Cardiac allograft vasculopathy (CAV) is an important adverse prognostic factor for pediatric heart transplant (HT) recipients. Invasive coronary angiography (ICA) is the gold standard for CAV detection but lacks sensitivity for early microvascular changes and cumulative radiation exposure is of concern. Real-time myocardial contrast echocardiography (RTMCE) using ultrasound enhancing (contrast) agents performed during dobutamine stress echocardiography (DSE) can assess myocardial function, perfusion, and microvascular integrity. The objective of this study was to determine the safety and feasibility of RTMCE during DSE to detect CAV in a pediatric HT population.
 
  HT patients 10-21years of age were recruited to undergo DSE with RTMCE to determine technical feasibility, test tolerability and adverse event rate, and detection of perfusion defects compared with ICA-detected CAV. Thirty-six patients from two centers were enrolled, with a mean age 13.5±4.3years; 21 (58%) were male. Wall motion and myocardial perent of CAV in pediatric HT recipients. Further assessment is warranted to determine whether this noninvasive technique could provide a reliable alternative to ICA.
 Dobutamine stress RTMCE appears to be safe and feasible for the assessment of CAV in pediatric HT recipients. Further assessment is warranted to determine whether this noninvasive technique could provide a reliable alternative to ICA.
  Functional models of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) underscore the role of internally-driven negative reinforcement. However, with the focus of these models being on negative emotions broadly, there is limited understanding of the effect of alcohol use to down-regulate specific forms of negative emotions or positive emotions generally. Among populations characterized by PTSD, there is growing evidence that positive emotions may elicit aversive reactions and thus be intentionally reduced, including via alcohol use.
 
  The current study examined the associations among PTSD symptom severity, alcohol use to down-regulate both negative (i.e., despondency and anger) and positive emotions, and alcohol misuse.
 
  Data were collected from 320 trauma-exposed, substance-using individuals in the community (M age=35.78, 46.9% women).
 
  Individuals with greater PTSD symptom severity reported significantly higher alcohol use to down-regulate despondency, anger, and positive emotions, which, in turn, were linked to greater alcohol misuse.
 
  Alcohol use may serve to down-regulate both negative (i.e., despondency and anger) and positive emotions, and these functions may help to explain the association of PTSD symptom severity to alcohol misuse. PTSD-AUD models may benefit from specifying a negatively reinforcing function of alcohol use in the context of positive emotions.
 Alcohol use may serve to down-regulate both negative (i.e., despondency and anger) and positive emotions, and these functions may help to explain the association of PTSD symptom severity to alcohol misuse. PTSD-AUD models may benefit from specifying a negatively reinforcing function of alcohol use in the context of positive emotions.S100A9, with its congener S100A8, belongs to the S100 family of calcium-binding proteins found exclusively in vertebrates. These two proteins are major constituents of neutrophils. In response to a pathological condition, they can be released extracellularly and become alarmins that induce both pro- and anti-inflammatory signals, through specific cell surface receptors. They also act as antimicrobial agents, mainly as a S100A8/A9 heterocomplex, through metal sequestration. The mechanisms whereby divalent cations modulate the extracellular functions of S100A8 and S100A9 are still unclear. Importantly, it has been proposed that these ions may affect both the ternary and quaternary structure of these proteins, thereby influencing their physiological properties. In the present study, we report the crystal structures of WT and C80A murine S100A9 (mS100A9), determined at 1.45 and 2.35 Å resolution, respectively, in the presence of calcium and zinc. These structures reveal a canonical homodimeric form for the protein. They also unravel an intramolecular disulfide bridge that stabilizes the C-terminal tail in a rigid conformation, thus shaping a second Zn-binding site per S100A9 protomer. In solution, mS100A9 apparently binds only two zinc ions per homodimer, with an affinity in the micromolar range, and aggregates in the presence of excess zinc. Using mass spectrometry, we demonstrate that mS100A9 can form both non-covalent and covalent homodimers with distinct disulfide bond patterns. Interestingly, calcium and zinc seem to affect differentially the relative proportion of these forms. We discuss how the metal-dependent interconversion between mS100A9 homodimers may explain the versatility of physiological functions attributed to the protein.
  Diffusion MRI (dMRI) data acquisition protocols are well-established on modern high-field clinical scanners for human studies. However, these protocols are not suitable for the chimpanzee (or other large-brained mammals) because of its substantial difference in head geometry and brain volume compared with humans. Therefore, an optimal dMRI data acquisition protocol dedicated to chimpanzee neuroimaging is needed.
 
  A multi-shot (4 segments) double spin-echo echo-planar imaging (MS-EPI) sequence and a single-shot double spin-echo EPI (SS-EPI) sequence were optimized separately for in vivo dMRI data acquisition of chimpanzees using a clinical 3T scanner.  https://www.selleckchem.com/products/LAQ824(NVP-LAQ824).html  Correction for severe susceptibility-induced image distortion and signal drop-off of the chimpanzee brain was performed and evaluated using FSL software. DTI indices in different brain regions and probabilistic tractography were compared. A separate DTI data set from n=34 chimpanzees (13 to 56 years old) was collected using the optimal protocol. Age-related chn optic nerve fiber integrity of chimpanzees, in contrast to previous results for both macaque monkeys and humans.
 The single-shot EPI-based acquisition protocol provided better image quality of dMRI for chimpanzee brains and is recommended for in vivo dMRI study or clinical diagnosis of chimpanzees (or other large animals) using a clinical scanner. Also, the tendency of FA decrease or diffusivity increase in the optic nerve of aged chimpanzees was seen but did not show significant age-related changes, suggesting aging may have less impact on optic nerve fiber integrity of chimpanzees, in contrast to previous results for both macaque monkeys and humans.