: In intention-to treat analysis 84 patients on C2 and 85 on T0 were included. Cumulative incidence of tBPAR C2 vs. T0 was 17.7% vs. 8.4% at 3 months (p=0.104), and 21.9% vs. 9.7% at 6 and 12 months (p=0.049). One-year cumulative mortality C2 vs. T0 was 15.5% vs. 5.9% (p=0.049) and graft loss 23.8% vs. 9.4% (p=0.015). Serum triglyceride and LDL-cholesterol was lower with T0 than with C2. Incidence of diarrhea in T0 vs, C2 was 64% vs. 31% (p≤0.001), with no other differences in safety and tolerability. Conclusions: In the first year after LT immunosuppression with T0 leads to less tBPAR and better patient-/re-transplant-free survival as compared to C2.</p

Donor diabetes mellitus is a risk factor for diminished outcome after liver transplantation:a nationwide retrospective cohort study

BACKGROUND: With the growing incidence of diabetes mellitus (DM), an increasing number of organ donors with DM can be expected. We sought to investigate the association between donor DM with early post-transplant outcomes. METHODS: From a national cohort of adult liver transplant recipients (1996-2016), all recipients transplanted with a liver from a DM donor (n=69) were matched 1:2 with recipients of livers from non-DM donors (n=138). The primary end-point included early post-transplant outcome, such as the incidence of primary non-function (PNF), hepatic artery thrombosis (HAT), and 90-day graft survival. Cox regression analysis was used to analyze the impact of donor DM on graft failure. RESULTS: PNF was observed in 5.8% of grafts from DM donors versus 2.9% of non-DM donor grafts (p=0.31). Recipients of grafts derived from DM donors had a higher incidence of HAT (8.7% vs. 2.2%, p=0.03) and decreased 90-day graft survival (88.4% [70.9-91.1] vs. 96.4% [89.6-97.8], p=0.03) compared to recipients of grafts from non-DM donors. The adjusted hazard ratio for donor DM on graft survival was 2.21 (1.08-4.53, p=0.03). CONCLUSION: Donor DM is associated with diminished outcome early after liver transplantation. The increased incidence of HAT after transplantation of livers from DM donors requires further research

Infantile hypertrophic pyloric stenosis in patients with esophageal atresia

Background: Patients born with esophageal atresia (EA) have a higher incidence of infantile hypertrophic pyloric stenosis (IHPS), suggestive of a relationship. A shared etiology makes sense from a developmental perspective as both affected structures are foregut derived. A genetic component has been described for both conditions as single entities and EA and IHPS are variable components in several monogenetic syndromes. We hypothesized that defects disturbing foregut morphogenesis are responsible for this combination of malformations. Methods: We investigated the genetic variation of 15 patients with both EA and IHPS with unaffected parents using exome sequencing and SNP array-based genotyping, and compared the results to mouse transcriptome data of the developing foregut. Results: We did not identify putatively deleterious de novo mutations or recessive variants. However, we detected rare inherited variants in EA or IHPS disease genes or in genes important in foregut morphogenesis, expressed at the proper developmental time-points. Two pathways were significantly enriched (p < 1 × 10−5): proliferation and differentiation of smooth muscle cells and self-renewal of satellite cells. Conclusions: None of our findings could fully explain the combination of abnormalities on its own, which makes complex inheritance the most plausible genetic explanation, most likely in combination with mechanical and/or environmental factors. As we did not find one defining monogenetic cause for the EA/IHPS phenotype, the impact of the corrective surgery could should be further investigated

The Vehicle, 1964, Vol. 6

Vol. 6 Table of Contents Milepostspage 2 John Fitzgerald Kennedy Memorial Pagepage 4 Sadness No. 4 (Sorgen)Sherry S. Frypage 5 Christian BurialRoger J. Barrypage 7 The World of BeautyDavid Helmpage 9 The Song of the LarksDon Kapraunpage 10 ContrastKeith Haierpage 13 PanoramaDaun Alan Leggpage 13 A Child\u27s View of DeathCherie Brondellpage 14 RegretLiz Puckettpage 16 Brutal WarMary H. Soukuppage 17 aloneLiz Puckettpage 18 MadgeLinda Galeypage 19 Moon WatchingJoel E. Hendrickspage 20 AnalysisLiz Puckettpage 21 UniverseRick Talleypage 21 Anyone Can Be A LuniticRick Towsonpage 22 I, Too, Have A Rendezvous with DeathElaine Lancepage 23 The ReturnRobert D. Thomaspage 24 NamesLarry Gatespage 25 Eternal MomentsDavid Helmpage 25 The Last DaysPauline B. Smithpage 26 BeliefRichard J. Wiesepage 27 StormPauline B. Smithpage 28 ExplosionLiz Puckettpage 29 Autumn EveJoel E. Hendrickspage 29 The Girl On the White PonyLarry Gatespage 31 HoffnungTerry Michael Salempage 33 Stone WallsDaun Alan Leggpage 34 AdorationGail M. Barenfangerpage 37 MirageRoy L. Carlsonpage 38 Nature and NonsenseRick Talleypage 39 A Step Through A Looking GlassMarilyn Henrypage 40 Thoughts of a Summer PastPauline B Smithpage 42 Indiana GrassLarry Gatespage 43 RedondillaRoberta Matthewspage 44 Summer LoveDaun Alan Leggpage 45 To Youth Reaching For MaturityDavid Helmpage 45 Thanksgiving DayJoel E. Hendrickspage 46 Sadness No. 6 (Schatten)Sherry S. Frypage 48https://thekeep.eiu.edu/vehicle/1012/thumbnail.jp