Association between glioma and neurodegenerative diseases risk: a two-sample bi-directional Mendelian randomization analysis.

Background: Earlier observational studies have demonstrated a correlation between glioma and the risk of neurodegenerative diseases (NDs), but the causality and direction of their associations remain unclear. The objective of this study was to ascertain the causal link between glioma and NDs using Mendelian randomization (MR) methodology. Methods: Genome-wide association study (GWAS) data were used in a two-sample bi-directional MR analysis. From the largest meta-analysis GWAS, encompassing 18,169 controls and 12,488 cases, summary statistics data on gliomas was extracted. Summarized statistics for NDs, including Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) were obtained from the GWAS of European ancestry. Inverse variance weighted (IVW) method was elected as the core MR approach with weighted median (WM) method and MR-Egger method as complementary methods. In addition, sensitivity analyses were performed. A Bonferroni correction was used to correct the results. Results: Genetically predicted glioma had been related to decreased risk of AD. Specifically, for all glioma (IVW: OR = 0.93, 95% CI = 0.90-0.96, p = 4.88 × 10-6) and glioblastoma (GBM) (IVW: OR = 0.93, 95% CI = 0.91-0.95, p = 5.11 × 10-9). We also found that genetically predicted all glioma has a suggestive causative association with MS (IVW: OR = 0.90, 95% CI = 0.81-1.00, p = 0.045). There was no evidence of causal association between glioma and ALS or PD. According to the results of reverse MR analysis, no discernible causal connection of NDs was found on glioma. Sensitivity analyses validated the robustness of the above associations. Conclusion: We report evidence in support of potential causal associations of different glioma subtypes with AD and MS. More studies are required to uncover the underlying mechanisms of these findings.

Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases.

OBJECTIVE: Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and lupus nephritis. We undertook this study to develop and evaluate a high-affinity APRIL/BAFF antagonist to overcome the clinical limitations of existing B cell inhibitors. METHODS: A variant of TACI-Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN-303). Povetacicept was compared to wild-type (WT) TACI-Fc and related molecules in vitro and in vivo. RESULTS: Povetacicept inhibited APRIL and BAFF more effectively than all evaluated forms of WT TACI-Fc and selective APRIL and BAFF inhibitors in cell-based reporter assays and primary human B cell assays, mediating potent suppression of B cell proliferation, differentiation, and immunoglobulin (Ig) secretion. In mouse immunization models, povetacicept significantly reduced serum immunoglobulin titers and antibody-secreting cells more effectively than anti-CD20 monoclonal antibodies, WT TACI-Fc, or APRIL and BAFF inhibitors. In the NZB × NZW mouse lupus nephritis model, povetacicept significantly enhanced survival and suppressed proteinuria, anti-double-stranded DNA antibody titers, blood urea nitrogen, glomerulonephritis, and renal immunoglobulin deposition. In the bm12 mouse lupus model, povetacicept significantly reduced splenic plasmablasts, follicular helper T cells, and germinal center B cells. In non-human primates, povetacicept was well tolerated, exhibited high serum exposure, and significantly decreased serum IgM, IgA, and IgG levels after a single dose. CONCLUSION: Enhanced APRIL and BAFF inhibition by povetacicept led to greater inhibition of B cell populations critical for autoantibody production compared to WT TACI-Fc and CD20-, APRIL-, or BAFF-selective inhibitors. Potent, dual inhibition by povetacicept has the potential to significantly improve clinical outcomes in autoantibody-related autoimmune diseases.

Preparation of gelatin/poly (γ-glutamic acid) hydrogels with stimulated response by hot-pressing preassembly and radiation crosslinking.

The conventional preparation method of natural polymers is low in strength, which limits the application of multi stimuli responsive hydrogels as intelligent wound dressings. In this work, interpenetrating gelatin and γ-polyglutamic acid (γ-PGA) hydrogels with good biocompatibility, biodegradability and mechanical properties were prepared by hot-pressing pre-gelation of gelatin/γ-PGA and synergistic with gamma irradiation. The effects of radiation crosslinking dosage on gel fraction, swelling ratio, tensile strength and surface morphology were investigated. The biocompatibility of radiation cross-linked hydrogel was evaluated by aseptic test, hemolysis test, cytotoxicity test, delayed hypersensitivity reaction as well as in vivo degradation studies from in vitro to in vivo. The optimized hydrogel irradiated by 25 kGy has good water retention and biodegradability, especially the stimulation of temperature, pH value, salt species and concentration. The mechanical strength, biocompatibility and responsive properties of the hydrogel indicate that the intelligent hydrogel prepared by this method is a good hydrogel biomaterial for developing interactive wound dressing.

Diesel Soot and Amine-Containing Organic Sulfate Aerosols in an Arctic Oil Field.

The rapid decrease in Arctic sea ice is motivating development and increasing oil and gas extraction activities. However, few observations of these local Arctic emissions exist, limiting the understanding of impacts on atmospheric composition and climate. To address this knowledge gap, the chemical composition of atmospheric aerosols was measured within the North Slope of Alaska oil fields during August and September 2016 using an aerosol time-of-flight mass spectrometer (ATOFMS) and a time-of-flight aerosol chemical speciation monitor (ToF-ACSM). Plumes from oil and gas extraction activities were characterized by soot internally mixed with sulfate (matching diesel soot) and organic carbon particles containing aminium sulfate salts. Sea spray aerosol at the coastal site was frequently internally mixed with sulfate and nitrate, from multiphase chemical processing from elevated NOx and SO2 within the oil field. Background (nonplume) air masses were characterized by aged combustion aerosol. No periods of "clean" (nonpolluted) Arctic air were observed. The composition of the nonrefractory aerosol measured with the ACSM was similar during plume and background periods and was consistent with the mass concentrations of nonrefractory particles measured by ATOFMS. Two ultrafine aerosol growth events were observed during oil field background periods and were correlated with fine mode amine-containing particles.

Source-specific Exposure to Contradictory Nutrition Information: Documenting Prevalence and Effects on Adverse Cognitive and Behavioral Outcomes.

Communication scholars have raised concerns that the media present contradictory or conflicting information on health, science, and political issues, speculating that such information may have adverse effects on public cognitions, affect, and behaviors. However, the evidence base for the effects of contradictory messages remains thin. Using nutrition as a case example, this study builds upon this nascent literature by employing a three-wave panel dataset from a survey with a nationally representative sample of American adults. We found that exposure to contradictory nutrition messages from television increases nutrition confusion, whereas exposure from print media decreases confusion. Moreover, nutrition confusion was positively associated with nutrition backlash, and nutrition backlash decreased engagement in fruit and vegetable consumption. Implications for campaigns and other communication interventions are discussed.

Latino and European American early adolescents' exposure to music with substance-use references: examining parent-child communication as a moderator.

This study hypothesized that frequent exposure to and attention to music with substance-use references would be indirectly related to alcohol, cigarette, or marijuana use through pro-substance-use beliefs (e.g., norms, outcome expectancies, and refusal efficacy). Parent-child communication, however, would attenuate such associations, which would differ by ethnicity. Multigroup mediation and moderation analyses were conducted, using cross-sectional survey data from 253 Latino and 308 European American 6th-8th grades students. For Latino and European American early adolescents, best-friend-injunctive norms and weak refusal efficacy were significant mediators, but not positive outcome expectancies. Descriptive norms were a significant mediator, but only for European American early adolescents. Although targeted parent-child communication and parental mediation did not moderate the associations between the music-exposure variables and the pro-substance-use beliefs variables, targeted parent-child communication attenuated the association between listening to favorite songs and alcohol consumption. Parental mediation attenuated the association between attention to music and alcohol consumption.