A Common Embryonic Origin of Stem Cells Drives Developmental and Adult Neurogenesis.

New neurons arise from quiescent adult neural progenitors throughout life in specific regions of the mammalian brain. Little is known about the embryonic origin and establishment of adult neural progenitors. Here, we show that Hopx+ precursors in the mouse dentate neuroepithelium at embryonic day 11.5 give rise to proliferative Hopx+ neural progenitors in the primitive dentate region, and they, in turn, generate granule neurons, but not other neurons, throughout development and then transition into Hopx+ quiescent radial glial-like neural progenitors during an early postnatal period. RNA-seq and ATAC-seq analyses of Hopx+ embryonic, early postnatal, and adult dentate neural progenitors further reveal common molecular and epigenetic signatures and developmental dynamics. Together, our findings support a "continuous" model wherein a common neural progenitor population exclusively contributes to dentate neurogenesis throughout development and adulthood. Adult dentate neurogenesis may therefore represent a lifelong extension of development that maintains heightened plasticity in the mammalian hippocampus.

Molecular landscapes of human hippocampal immature neurons across lifespan.

Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents1,2 and are dysregulated in multiple human neurological disorders3-5. Little is known about the molecular characteristics of adult human hippocampal imGCs, and even their existence is under debate1,6-8. Here we performed single-nucleus RNA sequencing aided by a validated machine learning-based analytic approach to identify imGCs and quantify their abundance in the human hippocampus at different stages across the lifespan. We identified common molecular hallmarks of human imGCs across the lifespan and observed age-dependent transcriptional dynamics in human imGCs that suggest changes in cellular functionality, niche interactions and disease relevance, that differ from those in mice9. We also found a decreased number of imGCs with altered gene expression in Alzheimer's disease. Finally, we demonstrated the capacity for neurogenesis in the adult human hippocampus with the presence of rare dentate granule cell fate-specific proliferating neural progenitors and with cultured surgical specimens. Together, our findings suggest the presence of a substantial number of imGCs in the adult human hippocampus via low-frequency de novo generation and protracted maturation, and our study reveals their molecular properties across the lifespan and in Alzheimer's disease.

Law enforcement and firearms: understanding firearm ownership and storage habits.

OBJECTIVE: This study seeks to better understand firearm ownership among law enforcement officers (LEO), with the goal of informing future firearm injury and suicide prevention efforts. We describe the frequency and sociodemographic correlates of firearm ownership and storage practices among, and examine the association between suicidal ideation and current firearm storage practices. METHODS: The present study used data from a large online study (n=6410) and included data from individuals who were currently or previously being employed as an LEO (n=369; M (SD) age=39.2 y (15.8 y), 75.2% male, 66.7% white). Self-report measures were used to assess for firearm ownership, storage habits and suicidal ideation. Descriptive statistics were used to describe the frequency of firearm ownership and logistic regressions were used to examine the extent to which demographic characteristics and suicidal ideation were associated with firearm ownership. RESULTS: Overall, 70.5% (n=261) of the sample reported firearm ownership. LEO who were older had significantly lower odds of reporting firearm ownership. Those who were married and those who reported lifetime suicidal ideation had significantly greater odds of reporting firearm ownership. Whereas firearm-owning LEO who reporting storing a firearm locked had significantly lower odds of reporting lifetime suicidal ideation, those who reported storing a firearm unloaded had significantly greater odds of reporting lifetime suicidal ideation. CONCLUSION: Findings have important public health implications and can be used to increase adherence with secure storage recommendations. Increasing secure storage may help reduce suicide risk among LEO, a sample at heightened risk for suicide.

Regional differences in firearm ownership, storage and use: results from a representative survey of five US states.

BACKGROUND: Firearm access and storage practices influence risk for injury and death; however, prior research has considered only national and regional differences on these variables, overlooking state-level differences. OBJECTIVES: To analyse and describe statewide differences in firearm ownership, storage and use in a representative sample of five US states. DESIGN: Variables were assessed via an online self-report survey administered between 29 April 2022 and 15 May 2022. SETTING: Surveys were completed online. PARTICIPANTS: Participants (n=3510) were members of knowledge panel, a probability-based sample recruited to be representative of US adults. All participants were aged 18+ and resided in one of five states: Colorado, Minnesota, Mississippi, New Jersey or Texas. MEASUREMENTS: We used χ2 tests to examine state differences in firearm ownership, childhood firearm experiences and purchasing. A series of analyses of covariance were then used to assess differences in firearm storage, firearms owned and carrying behaviours while adjusting for pertinent demographic characteristics. RESULTS: We found significant differences in firearm ownership across states. There were significantly more first-time firearm purchasers during the firearm purchasing surge in New Jersey. Both Mississippi and Texas have elevated rates of unsecure storage practices and firearm carrying outside of the home. LIMITATIONS: Results are cross-sectional and self-report. Findings may not generalise beyond the five states assessed in this survey. CONCLUSIONS: Public health messaging around firearm safety should account for differences in key firearm behaviours related to ownership, storage and use to ensure effective communication and reduce the risk of gun injury and death across states.

Predicting potential underreporting of firearm ownership in a nationally representative sample.

PURPOSE: This study utilized demographic and intrapersonal variables to identify individuals who may have falsely denied firearm ownership and determined if individuals can be divided into meaningful subgroups. METHODS: Participants were United States residents (N = 3500) recruited from January to June 2020. matched to the 2010 census data for age, race, sex, income, and education level. A Zero-Inflated Negative Binomial (ZINB) regression was utilized to determine potential underreporting of firearm ownership, and a latent class analysis was utilized to determine unique subgroups of those who were identified as underreporting firearm ownership in the ZINB. RESULTS: Participants (N = 1306) were identified as underreporting firearm ownership (excess zeros) based on a model that included demographic and intrapersonal variables. A latent class analysis indicated that among excess zeros, three unique subgroups exist. CONCLUSIONS: Determining who may be underreporting firearm ownership will allow for a more comprehensive understanding of firearm ownership in the US and more targeted safe storage messages that may reach those who own firearms and are at risk for firearm-related injury and death.

Female military service members and veterans: Understanding treatment seeking behavior and previous suicide risk among suicide decedents.

To examine the differences in treatment seeking behaviors, previous suicidal thoughts, previous suicide attempts, and disclosure of suicidal thoughts among female service members (SM)/Veteran suicide decedents who used a firearm and those who used another method. Data was acquired from the National Violent Death Reporting System which is maintained and monitored by the Center for Disease Control and Prevention. Data included in the present study were from suicide deaths that occurred between 2003-2018. Female SM/Veterans who died by firearm suicide had lower proportions of current mental health or substance use treatment, lifetime mental health or substance use treatment, and previous suicide attempts compared to those who used another method. Female SM/Veterans who die by firearm suicide are less likely to encounter mental health services than those who use another method. Conversations on secure firearm storage need to occur outside of the health care setting.

Determining who healthcare providers screen for firearm access in the United States.

Healthcare providers are well positioned to screen for firearm access to reduce risk of suicides, yet there is a limited understanding of how often and for whom firearm access screening occurs. The present study examined the extent to which providers screen for firearm access and sought to identify who has been screened in the past. The representative sample included 3510 residents from five US states who reported whether they have been asked about their access to firearms by a healthcare provider. The findings demonstrate that most participants have never been asked by a provider about firearm access. People who have been asked were more likely to be White, male, and firearm owners. Those with children under 17 years old in the home, that have been in mental health treatment, and report a history of suicidal ideation were more likely to be screened for firearm access. Although there are interventions for mitigating firearm related risks in healthcare settings, many providers may be missing the opportunity to implement these because they do not ask about firearm access.

Public Perception of Gun Violence-Related Headline Accuracy and the Credibility of Media Sources.

The present study sought to determine the extent to which the message or messenger is more important for news media portrayal of gun violence prevention. Exploratory analyses also examined factors related to Fox News and MSNBC credibility. Participants (N = 3,500) were US adults matched to the 2010 US Census on several demographic variables. Two mock headlines were presented: "Gun violence is result of mental health problems" and "Storing firearms in a safe can help prevent suicides." Headlines were reported to be from either Fox News or MSNBC. Participants then rated accuracy of the headline and credibility of the news source. Headline content did not predict perceived accuracy of the headline. Perceived credibility of the messenger was associated with perceived accuracy for both mock headlines. Exploratory analyses indicated several demographic factors related to Fox News and MSNBC credibility. Regardless of the content of a headline, the degree to which participants perceived it as accurate was associated with how credible they believed the source to be. These findings highlight the importance of credible media portrayal of accurate information on gun violence prevention.

Demographic differences in the type of firearm and location of bodily injury in firearm suicide decedents.

This study describes the type of firearm used and location of bodily injury among demographic subgroups of suicide decedents. Data on those who died by suicide via firearm from the National Violent Death Reporting System (N = 117,126) between the years 2003-2018 was utilized. A series of five logistic regression analyses examining the age of decedent, type of firearm, location of wound site, loaded vs. unloaded firearms, and locked vs. unlocked storage, using predictors including gender, race, who owns the firearm and age were performed. Findings have important public health implications. Increasing safe storage or removing the specific types of firearms one is likely to use in their death from the home during a time of crisis may decrease risk of suicide.

Examining characteristics and experiences of Black firearm owners.

OBJECTIVE: The present study sought to better understand the characteristics of those who own firearms in the Black community; and to understand how Black firearm owners differ from nonfirearm owning Black individuals on a variety of variables related to safety, threat concerns, and suicide risk. METHODS: Two samples were utilized in this study. The first was a subsample of those who identified as Black from a nationally representative sample (N = 502) seeking to understand firearm ownership within the United States. The second used a subsample of those who identified as Black (N = 1086) from a representative sample from New Jersey, Minnesota, and Mississippi. Variables related to safety and threat concerns were included in the second sample. RESULTS: In both samples, multiple demographic variables, such as being a woman and having higher education, predicted firearm ownership. In the second sample, experiences of everyday discrimination and crime experiences were associated with firearm ownership. Additionally, Black firearm owners reported significantly more suicidal ideation than Black nonfirearm owners. CONCLUSION: The findings demonstrate the unique characteristics and experiences of Black firearm owners and show that firearm ownership is associated with increased suicide risk factors for Black adults. Findings should be used to advocate for the creation of more culturally relevant suicide prevention and firearm means safety strategies.

An examination of preferred messengers on firearm safety for suicide prevention.

This study sought to determine differences in preferred messengers on the topic of safe firearm storage and suicide prevention between firearm owners and non-firearm owners, and among firearm owners of different racial groups and sexes. Participants were 6200 United States residents recruited via Qualtrics Panels to complete an online survey. Data were collected during March 2020. The total sample and all subsamples ranked law enforcement, current military personnel, and military veterans as the top three most credible sources to discuss firearm safety for suicide prevention. Significant differences existed among the mean ranking of sources between firearm owners and non-firearm owners as well as between several subgroups of firearm owners. The identical ranking of the top three sources indicates that these groups agree on the relative credibility of multiple sources, although the average level of credibility for particular sources may vary. These findings highlight that the effectiveness of messaging on safe firearm storage may hinge on the identity of the individual delivering the message and provide an initial roadmap for how to consider packaging specific messages.

Disseminated Legionella micdadei infection in a liver transplant patient presenting as pulmonary nodules and a laryngeal lesion.

We report a liver transplant patient with disseminated Legionella micdadei infection with pulmonary, laryngeal, and suspected muscle involvement. This organism, which stains weakly acid-fast, primarily affects immunocompromised patients. The diagnosis is difficult to make; in this case, the organism was identified via molecular diagnostics on laryngeal and pulmonary biopsy tissue.

Differentiating suicide decedents who died by firearm verse hanging.

This present study sought to examine how demographics and the availability of means for suicide converge to impact method selection between firearms and hanging, which are the two most lethal and commonly used methods for suicide in the United States. Data were collected as part of a larger online study that gathered information about suicide decedents and the circumstances around their death from family members and friends; the most common sources being parents, friends, and other family members. This study used data from those who died by suicide by firearm or hanging (n = 149); and was restricted to those who identified as male and white. The study examined if age, education, marital status, military affiliation, and firearm ownership impacted method selection. Results indicated that age and owning a firearm were associated with using a firearm in a suicide death. Additionally, those who used a firearm were significantly younger and more likely to own a firearm than those who used another method; and those who died by hanging were significantly younger than those who used another method. Findings from this study can be leveraged to improve the effectiveness of means safety efforts and create more personalised public health messages on firearm safe storage.

Essential workers: Past month suicidal ideation and COVID-19 stress.

OBJECTIVE: This study examined if essential workers (EW) reported higher past month suicidal ideation (SI) and coronavirus-19 (COVID-19) stress than non-EW, explored if the association between EW status and SI is indirect through COVID stress, and tested whether EW who identified as black, indigenous, and people of color (BIPOC) experienced more past month SI and COVID stress than white EW. METHODS: Participants (N = 3500) were predominately white and female. COVID-19 was assessed with the COVID-19 subscale. RESULTS: EWs reported higher past month ideation and COVID-19 stress than non-EWs. EWs who identified as BIPOC reported higher past month ideation and higher fears about economic consequences and compulsive checking and reassurance seeking subscales compared to White EWs. CONCLUSION: EWs experience higher rates of SI and stress than non-EW; and BIPOC EWs experience higher SI and stress than White EWs. Accessibility of support should be a priority for this group at high risk for both the physical and emotional burden of COVID-19.

Clinical outcomes and serologic response in solid organ transplant recipients with COVID-19: A case series from the United States.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. The clinical features, disease course, and serologic response of COVID-19 among immunosuppressed patients such as solid organ transplant (SOT) recipients, who are at presumed risk for more severe disease, are not well characterized. We describe our institutional experience with COVID-19 among 10 SOT patients, including the clinical presentation, treatment modalities, and outcomes of 7 renal transplant recipients, 1 liver transplant recipient, 1 heart transplant recipient, and 1 lung transplant recipient. In addition, we report the serologic response in SOT recipients, documenting a positive IgG response in all 7 hospitalized patients. We also review the existing literature on COVID-19 in SOT recipients to consolidate the current knowledge on COVID-19 in the SOT population for the transplant community.

ß1-integrin restricts astrocytic differentiation of adult hippocampal neural stem cells.

Integrins are transmembrane receptors that mediate cell-extracellular matrix and cell-cell interactions. The ß1-integrin subunit is highly expressed by embryonic neural stem cells (NSCs) and is critical for NSC maintenance in the developing nervous system, but its role in the adult hippocampal niche remains unexplored. We show that ß1-integrin expression in the adult mouse dentate gyrus (DG) is localized to radial NSCs and early progenitors, but is lost in more mature progeny. Although NSCs in the hippocampal subgranular zone (SGZ) normally only infrequently differentiate into astrocytes, deletion of ß1-integrin significantly enhanced astrocyte differentiation. Ablation of ß1-integrin also led to reduced neurogenesis as well as depletion of the radial NSC population. Activation of integrin-linked kinase (ILK) in cultured adult NSCs from ß1-integrin knockout mice reduced astrocyte differentiation, suggesting that at least some of the inhibitory effects of ß1-integrin on astrocytic differentiation are mediated through ILK. In addition, ß1-integrin conditional knockout also resulted in extensive cellular disorganization of the SGZ as well as non-neurogenic regions of the DG. The effects of ß1-integrin ablation on DG structure and astrogliogenesis show sex-specific differences, with the effects following a substantially slower time-course in males. ß1-integrin thus plays a dual role in maintaining the adult hippocampal NSC population by supporting the structural integrity of the NSC niche and by inhibiting astrocytic lineage commitment. GLIA 2016;64:1235-1251.

BMP signaling regulates the tempo of adult hippocampal progenitor maturation at multiple stages of the lineage.

Novel environmental stimuli, such as running and learning, increase proliferation of adult hippocampal neural stem cells (NSCs) and enlarge the population of new neurons. However, it remains unclear how increased numbers of new neurons can be generated in a time frame far shorter than the time required for proliferating stem cells to generate these neurons. Here, we show that bone morphogenetic protein (BMP) signaling in the subgranular zone regulates the tempo of neural progenitor cell (NPC) maturation by directing their transition between states of quiescence and activation at multiple stages along the lineage. Virally mediated overexpression of BMP4 caused NPC cell cycle exit and slowed the normal maturation of NPCs, resulting in a long-term reduction in neurogenesis. Conversely, overexpression of the BMP inhibitor noggin promoted NPC cell cycle entry and accelerated NPC maturation. Similarly, BMP receptor type 2 (BMPRII) ablation in Ascl1(+) intermediate NPCs accelerated their maturation into neurons. Importantly, ablation of BMPRII in GFAP(+) stem cells accelerated maturation without depleting the NSC pool, indicating that an increased rate of neurogenesis does not necessarily diminish the stem cell population. Thus, inhibition of BMP signaling is a mechanism for rapidly expanding the pool of new neurons in the adult hippocampus by tipping the balance between quiescence/activation of NPCs and accelerating the rate at which they mature into neurons.

Differences in reasons for secure and unsecure firearm storage: Results from a representative cross-sectional study of nine states.

Objectives: To examine factors that differentiate firearm owners who endorse specific reasons for secure and unsecure firearm storage. Methods: A subsample of firearm-owning adults (n = 3,119) drawn from a representative sample of adults (n = 7,785) residing in nine US states participated in an online survey. Results: The most common reason for not always using a gun safe was concerns that they render firearms too slow to access during an emergency (60.2%). The most common reasons for current firearm storage were ensuring ready access in case of emergency (59.7%) and preventing access by children and adolescents (44.6%). Firearm owners varied on their reasons based upon current storage habits, reasons for ownership, and the presence of firearms in the home. Conclusions: Firearm owners with children in the home are more likely to select storage methods they feel will prevent access by vulnerable individuals, whereas those who own for defensive purposes and those who store firearms loaded and unlocked are more likely to endorse storing their firearms for quick home defense and convenience and to see gun safes as unnecessary obstacles.