Search

Interleukin‐31 (IL‐31) is a Th2 cell–derived cytokine that has been closely linked to pruritic skin inflammation. More recently, enhanced IL‐31 serum levels have also been observed in patients with allergic rhinitis and allergic asthma. Therefore, the main aim of this study was to unravel the contribution of IL‐31 to allergen‐induced lung inflammation. We analyzed lung inflammation in response to the timothy grass (Phleum pratense) pollen allergen Phl p 5 in C57BL/6 wild‐type (wt) mice, IL‐31 transgenic (IL‐31tg) mice, and IL‐31 receptor alpha‐deficient animals (IL‐31RA−/−). IL‐31 and IL‐31RA levels were monitored by qRT‐PCR. Cellular infiltrate in bronchoalveolar lavage fluid (BALF) and lung tissue inflammation, mucus production as well as epithelial thickness were measured by flow cytometry and histomorphology. While allergen challenge induced IL‐31RA expression in lung tissue of wt and IL‐31tg mice, high IL‐31 expression was exclusively observed in lung tissue of IL‐31tg mice. Upon Phl p 5 challenge, IL‐31tg mice showed reduced numbers of leukocytes and eosinophils in BALF and lung tissue as well as diminished mucin expression and less pronounced epithelial thickening compared to IL‐31RA−/− or wt animals. These findings suggest that the IL‐31/IL‐31RA axis may regulate local, allergen‐induced inflammation in the lungs., This study describes a role for IL‐31 signaling in the context of allergen‐induced lung inflammation. Mice overexpressing IL‐31 develop less severe lung inflammation upon allergen exposure, characterized by decreased leukocyte infiltration, mucus production and epithelial thickening. Thus, our data indicate that IL‐31 signaling regulates allergen‐induced lung inflammation.

OBJECTIVE To evaluate IM injection of oxytetracycline as an experimental model to induce pain and assess the analgesic efficacy of flunixin meglumine (FM) in dairy cows. ANIMALS 15 healthy nonlactating Jersey (n = 10) and Holstein (5) cows. PROCEDURES In the first of 2 experiments, 5 Jerseys were administered oxytetracycline (10 mg/kg, IM), divided between the right side of the neck and left hind limb. The left side of the neck and right hind limb received sham injections. Cows were also randomly assigned to receive FM (2.2 mg/kg, IV; n = 3) or an equal volume of saline (0.9% NaCl) solution (0.044 mL/kg, IV; control; 2) once daily for 5 days. The mechanical nociceptive threshold (MNT) was measured before oxytetracycline administration and at predetermined times after each injection of the assigned treatment. Experiment 2 was similar to experiment 1 except it involved 5 Jerseys and 5 Holsteins, oxytetracycline was injected only in a hind limb, and the assigned treatment was administered for 10 days. RESULTS For both experiments, mean MNT for the oxytetracycline injection site was consistently less than that for the sham injection site in the hind limbs, and mean MNT at the hind limb oxytetracycline injection site for FM-treated cows was greater than that for control cows beginning on day 3. CONCLUSIONS AND CLINICAL RELEVANCE IM injection of oxytetracycline in a hind limb reliably induced signs of pain in dairy cows and, with validation, might be useful as an experimental model for assessing pain mitigation strategies in cattle.

Purpose Retailers are continuously seeking to improve upon the in-store shopping experience for their customers. The present research aims to examine consumers’ responses to one such initiative – the shopper solution – that, despite its growing marketplace prominence, remains largely unexamined in academic literature. Design/methodology/approach Two studies employed a 2(shopper solution: present vs. absent) between-subjects design. MANOVA and regression analyses were used to test hypothesized relationships. Findings Findings across two studies reveal that the presence (vs absence) of solutions positively influenced shoppers’ perceptions of shopping convenience, as well as their purchase intentions. These favorable effects also extended to the provider in higher word-of-mouth and loyalty intentions. Shopping convenience was identified as the mechanism underlying the impact of solutions, while “smart shopper” self-perceptions were shown to moderate these mediating effects. Practical implications Shopper solutions represent a low-cost, in-store marketing tactic that enhances shopping convenience. They are easy to implement, result in little to no overhead costs and can benefit both shoppers and retailers. Originality/value To the best of the authors’ knowledge, this research represents the first academic examination of the impact of shopper solutions. The authors identify key mediating and moderating influences of the effects of solutions.

Are your workdays created equal? Common wisdom suggests that employees experience Mondays differently from Fridays. However, few studies distinguish among workdays, inherently assuming that the employee experience is uniform across the workweek. In the current study, we examined the trajectories of employees’ experiences of job satisfaction and job stressors across the workweek. We proposed two competing theoretical perspectives that result in opposite predictions as to whether job dissatisfaction and perceived job stressors will be higher (“Monday blues”) or lower (“rested and recharged”) at the beginning of the workweek rather than later in the week. Employing a daily diary design with 139 employees (681 matched daily observations) working the traditional workweek, we found that employees reported experiencing lower levels of job satisfaction and perceived more job stressors (i.e., incivility and organizational constraints) at the beginning of the workweek as opposed to later in the week. Additionally, the relationship between perceived incivility and job satisfaction was stronger at the beginning of the workweek. Our findings were consistent with the “Monday blues” perspective and suggest that workdays are not created equal.

Two Gram-stain-negative, strictly aerobic, marine bacteria, designated as strains RKSG066T and RKSG123T, were isolated from a sponge Aplysina fistularis collected at a depth of 15 m off the west coast of San Salvador, The Bahamas. Investigation of nearly full-length 16S rRNA gene and whole genome-based phylogenies revealed that both strains belong to the order Cytophagales within the class Cytophagia and phylum Bacteroidetes . Strain RKSG066T formed a monophyletic clade with described members of the genus Fulvivirga , while strain RKSG123T formed a well-supported paraphyletic branch apart from this and other related genera within the family Flammeovirgaceae . For both RKSG066T and RKSG123T, optimal growth parameters were 30–37 °C, pH 7–8 and 2–3 % (w/v) NaCl; cells were catalase- and oxidase-positive, and flexirubin-type pigments were absent. The predominant fatty acids were iso-C15 : 0, C16 : 0, C18 : 0, iso-C17 : 0 3-OH, C16 : 1 ω5c, iso-C15 : 0 3-OH, C18 : 1 ω9c and iso-C15 : 1 G for RKSG066T, and iso-C17 : 0 3-OH, C16 : 1 ω5c, iso-C15 : 0, C16 : 0 3-OH and summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B) for RKSG123T. Menaquinone-7 was the major respiratory quinone for both strains. The DNA G+C contents of RKSG066T and RKSG123T were 39.5 and 36.7 mol%, respectively. On the basis of phylogenetic distinctiveness and polyphasic analysis, the type strain RKSG066T (=TSD-73T=LMG 29870T) is proposed to represent a novel species of the genus Fulvivirga , for which the name Fulvivirga aurantia sp. nov. is proposed. The type strain RKSG123T (=TSD-75T=LMG 30075T) is proposed to represent the type species of a novel genus and species with the proposed name Xanthovirga aplysinae gen. nov., sp. nov. Additionally, the genus Fulvivirga is emended to include strains of orange-pigmented colonies that contain the predominant cellular fatty acids C16 : 0, C18 : 0, C16 : 1 ω5c and C18 : 1 ω9c.

Most existing safety research focuses on climate and leadership, with most leadership studies investigating transformational leadership, which is likely to be more impactful when exhibited by execu...

To summarize quality of life (QoL) and its determinants, including disease severity, in individuals with developmental and epileptic encephalopathies (DEEs) through a tailored questionnaire.A questionnaire containing 89 items addressing demographic characteristics, genetic diagnosis, clinical features, and QoL was distributed to primary caregivers of individuals with DEEs through patient advocacy organizations. Composite scores were generated from the mean values of QoL items, grouped into domain scores.Out of 176 received responses, the most common genetic diagnoses reported were SCN2A (n=42/173, 24%), SLC6A1 (n=28/173, 16%), SCN1A (n=22/173, 13%), and KCNQ2 (n=21/173, 12%). Composite QoL scores centered around a mean score of 61.67 of 100 (SD 17.10). QoL scores were strongly associated with the number of days minimally disrupted by seizures, medication side effects, genetic diagnosis, and community type. The mean QoL scores for individuals with DEEs was significantly lower than for individuals with Rett syndrome, cerebral palsy, autism spectrum disorder, and Down syndrome.QoL in DEEs can be assessed through a standardized instrument. QoL only partially overlaps with objective measurements of disease severity and may represent an independent outcome measure in precision medicine trials.

Supplemental Material for The Forgotten Working Class: A Call to Action Based upon a Repeated Cross-Sectional Examination of the Relationships Among Social Class, Financial Satisfaction, and Exhaustion by Stacey R. Kessler and Melissa Gutworth in Group & Organization Management

Additional file 3: Supplementary Figure 2. Experimental design of acazicolcept (ALPN-101) treatment in Fra-2 Tg mice model. Twelve-week-old female Fra-2 transgenic mice were divided into two groups treated with: Fc control (n=8) and acazicolcept (n=11). Fc control or acazicolcept were injected intraperitoneally twice a week for six weeks. After six weeks of treatment, mice were euthanized, and lungs and spleen were collected for analysis.

Additional file 2: Supplementary Figure 1. Experimental design of acazicolcept (ALPN-101) treatment in HOCL-induced dermal fibrosis mice. 6-week-old BALB/C female mice were divided into three groups treated with : PBS (n=6), HOCL + Fc control (n=8), or HOCL + acazicolcept (n=8). Dermal fibrosis was induced by subcutaneous HOCL injections five days per week from day 1 to day 42. Test articles (Fc control or acazicolcept) were injected intraperitoneally twice a week. Mice were euthanized 42 days after the first HOCL injection and dorsal skin was collected.

Additional file 1: Supplementary Table 1. Clinical characteristics of the SSc cohort. ICOS serum levels were analysed on a cohort of 161 patients affected by SSc.

Additional file 4: Supplementary Figure 3. Gating strategy of T cell sub-populations and activation markers in Fra-2 Tg spleen. Spleen CD3+ T cells were selected in live-gated populations. From total live CD3+ T cells, CD4+ and CD8+ populations were selected. PD-1 (1) and CD69 (2) expression were analysed in CD4+ and CD8+ populations. Among CD4+ or CD8+ T cells, TCM (CD62L+ CD44+, in blue), TEM (CD44+ CD62L-, in purple) and na��ve T (CD62L+ CD44-, in green) were selected (3).

Additional file 5: Supplementary Figure 4. Gating strategy of ICOS, CD28, and anti-human IgG Fc within CD4+ and CD8+ T cell subsets from Fra-2 Tg spleen. Spleen CD3+ T cells were selected in live-gated populations. From total live CD3+ T cells, CD4+ and CD8+ populations were selected. ICOS (1), anti-human IgG Fc (2) and CD28 (3) staining was analysed in CD4+ and CD8+ populations.

Among mammals, the order Primates is exceptional in having a high taxonomic richness in which the taxa are arboreal, semiterrestrial, or terrestrial. Although habitual terrestriality is pervasive among the apes and African and Asian monkeys (catarrhines), it is largely absent among monkeys of the Americas (platyrrhines), as well as galagos, lemurs, and lorises (strepsirrhines), which are mostly arboreal. Numerous ecological drivers and species-specific factors are suggested to set the conditions for an evolutionary shift from arboreality to terrestriality, and current environmental conditions may provide analogous scenarios to those transitional periods. Therefore, we investigated predominantly arboreal, diurnal primate genera from the Americas and Madagascar that lack fully terrestrial taxa, to determine whether ecological drivers (habitat canopy cover, predation risk, maximum temperature, precipitation, primate species richness, human population density, and distance to roads) or species-specific traits (body mass, group size, and degree of frugivory) associate with increased terrestriality. We collated 150,961 observation hours across 2,227 months from 47 species at 20 sites in Madagascar and 48 sites in the Americas. Multiple factors were associated with ground use in these otherwise arboreal species, including increased temperature, a decrease in canopy cover, a dietary shift away from frugivory, and larger group size. These factors mostly explain intraspecific differences in terrestriality. As humanity modifies habitats and causes climate change, our results suggest that species already inhabiting hot, sparsely canopied sites, and exhibiting more generalized diets, are more likely to shift toward greater ground use.

Equine Infectious Anemia Virus (EIAV) is an important infection in equids, and its similarity to HIV creates hope for a potential vaccine. We analyze a within-host model of EIAV infection with antibody and cytotoxic T lymphocyte (CTL) responses. In this model, the stability of the biologically relevant endemic equilibrium, characterized by the coexistence of long-term antibody and CTL levels, relies upon a balance between CTL and antibody growth rates, which is needed to ensure persistent CTL levels. We determine the model parameter ranges at which CTL and antibody proliferation rates are simultaneously most influential in leading the system towards coexistence and can be used to derive a mathematical relationship between CTL and antibody production rates to explore the bifurcation curve that leads to coexistence. We employ Latin hypercube sampling and least squares to find the parameter ranges that equally divide the endemic and boundary equilibria. We then examine this relationship numerically via a local sensitivity analysis of the parameters. Our analysis is consistent with previous results showing that an intervention (such as a vaccine) intended to control a persistent viral infection with both immune responses should moderate the antibody response to allow for stimulation of the CTL response. Finally, we show that the CTL production rate can entirely determine the long-term outcome, regardless of the effect of other parameters, and we provide the conditions for this result in terms of the identified ranges for all model parameters.

Delirium is a disturbance of attention and awareness that represents a change from baseline mental status. Accurate diagnosis of delirium is of paramount importance to improving the management of pediatric delirium in the intensive care unit. Despite ongoing education, inconsistencies in delirium assessments occur. Here, we aimed to determine the extent of the problem and increase compliance with delirium assessments.We collected preintervention data to assess baseline compliance of delirium assessments in the Pediatric Intensive Care Unit (PICU) and Pediatric Cardiac Intensive Care Unit (PCICU) at Monroe Carell Jr Children's Hospital at Vanderbilt in November 2020. We executed 2 Plan-Do-Study-Act cycles with different interventions and collected data after each and approximately 1 year after the interventions. The first intervention consisted of virtual lectures on delirium assessments for the nursing staff. The second intervention included an educational handout and a new electronic medical record documentation tool.Five hundred five individual nurse-patient encounters were assessed and collected throughout the project. The mean compliance of delirium documentation before the interventions was 52.5%. Target compliance after interventions was 70%. Mean compliance was 70% after cycle 1, 78% after cycle 2, and 86% in March 2022.Using pre- and postintervention data from chart reviews and nurse interviews regarding delirium screenings, we found that interventions targeting nurse education and EMR flowsheet improved compliance with delirium assessment and documentation in the PICU and PCICU. Future work should focus on assessing the clinical implications of this project in diagnosing and treating delirium.

BackgroundPreclinical evidence supports combining checkpoint inhibition (CPI) with T cell costimulatory agonism to improve the breadth and durability of anti-tumor responses relative to CPI alone. Currently, there are a number of therapeutic approaches combining costimulatory receptor agonists (e.g. CD28, 4-1BB, OX40L, etc.) with tumor targeting agents and/or CPI. Identification of a pharmacodynamically-justified therapeutic dose can be challenging because traditional duration of target occupancy does not necessarily correlate with immunological activity in the case of costimulatory molecules, and an ‘always on’ dose risks immune exhaustion. ALPN-202, a variant CD80 vIgD-Fc fusion protein that mediates PD-L1-dependent CD28 costimulation and inhibits the PD-L1 and CTLA-4 checkpoints, is in development for the treatment of multiple advanced malignancies. To assess clinical CD28 agonism in the context of ALPN-202 treatment, we developed a novel, ex vivo whole blood target-dependent costimulation (TDC) assay.MethodsA TDC assay was developed using clinical samples from NEON-1 (NCT04186637), an ongoing dose escalation and expansion clinical trial of ALPN-202 for patients with advanced malignancies. The assay uses patient blood stimulated with paraformaldehyde-fixed, artificial antigen presenting cells (aAPC) expressing both cell-surface anti-CD3 and PD-L1. Pre-dose and end-of-infusion (EOI) blood was drawn from trial participants and co-cultured for 24 hours with the aAPCs in a pre-made assay plate. Plasma was collected and secreted IL-2 was quantified and used as a measure of PD-L1-dependent CD28 costimulation. Nonlinear regression was used to calculate area under the curve (AUC) for each condition, and sample AUC values were compared to a positive control (pre-dose blood stimulated with a fixed concentration of ALPN-202). Serum concentration of ALPN-202 and CD28 target saturation analyses were conducted concurrently to evaluate the exposure-response relationship.ResultsUsing the ex vivo TDC assay, ALPN-202 demonstrated PD-L1-dependent T cell costimulation at all dose levels tested to date in the NEON-1 clinical trial, consistent with preclinical assay development data. Similarly, CD28 target saturation levels on circulating T cells correlated with serum concentration of ALPN-202.ConclusionsWe have developed a novel ex vivo assay to assess induction of PD-L1-dependent CD28 costimulation in a therapeutic setting. This assay has been successfully employed to monitor controlled CD28 costimulation by the CD28 agonist therapeutic candidate ALPN-202, helping to establish a PK/PD relationship that is consistent with preclinical data. More broadly, this type of cell-based, ex vivo TDC assay could be adapted to assess costimulatory receptor engagement, particularly target-dependent costimulation, for other therapeutic agonists in clinical development.Ethics ApprovalThis study was approved by WCG IRB’s Human Subjects Review, approval number: 20211877.

Disability is an important and often overlooked component of diversity. Individuals with disabilities bring a rare perspective to science, technology, engineering, mathematics, and medicine (STEMM) because of their unique experiences approaching complex issues related to health and disability, navigating the healthcare system, creatively solving problems unfamiliar to many individuals without disabilities, managing time and resources that are limited by physical or mental constraints, and advocating for themselves and others in the disabled community. Yet, individuals with disabilities are underrepresented in STEMM. Professional organizations can address this underrepresentation by recruiting individuals with disabilities for leadership opportunities, easing financial burdens, providing equal access, fostering peer-mentor groups, and establishing a culture of equity and inclusion spanning all facets of diversity. We are a group of deaf and hard-of-hearing (D/HH) engineers, scientists, and clinicians, most of whom are active in clinical practice and/or auditory research. We have worked within our professional societies to improve access and inclusion for D/HH individuals and others with disabilities. We describe how different models of disability inform our understanding of disability as a form of diversity. We address heterogeneity within disabled communities, including intersectionality between disability and other forms of diversity. We highlight how the Association for Research in Otolaryngology has supported our efforts to reduce ableism and promote access and inclusion for D/HH individuals. We also discuss future directions and challenges. The tools and approaches discussed here can be applied by other professional organizations to include individuals with all forms of diversity in STEMM.