Preinjection With Ligation-Assisted Endoscopic Mucosal Resection for Barrett's Dysplasia and Early Esophageal Adenocarcinoma: Characteristic Histological Features of the Depth of Resection.

BACKGROUND AND AIM: Endoscopic mucosal resection (EMR) is an established technique for the diagnosis and treatment of high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) in Barrett's esophagus. Submucosal preinjection is not universally used or generally recommended when performing routine ligation-assisted EMR. Prior studies, however, have demonstrated evidence of at least superficial muscle injury on ligation-assisted EMR without submucosal injection. There are limited published data supporting any potential benefit of submucosal preinjection. Our aim was to review this technique and determine the rate of any degree of muscle injury in patients with Barrett's HGD and EAC treated with submucosal preinjection before ligation-assisted EMR. METHODS: Patients undergoing submucosal preinjection before ligation-assisted EMR for Barrett's esophagus at a single institution between 2012 and 2016 were identified. Data were collected regarding patient demographics and medical history, endoscopy and histopathology findings, adverse events, and subsequent outcomes. All EMR specimens were reviewed by an expert gastrointestinal pathologist. RESULTS: One hundred fifty consecutive EMR procedures were performed on 70 patients. Of 70 patients, 85.7% of patients were men, with a median age of 68 years. EAC was identified in 75 specimens (50%) and HGD in 44 specimens (29.3%). Deep resection margins were clear of adenocarcinoma in all specimens. Muscularis propria was not identified in any of the 150 specimens. There were no cases of post-EMR perforation. CONCLUSIONS: Preinjection before ligation-assisted EMR achieved complete excision with histologically clear margins, without histological evidence of any inadvertent muscularis propria.

Intracranial Hemorrhage as a Marker for Mycotic Aneurysm in Patients With Infective Endocarditis.

Background and Objective: Mycotic aneurysms are a significant complication of IE that can lead to intracranial hemorrhage (ICH) and occasionally require intervention before valve surgery. Digital subtraction angiography (DSA) remains the gold standard for the detection of mycotic aneurysms but is an invasive procedure with contrasted dye exposure. Our objective was to determine predictive factors for the presence of mycotic aneurysms in patients with known infective endocarditis (IE). Methods: IRB exemption was obtained from the University of Pittsburgh Medical Center. Patients with left-sided or right-sided endocarditis with patent foramen ovale (PFO) were identified. Records were retrospectively reviewed by an independent investigator. Patients were stratified by demographic information, diagnostic imaging, and clinical outcomes. Standard descriptive statistics were used for characterization. The χ2 analysis and Fisher exact test were used for categorical comparisons. The Student t test was used for group comparisons. Results: 36 cases of left-sided or right-sided endocarditis with PFO undergoing evaluation for valve surgery were identified. Twenty-seven patients underwent CNS imaging, and 24 underwent DSA. Six patients were found to have ICH on CNS imaging. Mycotic aneurysms were identified by DSA in 5 patients (13.9%), and of these patients, 4 (80%) presented with ICH and 1 with ischemic stroke. Notably, the patient who presented with ischemic stroke then developed ICH on follow-up CT imaging. The negative predictive value of the absence of ICH on initial CNS imaging for the presence of mycotic aneurysm was 97.4%. Discussion: Patients with left-sided and right-sided endocarditis with PFO and ICH on CNS imaging were more likely to have mycotic aneurysms detected through DSA than similar patients without ICH. Routine DSA screening for mycotic aneurysms may not be required in patients with endocarditis undergoing evaluation for valve surgery who present without ICH on CNS imaging.

The role of nutrition in space exploration: Implications for sensorimotor, cognition, behavior and the cerebral changes due to the exposure to radiation, altered gravity, and isolation/confinement hazards of spaceflight.

Multi-year crewed space exploration missions are now on the horizon; therefore, it is important that we understand and mitigate the physiological effects of spaceflight. The spaceflight hazards-radiation, isolation, confinement, and altered gravity-have the potential to contribute to neuroinflammation and produce long-term cognitive and behavioral effects-while the fifth hazard, distance from earth, limits capabilities to mitigate these risks. Accumulated evidence suggests that nutrition has an important role in optimizing cognition and reducing the risk of neurodegenerative diseases caused by neuroinflammation. Here we review the nutritional perspective of how these spaceflight hazards affect the astronaut's brain, behavior, performance, and sensorimotor function. We also assess potential nutrient/nutritional countermeasures that could prevent or mitigate spaceflight risks and ensure that crewmembers remain healthy and perform well during their missions. Just as history has taught us the importance of nutrition in terrestrial exploration, we must understand the role of nutrition in the development and mitigation of spaceflight risks before humans can successfully explore beyond low-Earth orbit.

Synthesis of ultra-high molecular weight poly(ethylene)-co-(1-hexene) copolymers through high-throughput catalyst screening.

A family of permethylindenyl titanium constrained geometry complexes, Me2SB(R'N,3-RI*)TiX2 ((3-R-η5-C9Me5)Me2Si(R'TiX2)), supported on solid polymethylaluminoxane (sMAO) are investigated as slurry-phase catalysts for ethylene/H2 homopolymerisation and ethylene/1-hexene copolymerisation by high-throughput catalyst screening. Me2SB( tBuN,I*)TiCl2 supported on sMAO [sMAO-Me2SB( tBuN,I*)TiCl2] is responsive to small quantities of H2 (<1.6%), maintaining high polymerisation activities (up to 4900 kgPE molTi -1 h-1 bar-1) and yielding polyethylenes with significantly decreased molecular weight (M w) (from 2700 to 41 kDa with 1.6% H2). In slurry-phase ethylene/1-hexene copolymerisation studies, a decrease in polymerisation activity and polymer molecular weights compared to ethylene homopolymerisation is observed. Compared to many solid supported system, these complexes all display high 1-hexene incorporation levels up to a maximum incorporation of 14.2 mol% for sMAO-Me2SB(iPrN,I*)TiCl2). We observe a proportionate increase in 1-hexene incorporation with concentration, highlighting the ability of these catalysts to controllably tune the amount of 1-hexene incorporated into the polymer chain to produce linear low-density polyethylene (LLDPE) materials.

Immunotherapeutic approaches for fungal infections.

Despite the availability of antifungal treatments, fungal infections are still causing morbidity all around the globe with unacceptably high mortality rates. A major driver for the rising incidence of serious fungal infections is due to a substantial increase in immunocompromised individuals with autoimmune diseases, cancers and transplants. Because of growing resistance in fungus to frontline triazole antifungals and the association of fungal disease with the immunocompromised host, adjunctive host-directed therapy is seen as a promising choice to improve patient outcomes. Immunotherapeutic treatments being explored as adjunct therapies to existing antifungal treatments include cytokine therapy, monoclonal antibodies and cellular immunotherapy. In this review, we give a brief overview of potential immunotherapies and recent developments in the field, which are needed to tackle the growing problem of fungal diseases.

Countermeasures-based Improvements in Stress, Immune System Dysregulation and Latent Herpesvirus Reactivation onboard the International Space Station - Relevance for Deep Space Missions and Terrestrial Medicine.

The International Space Station (ISS) has continued to evolve from an operational perspective and multiple studies have monitored both stress and the immune system of ISS astronauts. Alterations were ascribed to a potentially synergistic array of factors, including microgravity, radiation, psychological stress, and circadian misalignment. Comparing similar data across 12 years of ISS construction and operations, we report that immunity, stress, and the reactivation of latent herpesviruses have all improved in ISS astronauts. Major physiological improvements seem to have initiated approximately 2012, a period coinciding with improvements onboard ISS including cargo delivery and resupply frequency, personal communication, exercise equipment and protocols, food quality and variety, nutritional supplementation, and schedule management. We conclude that spaceflight associated immune dysregulation has been positively influenced by operational improvements and biomedical countermeasures onboard ISS. Although an operational challenge, agencies should therefore incorporate, within vehicle design limitations, these dietary, operational, and stress-relieving countermeasures into deep space mission planning. Specific countermeasures that have benefited astronauts could serve as a therapy augment for terrestrial acquired immunodeficiency patients.

Unified mild reaction conditions for C2-selective Pd-catalysed tryptophan arylation, including tryptophan-containing peptides.

Pd-mediated C-H bond functionalisation protocols have been designed and developed on tryptophan derivatives and tryptophan-containing peptides. The examination of different arylation reactions (three sets of different conditions A-C), all of which are notable for their low temperatures (≤40 °C), allowed identification of unified and complementary synthetic approaches toward a series of functionalised tryptophan-containing products. Tryptophan-containing peptides demonstrated to be susceptible to aromatic oxidation were successfully and selectively modified through the application of diaryliodonium salts in good yields.

A mild and selective Pd-mediated methodology for the synthesis of highly fluorescent 2-arylated tryptophans and tryptophan-containing peptides: a catalytic role for Pd(0) nanoparticles?

A Pd-mediated direct C-H bond functionalisation of tryptophan has been developed, both as a single amino acid residue and within peptides. Important mechanistic insight into this process has been gained by characterising a Pd catalytically competent nanoparticle phase which evolves during the early stages of reaction.