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No abstract available. Article truncated at 150 words. History of Present Illness: The patient is a 26-year-old woman with who was admitted to the hospital for second cycle of chemotherapy for a large mediastinal synovial sarcoma diagnosed 2 months prior to admission. Symptoms started 6 months prior to presentation with cough. She related the cough to her cigarette smoking and quit. Upon persistence of symptoms, she was evaluated by her physician who ordered imaging. Work-up revealed a large 12 x 14cm synovial sarcoma with internal necrosis that encased the subclavian artery, and descending thoracic aorta, inseparable from pericardium and left atrium. It also encased the pulmonary veins, pulmonary arteries, and airways. Malignancy was complicated by extensive left upper extremity DVT for which she has been on anticoagulation since her last admission, SVC syndrome, and severe mucositis. Past Medical History, Family History, and Social History: She has a past medical history significant for malignant melanoma surgically resected 7 years …

Objectives: Slow-growing nontuberculous mycobacteria (NTMs) are highly prevalent and routinely cause opportunistic intracellular infectious disease in immunocompromised hosts. Methods: The activity of the triple combination of antibiotics, clarithromycin (CLR), rifabutin (RFB), and clofazimine (CFZ), was evaluated and compared with the activity of single antibiotics as well as with double combinations in an in vitro biofilm assay and an in vivo murine model of Mycobacterium avium subsp. hominissuis (M. avium) lung infection. Results: Treatment of 1-week-old biofilms with the triple combination exerted the strongest effect of all (0.12 ± 0.5 × 107 CFU/mL) in reducing bacterial growth as compared to the untreated (5.20 ± 0.5 × 107/mL) or any other combination (≥0.75 ± 0.6 × 107/mL) by 7 days. The treatment of mice intranasally infected with M. avium with either CLR and CFZ or the triple combination provided the greatest reduction in CLR-sensitive M. avium bacterial counts in both the lung and spleen compared to any single antibiotic or remaining double combination by 4 weeks posttreatment. After 4 weeks of treatment with the triple combination, there were no resistant colonies detected in mice infected with a CLR-resistant strain. No clear relationships between treatment and spleen or lung organ weights were apparent after triple combination treatment. Conclusions: The biofilm assay data and mouse disease model efficacy results support the further investigation of the triple-antibiotic combination.

Background: Interspecies variations in mammalian red blood cells (RBCs) are observed in circulating RBC lifespan, cell size, fluidity, aggregation, water permeability, metabolism, lipid composition, and the overall proteome. Bovine RBC cell membrane is deficient in phosphatidylcholine and exhibits anomalies in the arrangement of phosphatidylethanolamine within the lipid bilayer. However, like human RBCs, virtually all the aminophospholipid phosphatidylserine (PS) is found within the cytoplasmic side of the cell membrane of intact circulating bovine RBCs. During apoptotic cell death of human and murine RBCs, PS translocates to the outer leaflet of the cell membrane via Ca2+-dependent and -independent signaling mechanisms. However, little is known about this process in bovine RBCs. Methods: Using cytofluorometry analyses, we characterized and compared the cell death responses in bovine and human RBCs in vitro exposed to various pathophysiologic cell stressors. Results: Ionic stress, by ionophore treatment, and oxidative stress enhanced cytoplasmic Ca2+ levels and cell membrane PS expression in both bovine and human RBCs. Fever-grade hyperthermia and energy starvation promoted Ca2+ influx and elevated reactive oxygen species levels in both human and bovine RBCs. However, bovine RBCs displayed minimal increases in PS expression elicited by hyperthermia, energy starvation, and extracellular hypertonicity as compared to human RBCs. In response to decreased extracellular osmolality, bovine RBCs exhibited significantly enhanced fragility as compared to human RBCs. Conclusions: Bovine RBCs display differential cell death patterns as compared to human RBCs, only partly explained by increased Ca2+ influx and oxidative stress. Premature removal of circulating RBCs could potentially contribute to the pathogenesis of anemia in cattle caused by a wide range of factors such as systemic diseases, parasitic infections, and nutritional deficiencies.

AKT is implicated in neurological disorders. AKT has three isoforms, AKT1/AKT2/AKT3, with brain cell type-specific expression that may differentially influence behavior. Therefore, we examined single Akt isoform, conditional brain-specific Akt1, and double Akt1/3 mutant mice in behaviors relevant to neuropsychiatric disorders. Because sex is a determinant of these disorders but poorly understood, sex was an experimental variable in our design. Our studies revealed AKT isoform- and sex-specific effects on anxiety, spatial and contextual memory, and fear extinction. In Akt1 mutant males, viral-mediated AKT1 restoration in the prefrontal cortex rescued extinction phenotypes. We identified a novel role for AKT2 and overlapping roles for AKT1 and AKT3 in long-term memory. Finally, we found that sex-specific behavior effects were not mediated by AKT expression or activation differences between sexes. These results highlight sex as a biological variable and isoform- or cell type-specific AKT signaling as potential targets for improving treatment of neuropsychiatric disorders.

Yellow Rail (Coturnicops noveboracensis) is a species of conservation concern, while the Eastern Black Rail (Laterallus jamaicensis jamaicensis) has recently been listed as Threatened. Both species winter primarily in coastal areas from Texas through North Carolina. Between-year winter site fidelities of these species have not previously been reported, so we analyzed the recapture histories of Yellow Rails banded in southeastern Oklahoma (from 2008 to 2018) and coastal Texas (from 2006 to 2018), as well as Black Rails banded in Texas from 2006 to 2018. We banded 111 Yellow Rails in Oklahoma and 421 Yellow Rails in Texas during this time, as well as 94 Black Rails in Texas. Although Yellow Rails were routinely recaptured within season, only five individuals were recaptured between years. All recaptured birds were in Texas. Black Rails likewise exhibited low interannual site fidelity, with no interannual recaptures. The apparent low interannual site fidelity of Yellow Rails (1.1% in Texas, 0% in Oklahoma) and Black Rails (0%) is similar to that reported for other grassland species wintering in grasslands in this area (e.g., LeConte’s Sparrow (Ammodramus leconteii), Henslow’s Sparrow (A. henslowii), and Sedge Wren (Cistothorus stellaris)), and we speculate that low site fidelity could potentially be advantageous for species that use early successional habitats.

Abstract Background A low cost and accurate method for detecting high-risk (HR) human papillomavirus (HPV) is important to permit HPV testing for cervical cancer prevention. We used a commercially available HPV method (H13, Hybribio) which was documented to function accurately in a reduced volume of cervical specimen to determine the most prevalent HPV types and the distribution of HPV infections in over 1795 cancer-free women in Guatemala undergoing primary screening for cervical cancer by cytology. Methods HR-HPV detection was attempted in cervical samples from 1795 cancer-free women receiving Pap smears using the Hybribio™ real-time PCR assay of 13 HR types. The test includes a globin gene internal control. HPV positive samples were sequenced to determine viral type. Age-specific prevalence of HPV was also assessed in the study population. Results A total of 13% (226/1717) of women tested HPV+, with 78 samples (4.3%) failing to amplify the internal control. The highest prevalence was found in younger women (

Despite recent breakthroughs in the field of Alzheimer's disease (AD) research, there remains no cure for this progressive, degenerative brain impairment, which has become 'the disease of the next century.' Given the fact that women are much more likely to be cast in the role of caregiver for a spouse or parent, more education about the disease is needed to equip these women with the tools that can reduce the burden that round-the-clock caregiving brings. Review of the literature reveals that very little research has examined the degree of awareness that women, and men, have about the full scope and magnitude of the caregiving experience. In the words of a caregiver whose husband of 16 years died after being afflicted with Alzheimer's for 14 of those years, 'Little does one know what lies ahead when the diagnosis is 'probable Alzheimer's'--chilling words, to be sure.' This article examines awareness in three groups of college students, many of whom, if present trends continue, will be future caregivers. [ABSTRACT FROM AUTHOR]

Following publication of the original article [1], an error was reported in the tagging of Joël Fokom Domgue in the author group. The tagging in this correction article has been fixed.

The 3 human RAS genes play pivotal roles regulating proliferation, differentiation, and survival in normal cells and become mutated in 15% to 20% of all human tumors and amplified in many others. In this report, we examined data from The Cancer Genome Atlas to investigate the relationship between RAS gene mutational status and messenger RNA expression. We show that all 3 RAS genes exhibit increased expression when they are mutated in a context-dependent manner. In the case of KRAS , this increase is manifested by a larger proportional increase in KRAS4A than KRAS4B , although both increase significantly. In addition, the mutational status of RAS genes can be associated with expression changes in other RAS genes, with most of these cases showing decreased expression. The mutational status associations with expression are recapitulated in cancer cell lines. Increases in expression are mediated by both copy number variation and contextual differences, including mutational status of epidermal growth factor receptor ( EGFR ) and BRAF . These findings potentially reveal an adaptive response during tumor evolution that is dependent on the mutational status of proximal genes in the RAS pathway and cellular context. Cell contextual differences in these adaptations may influence therapeutic responsiveness and alternative resistance mechanisms.

Breast cancer is a major cause of mortality in women; however, technologies for early stage screening and diagnosis (e.g., mammography and other imaging technologies) are not optimal for the accurate detection of cancer. This creates demand for a more effective diagnostic means to replace or be complementary to existing technologies for early discovery of breast cancer. Cancer neoantigens could reflect tumorigenesis, but they are hardly detectable at the early stage. Autoantibodies, however, are biologically amplified and hence may be measurable early on, making them promising biomarkers to discriminate breast cancer from healthy tissue accurately. In this review, we summarized the recent findings of breast cancer specific antigens and autoantibodies, which may be useful in early detection, disease stratification, and monitoring of treatment responses of breast cancer.

Acute and chronic pain conditions are often debilitating, inflicting severe physiological, emotional and economic costs and affect a large percentage of the global population. However, the development of therapeutic analgesic agents based primarily on targeted drug development has been largely ineffective. An alternative approach to analgesic development would be to develop low cost, high throughput, untargeted animal based behavioral screens that model complex nociceptive behaviors in which to screen for analgesic compounds. Here we describe the development of a behavioral based assay in zebrafish larvae that is effective in identifying small molecule compounds with analgesic properties. In a place aversion assay, which likely utilizes supraspinal neuronal circuitry, individually arrayed zebrafish larvae show temperature-dependent aversion to increasing and decreasing temperatures deviating from rearing temperature. Modeling thermal hyperalgesia, the addition of the noxious inflammatory compound and TRPA1 agonist allyl isothiocyanate sensitized heat aversion and reversed cool aversion leading larvae to avoid rearing temperature in favor of otherwise acutely aversive cooler temperatures. We show that small molecules with known analgesic properties are able to inhibit acute and/or sensitized temperature aversion.

Students in two graduate English seminars at Texas A&M were offered an introduction to TEI encoding and were surveyed as to their experiences. Four students presented short papers to the TEI meeting that incorporated both the survey responses and their own perspectives as relative newcomers to TEI. These papers demonstrate why it is important to incorporate TEI in the graduate curriculum, how that incorporation might best be approached, and what happens when TEI is viewed through a disciplinary lens.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA -B, and HLA -C class I genes (P(HLA-A-aa-site-62) = 7.4 × 10(-29); P (HLA-B-aa-site-116) = 6.5 × 10(-19); P (HLA-C-aa-site-156) = 6.8 × 10(-8) respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China.

Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb) from 186 primates representing 61 (~90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species.

Abstract Background To determine whether office, home, ambulatory daytime and nighttime blood pressure (BP) responses to antihypertensive drug therapy measure the same signal and which method provides greatest power to identify genetic predictors of BP response. Methods We analyzed office, home, ambulatory daytime and nighttime BP responses in hypertensive adults randomized to atenolol (N = 242) or hydrochlorothiazide (N = 257) in the Pharmacogenomic Evaluation of Antihypertensive Responses Study. Since different measured BP responses may have different predictors, we tested the "same signal" model by using linear regression methods to determine whether known predictors of BP response depend on the method of BP measurement. We estimated signal-to-noise ratios and compared power to identify a genetic polymorphism predicting BP response measured by each method separately and by weighted averages of multiple methods. Results After adjustment for pretreatment BP level, known predictors of BP response including plasma renin activity, race, and sex were independent of the method of BP measurement. Signal-to-noise ratios were more than 2-fold greater for home and ambulatory daytime BP responses than for office and ambulatory nighttime BP responses and up to 11-fold greater for weighted averages of all four methods. Power to identify a genetic polymorphism predicting BP response was directly related to the signal-to-noise ratio and, therefore, greatest with the weighted averages. Conclusion Since different methods of measuring BP response to antihypertensive drug therapy measure the same signal, weighted averages of the BP responses measured by multiple methods minimize measurement error and optimize power to identify genetic predictors of BP response.

Abstract Background Nearly one-third of the United States adult population suffers from hypertension. Hydrochlorothiazide (HCTZ), one of the most commonly used medications to treat hypertension, has variable efficacy. The renal epithelial sodium channel (ENaC) provides a mechanism for fine-tuning sodium excretion, and is a major regulator of blood pressure homeostasis. DOT1L, MLLT3, SIRT1, and SGK1 encode genes in a pathway that controls methylation of the histone H3 globular domain at lysine 79 (H3K79), thereby modulating expression of the ENaCα subunit. This study aimed to determine the role of variation in these regulatory genes on blood pressure response to HCTZ, and secondarily, untreated blood pressure. Methods We investigated associations between genetic variations in this candidate pathway and HCTZ blood pressure response in two separate hypertensive cohorts (clinicaltrials.gov NCT00246519 and NCT00005520). In a secondary, exploratory analysis, we measured associations between these same genetic variations and untreated blood pressure. Associations were measured by linear regression, with only associations with P ≤ 0.01 in one cohort and replication by P ≤ 0.05 in the other cohort considered significant. Results In one cohort, a polymorphism in DOT1L (rs2269879) was strongly associated with greater systolic (P = 0.0002) and diastolic (P = 0.0016) blood pressure response to hydrochlorothiazide in Caucasians. However, this association was not replicated in the other cohort. When untreated blood pressure levels were analyzed, we found directionally similar associations between a polymorphism in MLLT3 (rs12350051) and greater untreated systolic (P < 0.01 in both cohorts) and diastolic (P < 0.05 in both cohorts) blood pressure levels in both cohorts. However, when further replication was attempted in a third hypertensive cohort and in smaller, normotensive samples, significant associations were not observed. Conclusions Our data suggest polymorphisms in DOT1L, MLLT3, SIRT1, and SGK1 are not likely associated with blood pressure response to HCTZ. However, a possibility exists that rs2269879 in DOT1L could be associated with HCTZ response in Caucasians. Additionally, exploratory analyses suggest rs12350051 in MLLT3 may be associated with untreated blood pressure in African-Americans. Replication efforts are needed to verify roles for these polymorphisms in human blood pressure regulation.

Abstract Background Susceptibility variants identified by genome-wide association studies (GWAS) have modest effect sizes. Whether such variants provide incremental information in assessing risk for common 'complex' diseases is unclear. We investigated whether measured and imputed genotypes from a GWAS dataset linked to the electronic medical record alter estimates of coronary heart disease (CHD) risk. Methods Study participants (n = 1243) had no known cardiovascular disease and were considered to be at high, intermediate, or low 10-year risk of CHD based on the Framingham risk score (FRS) which includes age, sex, total and HDL cholesterol, blood pressure, diabetes, and smoking status. Of twelve SNPs identified in prior GWAS to be associated with CHD, four were genotyped in the participants as part of a GWAS. Genotypes for seven SNPs were imputed from HapMap CEU population using the program MACH. We calculated a multiplex genetic risk score for each patient based on the odds ratios of the susceptibility SNPs and incorporated this into the FRS. Results The mean (SD) number of risk alleles was 12.31 (1.95), range 6-18. The mean (SD) of the weighted genetic risk score was 12.64 (2.05), range 5.75-18.20. The CHD genetic risk score was not correlated with the FRS (P = 0.78). After incorporating the genetic risk score into the FRS, a total of 380 individuals (30.6%) were reclassified into higher-(188) or lower-risk groups (192). Conclusion A genetic risk score based on measured/imputed genotypes at 11 susceptibility SNPs, led to significant reclassification in the 10-y CHD risk categories. Additional prospective studies are needed to assess accuracy and clinical utility of such reclassification.

Abstract Background Antiretroviral treatment services delivered in hospital settings in Africa increasingly lack capacity to meet demand and are difficult to access by patients. We evaluate the effectiveness of nurse led primary care based antiretroviral treatment by comparison with usual hospital care in a typical rural sub Saharan African setting. Methods We undertook a prospective, controlled evaluation of planned service change in Lubombo, Swaziland. Clinically stable adults with a CD4 count > 100 and on antiretroviral treatment for at least four weeks at the district hospital were assigned to either nurse led primary care based antiretroviral treatment care or usual hospital care. Assignment depended on the location of the nearest primary care clinic. The main outcome measures were clinic attendance and patient experience. Results Those receiving primary care based treatment were less likely to miss an appointment compared with those continuing to receive hospital care (RR 0·37, p < 0·0001). Average travel cost was half that of those receiving hospital care (p = 0·001). Those receiving primary care based, nurse led care were more likely to be satisfied in the ability of staff to manage their condition (RR 1·23, p = 0·003). There was no significant difference in loss to follow-up or other health related outcomes in modified intention to treat analysis. Multilevel, multivariable regression identified little inter-cluster variation. Conclusions Clinic attendance and patient experience are better with nurse led primary care based antiretroviral treatment care than with hospital care; health related outcomes appear equally good. This evidence supports efforts of the WHO to scale-up universal access to antiretroviral treatment in sub Saharan Africa.

Abstract Background Microarray measurements are susceptible to a variety of experimental artifacts, some of which give rise to systematic biases that are spatially dependent in a unique way on each chip. It is likely that such artifacts affect many SNP arrays, but the normalization methods used in currently available genotyping algorithms make no attempt at spatial bias correction. Here, we propose an effective single-chip spatial bias removal procedure for Affymetrix 6.0 SNP arrays or platforms with similar design features. This procedure deals with both extreme and subtle biases and is intended to be applied before standard genotype calling algorithms. Results Application of the spatial bias adjustments on HapMap samples resulted in higher genotype call rates with equal or even better accuracy for thousands of SNPs. Consequently the normalization procedure is expected to lead to more meaningful biological inferences and could be valuable for genome-wide SNP analysis. Conclusions Spatial normalization can potentially rescue thousands of SNPs in a genetic study at the small cost of computational time. The approach is implemented in R and available from the authors upon request.

Abstract Background The developments of high-throughput genotyping technologies, which enable the simultaneous genotyping of hundreds of thousands of single nucleotide polymorphisms (SNP) have the potential to increase the benefits of genetic epidemiology studies. Although the enhanced resolution of these platforms increases the chance of interrogating functional SNPs that are themselves causative or in linkage disequilibrium with causal SNPs, commonly used single SNP-association approaches suffer from serious multiple hypothesis testing problems and provide limited insights into combinations of loci that may contribute to complex diseases. Drawing inspiration from Gene Set Enrichment Analysis developed for gene expression data, we have developed a method, named GLOSSI (Gene-loci Set Analysis), that integrates prior biological knowledge into the statistical analysis of genotyping data to test the association of a group of SNPs (loci-set) with complex disease phenotypes. The most significant loci-sets can be used to formulate hypotheses from a functional viewpoint that can be validated experimentally. Results In a simulation study, GLOSSI showed sufficient power to detect loci-sets with less than 10% of SNPs having moderate-to-large effect sizes and intermediate minor allele frequency values. When applied to a biological dataset where no single SNP-association was found in a previous study, GLOSSI was able to identify several loci-sets that are significantly related to blood pressure response to an antihypertensive drug. Conclusion GLOSSI is valuable for association of SNPs at multiple genetic loci with complex disease phenotypes. In contrast to methods based on the Kolmogorov-Smirnov statistic, the approach is parametric and only utilizes information from within the interrogated loci-set. It properly accounts for dependency among SNPs and allows the testing of loci-sets of any size.

Background: Minimizing harm from antimicrobials requires use of the narrowest spectrum drug, at an effective dose for the minimum effective duration. Many prescribers are not currently following these guidelines. To address suboptimal antimicrobial use, the underlying reasons must be understood., Objectives: To identify factors influencing choices of antimicrobial drug, dose, and duration for companion animals., Subjects: Twenty-two veterinarians treating companion animals in Australia. Diversity of participants was deliberately sought., Methods: Semistructured interviews were conducted online. Two case studies were discussed, and then a range of broader questions was posed. Transcripts were analyzed thematically, using an inductive approach., Results: Few participants chose guideline-concordant management for the case studies. Prescribing choices were influenced by a complex array of factors associated with the clinical case, pet owner, drug, veterinarian, veterinary colleagues, and external factors. Key factors driving broad-spectrum antimicrobial use included a sense of safety, habit, ease of administering the drug (especially in cats), pharmaceutical marketing, and the self-perpetuating dispensary cycle. Many participants were concerned about antimicrobial resistance, but insufficiently informed about how to minimize this risk. Several participants believed that longer duration of treatment and ensuring patients finish a predetermined course would decrease the risk of antimicrobial resistance and improve clinical outcomes., Conclusions and Clinical Importance: Veterinarians are engaged with the concept of antimicrobial stewardship, but face numerous practical barriers and require more information. In particular, improved education is needed on enhancing patient safety by minimizing both spectrum of activity and duration of treatment, and dispelling myths about "finishing the course.", (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

In Australia, antimicrobials are given an importance rating by the Australian Strategic and Technical Advisory Group on antimicrobial resistance. High importance antimicrobials are those essential for the treatment or prevention of infections in humans, where there are few or no treatment alternatives. In this study we consulted with experts from across human and animal health using the Delphi consensus-building process to establish the circumstances under which antimicrobials with high importance to human health could be used in animals in Australia. We used three rounds of online surveys. Group responses were provided to participants in each subsequent round to facilitate convergence of opinion. Consensus was defined as 80 % or more of respondents selecting the same option for a question. By the end of the third round, consensus was achieved on eight items. This included the use of high importance antimicrobials being appropriate if culture and sensitivity testing indicated the organism was resistant to low- and medium-rated antimicrobials that could be used to treat the case. If any high-importance antimicrobials are prescribed for animals there was also agreement that a clear indication for this use and justification for antimicrobial choice must be recorded in the medical history, along with the dose rate, route of administration, the duration and the time point for review of the condition and associated antimicrobial therapy. Appropriateness of use of high importance antimicrobials in critically ill animals where culture and sensitivity results are not available is still undefined. Further work is also required to establish which particular organisation should be notified of the use of high importance antimicrobials not registered for use in animals. The Delphi process was valuable in facilitating consensus amongst international experts from a broad range of health backgrounds and experience., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Hendra virus (HeV) is lethal to horses and a zoonotic threat to humans in Australia, causing severe neurological and/or respiratory disease with high mortality. An equine vaccine has been available since 2012. Foals acquire antibodies from their dams by ingesting colostrum after parturition, therefore it is assumed that foals of mares vaccinated against HeV will have passive HeV antibodies circulating during the first several months of life until they are actively vaccinated. However, no studies have yet examined passive or active immunity against HeV in foals. Here, we investigated anti-HeV antibody levels in vaccinated mares and their foals. Testing for HeV neutralising antibodies is cumbersome due to the requirement for Biosafety level 4 (BSL-4) containment to conduct virus neutralisation tests (VNT). For this study, a subset of samples was tested for HeV G-specific antibodies by both an authentic VNT with infectious HeV and a microsphere-based immunoassay (MIA), revealing a strong correlation. An indicative neutralising level was then applied to the results of a larger sample set tested using the MIA. Mares had high levels of HeV-specific neutralising antibodies at the time of parturition. Foals acquired high levels of maternal antibodies which then waned to below predictive protective levels in most foals by 6 months old when vaccination commenced. Foals showed a suboptimal response to vaccination, suggesting maternal antibodies may interfere with active vaccination. The correlation analysis between the authentic HeV VNT and HeV MIA will enable further high throughput serological studies to inform optimal vaccination protocols for both broodmares and foals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Antimicrobial stewardship programmes (ASPs) are critically important for improving the appropriate use of antimicrobial agents in veterinary practice., Methods: One of three ASPs was implemented in 135 Australian general veterinary practices in 2018-2020. The ASP interventions and the perceived impact they had on antimicrobial prescribing were assessed by the veterinarians working in these veterinary practices. An online survey was distributed to all 520 veterinarians working in the trial practices and 267 responses were analysed., Results: Most veterinarians (174/267, 65%) thought they had an ASP at their clinic and most respondents who said that they were aware that they had an ASP at their clinic indicated that they had changed the way they prescribed antimicrobials because of the trial (125/170, 74%). Antimicrobial prescribing guidelines, the traffic light system for indicating antimicrobial importance, delayed prescribing and antimicrobial stewardship champions were reported to have had the biggest impact., Limitations: All practices in the trial belong to a single corporate group, which may impact the external validity of these results when applied to general small animal practice., Conclusion: Antimicrobial stewardship has a positive impact on antimicrobial prescribing in veterinary medicine and future interventions should focus on the implementation of the effective interventions identified in this study., (© 2023 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Veterinarians sometimes prescribe antimicrobials even when they know or suspect that they are unnecessary. The drivers of this behaviour must be understood to design effective antimicrobial stewardship interventions. Semi-structured interviews were conducted with 22 veterinarians who treated companion animals in Australia. The Theory of Planned Behaviour was used to organise interview themes, focusing on a decision to withhold antimicrobial therapy in the absence of a clear indication. Many background factors influenced antimicrobial-withholding decisions, including the veterinarian's communication skills, general attitudes towards antimicrobial resistance (AMR), habits and energy levels. Client awareness of AMR and the veterinarian-client relationship were also important. Beliefs about the consequences of withholding antimicrobials (behavioural beliefs) were dominated by fears of the animal's condition deteriorating and of failing to meet client expectations. These fears, weighed against the seemingly distant consequences of AMR, were major barriers to withholding antimicrobials. Normative beliefs were primarily focused on the expected approval (or disapproval) of the client and of other veterinarians. Control beliefs about the difficulty of withholding antimicrobials centred around client factors, most importantly, their capacity to adequately monitor their animal, to pay for further investigations, or to undertake non-antimicrobial management, such as wound care, at home. The use of antimicrobials by companion animal veterinarians in the absence of a clear indication is often powerfully driven by behavioural beliefs, chiefly, fears of clinical deterioration and of failing to meet client expectations.

The timely implementation of antimicrobial stewardship interventions could delay or prevent the development of higher levels of antimicrobial resistance in the future. In food-producing animals in Australia, high-importance antimicrobials, as rated by the Australian Strategic and Technical Advisory Group (ASTAG), include virginiamycin and third-generation cephalosporins (in individual pigs or cattle). The use of high-importance antimicrobials in companion animals is more widespread and less regulated. There is no national antimicrobial use surveillance system for animals in Australia. Consequently, there is a gap in the knowledge about reasonable use across all sectors of veterinary practice. This study explored attitudes towards the use in veterinary medicine of antimicrobials with high importance to human health, and determined levels of agreement about the introduction of restrictions or other conditions on this use. An online survey was distributed via social media and email from June to December 2020 to veterinarians working in Australia. Of the 278 respondents working in clinical practice, 49% had heard of the ASTAG rating system, and 22% used a traffic light system for antimicrobial importance in their practice. Overall, 61% of participants disagreed that veterinarians should be able to prescribe high-importance antimicrobials without restrictions. If there were to be restrictions, there was most agreement amongst all respondents for only restricting high-importance antimicrobials (73%). There is a need for education, guidance, and practical support for veterinarians for prescribing high-importance antimicrobials alongside any restrictions.