Activation of mosquito immunity blocks the development of transmission-stage filarial nematodes.

Mosquito-borne helminth infections are responsible for a significant worldwide disease burden in both humans and animals. Accordingly, development of novel strategies to reduce disease transmission by targeting these pathogens in the vector are of paramount importance. We found that a strain of Aedes aegypti that is refractory to infection by Dirofilaria immitis, the agent of canine heartworm disease, mounts a stronger immune response during infection than does a susceptible strain. Moreover, activation of the Toll immune signaling pathway in the susceptible strain arrests larval development of the parasite, thereby decreasing the number of transmission-stage larvae. Notably, this strategy also blocks transmission-stage Brugia malayi, an agent of human lymphatic filariasis. Our data show that mosquito immunity can play a pivotal role in restricting filarial nematode development and suggest that genetically engineering mosquitoes with enhanced immunity will help reduce pathogen transmission.

A Survey of Veterinary Student and Veterinarian Perceptions of Shelter Medicine Employment.

Shelter medicine appears to be popular among prospective veterinarians, but there is a shortage of veterinarians entering the field to fill available positions. The reasons for this discordance are not well understand. This study describes veterinary students' interest in shelter medicine, their perceptions of common duties, and their perceptions of employment attributes in shelter medicine, compared with those of current veterinarians. The sample included 146 first-year students, 155 final-year students, and 221 veterinarians who self-completed an online survey between September 2020 and March 2021. We found high levels of interest in shelter medicine, with 40% of first- and 43% of final-year students indicating they were likely to consider working in shelter medicine. Outreach clinics (84% of first-year students, 86% of final-year students), access-to-care clinics (82%, 83%), and loan forgiveness programs (75%, 64%) encouraged many veterinary students to consider working in shelter medicine. The risk of compassion fatigue, burnout, and stress (70%, 68%); weekend work (51%, 59%); euthanasia decision making (49%, 47%); euthanasia (43%, 41%); and expected salaries of shelter veterinarians (39%, 37%) acted as deterrents. Kruskal-Wallis H tests revealed students reported more positive ratings than veterinarians for most shelter medicine duties and employment characteristics, with moderate to strong consensus within groups. Little difference appeared between first- and final-year students. This study highlights target areas for animal shelters to boost recruitment of newly graduated veterinarians. Increasing veterinary students' exposure to shelter medicine throughout their veterinary training may also help address their concerns regarding euthanasia, salary, and quality of care.

A Retrospective Analysis of Pre-/Post-Test Scores of Students Participating in Online Asynchronous Shelter Surgery Coursework.

The University of Pennsylvania School of Veterinary Medicine first offered the elective Student Shelter Opportunities I (SSOI) course in 2016 to provide pre-clinical students with an opportunity to engage with shelter medicine and high-quality, high-volume surgery (HQHVS) concepts. The course utilized online asynchronous coursework to deliver content that was completed on a self-guided timeline by students. With most of the veterinary medical curriculum delivered in a traditional classroom format, it is important to assess learning in this unique course format. There is also limited information on educational experiences in online shelter medicine coursework. This retrospective study aimed to evaluate student learning in the asynchronous online portion of the SSOI elective course using paired pre- and post-test scores from a multiple-choice type assessment. The study investigated how students' pre-test and post-test scores compared and whether time to completion of material influenced student assessment performance. Paired assessments from 400 students were analyzed, and a statistically significant increase was found in post-test scores compared to pre-test following completion of the online coursework (p < .001). There was no significant difference in the mean change in score from pre-test to post-test for students who completed the online course material in 30 days or less compared to those who completed it in greater than 30 days. This study's findings support online asynchronous learning as an effective option to teach veterinary students and can be considered in the development of veterinary coursework, including for curricular adjustments to increase online learning during the SARS-CoV-2 pandemic.

Shelter Medicine Sustainability from an Academic Perspective: Challenges and Issues.

A meeting of veterinary school faculty and partners, many associated with shelter medicine, and/or community medicine programming, was convened at the 2019 Shelter Medicine Veterinary Educators Conference in Pullman, WA to discuss challenges with shelter medicine program sustainability and defining the future. The discussion was facilitated by an outside consultant and is summarized in this manuscript. The goal of the meeting was to identify challenges and issues concerning the needs and goals for shelter medicine curricula to have long-term success in academic training. Four themes were identified in the transcripts including external pressure from leadership and other stakeholders, funder expectations, time horizons, and perceptions of shelters and shelter veterinarians. Addressing these challenges will be critical to ensuring stability in academic training in shelter medicine, a critical tool for both learning outcomes for general graduates and specific for veterinarians pursuing shelter medicine as a career.

In Vitro Biosensing of ß-Amyloid Peptide Aggregation Dynamics using a Biological Nanopore.

Alzheimer's disease and other neurodegenerative disorders are becoming more prevalent as advances in technology and medicine increase living standards and life expectancy. Alzheimer's disease is thought to initiate development early in the patient's life and progresses continuously into old age. This process is characterized molecularly by the amyloid hypothesis, which asserts that self-aggregating amyloid peptides are core to the pathophysiology in Alzheimer's progression. Precise quantification of amyloid peptides in human bodily fluid samples (i.e. cerebrospinal fluid, blood) may inform diagnosis and prognosis, and has been studied using established biosensing technologies like liquid chromatography, mass spectrometry, and immunoassays. However, existing methods are challenged to provide single molecule, quantitative analysis of the disease-causing aggregation process. Ultra-sensitive nanopore biosensors can step in to fill this role as a dynamic mapping tool. The work in this paper establishes characteristic signals of ß-amyloid 40 monomers, oligomers, and soluble aggregates, as well as a proof-of-concept foundation where a biological nanopore biosensor is used to monitor the extent of in vitro ß-amyloid 40 peptide aggregation at the single molecule level. This foundation allows for future work to expand in drug screening, diagnostics, and aggregation dynamic experiments.

Educational Research Report Development of International Learning Outcomes for Shelter Medicine in Veterinary Education: A Delphi Approach.

Shelter medicine is a veterinary discipline of growing importance. Formally accepted as a clinical specialty in the US in 2014, the practice of shelter medicine worldwide is expanding. As a topic in veterinary pre-registration (undergraduate) education, it is frequently used as an opportunity to teach primary care skills, but increasingly recognized as a subject worthy of teaching in its own right. The aim of this study was to use a Delphi consensus methodology to identify learning outcomes relevant to shelter medicine education. Shelter medicine educators worldwide in a variety of settings, including universities, non-governmental organizations and shelters were invited to participate. Participants were initially invited to share shelter medicine teaching materials. These were synthesized and formatted into Learning Outcomes (LOs) based on Bloom's taxonomy and organized into five subject-specific domains. Participants were then asked to develop and evaluate the identified LOs in two rounds of online surveys. Consensus was determined at > 80% of panelists selecting "agree" or "strongly agree" in response to the statement "please indicate whether you would advise that it should be included in a shelter medicine education program" for each LO. In the second survey, where re-wording of accepted LOs was suggested, preference was determined at > 50% agreement. Through this method, 102 agreed LOs have been identified and refined. These LOs, as well as those which did not reach consensus, are presented here. These are intended for use by shelter medicine educators worldwide, to enable and encourage the further development of this important veterinary discipline.

Development of International Learning Outcomes for Shelter Medicine in Veterinary Education: A Delphi Approach.

Shelter medicine is a veterinary discipline of growing importance. Formally accepted as a clinical specialty in the US in 2014, the practice of shelter medicine worldwide is expanding. As a topic in veterinary pre-registration (undergraduate) education, it is frequently used as an opportunity to teach primary care skills, but increasingly recognized as a subject worthy of teaching in its own right. The aim of this study was to use a Delphi consensus methodology to identify learning outcomes relevant to shelter medicine education. Shelter medicine educators worldwide in a variety of settings, including universities, non-governmental organizations and shelters were invited to participate. Participants were initially invited to share shelter medicine teaching materials. These were synthesized and formatted into Learning Outcomes (LOs) based on Bloom's taxonomy and organized into five subject-specific domains. Participants were then asked to develop and evaluate the identified LOs in two rounds of online surveys. Consensus was determined at > 80% of panelists selecting "agree" or "strongly agree" in response to the statement "please indicate whether you would advise that it should be included in a shelter medicine education program" for each LO. In the second survey, where re-wording of accepted LOs was suggested, preference was determined at > 50% agreement. Through this method, 102 agreed LOs have been identified and refined. These LOs, as well as those which did not reach consensus, are presented here. These are intended for use by shelter medicine educators worldwide, to enable and encourage the further development of this important veterinary discipline.

Is it all bleak? A systematic review of factors contributing to relationship change in dementia.

ABSTRACTBackground:The care of community-dwelling people with dementia often occurs in the context of pre-existing family relationships. The presence of dementia can result in changes to the quality of those relationships. The purpose of this systematic review is to identify factors that enhance or challenge the quality of spousal or offspring relationships in the context of dementia. METHODS: Both qualitative and quantitative studies were included in a systematic review of the literature. Thematic analysis of results was conducted that examined factors related to the relationship quality of community dwelling people with dementia and their spousal or offspring carer. Meta-analysis was not possible due to the heterogeneity of the included studies. RESULTS: Four themes were extracted from seven qualitative studies: connection to the carer role; identity of the people with dementia; current efforts to maintain relationship connection; and the dyads response to dementia. Each of these four themes incorporated positive and negative facets that impacted on relationship quality. An analysis of nine quantitative and one mixed methods studies identified four domains: influence of dementia characteristics; connection within the dyad; relationship response to stress and carer burden; and carer demographic factors. CONCLUSIONS: The findings of this review highlight relationship factors that are important for supporting relationship quality for the people with dementia and the carer individually, as well as for the dyad together. These findings extend an existing framework of relationship quality in dementia. Implications for interventions to enhance relationship quality in the dementia context are discussed.

Thymic stromal lymphopoietin and IL-33 modulate migration of hematopoietic progenitor cells in patients with allergic asthma.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) and IL-33 are considered important initiators of type 2 immunity. In asthmatic patients allergic inflammatory responses are associated with increased lung homing of bone marrow-derived CD34(+) hematopoietic progenitor cells (HPCs), which include eosinophil lineage-committed progenitor cells. In this study we investigated the role of TSLP and IL-33 in the recruitment of progenitor cells to the airways in asthmatic subjects. OBJECTIVES: We sought (i) to examine the effect of allergen inhalation challenge on expression levels of receptors for TSLP (thymic stromal lymphopoietin receptor [TSLPR] and CD127) and IL-33 (ST2) and (ii) investigate the functional effects of these cytokines on HPCs. METHODS: Consenting patients with mild atopic asthma (n = 19) with an FEV1 of 70% or greater and methacholine PC20 of 16 mg/mL or less were recruited. Blood- and sputum-extracted progenitors were phenotyped by flow cytometry before and 24 hours after allergen challenge. Functional responses, including cytokine production and migration to TSLP and IL-33, were assessed in vitro. RESULTS: Significant increases in mature eosinophil, HPC, and eosinophil lineage-committed progenitor cell counts in sputum were observed 24 hours after allergen and were associated with a significant allergen-induced increase in HPCs expressing TSLPR, CD127, and ST2. Pre-exposure to TSLP and IL-33 primed the migration of HPCs to a potent progenitor cell chemoattractant, stromal cell-derived factor 1α (CXCL12). Incubation with TSLP and IL-33 stimulated significant production of IL-5 and IL-13, but not IL-4, by HPCs. This priming effect was inhibited by blocking antibodies to TSLPR and ST2, respectively, and IL-13 receptor α1 in both scenarios. CONCLUSIONS: In allergic asthmatic responses increased lung homing of HPCs may be orchestrated by TSLP and IL-33 through an IL-13-dependent axis.

Does body satisfaction influence self-esteem in adolescents' daily lives? An experience sampling study.

This study examined, within the context of the Contingencies of Self-Worth model, state-based associations between self-esteem and body satisfaction using the experience sampling method. One hundred and forty-four adolescent girls (mean age = 14.28 years) completed up to 6 assessments per day for one week using Palm Digital Assistants, in addition to baseline measures of trait body satisfaction and self-esteem. Results showed considerable variation in both state-based constructs within days, and evidence of effects of body satisfaction on self-esteem, but not vice versa. Although these state-based associations were small in size and weakened as the time lag between assessments increased for the sample as a whole, individual differences in the magnitude of these effects were observed and predicted by trait self-esteem and body satisfaction. Collectively, these findings offer support for key tenets of the Contingencies of Self-Worth model.

Evaluation of peroxisome proliferator-activated receptor agonists on interleukin-5-induced eosinophil differentiation.

Peroxisome proliferator-activated receptor (PPAR) agonists have been suggested as novel therapeutics for the treatment of inflammatory lung disease, such as allergic asthma. Treatment with PPAR agonists has been shown to inhibit airway eosinophilia in murine models of allergic asthma, which can occur through several mechanisms including attenuated generation of chemoattractants (e.g. eotaxin) and decreased eosinophil migrational responses. In addition, studies report that PPAR agonists can inhibit the differentiation of several cell types. To date, no studies have examined the effects of PPAR agonists on interleukin-5 (IL-5) -induced eosinophil differentiation from haemopoietic progenitor cells. Non-adherent mononuclear cells or CD34(+) cells isolated from the peripheral blood of allergic subjects were grown for 2 weeks in Methocult(®) cultures with IL-5 (10 ng/ml) and IL-3 (25 ng/ml) in the presence of 1-1000 nm PPARα agonist (GW9578), PPARß/δ agonist (GW501516), PPARγ agonist (rosiglitazone) or diluent. The number of eosinophil/basophil colony-forming units (Eo/B CFU) was quantified by light microscopy. The signalling mechanism involved was assessed by phosphoflow. Blood-extracted CD34(+) cells cultured with IL-5 or IL-5 + IL-3 formed Eo/B CFU, which were significantly inhibited by rosiglitazone (100 nm, P < 0·01) but not GW9578 or GW501516. In addition, rosglitazone significantly inhibited IL-5-induced phosphorylation of extracellular signal-regulated kinase 1/2. We observed an inhibitory effect of rosiglitazone on eosinophil differentiation in vitro, mediated by attenuation of the extracellular signal-regulated kinase 1/2 signalling pathway. These findings indicate that the PPARγ agonist can attenuate tissue eosinophilia by interfering with local differentiative responses.

Inhibition of allergen-induced basophil activation by ASM-024, a nicotinic receptor ligand.

BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) were identified on eosinophils and shown to regulate inflammatory responses, but nAChR expression on basophils has not been explored yet. OBJECTIVE: We investigated surface receptor expression of nAChR α4, α7 and α1/α3/α5 subunits on basophils. Furthermore, we examined the effects of ASM-024, a synthetic nicotinic ligand, on in vitro anti-IgE and in vivo allergen-induced basophil activation. METHODS: Basophils were enriched from the peripheral blood of allergic donors and the expression of nAChR subunits and muscarinic receptors was determined. Purified basophils were stimulated with anti-IgE in the presence of ASM-024 with or without muscarinic or nicotinic antagonists for the measurement of CD203c expression and histamine release. The effect of 9 days of treatment with 50 and 200 mg ASM-024 on basophil CD203c expression was examined in the blood of mild allergic asthmatics before and after allergen inhalation challenge. RESULTS: nAChR α4, α7 and α1/α3/α5 receptor subunit expression was detected on basophils. Stimulation of basophils with anti-IgE increased CD203c expression and histamine release, which was inhibited by ASM-024 (10(-5) to 10(-)(3) M, p < 0.05). The effect of ASM-024 was reversed in the presence of muscarinic and nicotinic antagonists. In subjects with mild asthma, ASM-024 inhalation significantly inhibited basophil CD203c expression measured 24 h after allergen challenge (p = 0.03). CONCLUSION: This study shows that ASM-024 inhibits IgE- and allergen-induced basophil activation through both nicotinic and muscarinic receptors, and suggests that ASM-024 may be an efficacious agent for modulating allergic asthma responses.

Public perceptions of free-roaming dogs and cats in India and the United States.

In this cross-sectional study, we aimed to describe differences between India and the United States in public perceptions of free-roaming dogs and cats, concerns related to free-roaming animals, and preferred strategies for veterinary medical interventions and population management. Between August 2021 and February 2022, 498 individuals completed an online survey including 210 Indian respondents and 288 American respondents. Free-roaming dogs and cats were largely perceived as community animals among Indian respondents, with significantly more respondents indicating they should be allowed to roam freely compared with American respondents. Respondents from both countries were concerned about animal welfare, although Americans were significantly more likely to list animal welfare, public health and wildlife risks as significant concerns related to free-roaming cats and dogs. American respondents were also more likely to support adoption for sociable animals and euthanasia for unsociable animals, whereas Indian respondents were more likely to support spay/neuter, vaccinate and release strategies for both dogs and cats. Our findings speak to the importance of implementing tailored strategies for free-roaming cat and dog management based on local cultures and community perceptions of free-roaming animals.

A prospective study of mental wellbeing, quality of life, human-animal attachment, and grief among foster caregivers at animal shelters.

Foster care programs at animal shelters have emerged as an important tool for promoting animal welfare and supporting shelter life-saving efforts. Preliminary evidence suggests that foster caregiving may also be health-promoting for humans. The goals of this study were to investigate the experiences of foster caregivers at animal shelters based on measures of positive and negative affect, quality of life, and grief, and to describe human-animal attachment among foster populations. Between March 2022 and 2023, 131 foster caregivers from five shelters in the United States completed three online surveys before, during and after providing foster care to a shelter animal. Positive affect decreased significantly from baseline to post-foster (F = 5.71, p<0.01), particularly among dog caregivers (F = 6.17, p<0.01). Negative affect remained unchanged (F = 0.47, p = 0.63). Foster caregivers perceived their foster animal provided companionship, affection and emotional support, although dog foster caregivers reported significantly higher emotional (U = 313.50, p<0.01) and social/physical quality of life (t = 4.42, p<0.01) than cat foster caregivers. Caregivers reported low mean avoidant and anxious attachment, suggesting they were able to develop secure bonds with their foster animals. Retention of fosters was also strong, with 86% of caregivers reporting they were likely to provide foster care in the future. Our findings suggest that fostering at animal shelters may serve as a One Health intervention to offer companionship, affection and emotional support to human caregivers while promoting animal welfare. However, these benefits did not translate to improvements in caregiver mental wellbeing, so caution should be applied when considering foster caregiving as a potential mental health promotion tool.

Human in vitro blood barrier models: architectures and applications.

Blood barriers serve as key points of transport for essential molecules as well as lines of defense to protect against toxins. In vitro modeling of these barriers is common practice in the study of their physiology and related diseases. This review describes a common method of using an adaptable, low cost, semipermeable, suspended membrane to experimentally model three blood barriers in the human body: the blood-brain barrier (BBB), the gut-blood barrier (GBB), and the air-blood barrier (ABB). The GBB and ABB both protect from the outside environment, while the BBB protects the central nervous system from potential neurotoxic agents in the blood. These barriers share several commonalities, including the formation of tight junctions, polarized cellular monolayers, and circulatory system contact. Cell architectures used to mimic barrier anatomy as well as applications to study function, dysfunction, and response provide an overview of the versatility enabled by these cultural systems.

Understanding the Motivations of Foster Caregivers at Animal Shelters.

Foster care programs in animal shelters have been shown to benefit animals and shelters, but little is known about what motivates foster caregivers to volunteer. This cross-sectional study explored the motivations and expectations of 131 foster caregivers from five shelters within the United States who completed a pre-foster survey between March 2022 and March 2023. The most common motivations were animal- or community-based, such as the desire to provide an animal with love or do something positive for the community. Ordinal logistic regression models were used to investigate associations between caregivers' motivations and their prior foster experience, pet ownership history, age, gender, and foster animal species. The 18- to 29-year-old caregivers were most likely to expect companionship (OR 5.18, 95% CI 1.79-15.04), emotional support (OR 4.25, 95% CI 1.40-12.89), and to meet other community members through fostering (OR 5.04, 95% CI 1.85-13.74). Male caregivers were less likely to foster for emotional support than females (OR 0.12, 95% CI 0.03-0.48), while dog caregivers (OR 2.23, 95% CI 1.04-4.76) and non-pet-owners (OR 2.66, 95% CI 1.17-6.05) had greater odds of expecting companionship. This study highlights the importance of animal- and community-related benefits for foster caregivers and provides useful direction for shelters wanting to increase recruitment to expand their foster care programs.

Patterning amyloid-ß aggregation under the effect of acetylcholinesterase using a biological nanopore - an in vitro study.

Aggregation of amyloid-ß peptide (Aß) is hypothesized to be the primary cause of Alzheimer's disease (AD) progression. Aß aggregation has been widely studied using conventional sensing tools like emission fluorescence, electron microscopy, mass spectroscopy, and circular dichroism. However, none of these techniques can provide cost-efficient, highly sensitive quantification of Aß aggregation kinetics at the molecular level. Among the influences on Aß aggregation of interest to disease progression is the acceleration of Aß aggregation by acetylcholinesterase (AChE), which is present in the brain and inflicts the fast progression of disease due to its direct interaction with Aß. In this work, we demonstrate the ability of a biological nanopore to map and quantify AChE accelerated aggregation of Aß monomers to mixed oligomers and small soluble aggregates with single-molecule precision. This method will allow future work on testing direct and indirect effects of therapeutic drugs on AChE accelerated Aß aggregation as well as disease prognosis.

Body image during pregnancy: an evaluation of the suitability of the Body Attitudes Questionnaire.

BACKGROUND: Available data suggest that body dissatisfaction is common during pregnancy and may even be a precursor to post-natal depression. However, in order to accurately identify at-risk women, it is essential to first establish that body image measures function appropriately in pregnant populations. Our study examines the suitability of the Body Attitudes Questionnaire (BAQ) for measuring body dissatisfaction among pregnant women by comparing the psychometric functioning of the BAQ: (1) across key phases of pregnancy, and (2) between pregnant and non-pregnant women. METHODS: A total of 176 pregnant women from Melbourne, Victoria filled out a questionnaire battery containing demographic questions and the Body Attitudes Questionnaire at 16, 24, and 32 weeks during pregnancy. A comparison group of 148 non-pregnant women also completed the questionnaire battery at Time 1. Evaluations of the psychometric properties of the BAQ consisted of a series of measurement invariance tests conducted within a structural equation modelling framework. RESULTS: Although the internal consistency and factorial validity of the subscales of the BAQ were established across time and also in comparisons between pregnant and non-pregnant women, measurement invariance tests showed non-invariant item intercepts across pregnancy and also in comparison with the non-pregnant subgroup. Inspection of modification indices revealed a complex, non-uniform pattern of differences in item intercepts across groups. CONCLUSIONS: Collectively, our findings suggest that comparisons of body dissatisfaction between pregnant and non-pregnant women (at least based on the BAQ) are likely to be conflated by differential measurement biases that serve to undermine attempts to accurately assess level of body dissatisfaction. Researchers should be cautious in assessments of body dissatisfaction among pregnant women until a suitable measure has been established for use in this population. Given the fact that body dissatisfaction is often associated with maladaptive behaviours, such as unhealthy eating and extreme weight loss behaviours, and with ante-and post-natal depression, that have serious negative implications for women's health and well-being, and potentially also for the unborn foetus during pregnancy, developing a suitable body image screening tool, specific to the perinatal period is clearly warranted.

A Qualitative Analysis of Clinical Year Veterinary Student Journal Entries for a Shelter Medicine Rotation.

Veterinary medical schools are tasked with not only providing experiences necessary to graduate veterinarians proficient in the skills and knowledge used most frequently in private practice, but also develop expertise in animal behavior, welfare, ethics, veterinary forensics, and cultural competency. Integrating all these knowledge areas into the curriculum can be challenging. Shelter medicine is increasingly identified by educators as an optimal learning environment to offer exposure to these topics. It can not only meet learning objectives in veterinary medical curriculum, but also provide students with authentic learning experiences to engage in and gain a deeper understanding of cultural humility, implicit bias, diversity, and inclusion. This includes documentation of international learning outcomes for shelter medicine in veterinary medical curriculum. There have been no studies evaluating authentic learning experiences specific to shelter medicine programs and their impacts on students. The aim of this study was to determine the individual activities and thematic categories on which veterinary students chose to reflect on and their potential impacts during a clinical rotation in shelter medicine at Penn Vet through qualitative content analysis of their journal entries. In our study, students found experiences on the shelter medicine rotation to be beneficial to their growth as a future veterinarian, provided them with takeaways that they found applicable and practical, helped them self-identify knowledge gaps, and changed their perspectives on several important topics related to collective human and animal welfare. These results speak to the value perceived by students of the rotation and suggest an authentic learning experience through a shelter medicine program can help cultivate more practice-ready and culturally competent veterinary graduates.