Inflammation, Immunity, and Vaccines for Helicobacter

Helicobacter pylori represents the major etiologic agent of gastritis, gastric, and duodenal ulcer disease and can cause gastric cancer and mucosa-associated lymphoid tissue B-cell lymphoma. It is clear that the consequences of infection reflect diverse outcomes of the interaction of bacteria and host immune system. The hope is that by deciphering the deterministic rules – if any – of this interplay, we will eventually be able to predict, treat, and ultimately prevent disease. Over the past year, research on the immunology of this infection started to probe the role of small noncoding RNAs, a novel class of immune response regulators. Furthermore, we learned new details on how infection is detected by innate pattern recognition receptors. Induction of effective cell-mediated immunity will be key for the development of a vaccine, and new work published analyzed the relevance and contribution of CD4 T helper cell subsets to the immune reaction. Th17 cells, which are also induced during natural infection, were shown to be particularly important for vaccination. Cost-efficiency of vaccination was re-assessed and confirmed. Thus, induction and shaping of the effector roles of such protective Th populations will be a target of the newly described vaccine antigens, formulations, and modes of application that we also review here

Association between gastric intramucosal pH and splanchnic endotoxin, antibody to endotoxin, and tumor necrosis factor-alpha concentrations in patients undergoing cardiopulmonary bypass

OBJECTIVES: To determine the association between gastric intramucosal pH, a minimally invasive marker reflecting the adequacy of oxygen delivery to the gastrointestinal tract, and splanchnic endotoxin, antibody to endotoxin, and tumor necrosis factor (TNF)-alpha concentrations in patients undergoing cardiopulmonary bypass. DESIGN: Single-arm, prospective study. SETTING: University hospital. PATIENTS: Adults (n = 10) free of hepatic, pulmonary, and renal disease undergoing nonemergent coronary artery bypass surgery. INTERVENTIONS: After induction of general anesthesia and endotracheal intubation, a tonometer nasogastric tube was positioned in the stomach, and triple-lumen fiberoptic catheters were inserted into the hepatic vein and pulmonary artery. Hepatic venous and mixed venous blood samples were analyzed for endotoxin, antibody to endotoxin, and TNF-alpha at six times: 30 mins after induction of anesthesia (time 1); during vena caval cannulation (time 2); after 15 mins of hypothermic cardiopulmonary bypass (time 3); during spontaneous left ventricular ejection after release of the aortic cross-clamp, but before termination of cardiopulmonary bypass (time 4); 15 mins after termination of cardiopulmonary bypass (time 5); and 1 hr after termination of cardiopulmonary bypass (time 6). Gastric intramucosal pH, systemic oxygen delivery (DO2), mixed venous oxygen saturation, hepatic venous oxygen saturation, and hepatic venous lactate concentrations were recorded at these same times. Data for each variable were compared with baseline values (time 1) for statistical significance. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary bypass was associated with an increase (p \u3c .05) in systemic endotoxin concentrations from ventricular ejection until the end of the study. Virtually identical changes in the splanchnic circulation at this time approached, but did not reach, statistical significance, because hepatic venous endotoxin concentrations were higher than the mixed venous endotoxin concentrations at baseline (41.6 +/- 11.2 vs. 16.9 +/- 4.9 pg/mL). Gastric intramucosal pH was abnormal (\u3c 7.35) at 15 mins (p \u3e .05) and at 1 hr after termination of cardiopulmonary bypass (p \u3e .05). The relationship between endotoxin and gastric intramucosal pH was not statistically significant (p = .15). The decrease in endotoxin antibody was small and statistically insignificant. TNF-alpha was not detected in any patient. Systemic DO2 decreased (p \u3c .05) after 15 mins of hypothermic cardiopulmonary bypass, but returned to baseline values thereafter. There were no significant changes in mixed venous and hepatic venous oxygen saturation values. Splanchnic lactate concentrations increased at cannulation (p \u3c .05), after 15 mins of hypothermic cardiopulmonary bypass (p \u3c .05), and 15 mins after termination of cardiopulmonary bypass (p \u3c .05). CONCLUSIONS: These observations are consistent with the hypothesis that impaired gut-barrier function is responsible for endotoxemia occurring during cardiopulmonary bypass. It is unclear whether increased mucosal permeability and mucosal acidosis are causally related phenomena or simply independent markers of damage to gut epithelium

Observations of interplanetary dust by the Juno magnetometer investigation

One of the Juno magnetometer investigation's star cameras was configured to search for unidentified objects during Juno's transit en route to Jupiter. This camera detects and registers luminous objects to magnitude 8. Objects persisting in more than five consecutive images and moving with an apparent angular rate of between 2 and 18,000 arcsec/s were recorded. Among the objects detected were a small group of objects tracked briefly in close proximity to the spacecraft. The trajectory of these objects demonstrates that they originated on the Juno spacecraft, evidently excavated by micrometeoroid impacts on the solar arrays. The majority of detections occurred just prior to and shortly after Juno's transit of the asteroid belt. This rather novel detection technique utilizes the Juno spacecraft's prodigious 60 sq. m of solar array as a dust detector and provides valuable information on the distribution and motion of interplanetary (greater than a micron) dust. Plain Language Summary: The Juno magnetometer investigation uses star cameras co-located with the magnetic sensors at the outer end of one of Juno's solar arrays. These cameras compare images with an onboard star catalog to determine the orientation of the sensors in inertial space. They also serendipitously recorded multiple images of small particles excavated from the spacecraft by high-velocity dust impacts. We trace their trajectories back in time to demonstrate that they evolved from the spacecraft. This allows us to use the vast collecting area of Juno's solar arrays (60 sq. m)as a novel dust detector, sensitive to particles with a mass range never before measured in situ

Matching Tree-Level Matrix Elements with Interleaved Showers

We present an implementation of the so-called CKKW-L merging scheme for combining multi-jet tree-level matrix elements with parton showers. The implementation uses the transverse-momentum-ordered shower with interleaved multiple interactions as implemented in PYTHIA8. We validate our procedure using e+e--annihilation into jets and vector boson production in hadronic collisions, with special attention to details in the algorithm which are formally sub-leading in character, but may have visible effects in some observables. We find substantial merging scale dependencies induced by the enforced rapidity ordering in the default PYTHIA8 shower. If this rapidity ordering is removed the merging scale dependence is almost negligible. We then also find that the shower does a surprisingly good job of describing the hardness of multi-jet events, as long as the hardest couple of jets are given by the matrix elements. The effects of using interleaved multiple interactions as compared to more simplistic ways of adding underlying-event effects in vector boson production are shown to be negligible except in a few sensitive observables. To illustrate the generality of our implementation, we also give some example results from di-boson production and pure QCD jet production in hadronic collisions.Comment: 44 pages, 23 figures, as published in JHEP, including all changes recommended by the refere

Loss of life years after a hip fracture: Effects of age and sex

Background Patients with a hip fracture have a high mortality; however, it is not clear how large the loss of life-years is over an extended observation period