Peromyscus leucopus , Mus musculus , and humans have distinct transcriptomic responses to larval Ixodes scapularis bites.

Ixodes scapularis ticks are an important vector for at least six tick-borne human pathogens, including the predominant North American Lyme disease spirochete Borrelia burgdorferi . The ability for these ticks to survive in nature is credited, in part, to their ability to feed on a variety of hosts without excessive activation of the proinflammatory branch of the vertebrate immune system. While the ability for nymphal ticks to feed on a variety of hosts has been well-documented, the host-parasite interactions between larval I. scapularis and different vertebrate hosts is relatively unexplored. Here we report on the changes in the vertebrate transcriptome present at the larval tick bite site using the natural I. scapularis host Peromyscus leucopus deermouse, a non-natural rodent host Mus musculus (BALB/c), and humans. We note substantially less evidence of activation of canonical proinflammatory pathways in P. leucopus compared to BALB/c mice and pronounced evidence of inflammation in humans. Pathway enrichment analyses revealed a particularly strong signature of interferon gamma, tumor necrosis factor, and interleukin 1 signaling at the BALB/c and human tick bite site. We also note that bite sites on BALB/c mice and humans, but not deermice, show activation of wound-healing pathways. These data provide molecular evidence of the coevolution between larval I. scapularis and P. leucopus as well as expand our overall understanding of I. scapularis feeding. Significance: Ixodes scapularis tick bites expose humans to numerous diseases in North America. While larval tick feeding enables pathogens to enter the tick population and eventually spread to humans, how larval ticks interact with mammals has been understudied compared to other tick stages. Here we examined the transcriptomic response of a natural I. scapularis rodent host ( Peromyscus leucopus ), a non-native I. scapularis rodent host ( Mus musculus ), and an incidental host (humans). We find that there are differences in how all three species respond to larval I. scapularis , with the natural host producing the smallest transcriptomic signature of a canonical proinflammatory immune response and the incidental human host producing the most robust signature of inflammation in response to the larval tick. These data expand our understanding of the pressures on ticks in the wild and inform our ability to model these interactions in laboratory settings.

Creation of a Psychotic Disorders Research Advisory Board as a Shared Resource.

Community engagement is important for research, yet many researchers do not routinely seek feedback from people with lived experience. A key barrier to this engagement is that the resources required to create an advisory board may be unavailable to individual investigators, and creating an advisory board for a single study may often be impractical. In this column, the authors describe how to create a standing research advisory board that can serve as a shared resource for researchers and community members and provide a psychosis research advisory board example to aid discussion.

Readiness for treatment predicts depression outcomes in a partial hospital program.

Evidence-based interventions vary in effectiveness for individuals with depression, which has a large public health burden. Readiness for change or treatment can be an important individual difference predictor of depression outcomes. To inform public service initiatives targeting readiness for treatment, characterizing readiness across settings and levels of care is key. However, limited data exist on the role of readiness for treatment in acute psychiatric settings and in particular, partial hospital programs which are key points in the continuity of inpatient and outpatient care. The present study assessed readiness for treatment in terms of importance, confidence, and motivation to engage in a partial hospital program and tested whether higher levels of readiness were associated with better treatment outcomes among clients with depression. Participants (N = 192) with major depressive disorder rated their readiness for treatment (Readiness Rulers), depression (Patient Health Questionnaire-9), and global improvement (Clinical Global Impression Scale-Improvement Self-Report) while enrolled in a partial hospital program. Generalized linear regression models assessed the effect of baseline readiness on outcomes at discharge, adjusted for baseline level of the outcome, age, sex, race, and ethnicity. Greater baseline readiness predicted reduced depression and better global improvement at discharge. Higher confidence and motivation to engage in treatment, but not importance, were associated with better depression outcomes. Identifying and addressing readiness for treatment by leveraging public health systems and services (e.g., help lines, family interventions) prior to or upon starting a partial hospital program may be useful to maximize gains in treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cytology Techniques Can Provide Insight into Human Placental Structure Including Syncytiotrophoblast Nuclear Spatial Organisation.

The aim of this study was to provide the first systematic description of human placental cytology appearances and to investigate syncytiotrophoblast nuclear organisation patterns using cytology techniques. Term placentas from normal pregnancies were sampled using fine-needle aspiration (FNA) and direct scrapes. Standard histological examination was also performed to exclude pathological changes in the placentas being studied. Both Papanicolaou-stained cytospin preparations and air-dried Giemsa slides from FNA provided high-quality material for cytological assessment with good cellularity. Among the key features of the cytology preparations were villous "microbiopsies" that allowed for the three-dimensional appreciation of villous branching patterns. Cytological appearances, including nuclear characteristics of villous cytotrophoblast and syncytiotrophoblast, were also well demonstrated. In microbiopsies and detached villous trophoblast sheets, complex patterns of syncytiotrophoblast nuclear organisation, not previously described cytologically, were observed, including irregular spacing of nuclei, syncytioplasm windows and linear nuclear arrangements. This study showed that placental cytology (a) provides technically excellent material for cytological evaluation, (b) confirms the presence of complex nuclear organisational patterns in the syncytiotrophoblast by eliminating the possibility of tangential sectioning artefact, (c) provides superior nuclear detail over standard histological sections and (d) may be an untapped research resource for the investigation of normal and pathological processes because of its ability to look at the placenta in a novel way and through its potential for both ex vivo and in vivo placental sampling.

Borrelia burgdorferi initiates early transcriptional re-programming in macrophages that supports long-term suppression of inflammation.

Borrelia burgdorferi (Bb), the causative agent of Lyme disease, establishes a long-term infection and leads to disease manifestations that are the result of host immune responses to the pathogen. Inflammatory manifestations resolve spontaneously despite continued bacterial presence, suggesting inflammatory cells become less responsive over time. This is mimicked by in vitro repeated stimulations, resulting in tolerance, a phenotypic subset of innate immune memory. We performed comparative transcriptional analysis of macrophages in acute and memory states and identified sets of Tolerized, Hyper-Induced, Secondary-Induced and Hyper-Suppressed genes resulting from memory induction, revealing previously unexplored networks of genes affected by cellular re-programming. Tolerized gene families included inflammatory mediators and interferon related genes as would be predicted by the attenuation of inflammation over time. To better understand how cells mediate inflammatory hypo-responsiveness, we focused on genes that could mediate maintenance of suppression, such as Hyper-Induced genes which are up-regulated in memory states. These genes were notably enriched in stress pathways regulated by anti-inflammatory modulators. We examined one of the most highly expressed negative regulators of immune pathways during primary stimulation, Aconitate decarboxylase 1 (Acod1), and tested its effects during in vivo infection with Bb. As predicted by our in vitro model, we show its inflammation-suppressive downstream effects are sustained during in vivo long-term infection with Bb, with a specific role in Lyme carditis.

Single-cell RNA sequencing of murine ankle joints over time reveals distinct transcriptional changes following Borrelia burgdorferi infection.

Lyme disease is caused by the bacterial pathogen Borrelia burgdorferi, which can be readily modeled in laboratory mice. In order to understand the cellular and transcriptional changes that occur during B. burgdorferi infection, we conducted single-cell RNA sequencing (scRNA-seq) of ankle joints of infected C57BL/6 mice over time. We found that macrophages/monocytes, T cells, synoviocytes and fibroblasts all showed significant differences in gene expression of both inflammatory and non-inflammatory genes that peaked early and returned to baseline before the typical resolution of arthritis. Predictions of cellular interactions showed that macrophages appear to communicate extensively between different clusters of macrophages as well as with fibroblasts and synoviocytes. Our data give unique insights into the interactions between B. burgdorferi and the murine immune system over time and allow for a better understanding of mechanisms by which the dysregulation of the immune response may lead to prolonged symptoms in some patients.

A putative xanthine dehydrogenase is critical for Borrelia burgdorferi survival in ticks and mice.

Borrelia burgdorferi is a pathogenic bacterium and the causative agent of Lyme disease. It is exposed to reactive oxygen species (ROS) in both the vertebrate and tick hosts. While some mechanisms by which B. burgdorferi ameliorates the effects of ROS exposure have been studied, there are likely other unknown mechanisms of ROS neutralization that contribute to virulence. Here, we follow up on a three gene cluster of unknown function, bb_0554, bb_0555, and bb_0556, that our prior unbiased transposon insertional sequencing studies implicated in both ROS survival and survival in Ixodes scapularis. We confirmed these findings through genetic knockout and provide evidence that these genes are co-transcribed as an operon to produce a xanthine dehydrogenase. In agreement with these results, we found that B. burgdorferi exposure to either uric acid (a product of xanthine dehydrogenase) or allopurinol (an inhibitor of xanthine dehydrogenase) could modulate sensitivity to ROS in a bb_0554-bb_0556 dependent manner. Together, this study identifies a previously uncharacterized three gene operon in B. burgdorferi as encoding a putative xanthine dehydrogenase critical for virulence. We propose renaming this locus xdhACB.

Child Maltreatment Reporting Practices by a Person Most Knowledgeable for Children and Youth: A Rapid Scoping Review.

Child maltreatment is a global public health and child rights crisis made worse by the ongoing COVID-19 pandemic. While understanding the breadth of the child maltreatment crisis is foundational to informing prevention and response efforts, determining accurate estimates of child maltreatment remains challenging. Alternative informants (parents, caregivers, a Person Most Knowledgeable-PMK) are often tasked with reporting on children's maltreatment experiences in surveys to mitigate concerns associated with reporting child maltreatment. The overall purpose of this study was to examine child maltreatment reporting practices in surveys by PMKs for children and youth. The research question is: "What is the nature of the evidence of child maltreatment reporting practices in general population surveys by PMKs for children and youth?" A rapid scoping review was conducted to achieve the study's purpose. A search strategy was conducted in nine databases (e.g., MEDLINE, EBSCO, Scopus, Global Health, ProQuest). The findings from this review indicate that most studies involved PMK informants (i.e., maternal caregivers), included representative samples from primarily Western contexts, and utilized validated measures to assess child maltreatment. Half of the studies assessed involved multi-informant reports, including the PMKs and child/youth. Overall, the congruence between PMK-reported and child/youth-reported child maltreatment experiences was low-to-fair/moderate, and children/youth reported more maltreatment than the PMKs.

The PD-1/PD-L1 pathway is induced during Borrelia burgdorferi infection and inhibits T cell joint infiltration without compromising bacterial clearance.

The Lyme disease bacterial pathogen, Borrelia burgdorferi, establishes a long-term infection inside its mammalian hosts. Despite the continued presence of the bacteria in animal models of disease, inflammation is transitory and resolves spontaneously. T cells with limited effector functions and the inability to become activated by antigen, termed exhausted T cells, are present in many long-term infections. These exhausted T cells mediate a balance between pathogen clearance and preventing tissue damage resulting from excess inflammation. Exhausted T cells express a variety of immunoinhibitory molecules, including the molecule PD-1. Following B. burgdorferi infection, we found that PD-1 and its ligand PD-L1 are significantly upregulated on CD4+ T cells and antigen presenting cell subsets, respectively. Using mice deficient in PD-1, we found that the PD-1/PD-L1 pathway did not impact bacterial clearance but did impact T cell expansion and accumulation in the ankle joint and popliteal lymph nodes without affecting B cell populations or antibody production, suggesting that the PD-1/PD-L1 pathway may play a role in shaping the T cell populations present in affected tissues.

Pilot development and feasibility of telehealth Community Reinforcement and Family Training (CRAFT) for early psychosis and substance use.

Substance use is associated with poor outcomes for individuals with early psychosis. Community Reinforcement and Family Training (CRAFT) is an evidence-based approach that helps families to reduce substance use, engage in treatment, and improve family wellbeing, but it has not yet been studied for psychosis and substance use. The present study aimed to develop and evaluate a telehealth intervention utilizing CRAFT for families experiencing early psychosis and substance use. Twenty family members completed six to eight telehealth sessions of CRAFT adapted for early psychosis (CRAFT-EP). Participants completed an assessment battery at baseline, mid- and post-intervention, a three-month follow-up, surveys after each session, and a focus group to measure mean percentage of sessions completed, mean program satisfaction ratings, telehealth preference, and qualitative feedback. Participants had 100% session completion, and program satisfaction was at or near excellent for 99% of sessions. Half of participants preferred a primarily virtual hybrid program, whereas 45% preferred exclusively virtual visits. Communication was the most helpful topic, and participants requested additional written examples and resources. CRAFT-EP is feasible and acceptable to serve as the active intervention in a pilot randomized controlled trial comparing treatment as usual plus CRAFT-EP to treatment as usual.

A selective antibiotic for Lyme disease.

Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining its selectivity. Hygromycin A cleared the B. burgdorferi infection in mice, including animals that ingested the compound in a bait, and was less disruptive to the fecal microbiome than clinically relevant antibiotics. This selective antibiotic holds the promise of providing a better therapeutic for Lyme disease and eradicating it in the environment.

Distressed and distracted by COVID-19 during high-stakes virtual interviews: The role of job interview anxiety on performance and reactions.

Employers have increasingly turned to virtual interviews to facilitate online, socially distanced selection processes in the face of the COVID-19 pandemic. However, there is little understanding about the experience of job candidates in these virtual interview contexts. We draw from Event System Theory (Morgeson et al., 2015) to advance and test a conceptual model that focuses on a high-stress, high-stakes setting and integrates literatures on workplace stress with literatures on applicant reactions. We predict that when applicants ruminate about COVID-19 during an interview and have higher levels of COVID-19 exhaustion, they will have higher levels of anxiety during virtual interviews, which in turn relates to reduced interview performance, lower perceptions of fairness, and reduced intentions to recommend the organization. Further, we predict that three factors capturing COVID-19 as an enduring and impactful event (COVID-19 duration, COVID-19 cases, COVID-19 deaths) will be positively related to COVID-19 exhaustion. We tested our propositions with 8,343 job applicants across 373 companies and 93 countries/regions. Consistent with predictions, we found a positive relationship between COVID-19 rumination and interview anxiety, and this relationship was stronger for applicants who experienced higher (vs. lower) levels of COVID-19 exhaustion. In turn, interview anxiety was negatively related to interview performance, fairness perceptions, and recommendation intentions. Moreover, using a relevant subset of the data (n = 6,136), we found that COVID-19 duration and deaths were positively related to COVID-19 exhaustion. This research offers several insights for understanding the virtual interview experience embedded in the pandemic and advances the literature on applicant reactions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Working through an "infodemic": The impact of COVID-19 news consumption on employee uncertainty and work behaviors.

Uncertainty is a defining feature of the COVID-19 pandemic. However, because uncertainty is an aversive state, uncertainty reduction theory (URT) holds that employees try to manage it by obtaining information. To date, most evidence for the effectiveness of obtaining information to reduce uncertainty stems from research conducted in relatively stable contexts wherein employees can acquire consistent information. Yet, research on crises and news consumption provides reasons to believe that the potential for information to mitigate uncertainty as specified by URT may break down during crises such as the COVID-19 pandemic. Integrating URT with research on crises and news consumption, we predict that consuming news information during crises-which tends to be distressing, constantly evolving, and inconsistent-will be positively related to uncertainty. This in turn may have negative implications for employee goal progress and creativity; two work outcomes that take on substantial significance in times of uncertainty and the pandemic. We further predict that death anxiety will moderate this relationship, such that the link between employees' news consumption and uncertainty is stronger for those with lower levels of death anxiety, compared to those with higher levels. We test our theorizing via an experience-sampling study with 180 full-time employees, with results providing support for our conceptual model. Our study reveals important theoretical and practical implications regarding information consumption during crises such as the COVID-19 pandemic. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Genetic Background Amplifies the Effect of Immunodeficiency in Antibiotic Efficacy Against Borrelia burgdorferi.

Unrecognized immunodeficiency has been proposed as a possible cause of failure of antibiotics to resolve symptoms of Lyme disease. Here, we examined the efficacy of doxycycline in different immunodeficient mice to identify defects that impair antibiotic treatment outcomes. We found that doxycycline had significantly lower efficacy in the absence of adaptive immunity, specifically B cells. This effect was most pronounced in immunodeficient C3H mice compared with C57BL/6 mice, suggesting a role for genetic background beyond immunodeficiency. Addition of a single dose of ceftriaxone to doxycycline treatment effectively cleared infection in C3H mice with severe combined immunodeficiency.

Interactions between Borrelia burgdorferi and its hosts across the enzootic cycle.

The bacterial pathogen Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to humans through an Ixodes tick vector. B. burgdorferi is able to survive in both mammalian and tick hosts through careful modulation of its gene expression. This allows B. burgdorferi to adapt to the environmental and nutritional changes that occur when it is transmitted between the two hosts. Distinct interactions between the spirochete and its host occur at every step of the enzootic cycle and dictate the ability of the spirochete to survive until the next stage of the cycle. Studying the interface between B. burgdorferi, the Ixodes tick vector and the natural mammalian reservoirs has been made significantly more feasible through the complete genome sequences of the organisms and the advent of high throughput screening technologies. Ultimately, a thorough investigation of the interplay between the two domains (and two phyla within one domain) is necessary in order to completely understand how the pathogen is transmitted.

A work-family enrichment intervention: Transferring resources across life domains.

This study expands the work-family enrichment literature by integrating enrichment theory (Greenhaus & Powell, 2006), social-cognitive theory (Bandura, 2001), capitalization theory (e.g., Gable, Reis, Impett, & Asher, 2004), and creative cognition theory (e.g., Smith, Ward, & Finke, 1995), in order to advance a novel conceptual model of the effects of resource transfer training on enrichment and job satisfaction. The model was tested by developing and evaluating a work-to-family enrichment training program, the Resource Transfer Training, which was based on Greenhaus and Powell's (2006) enrichment theory and interpersonal capitalization theory (Ilies, Keeney, & Scott, 2011). The training was administered to 163 administrative employees using a longitudinal prepost experimental design. Consistent with hypotheses, findings indicated that, compared to a control training condition, the Resource Transfer Training increased development-based enrichment from work to family (the transfer of skills, knowledge and values). Furthermore, the effect of the training on both development-based and affect-based enrichment (the transfer of positive affect) was mediated by enrichment self-efficacy, and the indirect effects of the training on enrichment were moderated by initial social-emotional work resources. Finally, as hypothesized, enrichment self-efficacy and enrichment experiences sequentially mediated the effect of the training on job satisfaction. This work advances theory by demonstrating that human agency can facilitate enrichment experiences across roles, and by exploring new antecedents of enrichment through theoretically driven training components. It advances practice by devising and testing a work-to-family enrichment intervention that can serve as a tool for organizations to increase positive synergy between work and nonwork roles. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Working in a pandemic: Exploring the impact of COVID-19 health anxiety on work, family, and health outcomes.

The COVID-19 pandemic has unhinged the lives of employees across the globe, yet there is little understanding of how COVID-19 health anxiety (CovH anxiety)-that is, feelings of fear and apprehension about having or contracting COVID-19-impacts critical work, home, and health outcomes. In the current study, we integrate transactional stress theory (Lazarus & Folkman, 1984) with self-determination theory (Deci & Ryan, 2000) to advance and test a model predicting that CovH anxiety prompts individuals to suppress emotions, which has detrimental implications for their psychological need fulfillment. In turn, lack of psychological need fulfillment hinders employees' abilities to work effectively, engage with their family, and experience heightened well-being. Our model further predicts that handwashing frequency-a form of problem-focused coping-will mitigate the effects of CovH anxiety. We test our propositions using a longitudinal design that followed 503 employees across the first four weeks that stay-at-home and social distancing orders were enacted. Consistent with predictions, CovH anxiety was found to impair critical work (goal progress), home (family engagement) and health (somatic complaints) outcomes due to increased emotion suppression and lack of psychological need fulfillment. Further, individuals who frequently engage in handwashing behavior were buffered from the negative impact of CovH anxiety. Combined, our work integrates and extends existing theory and has a number of important practical implications. Our research represents a first step to understanding the work-, home-, and health-related implications of this unprecedented situation, highlighting the detrimental impact of the anxiety stemming from the COVID-19 pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).