Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help ...to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.
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•Integrative analysis of orthogonal data on response to vaccination•Strong association between plasma metabolomics and PBMC transcriptomics•Sterol metabolism integrates cellular and humoral responses•Metabolic phenotype, such as inositol phosphate metabolism, influences immune outcome
An integrated metabolic response underlies the immune response to shingles vaccine in humans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although millions of distinct virus species likely exist, only approximately 9000 are catalogued in GenBank's RefSeq database. We selectively enriched for the genomes of circular DNA viruses in over ...70 animal samples, ranging from nematodes to human tissue specimens. A bioinformatics pipeline, Cenote-Taker, was developed to automatically annotate over 2500 complete genomes in a GenBank-compliant format. The new genomes belong to dozens of established and emerging viral families. Some appear to be the result of previously undescribed recombination events between ssDNA and ssRNA viruses. In addition, hundreds of circular DNA elements that do not encode any discernable similarities to previously characterized sequences were identified. To characterize these 'dark matter' sequences, we used an artificial neural network to identify candidate viral capsid proteins, several of which formed virus-like particles when expressed in culture. These data further the understanding of viral sequence diversity and allow for high throughput documentation of the virosphere.
There have been numerous studies in humans and rodents substantiating the role of the gastrointestinal microbiome in the pathogenesis and progression of both type 1 and type 2 diabetes mellitus. ...Diabetes mellitus is a common endocrinopathy in dogs; however, little is known about the composition of the gut microbiome during the development and treatment of diabetes in this species. The objective of this pilot study was to characterize the gastrointestinal microbiome of dogs with diabetes mellitus at the time of diagnosis and over the first 12 weeks of insulin therapy and identify associations with glycemic control. Rectal swabs and serum for fructosamine measurement were collected from 6 newly diagnosed diabetic dogs at 2-week intervals for 12 weeks. Rectal samples were sequenced using 16S, ITS, and archaeal primers. Measures of alpha and beta diversity were assessed for changes over time; associations between absolute sequence variant (ASV) relative abundances and time and fructosamine concentration were identified using a microbiome-specific, multivariate linear effects model. No statistically significant changes over time were noted in alpha diversity and samples significantly grouped by dog rather than by time in the beta diversity analysis. However, multiple ASVs were negatively (Clostridium sensu stricto 1, Romboutsia, Collinsella) and positively (Streptococcus, Bacteroides, Ruminococcus gauveauii, Peptoclostridium) associated with time and two ASVs were positively associated with fructosamine (Enterococcus, Escherichia-Shigella). These changes in gastrointestinal microbial composition warrant further investigation of how they may relate to diabetes mellitus progression or control in dogs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Purpose
The purpose of this study was to quantify the prevalence of impostor phenomenon (IP) and to assess well-being in pharmacy residents, as well as analyze the effects of demographics on ...these outcomes.
Methods
A cross-sectional, survey-based study was performed. Pharmacy residency program directors and pharmacy directors were asked to forward an invitation email to actively enrolled postgraduate year 1 (PGY1) and postgraduate year 2 pharmacy residents in March 2019. The survey used the Clance Impostor Phenomenon Scale (CIPS) to identify IP and the Mayo Clinic Resident/Fellow Well-Being Index (RWBI) to assess resident well-being.
Results
Survey respondents were mostly female, enrolled in PGY1 programs and single with no children. Of the 720 responses included in the study, 57.5% (n = 414) were identified as “impostors” (CIPS score of ≥62), with a mean CIPS score of 64.0 (SD, 15.0). Prior mental health treatment and increased hours worked per week were significant predictors of IP. The greatest correlation was found in those working greater than 80 hours per week compared to less than 60 hours per week (ß = 9.845; P < 0.001). The mean RWBI score was 4.2 (SD, 1.8), with 47.8% (n = 344) of residents scoring ≥5, the cutoff for identifying those at greatest risk of distress. Age, previous mental health treatment, and increasing hours worked per week were significant predictors of RWBI ≥5. CIPS and RWBI scores were found to exhibit weak but significant correlation (ρ = 0.357; P < 0.001).
Conclusion
Pharmacy residents displayed significantly higher prevalence of IP vs comparable groups as well as significantly more distress with potential for a personal and/or professional consequence.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
•Sympathetic and parasympathetic arousal may jointly predict aggression.•Sympathetically-mediated overarousal predicted reactive relational aggression.•Parasympathetic augmentation predicted ...aggression at low sympathetic reactivity.•Effects only emerged in the context of a standardized social stressor.
This study investigated the joint effects of parasympathetic and sympathetic nervous system reactivity to social and non-social stressors on proactive (i.e., goal-directed, unemotional) and reactive (i.e., emotional, impulsive) functions of relational aggression. Two hundred and forty-seven (Mage=18.77years) participants completed a series of stressor tasks while their sympathetic arousal (i.e., skin conductance) and parasympathetic arousal (i.e., respiratory sinus arrhythmia) were assessed. Participants also provided self-reports of their aggressive behavior. In the standardized social stressor only, physiological reactivity was related to aggression, such that respiratory sinus arrhythmia augmentation predicted proactive relational aggression whereas heightened skin conductance reactivity predicted reactive relational aggression. Finally, in the context of low skin conductance reactivity, respiratory sinus arrhythmia augmentation was related to heightened proactive and reactive aggression, whereas respiratory sinus arrhythmia withdrawal was protective. Results suggest that the benefits hypothesized to accompany respiratory sinus arrhythmia withdrawal may only occur among individuals with low “fight or flight” stress responses. Findings extend research on the physiological indicators of aggression to relational aggression, and highlight the importance of assessing functions of aggression, as well as physiological reactivity to multiple stressors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
is a gram-negative, intracellular pathogen which can cause serious, potentially fatal, illness in humans. Species of
are found across the Northern Hemisphere and can infect a broad range of host ...species, including humans. Factors affecting the persistence of
in the environment and its epidemiology are not well understood, however, the ability of
to enter a viable but non-culturable state (VBNC) may be important. A broad range of bacteria, including many pathogens, have been observed to enter the VBNC state in response to stressful environmental conditions, such as nutrient limitation, osmotic or oxidative stress or low temperature. To investigate the transition into the VBNC state for
, we analyzed the attenuated live vaccine strain,
LVS grown under standard laboratory conditions. We found that
LVS rapidly and spontaneously enters a VBNC state in broth culture at 37°C and that this transition coincides with morphological differentiation of the cells. The VBNC bacteria retained an ability to interact with both murine macrophages and human erythrocytes in
assays and were insensitive to treatment with gentamicin. Finally, we present the first transcriptomic analysis of VBNC
, which revealed clear differences in gene expression, and we identify sets of differentially regulated genes which are specific to the VBNC state. Identification of these VBNC specific genes will pave the way for future research aimed at dissecting the molecular mechanisms driving entry into the VBNC state.
•LNP formulated mRNA encoding VZV gE antigen is highly immunogenic in NHP.•mRNA and protein vaccines showed comparable response magnitude and longevity in NHP.•NHP immunogenicity for protein and LAV ...vaccines mirrors human clincal data.
Shingles is a painful, blistering rash caused by reactivation of latent varicella-zoster virus (VZV) and most frequently occurs in elderly and immunocompromised individuals. Currently, two approved vaccines for the prevention of shingles are on the market, a live attenuated virus vaccine ZOSTAVAX® (Merck & Co., Inc., Kenilworth, NJ, USA) and an AS01B adjuvanted subunit protein vaccine Shingrix™ (Glaxo Smith Kline, Rockville, MD, USA). Human clinical immunogenicity and vaccine efficacy data is available for these two benchmark vaccines, offering a unique opportunity for comparative analyses with novel vaccine platforms and animal model translatability studies.
The studies presented here utilized non-human primates (NHP) to evaluate humoral and cellular immune response by three vaccine modalities: the new platform of lipid nanoparticle (LNP) formulated mRNA encoding VZV gE antigen (VZV gE mRNA/LNP) as compared with well-established platforms of live attenuated VZV (VZV LAV) and adjuvanted VZV gE subunit protein (VZV gE protein/adjuvant). The magnitude of response to vaccination with a single 100–200 μg mRNA dose or two 50 μg mRNA doses of VZV gE mRNA/LNP were comparable to two 50 μg protein doses of VZV gE protein/adjuvant, suggesting the VZV gE mRNA/LNP platform has the potential to elicit a robust immune response, and both modalities generated markedly higher responses than VZV LAV. Additionally, the slopes of decay for VZV-specific antibody titers were roughly similar across all three vaccines, indicating the magnitude of peak immunogenicity was the driving force in determining immune response longevity. Finally, vaccine-induced immunogenicity with VZV LAV and VZV gE protein/adjuvant in NHP closely resembled human clinical trials immune response data for ZOSTAVAX® and Shingrix™, helping to validate NHP as an appropriate preclinical model for evaluating these vaccines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Zostavax is a safe vaccine to prevent shingles/postherpetic neuralgia.•Zostavax is a weak stimulator of innate immune responses.•Zostavax changes several metabolomic pathways which are correlated ...with immune outcome.•Zostavax elicits polyfunctional VZV-specific CD4+ T cells and low CD8+ T cell responses.•Zostavax boosts antibody responses which are strongly influenced by pre-existing antibody levels.
Zostavax is a live-attenuated varicella zoster virus (VZV) vaccine recommended for use in adults >50 years of age to prevent shingles. The main risk factor for the development of shingles is age, which correlates with decreasing cell-mediated immunity. These data suggest a predominant role of T cell immunity in controlling VZV latency. However, other components of the immune system may also contribute. In this review, we will discuss how the immune system responds to Zostavax, focusing on recent studies examining innate immunity, transcriptomics, metabolomics, cellular, and humoral immunity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Addressing women’s intimate partner violence (IPV) perpetration is essential not only to their partners’ safety but also to their own as, for women who are victims of IPV, their IPV perpetration may ...be a risk factor for their own revictimization. Although many studies have examined risk factors for women’s IPV perpetration, results diverge with regard to whether demographic and mental health variables are reliable predictors. Results of several studies have demonstrated that when IPV victimization is examined concurrently with perpetration, demographic and mental health variables are no longer significant correlates. However, this research has been limited in that the type of IPV examined has been restricted to physical, psychological, and sexual abuse. In addition, some demographic variables (e.g., sexual orientation) have yet to be adequately examined. The current study extends this literature by concurrently assessing demographic, mental health, and IPV victimization variables as correlates of IPV perpetration among undergraduate women. Furthermore, the current study examined a wide range of IPV types (i.e., threats of physical abuse, physical abuse, sexual abuse, psychological maltreatment, stalking, cyberstalking). Among a final sample of 398 undergraduate women at a Midwestern public university, results demonstrated that while all variables (i.e., demographic, mental health, IPV victimization) were correlated with at least one type of IPV perpetration, only IPV victimization remained a unique significant correlate of perpetration for each of the six IPV perpetration types when variables were analyzed concurrently in hierarchical regression models. Demographic and mental health variables were nonsignificant correlates for most IPV perpetration types. These results corroborate previous studies and provide additional evidence that targeting women’s own victimization, safety planning, and de-escalation may be useful at decreasing violence against women’s partners as well as women’s own risk for revictimization.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK, VSZLJ
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