Radiolabeling human peripheral blood stem cells for positron emission tomography (PET) imaging in young rhesus monkeys.

These studies focused on a new radiolabeling technique with copper ((64)Cu) and zirconium ((89)Zr) for positron emission tomography (PET) imaging using a CD45 antibody. Synthesis of (64)Cu-CD45 and (89)Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC) was assessed in vitro (viability, population doubling times, colony forming units). hPBSC viability was maintained as the dose of (64)Cu-TETA-CD45 increased from 0 (92%) to 160 µCi/mL (76%, p>0.05). Radiolabeling efficiency was not significantly increased with concentrations of (64)Cu-TETA-CD45 >20 µCi/mL (p>0.50). Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 µCi/mL (p<0.05). For (89)Zr, there were no significant differences in viability (p>0.05), and a trend towards increased radiolabeling efficiency was noted as the dose of (89)Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 µCi/mL compared to 0-40 µCi/mL (p<0.05). A greater than 2,000 fold-increase in the level of (89)Zr-Df-CD45 labeling efficiency was observed when compared to (64)Cu-TETA-CD45. Similar to (64)Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 µCi/mL (p<0.05) (growth, colony formation). Taken together, 20 µCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×10(6) hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI), then 0.3 mCi of (89)Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that (89)Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high

Ixekizumab Efficacy and Safety with and without Concomitant Conventional Disease-modifying Antirheumatic Drugs (cDMARDs) in Biologic DMARD (bDMARD)-naive Patients with Active Psoriatic Arthritis (PsA): Results from SPIRIT-P1

Objective: To evaluate the efficacy and safety of ixekizumab alone or with concomitant conventional disease-modifying antirheumatic drugs (cDMARDs) versus placebo in patients with active psoriatic arthritis (PsA) as part of a SPIRIT-P1 subgroup analysis (NCT01695239). Methods: Patients were stratified by cDMARD use (concomitant cDMARDs use (including methotrexate) or none (past or naive use)) and randomly assigned to treatment groups (ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) or placebo). Efficacy was evaluated versus placebo at week 24 by the American College of Rheumatology criteria (ACR20/50/70), modified total Sharp score and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety was assessed according to cDMARD status. Results: Regardless of concomitant cDMARD usage, ACR20, ACR50 and ACR70 response rates were significantly higher versus placebo with IXEQ4W and IXEQ2W. The proportion of patients achieving HAQ-DI minimal clinically important difference was significantly higher versus placebo with IXEQ4W with concomitant cDMARD use and IXEQ2W, regardless of concomitant cDMARD use. Treatment-emergent adverse events (AE) were more frequent versus placebo for either ixekizumab-dosing regimen, regardless of concomitant cDMARD use. Serious AEs were not higher versus placebo, regardless of concomitant cDMARD use. Conclusion: Ixekizumab treatment improved measures of disease activity and physical function in patients with active PsA relative to placebo, when used with or without concomitant cDMARD therapy

Integral Field Spectroscopy of High-Redshift Star Forming Galaxies with Laser Guided Adaptive Optics: Evidence for Dispersion-Dominated Kinematics

We present early results from an ongoing study of the kinematic structure of star-forming galaxies at redshift z ~ 2 - 3 using integral-field spectroscopy of rest-frame optical nebular emission lines in combination with Keck laser guide star adaptive optics (LGSAO). We show kinematic maps of 3 target galaxies Q1623-BX453, Q0449-BX93, and DSF2237a-C2 located at redshifts z = 2.1820, 2.0067, and 3.3172 respectively, each of which is well-resolved with a PSF measuring approximately 0.11 - 0.15 arcsec (~ 900 - 1200 pc at z ~ 2-3) after cosmetic smoothing. Neither galaxy at z ~ 2 exhibits substantial kinematic structure on scales >~ 30 km/s; both are instead consistent with largely dispersion-dominated velocity fields with sigma ~ 80 km/s along any given line of sight into the galaxy. In contrast, DSF2237a-C2 presents a well-resolved gradient in velocity over a distance of ~ 4 kpc with peak-to-peak amplitude of 140 km/s. It is unlikely that DSF2237a-C2 represents a dynamically cold rotating disk of ionized gas as the local velocity dispersion of the galaxy (sigma = 79 km/s) is comparable to the observed shear. Using extant multi-wavelength spectroscopy and photometry we relate these kinematic data to physical properties such as stellar mass, gas fraction, star formation rate, and outflow kinematics and consider the applicability of current galaxy formation models.[Abridged]Comment: 19 pages, 10 figures (5 color); accepted for publication in ApJ. Version with full-resolution figures is available at http://www.astro.caltech.edu/~drlaw/Papers/OSIRIS_data1.pd

A Program to Treat Hepatitis B in North Korea: A Model of Antiviral Therapy in a Resource-poor Setting

Despite the well-proven, safe and effective therapies for hepatitis B infection, delivery of treatment remains a significant challenge in resource-poor settings. Geopolitical and economic restrictions present additional difficulties in providing care in North Korea. However, treatment of patients with chronic hepatitis B remains a top priority for both the North Korean Ministry of Public Health and international agencies working in North Korean hepatitis healthcare facilities. Working in partnership, a path was created to institute this much-needed program. A consortium of United States and Australian humanitarian non-governmental organizations along with generous individual and corporate donors working in concert with local and national health authorities have succeeded in establishing the first hepatitis B treatment program in North Korea. The essential elements of this program include renovation of existing hepatitis hospitals, access to antiviral medications, establishment of laboratory facilities, creation of medical documentation and record-keeping, training of local health care professionals, and quarterly visits by international volunteer physicians and laboratory experts. Management and treatment decisions are made bilaterally. To date, nearly 1,500 patients have been evaluated, and over 800 have been started on long-term antiviral therapy. It is envisioned that this program will eventually be managed and funded by the Democratic People\u27s Republic of Korea Ministry of Public Health. This program\u27s success demonstrates a potential model for delivery of antiviral therapy for patients suffering from hepatitis B in other developing countries

Design, engineering and utility of biotic games

Games are a significant and defining part of human culture, and their utility beyond pure entertainment has been demonstrated with so-called ‘serious games’. Biotechnology – despite its recent advancements – has had no impact on gaming yet. Here we propose the concept of ‘biotic games’, i.e., games that operate on biological processes. Utilizing a variety of biological processes we designed and tested a collection of games: ‘Enlightenment’, ‘Ciliaball’, ‘PAC-mecium’, ‘Microbash’, ‘Biotic Pinball’, ‘POND PONG’, ‘PolymerRace’, and ‘The Prisoner's Smellemma’. We found that biotic games exhibit unique features compared to existing game modalities, such as utilizing biological noise, providing a real-life experience rather than virtual reality, and integrating the chemical senses into play. Analogous to video games, biotic games could have significant conceptual and cost-reducing effects on biotechnology and eventually healthcare; enable volunteers to participate in crowd-sourcing to support medical research; and educate society at large to support personal medical decisions and the public discourse on bio-related issues

Structure and function of membrane proteins encapsulated in a polymer-bound lipid bilayer

New technologies for the purification of stable membrane proteins have emerged in recent years, in particular methods that allow the preparation of membrane proteins with their native lipid environment. Here, we look at the progress achieved with the use of styrene-maleic acid copolymers (SMA) which are able to insert into biological membranes forming nanoparticles containing membrane proteins and lipids. This technology can be applied to membrane proteins from any host source, and, uniquely, allows purification without the protein ever being removed from a lipid bilayer. Not only do these SMA lipid particles (SMALPs) stabilise membrane proteins, allowing structural and functional studies, but they also offer opportunities to understand the local lipid environment of the host membrane. With any new or different method, questions inevitably arise about the integrity of the protein purified: does it retain its activity; its native structure; and ability to perform its function? How do membrane proteins within SMALPS perform in existing assays and lend themselves to analysis by established methods? We outline here recent work on the structure and function of membrane proteins that have been encapsulated like this in a polymer-bound lipid bilayer, and the potential for the future with this approach

A hypoenergetic diet with decreased protein intake does not reduce lean body mass in trained females

Purpose Increasing protein intake during energy restriction (ER) attenuates lean body mass (LBM) loss in trained males. However, whether this relationship exists in trained females is unknown. This study examined the impact of higher compared to lower protein intakes (35% versus 15% of energy intake) on body composition in trained females during 2 weeks of severe ER. Methods Eighteen well-trained females completed a 1-week energy balanced diet (HD100), followed by a 2-week hypoenergetic (40% ER) diet (HD60). During HD60, participants consumed either a high protein (HP; 35% protein, 15% fat) or lower protein (CON; 15% protein, 35% fat) diet. Body composition, peak power, leg strength, sprint time, and anaerobic endurance were assessed at baseline, pre-HD60, and post-HD60. Results Absolute protein intake was reduced during HD60 in the CON group (from 1.6 to 0.9 g·d·kgBM−1) and maintained in the HP group (~ 1.7 g·d·kgBM−1). CON and HP groups decreased body mass equally during HD60 (− 1.0 ± 1.1 kg; p = 0.026 and − 1.1 ± 0.7 kg; p = 0.002, respectively) and maintained LBM. There were no interactions between time point and dietary condition on exercise performance. Conclusion The preservation of LBM during HD60, irrespective of whether absolute protein intake is maintained or reduced, contrasts with findings in trained males. In trained females, the relationship between absolute protein intake and LBM change during ER warrants further investigation. Future recommendations for protein intake during ER should be expressed relative to body mass, not total energy intake, in trained females

Timing of births and oral contraceptive use influences ovarian cancer risk

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139076/1/ijc30910_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139076/2/ijc30910.pd