Safety evaluation of adenovirus type 4 and type 7 vaccine live, oral in military recruits

AbstractBefore the widespread adoption of vaccination, adenovirus type 4 and type 7 were long associated with respiratory illnesses among military recruits. When supplies were depleted and vaccination was suspended in 1999 for approximately a decade, respiratory illnesses due to adenovirus infections resurged. In March 2011, a new live, oral adenovirus vaccine was licensed by the US Food and Drug Administration and was first universally administered to military recruits in October 2011, leading to rapid, dramatic elimination of the disease within a few months. As part of licensure, a postmarketing study (Sentinel Surveillance Plan) was performed to detect potential safety signals within 42days after immunization of military recruits. This study retrospectively evaluated possible adverse events related to vaccination using data from the Armed Forces Health Surveillance Branch Defense Medical Surveillance System (DMSS) database. Among 100,000 recruits who received the adenovirus vaccine, no statistically significant greater risk of prespecified medical events was observed within 42days after vaccination when compared with a historical cohort of 100,000 unvaccinated recruits. In an initial statistical analysis of International Classification of Disease, 9th Revision, Clinical Modification codes, a statistically significant higher risk for 19 other (not prespecified) medical events occurring in 5 or more recruits was observed among vaccinated compared with unvaccinated groups. After case record data abstraction for attribution and validation, two events (psoriasis [21 vs 7 cases] and serum reactions [12 vs 4 cases]) occurred more frequently in the vaccinated cohort. A causal relation of these rare events with adenovirus vaccination could not be established given confounding factors in the DMSS, such as coadministration of other vaccines and incomplete or inaccurate medical information, for some recruits. Prospective surveillance assessing these uncommon, but potentially relevant, immune-related symptoms may be beneficial in defining potential causal association with adenovirus vaccination

C5′- and C3′-sugar radicals produced via photo-excitation of one-electron oxidized adenine in 2′-deoxyadenosine and its derivatives

We report that photo-excitation of one-electron-oxidized adenine [A(-H)•] in dAdo and its 2′-deoxyribonucleotides leads to formation of deoxyribose sugar radicals in remarkably high yields. Illumination of A(-H)• in dAdo, 3′-dAMP and 5′-dAMP in aqueous glasses at 143 K leads to 80-100% conversion to sugar radicals at C5′ and C3′. The position of the phosphate in 5′- and 3′-dAMP is observed to deactivate radical formation at the site of substitution. In addition, the pH has a crucial influence on the site of sugar radical formation; e.g. at pH ∼5, photo-excitation of A(-H)• in dAdo at 143 K produces mainly C5′• whereas only C3′• is observed at high pH ∼12. (13)C substitution at C5′ in dAdo yields (13)C anisotropic couplings of (28, 28, 84) G whose isotropic component 46.7 G identifies formation of the near planar C5′•. A β-(13)C 16 G isotropic coupling from C3′• is also found. These results are found to be in accord with theoretically calculated (13)C couplings at C5′ [DFT, B3LYP, 6-31(G) level] for C5′• and C3′•. Calculations using time-dependent density functional theory [TD-DFT B3LYP, 6-31G(d)] confirm that transitions in the near UV and visible induce hole transfer from the base radical to the sugar group leading to sugar radical formation

Deletion of the trpc4 gene and its role in simple and complex strategic learning

The TRPC4 ion channel is expressed extensively in corticolimbic and a subpopulation of midbrain dopamine neurons. While TRPC4 knockout (KO) rats exhibit reduced sociability and social exploration, little is known about the role of TRPC4 in motivation and learning. To identify a function for TRPC4 channels in learning processes  we tested TRPC4 KO and normal wild type (WT) rats. TRPC4 KO and WT rats exhibited no differences in Y-­maze learning or simple discrimination learning. Furthermore, on a more complex serial reversal shift task designed  to assess strategic learning where the reward and non-­reward cues were repeatedly reversed between training sessions both TRPC4 KO and WT rats   performed equally well. Finally, we found no   performance differences when using a conditional reversal shift task where a tone signals the reversal of reward and non-reward cues within sessions. These data suggest that although TRPC4 channels may play a role in social interaction/anxiety  they exert a minimal role in simple and complex strategic learning

Preservation of the metaproteome: variability of protein preservation in ancient dental calculus.

Proteomic analysis of dental calculus is emerging as a powerful tool for disease and dietary characterisation of archaeological populations. To better understand the variability in protein results from dental calculus, we analysed 21 samples from three Roman-period populations to compare: 1) the quantity of extracted protein; 2) the number of mass spectral queries; and 3) the number of peptide spectral matches and protein identifications. We found little correlation between the quantity of calculus analysed and total protein identifications, as well as no systematic trends between site location and protein preservation. We identified a wide range of individual variability, which may be associated with the mechanisms of calculus formation and/or post-depositional contamination, in addition to taphonomic factors. Our results suggest dental calculus is indeed a stable, long-term reservoir of proteins as previously reported, but further systematic studies are needed to identify mechanisms associated with protein entrapment and survival in dental calculus

Death receptor 3 (TNFRSF25) increases mineral apposition by osteoblasts and region specific new bone formation in the axial skeleton of male DBA/1 mice

Fraser L. Collins and this work were funded by an Arthritis Research UK PhD studentship (Grant Code: 18598) awarded to Anwen S. Williams, Eddie C. Y. Wang, and Michael D. Stone. Eddie C. Y. Wang was additionally funded by MRC Project Grant G0901119. Funding for open access was kindly provided by Cardiff University.Peer reviewedPublisher PD

Stabilization of black phosphorus by sonication-assisted simultaneous exfoliation and functionalization

Black phosphorus (BP) has extraordinary properties, but its ambient instability remains a critical challenge. Functionalization has been employed to overcome the sensitivity of BP to ambient conditions while preserving its properties. Herein, a simultaneous exfoliation–functionalization process is reported that functionalizes BP flakes during exfoliation and thus provides increased protection, which can be attributed to minimal exposure of the flakes to ambient oxygen and water. A tetrabutylammonium salt was employed for intercalation of BP, resulting in the formation of flakes with large lateral dimensions. The addition of an aryl iodide or an aryl iodonium salt to the exfoliation solvent creates a scalable strategy for the production of functionalized few‐layer BP flakes. The ambient stability of functionalized BP was prolonged to a period of one week, as revealed by STEM, AFM, and X‐ray photoelectron spectroscopy

Percutaneous Coronary Intervention in Patients With a History of Gastrointestinal Bleeding (From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium)

Potent antithrombotic agents are routinely prescribed after percutaneous coronary intervention (PCI) to reduce ischemic complications. However, in patients who are at an increased bleeding risk, this may pose significant risks. We sought to evaluate the association between a history of gastrointestinal bleeding (GIB) and outcomes after PCI. We linked clinical registry data from PCIs performed at 48 Michigan hospitals between 1/2013 and 3/2018 to Medicare claims. We used 1:5 propensity score matching to adjust for patient characteristics. In-hospital outcomes included bleeding, transfusion, stroke or death. Post-discharge outcomes included 90-day all-cause readmission and long-term mortality. Of 30,206 patients, 1.1% had a history of GIB. Patients with a history of GIB were more likely to be older, female, and have more cardiovascular comorbidities. After matching, those with a history of GIB (n = 312) had increased post-procedural transfusions (15.7% vs 8.4%; p \u3c 0.001), bleeding (11.9% vs 5.2%; p \u3c 0.001), and major bleeding (2.8% vs 0.6%; p = 0.004). Ninety-day readmission rates were similar among those with and without a history of GIB (34.3% vs 31.3%; p = 0.318). There was no significant difference in post-discharge survival (1 year: 78% vs 80%; p = 0.217; 5 years: 54% vs 51%; p = 0.189). In conclusion, after adjusting for baseline characteristics, patients with a history of GIB had increased risk of post-PCI in-hospital bleeding complications. However, a history of GIB was not significantly associated with 90-day readmission or long-term survival

Using the Community Readiness Model to Select Communities for a Community-Wide Obesity Prevention Intervention

To build on a growing interest in community-based obesity prevention programs, methods are needed for matching intervention strategies to local needs and assets. We used the Community Readiness Model (CRM), a structured interview guide and scoring system, to assess community readiness to act on childhood obesity prevention, furthering a replication study of a successful intervention