ABSTRACT
In August 2022, the Food and Drug Administration authorized JYNNEOS vaccine (modified vaccinia Ankara vaccine, Bavarian Nordic), a 2-dose series used for the prevention of Monkeypox virus infection, to be administered via a dose-sparing intradermal route, in addition to the previously authorized subcutaneous route. The California Department of Public Health investigated whether demographic disparities in vaccination series completion varied by route of administration of the recipient's first dose. Among California residents who received their first dose during August 9, 2022-March 31, 2023, a total of 59.8% received a second dose. Series completion was highest among non-Hispanic White persons (64.1%), persons aged ≥65 years (72.6%), and adults with male sex assignment at birth (62.1%); series completion was lowest among non-Hispanic Black or African American persons (51.3%), persons aged 18-24 years (42.9%), and adults assigned female sex at birth (42.8%). When the first dose was received by subcutaneous administration, overall series completion was 58.8% compared with 60.2% when the first dose was administered intradermally. Odds of series completion across all race and ethnicity groups, persons aged 18-64 years, community health conditions, and persons assigned male sex at birth were not greater when the first dose was administered subcutaneously compared with intradermally. Intradermal use of JYNNEOS vaccine did not lower overall 2-dose series completion rates. Continued efforts are needed to ensure persons at risk for Monkeypox virus infection receive both recommended doses.
Subject(s)
Mpox (monkeypox) , Smallpox Vaccine , Adult , Female , Humans , Infant, Newborn , Male , California/epidemiology , Ethnicity , Vaccination , Healthcare DisparitiesABSTRACT
The hypocretin receptor (HcrtR) antagonist almorexant (ALM) has potent hypnotic actions but little is known about neurocognitive performance in the presence of ALM. HcrtR antagonists are hypothesized to induce sleep by disfacilitation of wake-promoting systems whereas GABAA receptor modulators such as zolpidem (ZOL) induce sleep through general inhibition of neural activity. To test the hypothesis that less functional impairment results from HcrtR antagonist-induced sleep, we evaluated the performance of rats in the Morris Water Maze in the presence of ALM vs. ZOL. Performance in spatial reference memory (SRM) and spatial working memory (SWM) tasks were assessed during the dark period after equipotent sleep-promoting doses (100 mg/kg, po) following undisturbed and sleep deprivation (SD) conditions. ALM-treated rats were indistinguishable from vehicle (VEH)-treated rats for all SRM performance measures (distance traveled, latency to enter, time within, and number of entries into, the target quadrant) after both the undisturbed and 6 h SD conditions. In contrast, rats administered ZOL showed impairments in all parameters measured compared to VEH or ALM in the undisturbed conditions. Following SD, ZOL-treated rats also showed impairments in all measures. ALM-treated rats were similar to VEH-treated rats for all SWM measures (velocity, time to locate the platform and success rate at finding the platform within 60 s) after both the undisturbed and SD conditions. In contrast, ZOL-treated rats showed impairments in velocity and in the time to locate the platform. Importantly, ZOL rats only completed the task 23-50% of the time while ALM and VEH rats completed the task 79-100% of the time. Thus, following equipotent sleep-promoting doses, ZOL impaired rats in both memory tasks while ALM rats performed at levels comparable to VEH rats. These results are consistent with the hypothesis that less impairment results from HcrtR antagonism than from GABAA-induced inhibition.
ABSTRACT
Deficits in sleep and circadian organization have been identified as common early features in patients with Huntington's disease that correlate with symptom severity and may be instrumental in disease progression. Studies in Huntington's disease gene carriers suggest that alterations in the electroencephalogram may reflect underlying neuronal dysfunction that is present in the premanifest stage. We conducted a longitudinal characterization of sleep/wake and electroencephalographic activity in the R6/2 mouse model of Huntington's disease to determine whether analogous electroencephalographic 'signatures' could be identified early in disease progression. R6/2 and wild-type mice were implanted for electroencephalographic recordings along with telemetry for the continuous recording of activity and body temperature. Diurnal patterns of activity and core body temperature were progressively disrupted in R6/2 mice, with a large reduction in the amplitude of these rhythms apparent by 13 weeks of age. The diurnal variation in sleep/wake states was gradually attenuated as sleep became more fragmented and total sleep time was reduced relative to wild-type mice. These genotypic differences were augmented at 17 weeks and evident across the entire 24-h period. Quantitative electroencephalogram analysis revealed anomalous increases in high beta and gamma activity (25-60 Hz) in all sleep/wake states in R6/2 mice, along with increases in theta activity during both non-rapid eye movement and rapid eye movement sleep and a reduction of delta power in non-rapid eye movement sleep. These dramatic alterations in quantitative electroencephalographic measures were apparent from our earliest recording (9 weeks), before any major differences in diurnal physiology or sleep/wake behaviour occurred. In addition, the homeostatic response to sleep deprivation was greatly attenuated with disease progression. These findings demonstrate the sensitivity of quantitative electroencephalographic analysis to identify early pathophysiological alterations in the R6/2 model of Huntington's disease and suggest longitudinal studies in other preclinical Huntington's disease models are needed to determine the generality of these observations as a potential adjunct in therapeutic development.
