Hepatitis Vaccination of Men Who Have Sex with Men at Gay Pride Events

Prevention researchers have advocated primary prevention such as vaccination in alternative venues. However, there have been major questions about both the attendance of, and the ability to, vaccinate high-risk individuals in such settings. The current study seeks to assess the feasibility of vaccinating high-risk men who have sex with men (MSM) at Gay Pride events. The research questions are: Do gay men who are sampled at Gay Pride events engage in more or less risky behavior than gay men sampled at other venues? Do the gay men who receive hepatitis vaccinations at Gay Pride engage in more or less risky behavior than gay men at Gay Pride who do not receive hepatitis vaccination? Of the 3689 MSM that completed the Field Risk Assessment (FRA), 1095/3689 = 29.68% were recruited at either the 2006 or 2007 Long Beach, California Gay Pride events. The remaining, 2594/3689 = 70.32% were recruited at Long Beach gay bars, gay community organizations and institutions, and through street recruitment in various gay enclaves in the Long Beach area. Logistic regression analysis yielded eight factors that were associated with non-attendance of Gay Pride: Age, had sex while high in the last 12 months, had unprotected anal intercourse (UAI) in the last 12 months, had sex for drugs/money in the last 12 months, been diagnosed with a sexually transmitted infection (STI) in the last 12 months, used nitrites (poppers) in the last 12 months, and used methamphetamine in the last 12 months. Identifying as White, Asian, or African American compared to Hispanic was also associated with non-attendance. Bivariate analysis indicated that, of the MSM sampled at Gay Pride, 280/1095 = 25.57% received a hepatitis vaccination there. The MSM sampled at Gay Pride who reported engaging in UAI or having used any stimulant (cocaine, crack-cocaine, or methamphetamine) in the last 12 months were more likely to receive hepatitis vaccination on-site. The results provide evidence for the viability of successfully vaccinating high-risk MSM at Gay Pride events. However, it is vital that no-cost vaccinations are also funded in other community settings such as STI clinics, drug treatment programs, prisons, universities, and other community resource centers in order to reach those additional high-risk MSM who do not attend Gay Pride

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Comparison of AMP and NADH binding to glycogen phosphorylase b.

The binding sites for the allosteric activator, AMP, to glycogen phosphorylase b are described in detail utilizing the more precise knowledge of the native structure obtained from crystallographic restrained least-squares refinement than has hitherto been available. Localized conformational changes are seen at the allosteric effector site that include shifts of between 1 and 2 A for residues Tyr75 and Arg309 and very small shifts for the region of residues 42 to 44 from the symmetry-related subunit. Kinetic studies demonstrate that NADH inhibits the AMP activation of glycogen phosphorylase b. Crystallographic binding studies at 3.5 A resolution show that NADH binds to the same sites on the enzyme as AMP, i.e. the allosteric effector site N, which is close to the subunit-subunit interface, and the nucleoside inhibitor site I, which is some 12 A from the catalytic site. The conformations of NADH at the two sites are different but both conformations are "folded" so that the nicotinamide ring is close (approx. 6 A) to the adenine ring. These conformations are compared with those suggested from solution studies and with the extended conformations observed in the single crystal structure of NAD+ and for NAD bound to dehydrogenases. Possible mechanisms for NADH inhibition of phosphorylase activation are discussed

Comparative User Testing of Australian and UK Over-the-Counter Labels and Leaflets for Diclofenac

Background: Limited research has evaluated the consumer usability of written information available with similar over-the-counter (OTC) products in different countries. This study evaluated the usability of labels and leaflets for Australian and UK OTC diclofenac products and explored consumer perspectives on their design, content, usability, and potential improvements. Methods: Australian and UK OTC diclofenac products were selected for user testing. Demographically matched groups of Australian and UK consumers were recruited to user test each label and leaflet set to determine whether 9 salient clinical messages could be found and understood. Consumer perspectives on the tested label and leaflet were explored using semi-structured interviews as part of user testing. Results: Forty consumers user tested the Voltaren Rapid 25 (Australia) and Voltarol Pain-eze Extra Strength 25-mg tablets (UK) information (10 participants per brand per country). Dosage, maximum daily dose, and contraindications information was found and understood by most (≥9/10 per group), except the Voltaren dosage which was misunderstood by 4/20. However, 12/20 could not locate the maximum duration of continuous use in the Voltaren leaflet. Participants had difficulty determining that another nonsteroidal anti-inflammatory drug could not be used with diclofenac (7/20 and 9/20 understood this in the Voltaren and Voltarol groups, respectively). Suggested label and leaflet improvements included increased font size, bolding/highlighting, and color. Conclusion: When evaluated in both countries, not all key clinical information was effectively communicated by information accompanying Australian and UK diclofenac products. Improvements in how information is communicated are needed