Search

The 4Φ9/2 ground state of the Ni+2 diatomic molecular cation is determined experimentally from temperature and magnetic-field-dependent x-ray magnetic circular dichroism spectroscopy in a cryogenic ion trap, where an electronic and rotational temperature of 7.4±0.2 K was reached by buffer gas cooling of the molecular ion. The contribution of the spin dipole operator to the x-ray magnetic circular dichroism spin sum rule amounts to 7 Tz = 0.17 ± 0.06 μB per atom, approximately 11% of the spin magnetic moment. We find that, in general, homonuclear diatomic molecular cations of 3d transition metals seem to adopt maximum spin magnetic moments in their electronic ground states. [ABSTRACT FROM AUTHOR]

Background We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. Methods We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. Results Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P =.37), and number of diarrheal episodes increased by 2.32 (P =.87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls. Conclusions Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy. Clinical Trials Registration NCT03341767. [ABSTRACT FROM AUTHOR]

Background In a previously reported Co FAR study, 55 subjects with egg allergy underwent randomized, placebo-controlled egg oral immunotherapy ( eOIT). Active treatment induced desensitization in most and sustained unresponsiveness ( SU) in a smaller subset. We hypothesized that component-resolved analysis of IgE, IgG4, IgA, IgA1, and IgA2 may identify potential biomarkers of SU in OIT subjects. Methods Longitudinal samples for 51 egg-allergic subjects (37 active and 14 placebo) were available. Egg white ( EW)-, ovalbumin ( OVA)-, and ovomucoid ( OVM)-specific levels of IgA, IgA1, and IgA2 were quantified by ELISA. IgE and IgG4 to these antigens were quantified using Immuno CAP ®. Clinical responders achieved SU to egg; all others were considered nonresponders. Between-group comparisons were made among active and placebo, as well as responders and nonresponders. Results No placebo subjects achieved responder status. Through month 48, among the 37 active subjects, baseline IgE- OVM was lower in responders (median 3.97 kU/l, n = 19) than in nonresponders (10.9 kU/l, n = 18, P = 0.010). Logistic regression analysis revealed that lower baseline IgE- EW ( P = 0.038), IgE- OVM ( P = 0.032), and a higher IgG4/IgE- OVM ratio ( P = 0.013) were associated with clinical response. Relative increases in IgG4- EW, IgA- EW, and IgA2- EW were observed in responders ( P = 0.024, 0.024, and 0.029, respectively). IgG4/IgE, IgA/IgE, and IgA2/IgE ratios for EW and IgA/IgE ratio for OVA were found to be significantly elevated among responders ( P = 0.004, 0.009, 0.028, and 0.008, respectively). Conclusions Increased IgG4- EW, IgA- EW, and IgA2- EW during eOIT are associated with clinical response to eOIT. Lower pretreatment IgE- EW and IgE- OVM are also associated with SU. Future studies are needed to evaluate and validate these potential biomarkers. [ABSTRACT FROM AUTHOR]

Background Immunotherapy for peanut allergy may be limited by the risk of adverse reactions. Objective To investigate the safety and immunologic effects of a vaccine containing modified peanut proteins. Methods This was a phase 1 trial of EMP-123, a rectally administered suspension of recombinant Ara h 1, Ara h 2, and Ara h 3, modified by amino acid substitutions at major IgE-binding epitopes, encapsulated in heat/phenol-killed E. coli. Five healthy adults were treated with 4 weekly escalating doses after which 10 peanut-allergic adults received weekly dose escalations over 10 weeks from 10 mcg to 3063 mcg, followed by three biweekly doses of 3063 mcg. Results There were no significant adverse effects in the healthy volunteers. Of the 10 peanut-allergic subjects [4 with intermittent asthma, median peanut IgE 33.3 kUA/l (7.2-120.2), and median peanut skin prick test wheal 11.3 mm (6.5-18)]; four experienced no symptoms; one had mild rectal symptoms; and the remaining five experienced adverse reactions preventing completion of dosing. Two were categorized as mild, but the remaining three were more severe, including one moderate reaction and two anaphylactic reactions. Baseline peanut IgE was significantly higher in the five reactive subjects (median 82.4 vs 17.2 kUA/l, P = 0.032), as was baseline anti-Ara h 2 IgE (43.3 versus 8.3, P = 0.036). Peanut skin test titration and basophil activation (at a single dilution) were significantly reduced after treatment, but no significant changes were detected for total IgE, peanut IgE, or peanut IgG4. Conclusions Rectal administration of EMP-123 resulted in frequent adverse reactions, including severe allergic reactions in 20%. [ABSTRACT FROM AUTHOR]

Background Rapid-release testing reduces the waiting period for administration of time-sensitive cell-therapy products. Current assay systems are labor intensive and time consuming. The Endosafe® portable test system (PTS™) is a chromogenic Limulus amebocyte lysate (LAL) portable endotoxin detection system that provides quantitative results in approximately 15 min. To evaluate Endosafe® performance with cell-therapy products, side-by-side testing of traditional LAL systems and the Endosafe® system was conducted at the Production Assistance for Cellular Therapies (PACT) facilities and the National Institutes of Health's Department of Transfusion Medicine, USA. Methods Charles River Laboratories provided each center with a PTS™ reader and two commercially prepared lyophilized reference standard endotoxin (RSE) vials. All samples tested with the Endosafe® system used 0.05-5.0 endotoxin unit/mL (EU/mL) sensitivity cartridges provided by Charles River. Each vial was reconstituted with LAL water and tested in triplicate using the Endosafe® and in-house LAL methods. Subsequently, each center tested the endotoxin content of standard dilutions of cell-therapy products, thus creating paired test results for each sample. Additionally, fabricated endotoxin-positive samples containing varying concentrations of endotoxin were prepared and shipped to all centers to perform blinded testing. Results Valid paired results, based on each center's LAL method and the Endosafe® system criteria, were analyzed. Endotoxin detection between paired results was equivalent in most cases. Discussion The Endosafe® system provided reliable results with products typically produced in cell-therapy manufacturing facilities, and would be an appropriate test on which to base the release of time-sensitive cell-therapy products. [ABSTRACT FROM AUTHOR]

To determine the impact of neutropenia on the pharmacokinetics of meropenem, 14 patients with fever and neutropenia were given 1 g of meropenem i.v. every 8 h as an infusion over 30 min. The volume of distribution (16.2 1/1.73 m2) and the nonrenal clearance [75 ml/(min x 1.73 m2)] in this group were significantly increased compared to healthy subjects studied previously with identical techniques. The kinetic study was repeated when the patients had a normal temperature and a raised neutrophil count; most kinetic variables did not differ from the findings on the first day of treatment. The pharmacokinetic profile of meropenem in febrile neutropenic patients differs from earlier findings in healthy subjects. Considering these data and known minimum inhibitory concentration values for common pathogens, meropenem administered every 6 to 8 h seems an appropriate regimen in patients with febrile neutropenia. The shorter time interval may be used for treatment of Pseudomonas infection. [ABSTRACT FROM AUTHOR]