Astrocyte expression of aging-associated markers positively correlates with neurodegeneration in the frontal lobe of the rhesus macaque brain.

Introduction: As the population over the age of 65 increases, rates of neurodegenerative disorders and dementias will rise - necessitating further research into the cellular and molecular mechanisms that contribute to brain aging. With the critical importance of astrocytes to neuronal health and functioning, we hypothesized that alterations in astrocyte expression of aging-associated markers p16INK4a (p16) and sirtuin 1 (SIRT1) with age would correlate with increased rates of neurodegeneration, as measured by FluoroJade C (FJC) staining. Methods: To test this hypothesis, 19 rhesus macaques at the Tulane National Primate Research Center were selected based on the following criteria: archival FFPE CNS tissue available to use, no noted neuropathology, and an age range of 5-30 years. Tissues were cut at 5 µm and stained for GFAP, p16, SIRT1, and FJC, followed by whole-slide imaging and HALO® image analysis for percentage of marker-positive cells and relative intensity of each stain. Results: We found the percentage of p16+ cells increases with age in total cells and astrocytes of the frontal (p = 0.0021, p = 0.0012 respectively) and temporal (p = 0.0226, p = 0.0203 respectively) lobes, as well as the relative intensity of p16 staining (frontal lobe: p = 0.0060; temporal lobe: p = 0.0269). For SIRT1, we found no correlation with age except for an increase in the relative intensity of SIRT1 in the temporal lobe (p = 0.0033). There was an increase in neurodegeneration, as measured by the percentage of FJC+ cells in the frontal lobe with age (p = 0.0057), as well as in the relative intensity of FJC staining in the frontal (p = 0.0030) and parietal (p = 0.0481) lobes. Importantly, increased p16 and SIRT1 expression in astrocytes correlated with increasing neurodegeneration in the frontal lobe (p = 0.0009, p = 0.0095 respectively). Discussion: Together, these data suggest that age-associated alterations in astrocytes contribute to neurodegeneration and provide a target for mechanistic studies in the future.

Sex-disaggregated effectiveness data reporting in COVID-19 vaccine research: a systematic review.

BACKGROUND: Sex and gender are believed to influence vaccine response. Yet, the relationship between sex and gender and COVID-19 vaccine efficacy is poorly understood and remains under-investigated. METHODS: We conducted a systematic review to determine whether and to what extent post-approval COVID-19 vaccine effectiveness (VE) studies report sex-disaggregated VE data. We searched four publication and pre-publication databases and additional grey literature sources for relevant published/preprint studies released between 1 January 2020 and 1 October 2021 (i.e., pre-Omicron era). We included observational studies providing VE estimates for one or more licensed/approved COVID-19 vaccines and including both males and females. Two reviewers independently assessed study eligibility, extracted data, and assessed risk-of-bias through a modified version of Cochrane's ROBINS-I tool. A qualitative data synthesis was performed. RESULTS: Here we show that, among 240 eligible publications, 68 (28.3%) do not report the sex distribution among participants. Only 21/240 (8.8%) studies provide sex-disaggregated VE estimates, and high between-study heterogeneity regarding design, target population, outcomes, and vaccine type/timing prevent the assessment of sex in determining COVID-19 VE across studies. CONCLUSIONS: Our findings indicate that few COVID-19 vaccine research publications account for sex. Improved adherence to recommended reporting guidelines will ensure that the evidence generated can be used to better understand the relationship between sex and gender and VE.

The level of protection that vaccines provide against COVID-19 might depend on a person's sex or gender. However, sex and gender are not always reported in studies on the effectiveness of COVID-19 vaccines. Here, we systematically reviewed the literature on COVID-19 vaccine effectiveness and looked at whether the studies we found separated out their data on vaccine effectiveness by participants' sex. Out of the 240 publications we identified, 68 (28.3%) did not report the sex of the participants in their study, and only 21 studies (8.8%) reported vaccine effectiveness data separated by sex. These results show that a substantial proportion of COVID-19 vaccine research publications do not account for sex. Efforts should be made by researchers to study and report the relationship between sex and vaccine effectiveness, to help to optimise vaccination strategies so that all people are adequately protected.

A comparison of national vaccination policies to prevent serogroup B meningococcal disease.

OBJECTIVES: To understand the global landscape of prevention and control efforts targeting serogroup B meningococcal (MenB) disease and to identify the key challenges and gaps yet to be addressed. METHODS: We conducted a comprehensive review of policies and practices for the use of protein-based MenB vaccines (Bexsero® [GlaxoSmithKline] and Trumenba® [Pfizer]) in all countries (n = 58) where either or both vaccine is authorized for use. We searched the literature (PubMed) and websites of health ministries and other relevant agencies to identify policy documents and plans and collect information about implementation timelines, target groups, vaccines being used, recommended schedules, and coverage data. Experts in the field were contacted for additional details andclarifications, as needed. RESULTS: We found evidence of a national MenB vaccination policy in 24 out of 58 countries where one or both protein-based MenB vaccines are authorized. Of these, 15 countries have included MenB vaccination in their immunization plans for at least one age-based risk group (mostly infants), 21 have issued recommendations for various risk groups based on underlying medical conditions (e.g. asplenia), and 13 have done so for select groups at increased risk of exposure (e.g. laboratory staff). Recommended vaccination schedules and number of doses, where available, varied widely. Vaccination coverage data for age-based risk groups were not obtained for most countries. CONCLUSIONS: Our findings highlighted the significant heterogeneity in recommendations for MenB vaccination across countries. Greater transparency in reporting MenB vaccination recommendations and more robust data on implementation and the impact of vaccination would better facilitate optimizing MenB prevention strategies.

Child Marriage or Statutory Rape? A Comparison of Law and Practice Across the United States.

PURPOSE: In many U.S. states, children can legally marry at an earlier age than they can legally consent to sex, leading to situations in which sex between spouses may be a criminal act. Some states exempt sex between married persons from their definition of statutory rape, which may create perverse incentives for child marriage. We estimated the number of child marriages that violated statutory rape laws across the United States since January 1, 2000. METHODS: We created a longitudinal database of statutory rape laws in place from 2000 to 2020 in each state. Using data from marriage certificates filed in 44 states and Washington, DC, we compared the age of married spouses with the text of state-specific statutory rape laws in place at the time the marriages occurred. RESULTS: Child marriages violated statutory rape laws in 14 states. The proportion of child marriages that violated statutory rape laws varied from 1% to over 50%. In 33 states, some or all statutory rape laws exempted sex between married couples from the definition of crimes. In these states, the proportion of child marriages that would have been crimes, without these exemptions, varied from less than 1% to over 80%. CONCLUSIONS: Our results highlight the blurred legal and conceptual boundaries between child marriage and sexual violence. The simultaneous legality of child marriage and marital exemptions to statutory rape laws provide legal loopholes for sexual acts with children that would otherwise be considered crimes. Marital exemptions to statutory rape laws may also incentivize a substantial portion of child marriages.

Extracellular Vesicles as a Means of Viral Immune Evasion, CNS Invasion, and Glia-Induced Neurodegeneration.

Extracellular vesicles (EVs) are small, membrane-bound vesicles released by cells as a means of intercellular communication. EVs transfer proteins, nucleic acids, and other biologically relevant molecules from one cell to another. In the context of viral infections, EVs can also contain viruses, viral proteins, and viral nucleic acids. While there is some evidence that the inclusion of viral components within EVs may be part of the host defense, much of the research in this field supports a pro-viral role for EVs. Packaging of viruses within EVs has repeatedly been shown to protect viruses from antibody neutralization while also allowing for their integration into cells otherwise impervious to the virus. EVs also bidirectionally cross the blood-brain barrier (BBB), providing a potential route for peripheral viruses to enter the brain while exiting EVs may serve as valuable biomarkers of neurological disease burden. Within the brain, EVs can alter glial activity, increase neuroinflammation, and induce neurotoxicity. The purpose of this mini-review is to summarize research related to viral manipulation of EV-mediated intercellular communication and how such manipulation may lead to infection of the central nervous system, chronic neuroinflammation, and neurodegeneration.