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Intervertebral disc disease (IVDD) is a very common cause of spinal cord compression in dogs. The errors of human surgeons operating on the wrong level or wrong side is a recognized problem and has been largely analyzed. To date, little information is available regarding these errors in dogs. The objective of this study was to assess the accuracy of disc localization prior to possible surgery for IVDD to ensure the surgeon begins their incision directly over the extruded disc. Eighty-five chondrodystrophic or brachycephalic dogs that presented with IVDD confirmed by CT or MRI scan were included in the study. Two small Backhaus clamps were placed cranial and caudal to the lesion site and a control clamp placed at the wing of the ilium. The main interest was whether the surgeon was able to preoperatively pinpoint the correct site for the surgery. Dorsoventral radiographs were taken to verify by another person if the clamps had been placed in the correct position. If the result was incorrect, the surgeon was asked to try again without knowing that the clamps were incorrect, and another radiograph was taken. This was repeated until the position was correct. The results were recorded as correct or incorrect and the number of attempts were registered. The results suggested no significant trend over time for any of the outcomes examined. There were some slight improvements over time, but none of the results was close to statistical significance. The findings of the study showed that in the thoracolumbar region the surgeon has a higher chance of incorrectly marking the exact site for surgery.

Asthma is a complex disease caused by genetic and environmental factors. Studies show that wheezing during rhinovirus infection correlates with childhood asthma development. Over 150 non-coding risk variants for asthma have been identified, many affecting gene regulation in T cells, but the effects of most risk variants remain unknown. We hypothesized that airway epithelial cells could also mediate genetic susceptibility to asthma given they are the first line of defense against respiratory viruses and allergens. We integrated genetic data with transcriptomics of airway epithelial cells subject to different stimuli. We demonstrate that rhinovirus infection significantly upregulates childhood-onset asthma-associated genes, particularly in non-ciliated cells. This enrichment is also observed with influenza infection but not with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or cytokine activation. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma., Competing Interests: Declaration of interests J.A.B. has served on scientific advisory boards for Siolta Therapeutics, Third Harmonic Bio, and Sanofi/Aventis. N.A.B. has served on scientific advisory boards for Regeneron., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Screening asthma patients for atopy facilitates management. Since 2010, the core biomarker for screening asthma subjects for atopic status has been the qualitative Phadiatop. multi-aeroallergen screen. A more quantitative macroarray, the Allergy Explorer (ALEX 2 ), shows promise as an alternative., Objective: The study's goal was to examine the pros and cons of the use of ALEX 2 in the screening of asthma patients for atopic status., Methods: We evaluated the atopic (IgE-sensitization) status in asthmatic Amish and Hutterite farm children using the ImmunoCAP and ALEX 2 assays in Phadiatop equivocal and positive subjects., Results: All 42 asthmatic children were analyzed by Phadiatop and total serum IgE. Of these, 22 had a negative Phadiatop (<0.1 kUa/L) and total IgE <100 kU/L which defined them as non-atopic and they were excluded from ALEX 2 testing. Of six children with equivocal Phadiatops (0.1-0.2 kUa/L-Group 1) and three children with a negative Phadiatop but total IgE >100 kUa/L (group 3), 44% ( n  = 4) had detectable IgE antibody by ALEX 2 to mite, tree pollen, and other allergens not detected by Phadiatop, but confirmed by allergen-specific ImmunoCAP testing. In 11 Phadiatop positive subjects (>0.2 kUa/L-group 2), all but one were positive by ALEX 2 . IgE antibody specific for mold and rabbit aeroallergens matched their agricultural and pet exposure history. Three children were positive for IgE antibody to allergens in the profilin, nsLTP, or PR-10 cross-reactive protein families., Conclusion: Judicious use of ALEX 2 's enhanced specificity data not provided by the Phadiatop can aid in the interpretation of sensitization patterns and planning management of atopic asthmatics, but sensitization relevance must be confirmed by the patient's clinical history.

Background: Ultrasound-guided kidney biopsy is an essential diagnostics method that can increase the accuracy of the differential diagnosis between acute and chronic nephropathies. In addition, it will help clinicians perform an etiologic diagnosis, issue a prognosis, and orient therapy for the majority of parenchymal nephropathies. Due to the relative invasiveness and potential adverse effects, the use of kidney biopsies is limited among practitioners., Results: Twenty-eight dogs, of mixed breed and variable ages, of which 11 (39, 29%) were males and 17 (60, 71%) were females, were examined and underwent an ultrasound-guided kidney biopsy to establish a definitive diagnosis. The patients were presented with a variety of diffuse nephropathies, such as kidney lymphoma: 1 (3.57%), glomerulonephritis: 13 (46.43%), tubulointerstitial nephritis: 11 (39.29%), and nephrocalcinosis. A total of 3 (10.71%) of 18 (64.29%) were in acute kidney injury, and 10 (35.71%) were CKD patients. The type and the severity of the kidney lesions were correlated with changes in the urinary n-acetyl-beta-d-glucosaminidase index (iNAG. To quantify the side effects of percutaneous kidney biopsy, the magnitude of post-biopsy hematuria and changes in urinary iNAG activity were evaluated. The results indicate a significant post-biopsy increase in the urinary iNAG activity in all the patients that underwent this procedure (100.08 ± 34.45 U/g), with a pre-biopsy iNAG vs. 147.65 ± 33.26 U/g post-biopsy iNAG ( p < 0.001), suggesting an intensification in the kidney tubular damage that comes consecutives to kidney puncture and sampling. Transitory macro- or microhematuria were constant findings in all the dogs that underwent ultrasound-guided kidney biopsy, but the magnitude and extent could not be associated with the platelet count (PLT 109/L), aPTT (s), and PT (s) levels in our patients, and they were also resolved after 12-24 h without therapeutic interventions., Conclusions: Ultrasound-guided renal biopsy was shown to be a minimally invasive diagnostic procedure that causes transient and limited effects on kidney structures. Although these effects were minor and resolved without intervention, we feel that the benefit of obtaining higher-quality biopsied tissue outweighs the higher risks associated with this procedure.

Asthma has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A goal of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to understand multi-omic signatures of asthma focusing on populations of African ancestry. RNASeq and DNA methylation data are generated from nasal epithelium including cases (current asthma, N = 253) and controls (never-asthma, N = 283) from 7 different geographic sites to identify differentially expressed genes (DEGs) and gene networks. We identify 389 DEGs; the top DEG, FN1, was downregulated in cases (q = 3.26 × 10 -9 ) and encodes fibronectin which plays a role in wound healing. The top three gene expression modules implicate networks related to immune response (CEACAM5; p = 9.62 × 10 -16 and CPA3; p = 2.39 × 10 -14 ) and wound healing (FN1; p = 7.63 × 10 -9 ). Multi-omic analysis identifies FKBP5, a co-chaperone of glucocorticoid receptor signaling known to be involved in drug response in asthma, where the association between nasal epithelium gene expression is likely regulated by methylation and is associated with increased use of inhaled corticosteroids. This work reveals molecular dysregulation on three axes - increased Th2 inflammation, decreased capacity for wound healing, and impaired drug response - that may play a critical role in asthma within the African Diaspora., (© 2024. The Author(s).)

Polygenic risk score (PRS) prediction of complex diseases can be improved by leveraging related phenotypes. This has motivated the development of several multi-trait PRS methods that jointly model information from genetically correlated traits. However, these methods do not account for vertical pleiotropy between traits, in which one trait acts as a mediator for another. Here, we introduce endoPRS, a weighted lasso model that incorporates information from relevant endophenotypes to improve disease risk prediction without making assumptions about the genetic architecture underlying the endophenotype-disease relationship. Through extensive simulation analysis, we demonstrate the robustness of endoPRS in a variety of complex genetic frameworks. We also apply endoPRS to predict the risk of childhood onset asthma in UK Biobank by leveraging a paired GWAS of eosinophil count, a relevant endophenotype. We find that endoPRS significantly improves prediction compared to many existing PRS methods, including multi-trait PRS methods, MTAG and wMT-BLUP, which suggests advantages of endoPRS in real-life clinical settings.

Designing smart (bio)interfaces with the capability to sense and react to changes in local environments offers intriguing possibilities for new surface-based sensing devices and technologies. Polymer brushes make ideal materials to design such adaptive and responsive interfaces given their large variety of functional and structural possibilities as well as their outstanding abilities to respond to physical, chemical, and biological stimuli. Herein, a practical sensory interface for glucose detection based on auto-fluorescent polymer brushes decorated with phenylboronic acid (PBA) receptors is presented. The glucose-responsive luminescent surfaces, which are capable of translating conformational transitions triggered by pH variations and binding events into fluorescent readouts without the need for fluorescent dyes, are grown from both nanopatterned and non-patterned substrates. Two-photon laser scanning confocal microscopy and atomic force microscopy (AFM) analyses reveal the relationship between the brush conformation and glucose concentration and confirm that the phenylboronic acid functionalized brushes can bind glucose over a range of physiologically relevant concentrations in a reversible manner. The combination of auto-fluorescent polymer brushes with synthetic receptors presents a promising avenue for designing innovative and robust sensing systems, which are essential for various biomedical applications, among other uses., (© 2024 Wiley‐VCH GmbH.)

Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks, integration of different omics data types, cross-disciplinary interaction, strategies for overcoming current limitations, and the overarching goal to improve scientific understanding and care of asthma and allergic diseases., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Most genetic studies of asthma and allergy have focused on common variation in individuals primarily of European ancestry. Studying the role of rare variation in quantitative phenotypes and in asthma phenotypes in populations of diverse ancestries can provide additional, important insights into the development of these traits., Objective: We sought to examine the contribution of rare variants to different asthma- or allergy-associated quantitative traits in children with diverse ancestries and explore their role in asthma phenotypes., Methods: We examined whole-genome sequencing data from children participants in longitudinal studies of asthma (n = 1035; parent-identified as 67% Black and 25% Hispanic) to identify rare variants (minor allele frequency < 0.01). We assigned variants to genes and tested for associations using an omnibus variant-set test between each of 24,902 genes and 8 asthma-associated quantitative traits. On combining our results with external data on predicted gene expression in humans and mouse knockout studies, we identified 3 candidate genes. A burden of rare variants in each gene and in a combined 3-gene score was tested for its associations with clinical phenotypes of asthma. Finally, published single-cell gene expression data in lower airway mucosal cells after allergen challenge were used to assess transcriptional responses to allergen., Results: Rare variants in USF1 were significantly associated with blood neutrophil count (P = 2.18 × 10 -7 ); rare variants in TNFRSF21 with total IgE (P = 6.47 × 10 -6 ) and PIK3R6 with eosinophil count (P = 4.10 × 10 -5 ) reached suggestive significance. These 3 findings were supported by independent data from human and mouse studies. A burden of rare variants in TNFRSF21 and in a 3-gene score was associated with allergy-related phenotypes in cohorts of children with mild and severe asthma. Furthermore, TNFRSF21 was significantly upregulated in bronchial basal epithelial cells from adults with allergic asthma but not in adults with allergies (but not asthma) after allergen challenge., Conclusions: We report novel associations between rare variants in genes and allergic and inflammatory phenotypes in children with diverse ancestries, highlighting TNFRSF21 as contributing to the development of allergic asthma., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)