Dynamic imaging of the lungs using x-ray phase contrast

High quality real-time imaging of lungs in vivo presents considerable challenges. We demonstrate here that phase contrast x-ray imaging is capable of dynamically imaging the lungs. It retains many of the advantages of simple x-ray imaging, whilst also being able to map weakly absorbing soft tissues based on refractive index differences. Preliminary results reported herein show that this novel imaging technique can identify and locate airway liquid and allows lung aeration in newborn rabbit pups to be dynamically visualized.     

Invertebrate muscles: muscle specific genes and proteins

This is the first of a projected series of canonic reviews covering all invertebrate muscle literature prior to 2005 and covers muscle genes and proteins except those involved in excitation-contraction coupling (e.g., the ryanodine receptor) and those forming ligand- and voltage-dependent channels. Two themes are of primary importance. The first is the evolutionary antiquity of muscle proteins. Actin, myosin, and tropomyosin (at least, the presence of other muscle proteins in these organisms has not been examined) exist in muscle-like cells in Radiata, and almost all muscle proteins are present across Bilateria, implying that the first Bilaterian had a complete, or near-complete, complement of present-day muscle proteins. The second is the extraordinary diversity of protein isoforms and genetic mechanisms for producing them. This rich diversity suggests that studying invertebrate muscle proteins and genes can be usefully applied to resolve phylogenetic relationships and to understand protein assembly coevolution. Fully achieving these goals, however, will require examination of a much broader range of species than has been heretofore performed.     

Rearrangement of Valproate Glucuronide in a Patient with Drug-Associated Hepatobiliary and Renal Dysfunction

Formation of beta-glucuronidase-resistant "glucuronides" of valproic acid (VPA) by intramolecular rearrangement of biosynthetic valproate glucuronide in vivo was investigated in a patient diagnosed with VPA-associated hepatobiliary and renal dysfunction. Plasma elimination half-life of VPA following cessation of the drug was 13.9 h. At the time of the toxicity, the concentration of conjugated VPA in plasma was very high (36-54% of nonconjugated VPA levels) relative to that in normal patients (2.9%). The fraction of conjugated VPA resistant to beta-glucuronidase hydrolysis was 0.28-0.47 in plasma and 0.15-0.42 in urine. The corresponding fraction in urine from normal patients receiving VPA therapy was 0.044. The evidence was consistent with retarded elimination of biosynthetic VPA glucuronide caused by renal and hepatobiliary dysfunction. Consequent prolongation of circulation of VPA glucuronide at the slightly alkaline pH of blood would permit extensive intramolecular rearrangement which is known to be pH-, temperature-, and time-dependent. The biological consequences of the presence of such beta-glucuronidase-resistant conjugated VPA in vivo are largely unknown.     

Esophageal transit scintigraphy--a cautionary note

Esophageal transit scintigraphy and esophageal manometry were compared in forty-two patients with symptoms of esophageal disease. Fifteen healthy volunteers were studied as a control group for the scintigraphic investigation. Agreement between the tests was present in 79% of patients. In all the five patients in whom the esophageal manometry was abnormal and the esophageal transit study was normal, the manometric finding was "giant esophageal contractions." In four of the control group an abnormal transit pattern was observed on one of two esophageal studies. Esophageal transit scintigraphy has some limitations as a screening test for esophageal motor dysfunction.     

Intuitive Eating is Associated With Higher Fruit and Vegetable Intake Among Adults

ObjectiveAssess how intuitive eating relates to dietary intake.MethodsSurvey data were collected in Project Eating and Activity in Teens and Young Adults, the fourth wave of a longitudinal cohort study (weighted n = 1,830, 49% women; mean age = 31 years). Intuitive eating was assessed using a 7-item scale adapted from the Intuitive Eating Scale and Intuitive Eating Scale-2. Dietary intake was measured via a semiquantitative food frequency questionnaire. Mean servings were stratified by gender and intuitive eating quartiles and adjusted for sociodemographic characteristics and caloric intake.ResultsWomen and men in the top intuitive eating quartile consumed 0.6–0.3 servings more fruit and 0.4–0.6 servings more vegetables daily, respectively, compared with the bottom quartile, whereas men in the top quartile also consumed 0.6 servings fewer whole grains (all P < 0.05) than the bottom quartile.Conclusions and ImplicationsIntuitive eating shows promise as a healthier alternative to practices such as dieting.     

Novel second-generation rexinoid induces growth arrest and reduces cancer cell stemness in human neuroblastoma patient-derived xenografts

IntroductionThe poor therapeutic efficacy seen with current treatments for neuroblastoma may be attributed to stem cell-like cancer cells (SCLCCs), a subpopulation of cancer cells associated with poor prognosis and disease recurrence. Retinoic acid (RA) is a differentiating agent used as maintenance therapy for high-risk neuroblastoma but nearly half of children treated with RA relapse. We hypothesized that 6-Methyl-UAB30 (6-Me), a second-generation rexinoid recently developed with a favorable toxicity profile compared to RA, would reduce cancer cell stemness in human neuroblastoma patient-derived xenografts (PDXs).MethodsCells from three neuroblastoma PDXs were treated with 6-Me and proliferation, viability, motility, and cell-cycle progression were assessed. CD133 expression, sphere formation, and mRNA abundance of stemness and differentiation markers were evaluated using flow cytometry, in vitro extreme limiting dilution analysis, and real-time PCR, respectively.ResultsTreatment with 6-Me decreased proliferation, viability, and motility, and induced cell-cycle arrest and differentiation in all three neuroblastoma PDXs. In addition, 6-Me treatment led to decreased CD133 expression, decreased sphere-forming ability, and decreased mRNA abundance of Oct4, Nanog, and Sox2, indicating decreased cancer cell stemness.Conclusions6-Me decreased oncogenicity and reduced cancer cell stemness of neuroblastoma PDXs, warranting further exploration of 6-Me as potential novel therapy for neuroblastoma.     

Primary hyperoxaluria diagnosed after kidney transplant: A review of the literature and case report of aggressive renal replacement therapy and lumasiran to prevent allograft loss

Primary hyperoxaluria type 1 is a rare inherited disorder caused by abnormal liver glyoxalate metabolism leading to overproduction of oxalate, progressive kidney disease, and systemic oxalosis. While the disorder typically presents with nephrocalcinosis, recurrent nephrolithiasis, and/or early chronic kidney disease, the diagnosis is occasionally missed until it recurs after kidney transplant. Allograft outcomes in these cases are typically very poor, often with early graft loss. Here we present the case of a child diagnosed with primary hyperoxaluria type 1 after kidney transplant who was able to maintain kidney function, thanks to aggressive renal replacement therapy as well as initiation of a new targeted therapy for this disease. This case highlights the importance of having a high index of suspicion for primary hyperoxaluria in patients with chronic kidney disease and nephrocalcinosis/nephrolithiasis or with end stage kidney disease of uncertain etiology, as initiating therapies early on may prevent poor outcomes.     

Small animal jet injection technique results in enhanced immunogenicity of hantavirus DNA vaccines

DNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested the possibility that a device developed for human intradermal medicine delivery might be adapted to successfully deliver a DNA vaccine to small animals. Disposable syringe jet injection (DSJI) does not currently exist for small animals. However, a commercialized, human intradermal device used to to administer medicines to the human dermis in a 0.1 mL volume was evaluated in Syrian hamsters. Here, we found that hantavirus DNA vaccines administered to hamsters using DSJI were substantially more immunogenic than the same vaccines delivered by needle/syringe or particle mediated epidermal delivery (gene gun) vaccination. By adjusting how the device was used we could deliver vaccine to either subcutaneous tissues, or through the skin into the muscle. RNA and/or antigen expression was detected in epidermal, subepidermal and fibroblast cells. We directly compared six optimized and non-optimized hantavirus DNA vaccines in hamsters. Optimization, including codon-usage and mRNA stability, did not necessarily result in increased immunogenicity for all vaccines tested; however, optimization of the Andes virus (ANDV) DNA vaccine protected vaccinated hamsters from lethal disease. This is the first time active vaccination with an ANDV DNA vaccine has shown protective efficacy in the hamster model. The adaptation of a human intradermal jet injection device for use as a method of subcutaneous and intramuscular jet injection of DNA vaccines will advance the development of nucleic acid based medical countermeasures for diseases modeled in hamsters.