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Antibody responses to intramuscular half-dose TIV in healthy, previously immunized adults were not substantially inferior to the full-dose vaccine, particularly for ages 18 to 49 years. Significantly higher geometric mean titer responses in women were identified for all ages, regardless of dose or influenza strain. Half-dose vaccination may be an effective strategy for healthy adults younger than 50 years in the setting of an influenza vaccine shortage.

Ab initio molecular orbital calculations were performed at the SCF and MP2 levels, using a 6-31G basis set, for complexes of CO 2 with carbonyl compounds. The specific interaction between CO 2 and the carbonyl oxygen can be described as a Lewis acid-base reaction. Two different geometries, one having C 2V symmetry and the other having C s symmetry, were studied. The C s symmetry was found to yield stronger binding of the CO 2 complexes. The degeneracy of the ν 2 bending mode in free CO 2 was lifted when the CO 2 was bound. The calculated ν 2 splittings at the SCF level, using a 6-31G basis set, were comparable to literature values determined by IR spectroscopy of CO 2 -impregnated polymers. When steric hindrance was present, the binding energy of CO 2 to carbonyls was reduced, resulting in lower ν 2 splittings. The interaction energy between benzene and CO 2 was determined to be much lower than that associated with a carbonyl oxygen and CO 2 . The preference of CO 2 for the carbonyl group over the benzene ring, along with the role that steric hindrance plays, allows an understanding of the specific interactions of CO 2 with polymers.

BackgroundAlthough myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined.PurposeThe study’s primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization.MethodsNew onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).ResultsNew onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group.ConclusionsPassive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.

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Dr Wilson had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Richards and Keshavarz contributed equally.

SUMMARY XPG is a structure-specific endonuclease required for nucleotide excision repair, and incision-defective Xpg mutations cause the skin cancer-prone syndrome xeroderma pigmentosum. Truncating mutations instead cause the neurodevelopmental progeroid disorder Cockayne syndrome, but little is known about how XPG loss results in this devastating disease. We identify XPG as a partner of BRCA1 and BRCA2 in maintaining genomic stability through homologous recombination (HRR). XPG depletion causes DNA double-strand breaks, chromosomal abnormalities, cell-cycle delays, defective HRR, inability to overcome replication fork stalling, and replication stress. XPG directly interacts with BRCA2, RAD51, and PALB2, and XPG depletion reduces their chromatin binding and subsequent RAD51 foci formation. Upstream in HRR, XPG interacts directly with BRCA1. Its depletion causes BRCA1 hyper-phosphorylation and persistent chromatin binding. These unexpected findings establish XPG as an HRR protein with important roles in genome stability and suggest how XPG defects produce severe clinical consequences including cancer and accelerated aging.

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