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Subtype B HIV-1 has been the primary driver of the HIV-1 epidemic in the United States (U.S.) for over forty years and is also a prominent subtype in the Americas, Europe, Australia, the Middle East and North Africa. In this study, the neutralization profiles of contemporary subtype B Envs from the U.S. were assessed to characterize changes in neutralization sensitivities over time. We generated a panel of 30 contemporary pseudoviruses (PSVs) and demonstrated continued diversification of subtype B Env from the 1980s up to 2018. Neutralization sensitivities of the contemporary subtype B PSVs were characterized using 31 neutralizing antibodies (NAbs) and were compared with strains from earlier in the HIV-1 pandemic. A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 NAbs for the contemporary as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the NAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A meta-analysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Zika virus infection is a threat to at-risk populations, causing major birth defects and serious neurological complications. Development of a safe and efficacious Zika virus vaccine is, therefore, a global health priority. Assessment of heterologous flavivirus vaccination is important given co-circulation of Japanese encephalitis virus and yellow fever virus with Zika virus. We investigated the effect of priming flavivirus naive participants with a licensed flavivirus vaccine on the safety and immunogenicity of a purified inactivated Zika vaccine (ZPIV)., Methods: This phase 1, placebo-controlled, double-blind trial was done at the Walter Reed Army Institute of Research Clinical Trials Center in Silver Spring, MD, USA. Eligible participants were healthy adults aged 18-49 years, with no detectable evidence of previous flavivirus exposure (by infection or vaccination), as measured by a microneutralisation assay. Individuals with serological evidence of HIV, hepatitis B, or hepatitis C infection were excluded, as were pregnant or breastfeeding women. Participants were recruited sequentially into one of three groups (1:1:1) to receive no primer, two doses of intramuscular Japanese encephalitis virus vaccine (IXIARO), or a single dose of subcutaneous yellow fever virus vaccine (YF-VAX). Within each group, participants were randomly assigned (4:1) to receive intramuscular ZPIV or placebo. Priming vaccinations were given 72-96 days before ZPIV. ZPIV was administered either two or three times, at days 0, 28, and 196-234. The primary outcome was occurrence of solicited systemic and local adverse events along with serious adverse events and adverse events of special interest. These data were analysed in all participants receiving at least one dose of ZPIV or placebo. Secondary outcomes included measurement of neutralizing antibody responses following ZPIV vaccination in all volunteers with available post-vaccination data. This trial is registered at ClinicalTrials.gov, NCT02963909., Findings: Between Nov 7, 2016, and Oct 30, 2018, 134 participants were assessed for eligibility. 21 did not meet inclusion criteria, 29 met exclusion criteria, and ten declined to participate. 75 participants were recruited and randomly assigned. 35 (47%) of 75 participants were male and 40 (53%) were female. 25 (33%) of 75 participants identified as Black or African American and 42 (56%) identified as White. These proportions and other baseline characteristics were similar between groups. There were no statistically significant differences in age, gender, race, or BMI between those who did and did not opt into the third dose. All participants received the planned priming IXIARO and YF-VAX vaccinations, but one participant who received YF-VAX dropped out before receipt of the first dose of ZPIV. 50 participants received a third dose of ZPIV or placebo, including 14 flavivirus-naive people, 17 people primed with Japanese encephalitis virus vaccine, and 19 participants primed with yellow fever vaccine. Vaccinations were well tolerated across groups. Pain at the injection site was the only adverse event reported more frequently in participants who received ZPIV than in those who received placebo (39 [65%] of 60 participants, 95% CI 51·6-76·9 who received ZPIV vs three [21·4%] of 14 who received placebo; 4·7-50·8; p=0·006). No patients had an adverse event of special interest or serious adverse event related to study treatment. At day 57, the flavivirus-naive volunteers had an 88% (63·6-98·5, 15 of 17) seroconversion rate (neutralising antibody titre ≥1:10) and geometric mean neutralising antibody titre (GMT) against Zika virus of 100·8 (39·7-255·7). In the Japanese encephalitis vaccine-primed group, the day 57 seroconversion rate was 31·6% (95% CI 12·6-56·6, six of 19) and GMT was 11·8 (6·1-22·8). Participants primed with YF-VAX had a seroconversion rate of 25% (95% CI 8·7-49·1, five of 20) and GMT of 6·6 (5·2-8·4). Humoral immune responses rose substantially following a third dose of ZPIV, with seroconversion rates of 100% (69·2-100; ten of ten), 92·9% (66·1-99·8; 13 of 14), and 60% (32·2-83·7, nine of 15) and GMTs of 511·5 (177·6-1473·6), 174·2 (51·6-587·6), and 79 (19·0-326·8) in the flavivirus naive, Japanese encephalitis vaccine-primed, and yellow fever vaccine-primed groups, respectively., Interpretation: We found ZPIV to be well tolerated in flavivirus naive and primed adults but that immunogenicity varied significantly according to antecedent flavivirus vaccination status. Immune bias towards the flavivirus antigen of initial exposure and the timing of vaccination may have impacted responses. A third ZPIV dose overcame much, but not all, of the discrepancy in immunogenicity. The results of this phase 1 clinical trial have implications for further evaluation of ZPIV's immunisation schedule and use of concomitant vaccinations., Funding: Department of Defense, Defense Health Agency; National Institute of Allergy and Infectious Diseases; and Division of Microbiology and Infectious Disease., Competing Interests: Declaration of interests SJT is a data and safety monitoring board member for the Moderna Zika trial and is compensated for his time. He has also supported the WHO R&D blueprint and vaccine TPP working groups in exchange for no compensation. SJT, KHE, and RDLB are named patent holders (WO2017210215A1) for the Zika inactivated vaccine evaluated in this clinical trial. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: COVID-19 vaccines have been critical for protection against severe disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but gaps remain in our understanding of the immune responses that contribute to controlling subclinical and mild infections., Methods: Vaccinated, active-duty US military service members were enrolled in a non-interventional, minimal-risk, observational study starting in May, 2021. Clinical data, serum, and saliva samples were collected from study participants and were used to characterise the humoral immune responses to vaccination and to assess its impact on clinical and subclinical infections, as well as virologic outcomes of breakthrough infections (BTI) including viral load and infection duration., Findings: The majority of VIRAMP participants had received the Pfizer COVID-19 vaccine and by January, 2022, N = 149 had a BTI. The median BTI duration (PCR+ days) was 4 days and the interquartile range was 1-8 days. Participants that were nucleocapsid seropositive prior to their BTI had significantly higher levels of binding and functional antibodies to the spike protein, shorter median duration of infections, and lower median peak viral loads compared to seronegative participants. Furthermore, levels of neutralising antibody, ACE2 blocking activity, and spike-specific IgA measured prior to BTI also correlated with the duration of infection., Interpretation: We extended previous findings and demonstrate that a subset of vaccine-induced humoral immune responses, along with nucleocapsid serostatus are associated with control of SARS-CoV-2 breakthrough infections in the upper airways., Funding: This work was funded by the DoD Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) in collaboration with the Defense Health Agency (DHA) COVID-19 funding initiative for the VIRAMP study., Competing Interests: Declaration of interests KM (Allucent) was contracted by the US Department of Defense to conduct the VIRAMP clinical study, to perform testing on clinical study samples, and to collect epidemiologic data. JC served as the Acting Chief Medical Officer for the Vaccine Acceleration Program at the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense that funded the VIRAMP clinical study, and was involved with clinical study design and establishing collaborations for analysis of samples. The other authors declare no conflicts of interest., (Published by Elsevier B.V.)

Objective: Validate the performance characteristics of two analyte specific, laboratory developed tests (LDTs) for the quantification of SARS-CoV-2 subgenomic RNA (sgRNA) and viral load on the Hologic Panther Fusion® using the Open Access functionality., Methods: Custom-designed primers/probe sets targeting the SARS-CoV-2 Envelope gene (E) and subgenomic E were optimized. A 20-day performance validation following laboratory developed test requirements was conducted to assess assay precision, accuracy, analytical sensitivity/specificity, lower limit of detection and reportable range., Results: Quantitative SARS-CoV-2 sgRNA (LDT-Quant sgRNA) assay, which measures intermediates of replication, and viral load (LDT-Quant VLCoV) assay demonstrated acceptable performance. Both assays were linear with an R2 and slope equal to 0.99 and 1.00, respectively. Assay precision was evaluated between 4-6 Log10 with a maximum CV of 2.6% and 2.5% for LDT-Quant sgRNA and LDT-Quant VLCoV respectively. Using negative or positive SARS-CoV-2 human nasopharyngeal swab samples, both assays were accurate (kappa coefficient of 1.00 and 0.92). Common respiratory flora and other viral pathogens were not detected and did not interfere with the detection or quantification by either assay. Based on 95% detection, the assay LLODs were 729 and 1206 Copies/mL for the sgRNA and VL load LDTs, respectively., Conclusion: The LDT-Quant sgRNA and LDT-Quant VLCoV demonstrated good analytical performance. These assays could be further investigated as alternative monitoring assays for viral replication; and thus, medical management in clinical settings which could inform isolation/quarantine requirements., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The platelet-derived growth factor-BB (PDGF-BB) pathway provides critical regulation of cerebrovascular pericytes, orchestrating their investment and retention within the brain microcirculation. Dysregulated PDGF Receptor-beta (PDGFRβ) signaling can lead to pericyte defects that compromise blood-brain barrier (BBB) integrity and cerebral perfusion, impairing neuronal activity and viability, which fuels cognitive and memory deficits. Receptor tyrosine kinases such as PDGF-BB and vascular endothelial growth factor-A (VEGF-A) are often modulated by soluble isoforms of cognate receptors that establish signaling activity within a physiological range. Soluble PDGFRβ (sPDGFRβ) isoforms have been reported to form by enzymatic cleavage from cerebrovascular mural cells, and pericytes in particular, largely under pathological conditions. However, pre-mRNA alternative splicing has not been widely explored as a possible mechanism for generating sPDGFRβ variants, and specifically during tissue homeostasis. Here, we found sPDGFRβ protein in the murine brain and other tissues under normal, physiological conditions. Utilizing brain samples for follow-on analysis, we identified mRNA sequences corresponding to sPDGFRβ isoforms, which facilitated construction of predicted protein structures and related amino acid sequences. Human cell lines yielded comparable sequences and protein model predictions. Retention of ligand binding capacity was confirmed for sPDGFRβ by co-immunoprecipitation. Visualizing fluorescently labeled sPDGFRβ transcripts revealed a spatial distribution corresponding to murine brain pericytes alongside cerebrovascular endothelium. Soluble PDGFRβ protein was detected throughout the brain parenchyma in distinct regions, such as along the lateral ventricles, with signals also found more broadly adjacent to cerebral microvessels consistent with pericyte labeling. To better understand how sPDGFRβ variants might be regulated, we found elevated transcript and protein levels in the murine brain with age, and acute hypoxia increased sPDGFRβ variant transcripts in a cell-based model of intact vessels. Our findings indicate that soluble isoforms of PDGFRβ likely arise from pre-mRNA alternative splicing, in addition to enzymatic cleavage mechanisms, and these variants exist under normal physiological conditions. Follow-on studies will be needed to establish potential roles for sPDGFRβ in regulating PDGF-BB signaling to maintain pericyte quiescence, BBB integrity, and cerebral perfusion-critical processes underlying neuronal health and function, and in turn, memory and cognition.

The platelet-derived growth factor-BB (PDGF-BB) pathway provides critical regulation of cerebrovascular pericytes, orchestrating their investment and retention within the brain microcirculation. Dysregulated PDGF Receptor-beta (PDGFRβ) signaling can lead to pericyte defects that compromise blood-brain barrier (BBB) integrity and cerebral perfusion, impairing neuronal activity and viability, which fuels cognitive and memory deficits. Receptor tyrosine kinases (RTKs) like PDGF-BB and vascular endothelial growth factor-A (VEGF-A) are often modulated by soluble isoforms of cognate receptors that establish signaling activity within a physiological range. Soluble PDGFRβ (sPDGFRβ) isoforms have been reported to form by enzymatic cleavage from cerebrovascular mural cells, and pericytes in particular, largely under pathological conditions. However, pre-mRNA alternative splicing has not been widely explored as a possible mechanism for generating sPDGFRβ variants, and specifically during tissue homeostasis. Here, we found sPDGFRβ protein in the murine brain and other tissues under normal, physiological conditions. Utilizing brain samples for follow-on analysis, we identified mRNA sequences corresponding to sPDGFRβ isoforms, which facilitated construction of predicted protein structures and related amino acid sequences. Human cell lines yielded comparable sequences and protein model predictions. Retention of ligand binding capacity was confirmed for sPDGFRβ by co-immunoprecipitation. Visualizing fluorescently labeled sPDGFRβ transcripts revealed a spatial distribution corresponding to murine brain pericytes alongside cerebrovascular endothelium. Soluble PDGFRβ protein was detected throughout the brain parenchyma in distinct regions such as along the lateral ventricles, with signals also found more broadly adjacent to cerebral microvessels consistent with pericyte labeling. To better understand how sPDGFRβ variants might be regulated, we found elevated transcript and protein levels in the murine brain with age, and acute hypoxia increased sPDGFRβ variant transcripts in a cell-based model of intact vessels. Our findings indicate that soluble isoforms of PDGFRβ likely arise from pre-mRNA alternative splicing, in addition to enzymatic cleavage mechanisms, and these variants exist under normal physiological conditions. Follow-on studies will be needed to establish potential roles for sPDGFRβ in regulating PDGF-BB signaling to maintain pericyte quiescence, BBB integrity, and cerebral perfusion - critical processes underlying neuronal health and function, and in turn memory and cognition.

Humans with high-grade gliomas have a poor prognosis, with a mean survival time of just 12-18 months for patients who undergo standard-of-care tumor resection and adjuvant therapy. Currently, surgery and chemoradiotherapy serve as standard treatments for this condition, yet these can be complicated by the tumor location, growth rate and recurrence. Currently, gadolinium-based, contrast-enhanced magnetic resonance imaging (CE-MRI) serves as the predominant imaging modality for recurrent high-grade gliomas, but it faces several drawbacks, including its inability to distinguish tumor recurrence from treatment-related changes and its failure to reveal the entirety of tumor burden (de novo or recurrent) due to limitations inherent to gadolinium contrast. As such, alternative imaging modalities that can address these limitations, including positron emission tomography (PET), are worth pursuing. To this end, the identification of PET-based markers for use in imaging of recurrent high-grade gliomas is paramount. This review will highlight several PET radiotracers that have been implemented in clinical practice and provide a comparison between them to assess the efficacy of these tracers.

Antibiotic use and misuse continue to be a worldwide concern with the increasing rate of antimicrobial resistance, lack of new antibiotics in the pipeline, and rising health care costs. Despite studies that attempt to distinguish between factors associated with antibiotic use and misuse (e.g., knowledge and beliefs and provider-patient communication), few studies have tested comparative hypotheses related to antibiotic use behavior. This study 1) compares two theoretical models (health belief and patient-centered communication) to learn which best represents the pathways associated with antibiotic use; and 2) describes urban consumers' knowledge, beliefs, and behaviors regarding antibiotic use. Interviewers completed 505 intercept surveys across six clinic- and community-based sites in Southeast Michigan. Structural equation modeling was utilized to compare two competing theoretical models predicting antibiotic behavior. Findings support the assertion that a patient-provider communication model fits the data better than the null model. Descriptive statistical analysis explicated participant knowledge was mixed. While many participants knew correct general facts about antibiotics, 35% of the sample put forth that they believed that antibiotics cure colds and flu and over half (57%) endorsed the belief that antibiotics are good for treating infections caused by viruses. The implications for theory and practice are discussed including the need for clinicians to target communication strategies for the populations that they serve.

Background: Vascular pericytes stabilize blood vessels and contribute to their maturation, while playing other key roles in microvascular function. Nevertheless, relatively little is known about involvement of their precursors in the earliest stages of vascular development, specifically during vasculogenesis., Methods: We combined high-power, time-lapse imaging with transcriptional profiling of emerging pericytes and endothelial cells in reporter mouse and cell lines. We also analyzed conditional transgenic animals deficient in Cx43/Gja1 (connexin 43/gap junction alpha-1) expression within Ng2+ cells., Results: A subset of Ng2-DsRed+ cells, likely pericyte/mural cell precursors, arose alongside endothelial cell differentiation and organization and physically engaged vasculogenic endothelium in vivo and in vitro. We found no overlap between this population of differentiating pericyte/mural progenitors and other lineages including hemangiogenic and neuronal/glial cell types. We also observed cell-cell coupling and identified Cx43-based gap junctions contributing to pericyte-endothelial cell precursor communication during vascular assembly. Genetic loss of Cx43/Gja1 in Ng2+ pericyte progenitors compromised embryonic blood vessel formation in a subset of animals, while surviving mutants displayed little-to-no vessel abnormalities, suggesting a resilience to Cx43/Gja1 loss in Ng2+ cells or potential compensation by additional connexin isoforms., Conclusions: Together, our data suggest that a distinct pericyte lineage emerges alongside vasculogenesis and directly communicates with the nascent endothelium via Cx43 during early vessel formation. Cx43/Gja1 loss in pericyte/mural cell progenitors can induce embryonic vessel dysmorphogenesis, but alternate connexin isoforms may be able to compensate. These data provide insight that may reshape the current framework of vascular development and may also inform tissue revascularization/vascularization strategies.

Electronic dating violence is a form of violence perpetrated through electronics between dating partners and is associated with worse mental health, greater risk of substance use, and increased risk of in-person forms of dating violence. Though prevalent and seeming to increase in occurrence across adolescence, little is known about trajectories of electronic dating violence throughout adolescence and both risk and protective factors predicting a given trajectory. Latent growth models were used to evaluate change over time in three specific domains of electronic dating violence: harassment, coercion, and monitoring. Data are drawn from two cohorts who were surveyed annually for four years (2013-2017) from age 12 to 15 (n = 543; 48.3% female) and 15 to 18 (n = 597, 46.6% female), respectively. For all three domains of electronic dating violence, a quadratic model fit best. In general, electronic dating violence increased from early adolescence until a peak around age 16 or 17, and then leveled off. Threat-based adverse childhood experiences (i.e., exposure to physical child abuse, parental intimate partner violence, etc.) and earlier engagement in dating behaviors increased long-term risk for both age cohorts. Protective factors such as parental monitoring decreased risk but seemed to only have protective influence at developmentally-specific periods (i.e., during the developmental period of early adolescence). A better understanding of the risk and protective factors that affect the increase of electronic dating violence during adolescence is necessary to develop effective age-appropriate prevention and intervention strategies for youth., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Electronic forms of dating violence among youth are common yet little is known about how these forms of violence overlap with the commonly studied domains of physical, sexual and verbal teen dating violence. Using factor analysis and latent class analysis, this study identifies patterns of electronic, verbal, physical and sexual dating violence victimization and perpetration in 9th and 12th graders. Data are from 470 9th (n = 190; 60.5% female; mean age = 12.0 years, age range: 11.3-13.8) and 12th graders (n = 280; 63.9% female; mean age = 14.9 years, age range: 14.0-16.6) from southeastern Michigan. A 5-class solution for 9th graders and a 6-class solution for 12th graders were selected given fit and interpretability. Classes were characterized by domain(s) of violence, as opposed to perpetration or victimization. Three domains of electronic dating aggression were identified: monitoring, harassment, and coercion. Electronic dating aggression was present in the majority of classes, and overlapped substantially with other domains of violence. The highest risk class had risk of victimization and perpetration for all types of dating violence (electronic monitoring, electronic harassment, electronic coercion, verbal violence, physical violence and sexual violence). Drug use and experiencing one or more adverse childhood experiences predicted membership in a higher risk group for the older cohort, while alcohol consumption predicted higher risk for the younger cohort. The findings from this study show overlap between dating violence domains and imply that domains of electronic dating violence are important to consider in conjunction with physical, sexual and verbal domains, to address teen dating violence., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Sexting has emerged as a significant public health issue. Sexting is associated with substance use and other sexual behaviors, such as oral and vaginal sex (Houck et al., 2014; Temple & Choi, 2014). Current studies on sexting are often cross-sectional, limiting the ability to determine the temporal order of sexting and sexual behaviors. Additionally, studies focus on samples of young adults (Benotsch et al., 2013). The current study extends the literature by examining sexting and sexual behaviors longitudinally among adolescents and examines race and gender differences that play a role in sexting., Methods: The current study utilizes a prospective, 4-year longitudinal study of 1240 adolescents (aged 11-17) living in the Midwestern United States. Overall, the sample was 10% Black males, 11% Black females, 34% White Males, 31% White females, and 15% identified as Other. Analysis includes an autoregressive model with cross-lagged effects in MPlus., Results: Sexting (T1) predicted oral and sexual encounters (T4) for Black males, White males, and White females but not for Black females. Oral sex and sexual encounters (T4) did not predict any sexting (T1) for all groups. Therefore, analysis establishes sexting as an antecedent to sexual behaviors for Black males, White males, and White females. Sexting and sexual behaviors did not have a significant association for Black females., Conclusions: This study identifies sexting as a precursor to sexual behaviors among adolescents. Therefore, when tailoring programs for safe sex among these populations, focusing on sexting may reduce other sexual risky behaviors., (Copyright © 2021 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a SARS-CoV-2 spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the Alpha (B.1.1.7), and Beta (B.1.351) VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose vaccinations. Dose-dependent SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the B.1.1.7 and B.1.351 VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) immunogen dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose two vaccinations. SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.

Pericytes are critical for microvascular stability and maintenance, among other important physiological functions, yet their involvement in vessel formation processes remains poorly understood. To gain insight into pericyte behaviors during vascular remodeling, we developed two complementary tissue explant models utilizing 'double reporter' animals with fluorescently-labeled pericytes and endothelial cells (via Ng2:DsRed and Flk-1:eGFP genes, respectively). Time-lapse confocal imaging of active vessel remodeling within adult connective tissues and embryonic skin revealed a subset of pericytes detaching and migrating away from the vessel wall. Vessel-associated pericytes displayed rapid filopodial sampling near sprouting endothelial cells that emerged from parent vessels to form nascent branches. Pericytes near angiogenic sprouts were also more migratory, initiating persistent and directional movement along newly forming vessels. Pericyte cell divisions coincided more frequently with elongating endothelial sprouts, rather than sprout initiation sites, an observation confirmed with in vivo data from the developing mouse brain. Taken together, these data suggest that (i) pericyte detachment from the vessel wall may represent an important physiological process to enhance endothelial cell plasticity during vascular remodeling, and (ii) pericyte migration and proliferation are highly synchronized with endothelial cell behaviors during the coordinated expansion of a vascular network., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Purpose of Review: Pericytes are essential components of capillaries in many tissues and organs, contributing to vessel stability and integrity, with additional contributions to microvascular function still being discovered. We review current and foundational studies identifying pericyte differentiation mechanics and their roles in the earliest stages of vessel formation., Recent Findings: Recent advances in pericyte-focused tools and models have illuminated critical aspects of pericyte biology including their roles in vascular development.Pericytes likely collaborate with endothelial cells undergoing vasculogenesis, initiating direct interactions during sprouting and intussusceptive angiogenesis. Pericytes also provide important regulation of vascular growth including mechanisms underlying vessel pruning, rarefaction, and subsequent regrowth., Competing Interests: Conflict of Interest None of the authors have any conflicts of interest to disclose. This work was supported in part by funding from the National Institutes of Health (R01-HL146596 to J.C.C.), the National Science Foundation (CAREER Award 1752339 to J.C.C.), and the American Heart Association (19TPA34910121 to J.C.C. and 19POST34380560 to L.B.P.).

There is limited research on the short-term effects of ACEs on Black children and youth. Black children and youth are disproportionately exposed to abuse, neglect, and other victimizations (Drake et al. 2009; Wade et al. Journal of Family Issues, 17 (3), 283-316, 2014). Investigating ACEs will provide a broader understanding of childhood trauma on developmental processes. The current study investigates how ACES impacts psychological distress, substance use, and delinquency among Black children and youth. Hypotheses were tested using a subsample of longitudinal data from 265 participants who were recruited from six school districts in Southeast Michigan. ACEs at T1 significantly predicted depressive symptoms at T2 (β = .19, p  < .05), which in turn predicted substance use (β = .20, p  < .05), and delinquency (β = .19, p < .05). Psychological distress also mediated the associations between ACEs and substance use, and delinquency. To engage youth in prevention/interventions and practice, it is important to understand the contexts in which they develop i.e. having knowledge on the specific type of victimization instances that Black youth may experience more than their peers as well as the social factors. Therefore, taking a trauma-informed approach that will acknowledge the adverse childhood experiences that youth went through and to understand how these experiences shape their development through adolescence may be efficacious., Competing Interests: Conflict of InterestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© Springer Nature Switzerland AG 2020.)

In 2014, government officials in the City of Flint, Michigan switched the municipal water source from the Detroit Water System (water source: Lake Huron) to the Flint River. During this time, an estimated 102,000 Flint residents were potentially exposed to multiple chemical (e.g., lead) and biological threats (e.g., Legionella). After the switch to water sourced from the Flint River, Flint residents consistently reported concerns over water quality while also experiencing rashes, hair loss, and other health problems, including anxiety and depression. This study 1) reports on the Flint Water Crisis and its subsequent impact on residents' stress, coping, resilience and trust and 2) describes a process methodology that trained, hired and deployed Flint residents as members of a multidisciplinary research team. A random sample of 320 Flint residents underwent household-based interviews to assess their health and mental health needs. Concomitantly, household water samples were obtained and residents were connected to known resources based on interview responses relative to need. This study found that declines in health and mental health status were correlated with increased stressors (i.e., fatigue, financial concern, anxiety), coping and less resilience or the capacity to recover. Perceived trust in government officials was significantly lower after the water crisis. While the water crisis generated numerous stressors, the event also galvanized community competence to engage in solution-focused coping and other adaptive capacities. By assessing and building upon Flint residents' resilience, community resource specialists, identified and subsequently strengthened city residents' ability to survive devastating challenges.

Preterm delivery occurs at extraordinarily higher rates among Black women than among women of any other race or ethnicity. For those children who survive, many face a lifetime of health and developmental challenges as well as difficulties in school and life. Previous studies have provided substantive evidence that the preterm delivery disparity experienced by Black women is associated with ongoing distress caused by racism. Our study examines rates of preterm delivery for Black women in the USA to determine the level of risk associated with living in specific states. Using a logistic regression model, we examined the impact of the delivery state, controlling for known clinical, economic, and demographic risk factors. We found that 32 of the 35 states included in our analysis were associated with a statistically significantly increased risk of preterm delivery among Black women, as compared to the state with the lowest preterm delivery rate for Black women. These findings allowed us to organize states into a continuum of preterm delivery risk. Because of the harmful effects of preterm delivery and its disproportionate impact among Black women and infants, we recommend that a measure of preterm delivery be included in any state plan to assess, intervene in, and monitor racial disparities.

Vascular pericytes provide critical contributions to the formation and integrity of the blood vessel wall within the microcirculation. Pericytes maintain vascular stability and homeostasis by promoting endothelial cell junctions and depositing extracellular matrix (ECM) components within the vascular basement membrane, among other vital functions. As their importance in sustaining microvessel health within various tissues and organs continues to emerge, so does their role in a number of pathological conditions including cancer, diabetic retinopathy, and neurological disorders. Here, we review vascular pericyte contributions to the development and remodeling of the microcirculation, with a focus on the local microenvironment during these processes. We discuss observations of their earliest involvement in vascular development and essential cues for their recruitment to the remodeling endothelium. Pericyte involvement in the angiogenic sprouting context is also considered with specific attention to crosstalk with endothelial cells such as through signaling regulation and ECM deposition. We also address specific aspects of the collective cell migration and dynamic interactions between pericytes and endothelial cells during angiogenic sprouting. Lastly, we discuss pericyte contributions to mechanisms underlying the transition from active vessel remodeling to the maturation and quiescence phase of vascular development., (© 2019 John Wiley & Sons Ltd.)

Feedback mechanisms are critical components of many pro-angiogenic signaling pathways that keep vessel growth within a functional range. The Vascular Endothelial Growth Factor-A (VEGF-A) pathway utilizes the decoy VEGF-A receptor Flt-1 to provide negative feedback regulation of VEGF-A signaling. In this study, we investigated how the genetic loss of flt-1 differentially affects the branching complexity of vascular networks in tissues despite similar effects on endothelial sprouting. We selectively ablated flt-1 in the post-natal retina and found that maximum induction of flt-1 loss resulted in alterations in endothelial sprouting and filopodial extension, ultimately yielding hyper-branched networks in the absence of changes in retinal astrocyte architecture. The mosaic deletion of flt-1 revealed that sprouting endothelial cells flanked by flt-1 - / - regions of vasculature more extensively associated with underlying astrocytes and exhibited aberrant sprouting, independent of the tip cell genotype. Overall, our data support a model in which tissue patterning features, such as retinal astrocytes, integrate with flt-1 -regulated angiogenic molecular and cellular mechanisms to yield optimal vessel patterning for a given tissue.

Pericyte investment into new blood vessels is essential for vascular development such that mis-regulation within this phase of vessel formation can contribute to numerous pathologies including arteriovenous and cerebrovascular malformations. It is critical therefore to illuminate how angiogenic signaling pathways intersect to regulate pericyte migration and investment. Here, we disrupted vascular endothelial growth factor-A (VEGF-A) signaling in ex vivo and in vitro models of sprouting angiogenesis, and found pericyte coverage to be compromised during VEGF-A perturbations. Pericytes had little to no expression of VEGF receptors, suggesting VEGF-A signaling defects affect endothelial cells directly but pericytes indirectly. Live imaging of ex vivo angiogenesis in mouse embryonic skin revealed limited pericyte migration during exposure to exogenous VEGF-A. During VEGF-A gain-of-function conditions, pericytes and endothelial cells displayed abnormal transcriptional changes within the platelet-derived growth factor-B (PDGF-B) and Notch pathways. To further test potential crosstalk between these pathways in pericytes, we stimulated embryonic pericytes with Notch ligands Delta-like 4 (Dll4) and Jagged-1 (Jag1) and found induction of Notch pathway activity but no changes in PDGF Receptor-β (Pdgfrβ) expression. In contrast, PDGFRβ protein levels decreased with mis-regulated VEGF-A activity, observed in the effects on full-length PDGFRβ and a truncated PDGFRβ isoform generated by proteolytic cleavage or potentially by mRNA splicing. Overall, these observations support a model in which, during the initial stages of vascular development, pericyte distribution and coverage are indirectly affected by endothelial cell VEGF-A signaling and the downstream regulation of PDGF-B-PDGFRβ dynamics, without substantial involvement of pericyte Notch signaling during these early stages.

Background: Malpractice liability is an ongoing problem in obstetrics. However, developing, sustaining, and spreading effective interventions is challenging. The aim of this study is to examine the spread and sustainability of a multilevel integrated practice and coordinated communication model 66 months after its original implementation., Methods: Data on labor and delivery patients from 37 hospitals (5 beta sites and 32 expansion sites) were analyzed for the 81-month time period from January 2010 through September 2016., Results: High-risk occurrence rates per 1000 live births decreased by over 70% at both beta and expansion sites. The likelihood of a high-risk occurrence was statistically significantly lower during the final study period than in the preintervention period at both beta sites (odds ratio [OR] = 0.218; p < .0001) and expansion sites (OR = 0.288; p < .001)., Conclusion: The multilevel integrated practice and coordinated communication model was successfully spread and sustained. Key elements contributing to this success included developing and maintaining evidence-based guidelines, ensuring leadership buy-in and support, collecting and reporting performance measures, holding teams accountable, providing training, and ensuring transparent communication., (© 2018 American Society for Health Care Risk Management of the American Hospital Association.)

Secure attachment relationships have been linked to social competence in at-risk children. In the current study, we examined the role of parent secure base scripts in predicting at-risk kindergarteners' social competence. Parent representations of secure attachment were hypothesized to mediate the relationship between lower family cumulative risk and children's social competence. Participants included 106 kindergarteners and their primary caregivers recruited from three urban charter schools serving low-income families as a part of a longitudinal study. Lower levels of cumulative risk predicted greater secure attachment representations in parents, and scores on the secure base script assessment predicted children's social competence. An indirect relationship between lower cumulative risk and kindergarteners' social competence via parent secure base script scores was also supported. Parent script-based representations of the attachment relationship appear to be an important link between lower levels of cumulative risk and low-income kindergarteners' social competence. Implications of these findings for future interventions are discussed.

Objective: Pericytes are specialized perivascular cells embedded within the basement membrane. These cells envelope the abluminal surface of endothelial cells and promote microvessel homeostasis. Recent discoveries of unique pericyte functions, particularly in neural tissues, underscore the need for overcoming existing challenges in establishing a functionally validated pericyte cell line. Here, we present methodologies for addressing these challenges as well as an embryonic pericyte cell line for use with in vitro and ex vivo experimental models., Methods: We isolated an enriched population of NG2:DsRed+ pericytes from E12.5 mice. This pericyte cell line was compared to MEFs with respect to gene expression, cell morphology and migration, and engagement with endothelial cells during junction stabilization and angiogenesis., Results: NG2+ pericytes displayed gene expression patterns, cell morphology, and 2D migration behaviors distinct from MEFs. In three different vessel formation models, pericytes from this line migrated to and incorporated into developing vessels. When co-cultured with HUVECs, these pericytes stimulated more robust VE-Cadherin junctions between HUVECs as compared to MEFs, as well as contributed to HUVEC organization into primitive vascular structures., Conclusions: Our data support use of this pericyte cell line in a broad range of models to further understand pericyte functionality during normal and pathological conditions., (© 2018 John Wiley & Sons Ltd.)

Von Hippel-Lindau (VHL) gene mutations induce neural tissue hemangioblastomas, as well as highly vascularized clear cell renal cell carcinomas (ccRCCs). Pathological vessel remodeling arises from misregulation of HIFs and VEGF, among other genes. Variation in disease penetrance has long been recognized in relation to genotype. We show Vhl mutations also disrupt Notch signaling, causing mutation-specific vascular abnormalities, e.g., type 1 (null) vs. type 2B (murine G518A representing human R167Q). In conditional mutation retina vasculature, Vhl-null mutation (i.e., UBCCreER/+Vhlfl/fl) had little effect on initial vessel branching, but it severely reduced arterial and venous branching at later stages. Interestingly, this mutation accelerated arterial maturation, as observed in retina vessel morphology and aberrant α-smooth muscle actin localization, particularly in vascular pericytes. RNA sequencing analysis identified gene expression changes within several key pathways, including Notch and smooth muscle cell contractility. Notch inhibition failed to reverse later-stage branching defects but rescued the accelerated arterialization. Retinal vessels harboring the type 2B Vhl mutation (i.e., UBCCreER/+Vhlfl/2B) displayed stage-specific changes in vessel branching and an advanced progression toward an arterial phenotype. Disrupting Notch signaling in type 2B mutants increased both artery and vein branching and restored arterial maturation toward nonmutant levels. By revealing differential effects of the null and type 2B Vhl mutations on vessel branching and maturation, these data may provide insight into the variability of VHL-associated vascular changes - particularly the heterogeneity and aggressiveness in ccRCC vessel growth - and also suggest Notch pathway targets for treating VHL syndrome.

Objective: To re-examine the risk factors for shoulder dystocia given the increasing rates of obesity and diabetes in pregnant women., Design: Retrospective observational study., Setting: Five hospitals located in Wisconsin, Florida, Maryland, Michigan, and Alabama., Participants: We evaluated 19,236 births that occurred between April 1, 2011, and July 25, 2013., Methods: Data were collected from electronic medical records and used to evaluate the risk of shoulder dystocia. Data were analyzed using a generalized linear mixed model, which controlled for clustering due to site., Results: When insulin was prescribed, gestational diabetes was associated with an increased risk of shoulder dystocia (odds ratio = 2.10, 95% confidence interval [1.01, 4.37]); however, no similar association was found with regard to gestational diabetes treated with glycemic agents or through diet. Use of epidural anesthesia was associated with an increased risk for shoulder dystocia (odds ratio = 3.47, 95% confidence interval [2.72, 4.42]). Being Black or Hispanic, being covered by Medicaid or having no insurance, infant gestational age of 41 weeks or greater, and chronic diabetes were other significant risk factors., Conclusion: With the changing characteristics of pregnant women, labor and birth clinicians care for more pregnant women who have an increased risk for shoulder dystocia. Our findings may help prospectively identify women with the greatest risk., (Copyright © 2018 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Psychopathic traits are a manifestation of a personality pathology that comprises a core affective-interpersonal dysfunction (callous-unemotional traits) and an impulsive-antisocial behavioral component. Of particular importance, psychopathic traits are associated with the perpetration of some of the most severe acts of violence, and they appear to indicate a subset of youth at risk for earlier onset, greater frequency, and persistence of violent offending. Although these youth represent a minority of the population, they commit a significant proportion of the violence in the general community. In our review, we highlight evidence of a unique neurobiological predisposition that underlies the core affective deficits and describe contemporary accounts for the developmental processes leading to the antisocial behavior associated with psychopathy. Current evidence suggests that, for this subset of youth, the structure and function of neural circuitry supporting emotion processing, reward learning, decision making, and the development of emotion related to empathy may be crucial to understanding why they are at risk for violence. In particular, a reward dominant pattern of neurobehavioral conditioning may explain how these youth progress to some of the most severe and persistent forms of violence. However, this pattern of conditioning may also be essential to the primary prevention of such deleterious behavior. We suspect that effective strategies to prevent such violence may ultimately be informed by understanding these affective and motivational mechanisms.

Maternal depressive symptoms predict negative child behaviors, including internalizing problems. However, protective factors, such as positive emotionality and positive parenting behaviors, may play an important a role in attenuating associations between maternal depressive symptoms and child behavior problems. This manuscript presents two studies that examined buffers of links between maternal depressive symptoms and child internalizing problems. Each study examined samples of primarily African American families with young children in an impoverished large city in the Midwestern United States. Families were recruited from kindergarten classes and Women, Infants, and Children (WIC) centers. In both studies, indicators of mothers' positivity, as measured by text based analysis of positive emotion word use or behavioral observation of positive parenting behaviors, attenuated links between maternal depressive symptoms and child internalizing problems. The results suggest that risk for internalizing problems within the context of maternal depressive symptoms is reduced when parents experience and express more positive emotions and behaviors.

Aim: The aim was to study the development, design, and implementation of a patient consent and enrollment initiative to identify strategies that enhanced participation., Background: Consent and enrollment of patients, especially pregnant women, remains a challenge in healthcare research. Although many barriers have been identified, strategies to consistently improve consent and enrollment are less defined., Methods: A case study was conducted on a consent and enrollment approach aimed at optimizing participation of mothers who delivered their infants from July 1, 2010 through June 30, 2013. Data were gathered through practitioner interviews, focus groups, and documentation review for each year of the study., Results: A total of 19,236 mothers enrolled, representing an 85% enrollment rate at the five study sites. Enrollment rates improved over time with increased nursing engagement in patient recruitment, site specific adaptations and patient education strategies., Conclusions: Nursing's active role in implementation and rapid feedback loop of a multifaceted consent and enrollment program showed promise., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Incarcerated youth experience high rates of violence exposure (VE), cognitive processing (CP) deficits, and mental health (MH) problems. It is not clear whether VE combined with CP deficits are particularly salient risk factors for MH dysfunction. Male incarcerated youth offenders ( n = 115) completed standardized self-reports of MH and VE. CP was measured with executive functioning tasks and academic assessments. Person-centered Ward's Squared Euclidian Distance cluster analysis was used to examine unique patterns of CP and VE. Cluster analysis defined five distinct profiles of MH functioning, CP, and VE rates within incarcerated adolescents. Two groups, with high rates of VE and CP deficits, showed high rates of MH problems. Linear techniques may obscure important differences within this population.

Objectives: To evaluate an external quality assurance (EQA) program for the laboratory diagnosis of human papillomavirus (HPV) disease that was established to improve international research capability within the Division of AIDS at the National Institute of Allergy and Infectious Disease-supported Adult AIDS Clinical Trials Group network., Methods: A three-component EQA scheme was devised comprising assessments of diagnostic accuracy of cytotechnologists and pathologists using available EQA panels, review of quality and accuracy of clinical slides from local sites by an outside expert, and HPV DNA detection using a commercially available HPV test kit., Results: Seven laboratories and 17 pathologists in Africa, India, and South America participated. EQA scores were suboptimal for EQA proficiency testing panels in three of seven laboratories. There was good agreement between the local laboratory and the central reader 70% of the time (90% confidence interval, 42%-98%). Performance on the College of American Pathologists' HPV DNA testing panel was successful in all laboratories tested., Conclusions: The prequalifying EQA round identified correctable issues that will improve the laboratory diagnosis of HPV-related cervical disease at the participating international study sites and will provide a mechanism for ongoing education and continuous quality improvement.

Background: How to recruit minority participants into research studies has been an issue since 1993, when NIH funding guidelines required minorities to be included as research participants., Objective: The purpose of this analysis was to determine what factors affected recruitment of asthmatic minorities into a large bronchoconstrictor study involving African-Americans, Hispanics/Mexican Americans, Asian/Pacific Islanders, and whites with mild asthma (forced expiratory volume in the first second of expiration > or = 70%)., Methods: Ethnic minorities were recruited for 3 years. Recruitment strategies included physician and clinic referrals, newspaper ads, posters in health care settings, asthma databases, and electronic resources., Findings: After 3 years, the total number of referrals was 650, with 50 from medical doctor clinic settings and 600 from all of the other resources. The inclusion/exclusion criteria were clearly listed, but only 64.5% (419/650) of respondents met inclusion criteria. Of these, only 31.9% (134/419) [corrected] met pulmonary function testing criteria. Only 5, or 1% of the 50 medical doctor clinic referrals met inclusion criteria--1 participated. A total of 106, or 82.8%, completed all of the study procedures; for 87.7% of participants this was their first research experience. Hispanics/Mexican Americans accounted for only 14.8% of the total recruitment responses., Conclusion: We believe our recruitment strategies did encourage ethnic minorities to participate, but the inclusion criteria of a positive methacholine response proved to be a study enrollment barrier.

Objective: There is little asthma research that compares ethnic differences in airway responsiveness and word descriptors among African Americans, Hispanic-Mexican Americans, Asian-Pacific Islanders, and Whites. Thus, identifying ethnic differences in symptom descriptors and airway responsiveness may improve health outcomes by educating health professionals about treatment decisions that are culturally and ethnically sensitive., Methods: Specific Inclusion criteria-forced expiratory volume in one second (FEV(1)) >or= 70% predicted normal; provocative concentration causing a 30% fall in FEV(1) (PC(30))

Our objectives were to evaluate: 1) the efficacy of the Sperm Mobility Test on commercial turkey farms, and 2) the influence of sperm mobility phenotype on fertility when insemination parameters are varied. In research flocks, differences in sperm mobility among toms are predictive of fertility. We wanted to test the efficacy of this sire selection test in practical, real-world situations, evaluating its usefulness in terms of assessing large numbers of toms, different strains of turkeys, and variable management practices. Utilizing field study results, controlled studies were then conducted to improve test parameters. For the field trials, semen from each of 405 breeder toms (11 strains or lines) was evaluated either in duplicate (n = 285) or in triplicate (n = 120). Sperm mobility was normally distributed among all toms tested, except for one strain. Because the sperm mobility indices for toms evaluated in these field trials were higher than those observed in research flocks, the Sperm Mobility Test was modified to increase the separation between high and low sperm mobility phenotypes by increasing the concentration of Accudenz. To determine the effects of sperm mobility and insemination dose on sustained fertility through time, hens from a research flock were inseminated twice before the onset of lay with sperm from toms classified as high-, average-, or low-mobility in concentrations of 25 to 400 million sperm per artificial insemination dose, and egg fertility was evaluated over a 5-wk period. Toms with the high-mobility sperm phenotype maintained higher fertility (P < 0.05) over the 5-wk period at all insemination doses compared with toms with low-mobility sperm. Toms with high-mobility sperm sired equal numbers of poults in a sperm competition study in which numbers favored low-mobility toms by 3:1. These results demonstrate that the Sperm Mobility Test can be used for on-farm evaluation of semen quality of toms in commercial flocks and that sperm mobility influences fertility and sire fitness.

Background: Clinical trials testing candidate human immunodeficiency virus type 1 (HIV-1) vaccines have required the use of HIV neutralization assays to detect responses to specific geographic subtypes of HIV-1. The variability in results seen with current p24 neutralization assay endpoints prompted us to assess the utility of flow cytometry for monitoring the neutralization of HIV-1 primary isolates., Methods: A modified neutralization assay was performed using CD8-depleted peripheral blood mononuclear cells (PBMC). The cells were fixed, permeabilized, stained with a directly conjugated HIV-1 p24 monoclonal antibody, and analyzed by flow cytometry. HIV-1 subtype B' and E primary isolates were tested using pooled sera or plasma from subtype B' or E infected patients., Results: Primary isolate cultures (without neutralizing antibody) showed from 18% to 42% p24(+) cells, depending on the virus. Less than 0.2% p24(+) cells were detected in uninfected cultures. Subtype-specific neutralization of viruses was observed using plasma or serum pools; neutralization ranged from 0% to 99% reduction of infected cells., Conclusions: Flow cytometric detection of intracellular HIV-1 p24 can be used as an endpoint assay to assess neutralization of HIV-1 subtypes B' and E primary isolates. This enumerative method has the advantage of identifying intracellular p24 in specific subsets at an early culture timepoint. It also provides an alternative quantitative endpoint for HIV neutralization assays., (Copyright 2000 Wiley-Liss, Inc.)

Infection is very common in thalassemia and is one of the major causes of death. To date, it is not quite clear why these patients are susceptible to infection. In this study, lymphocyte immunophenotyping for CD3(+) (T-cells), CD3(+)CD4(+) (T-helper/inducer cells), CD3(+)CD8(+) (T-suppressor/cytotoxic cells), CD3(-)CD19(+) (B-cells), and CD3(-)CD16/56(+) (natural killer cells) subsets and expression of the activation antigen CD69 on CD3(+)CD4(+) and CD3(+)CD8(+) T-cells were determined in the whole blood of thalassemia patients, using a three-color flow cytometric technique. Results showed that only splenectomized beta-thalassemia/hemoglobin (Hb) E patients displayed a marked increase in absolute number of all lymphocytes. In addition, splenectomized beta-thalassemia/Hb E showed a significantly lower percentage of CD3(+) cells, with a corresponding increase in CD19(+) cells. These differences, when compared with normal subjects and other thalassemia patients, may be attributed to splenectomy. alpha-thalassemia patients, on the other hand, showed no significant difference from the normal group. While lymphocyte subsets in splenectomized beta-thalassemia/Hb E patients showed an abnormal distribution, T-cell activation in these patients was not different from the activation seen in normal subjects. This implies that thalassemia patients, during the steady state of disease, appear to have normal T-lymphocyte function with only moderate abnormalities of T- and B-lymphocyte subsets., (Copyright 2000 Wiley-Liss, Inc.)

We evaluated a flow cytometric (FCM) two-color immunophenotyping of CD3+/CD4+ T-helper and CD3+/CD8+ T-suppressor lymphocytes in whole blood samples from HIV-infected individuals using monoclonal antibody reagents from three different manufacturers. Lymphocytes were firstly determined using CD45/CD14 in association with a forward scatter/side scatter gating strategy. CD3+/CD4+ and CD3+/CD8+ were then determined and compared. Reagents from all manufacturers showed good separation of lymphocytes, monocytes and granulocytes with high purity and recovery. There was a good correlation of the percentage of CD3+/CD4+ and CD3+/CD8+ lymphocytes amongst each of the manufacturer's reagents, but the fluorescent intensities of positive cells were not the same. This difference can result in poor discrimination of positive and negative non CD3 cells leading to erroneous results.

"The objectives of this paper are to determine the relationship between racial residential segregation and (1) the spatial concentration of low- and high-income households, and (2) the socioeconomic characteristics of racial minority households. The three largest racial minority groups are compared (blacks, Hispanics, and Asians) in the largest 45 metropolitan areas in the United States. Data were obtained from the U.S. bureau of the Census' Population and Housing Summary Tape files. The results revealed that residential segregation of blacks was distinctly different from Asians and Hispanics. Moreover, for Asians and Hispanics, their socioeconomic characteristics matter in their level of residential segregation. For black households, however, their socioeconomic characteristics matter little.", (excerpt)

The aims of this study were to determine the radiosensitivities of murine thymic and splenic CD4+ and CD8+ lymphocytes and to evaluate the regeneration of these cells in a model of radiation-induced hematopoietic and immune suppression. CD4+ and CD8+ cells were quantitated using two-color flow-cytometric analysis. Cells obtained from C3H/HeN mice 24 hours after exposure to 0.25-8.0 Gy (0.4 Gy/min) 60Co were used to determine D0 values. Thymic CD4+ cells contained a radiosensitive subpopulation with a D0 of 0.97 +/- 0.05 Gy and a radioresistant subpopulation that survived exposures up to 8.0 Gy. CD8+ cells also contained a radiosensitive subpopulation with a D0 of 1.24 +/- 0.05 Gy and a radioresistant subpopulation with a D0 of 3.93 +/- 2.01 Gy. Double-positive thymic CD4+/CD8+ cells were uniformly radiosensitive, with a D0 of 1.03 +/- 0.28 Gy. Multiple T lymphocyte subpopulations based on radiosensitivity and CD4/CD8 antigen expression were also observed in the spleen. When mice were exposed to a sublethal 6.5-Gy radiation dose and recovery of T lymphocyte subsets was monitored, the relative radioresistance of CD4+ cells resulted in a selective enrichment of these cells among the surviving thymocytes and splenic lymphocytes. This relative enrichment of CD4+ cells became even more prominent 7 days after irradiation, when atrophy of the organs was greatest. Similar, although less dramatic, effects were observed for CD8+ cells. These studies demonstrate that (1) multiple T lymphocyte subpopulations can be identified based on radiosensitivity and CD4/CD8 antigen expression; (2) both CD4+ and CD8+ cells contain radioresistant subpopulations, with the CD4+ subpopulation being more resistant than the CD8+ subpopulation; and (3) although the number of radioresistant CD4+ cells is quite small, they persist in increased proportions during the periods preceding and corresponding to postirradiation hematopoietic recovery.

Many causative factors have been cited for our present national nursing shortage. Some of these are: the "baby bust" of the late sixties and seventies, the women's movement, inadequate salaries, and shift work. Yes, an untapped pool of potential applicants exists--men. This article asks why nursing is "where the boys aren't."

An unusual case of tuberous sclerosis is presented in which splenomegaly and abdominal pain predominated. The clinical manifestations of the disease are discussed, and the generalized hamartonmatous nature of the diseases is emphasized.

A study was conducted to investigate water and feed intake patterns, abdominal fat and carcass lipid levels, feed efficiency and growth in high (H) and low (L) body weight lines of Japanese quail divergently selected under complete diet (CD) or split diet (SD) environments. Birds under the SD environment could self-select from high-protein low-energy or low-protein high-energy diets. Progeny from both the selected and control (C) lines were evaluated under the SD environment in Generations 6 and 10, and under the CD environment in Generation 10. Under the SD environment, body weights of the H lines were similar as were body weights of the L lines; however, under the CD environment, there were significant differences between H lines and between L lines. Body weights were higher under the CD than under the SD environment. Differences between H and L lines in body weights and 1-wk relative growth rates within SD and CD environments were attributed to differences in water and feed consumption and feed efficiency. Water consumption was greater in the SD than CD environments. Feed consumption was greater in the SD than CD environment from 0 to 2 wk of age; thereafter, feed consumption was higher in the CD environment. Abdominal fat and carcass lipid levels were greater in H than L lines, with the magnitude of the difference greater in the SD environment, indicating that the SD may be a better environment than the CD environment for the study of abdominal fat and carcass lipids in Japanese quail.

Studies were conducted to investigate the influence of dietary salt on water consumption and subsequent carcass lipids in Japanese quail at various ages. In Experiment 1, randombred nongrowth-selected (C) quail were fed 28% protein diets containing .0, .4, .8, 1.6, and 3.2% added salt. In Experiment 2, growth-selected P- and C-line quail were fed 20%-protein diets containing .4% and 3.2% added salt. The different dietary salt levels did not exert a consistent effect on body weight in Experiment 1. There was no adverse effect of salt level on feed consumption and efficiency and no direct effect on abdominal fat or carcass lipid levels. High salt (1.6 and 3.2%) stimulated water consumption and increased water:feed ratios. Water:feed ratios were higher for quail than for broilers, suggesting a species difference. In Experiment 2, C-line quail demonstrated similar effects to the high-salt (3.2%) diet in Experiment 1. High salt (3.2%) adversely affected body weight, feed consumption, abdominal fat, and carcass lipid in P-line quail. There was no affect on feed efficiency, and a substantial stimulation of water consumption with concomitantly increased water:feed ratios. The relatively low abdominal fat observed at 4 weeks of age indicate that nongrowth-selected quail may not be a good model for the study of abdominal fat in broilers.

Japanese quail were divergently selected for 4-wk body weight under two different nutritional environments. In one environment quail were divergently selected for high and low body weight (H and L) under a split diet (SD) with quail having the opportunity to self-select feed from high protein and high energy diets. In the other environment, quail were similarly selected (H and L) under a normal (28% protein) complete diet (CD). After 11 generations of selection, H-SD and H-CD lines were 48.9 and 49.7% higher in 4-wk body weight than controls. Quail from L-SD and L-CD lines were 46.5 and 45.4% lower in 4-wk body weight than controls. Realized heritabilities for 4-wk body weight were .36 +/- .03, .30 +/- .03, .52 +/- .02, and .47 +/- .03 for H-SD, L-SD, H-CD, and L-CD lines, respectively. Selection differentials were significantly higher in the SD than in the CD environment. Changes in 2-wk, adult body, and egg weight across generations paralleled that of the trait under selection (4-wk body weight). Selection also resulted in decreased hatchability and egg production with increased age to sexual maturity in both environments. The SD environment was determined to be a stress environment because of birds' inferior growth there compared with growth in the CD environment. Rate of growth, however, to reach adult body size was superior for L-SD quail once the stress environment was removed. There was also evidence that eggs were larger for quail in the SD than the CD environment.