Characterization and in vitro susceptibility profile of bacterial samples harvest from canine chronic otitis

This study aimed to identify which are the most frequent bacteria evolved in cases of chronic otitis in dogs in the metropolitan region of Curitiba, as well to determine their in vitro antimicrobial susceptibility. Data of positive bacterial culture from dogs affected by chronic or recurrent otitis were compiled from the records of the veterinary hospital of Pontifícia Universidade Católica do Paraná, Curitiba, southern Brazil. In a period of 16 months, a total of 83 bacterial cultures were performed, resulting in 192 isolates. All isolates were submitted to antimicrobial susceptibility tests, based on the Kirby-Bauer technique using 17 drugs from 8 antibiotic classes (?-lactams, aminoglycosides, lincosamides, macrolides, polypeptides, quinolones, tetracyclines, and amphenicols). The five most frequent bacterial isolates were Staphylococcus spp. (58.32%), Proteus spp. (14.58%), Escherichia coli (9.90%) and Pseudomonas spp. (8.33%). The four most effective antibiotics were amikacin (13.29%), neomycin (24.47%), gentamicin (25.52%) and tobramycin (26.70%); however, these aminoglycosides may cause ototoxicity, and their use should be restricted when the tympanic membrane is intact. Quinolones also showed antimicrobial effectiveness, with 29.17% of the isolates showing resistance to ciprofloxacin and 29.69% to enrofloxacin. According to the results, it can be concluded that aminoglycosides and quinolones were effective against microorganisms of canine chronic otitis

Updating test-day milk yield factors for use in genetic evaluations and dairy production systems: a comprehensive review

Various methods have been proposed to estimate daily yield from partial yields, primarily to deal with unequal milking intervals. This paper offers an exhaustive review of daily milk yields, the foundation of lactation records. Seminal advancements in the late 20th century concentrated on two main adjustment metrics: additive additive correction factors (ACF) and multiplicative correction factors (MCF). An ACF model provides additive adjustments to two times AM or PM milk yield, which then becomes the estimated daily yields, whereas an MCF is a ratio of daily yield to the yield from a single milking. Recent studies highlight the potential of alternative approaches, such as exponential regression and other nonlinear models. Biologically, milk secretion rates are not linear throughout the entire milking interval, influenced by the internal mammary gland pressure. Consequently, nonlinear models are appealing for estimating daily milk yields as well. MCFs and ACFs are typically determined for discrete milking interval classes. Nonetheless, large discrete intervals can introduce systematic biases. A universal solution for deriving continuous correction factors has been proposed, ensuring reduced bias and enhanced daily milk yield estimation accuracy. When leveraging test-day milk yields for genetic evaluations in dairy cattle, two predominant statistical models are employed: lactation and test-day yield models. A lactation model capitalizes on the high heritability of total lactation yields, aligning closely with dairy producers’ needs because the total amount of milk production in a lactation directly determines farm revenue. However, a lactation yield model without harnessing all test-day records may ignore vital data about the shapes of lactation curves needed for informed breeding decisions. In contrast, a test-day model emphasizes individual test-day data, accommodating various intervals and recording plans and allowing the estimation of environmental effects on specific test days. In the United States, the patenting of test-day models in 1993 used to restrict the use of test-day models to regional and unofficial evaluations by the patent holders. Estimated test-day milk yields have been used as if they were accurate depictions of actual milk yields, neglecting possible estimation errors. Its potential consequences on subsequent genetic evaluations have not been sufficiently addressed. Moving forward, there are still numerous questions and challenges in this domain

The Resilient Dairy Genome Project - a general overview of methods and objectives related to feed efficiency and methane emissions.

The Resilient Dairy Genome Project (RDGP) is an international large-scale applied research project that aims to generate genomic tools to breed more resilient dairy cows. In this context, improving feed efficiency and reducing greenhouse gases from dairy is a high priority. The inclusion of traits related to feed efficiency (e.g., dry matter intake [DMI]) or greenhouse gases (e.g., methane emissions [CH4]) relies on available genotypes as well as high quality phenotypes. Currently, 7 countries, i.e., Australia [AUS], Canada [CAN], Denmark [DNK], Germany [DEU], Spain [ESP], Switzerland [CHE], and United States of America [USA] contribute with genotypes and phenotypes including DMI and CH4. However, combining data is challenging due to differences in recording protocols, measurement technology, genotyping, and animal management across sources. In this study, we provide an overview of how the RDGP partners address these issues to advance international collaboration to generate genomic tools for resilient dairy. Specifically, we describe the current state of the RDGP database, data collection protocols in each country, and the strategies used for managing the shared data. As of February 2022, the database contains 1,289,593 DMI records from 12,687 cows and 17,403 CH4 records from 3,093 cows and continues to grow as countries upload new data over the coming years. No strong genomic differentiation between the populations was identified in this study, which may be beneficial for eventual across-country genomic predictions. Moreover, our results reinforce the need to account for the heterogeneity in the DMI and CH4 phenotypes in genomic analysis

Multi-ancestry genome-wide association study of asthma exacerbations

Altres ajuts: European Regional Development Fund "ERDF A way of making Europe"; Allergopharma-EAACI award 2021; SysPharmPedia grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020; Sandler Family Foundation; American Asthma Foundation; RWJF Amos Medical Faculty Development Program; National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL117004, R01HL128439, R01HL135156, X01HL134589, R01HL141992, R01HL141845); National Institute of Health and Environmental Health Sciences (R01ES015794, R21ES24844); National Institute on Minority Health and Health Disparities (NIMHD) (P60MD006902, R01MD010443, R56MD013312); National Institute of General Medical Sciences (NIGMS) (RL5GM118984); Tobacco-Related Disease Research Program (24RT-0025, 27IR-0030); National Human Genome Research Institute (NHGRI) (U01HG009080); GlaxoSmithKline and Utrecht Institute for Pharmaceutical Sciences; Slovenian Research Agency (P3-0067); SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (C3330-16-500106); NHS Research Scotland; Wellcome Trust Biomedical Resource (099177/Z/12/Z); Genotyping National Centre (CeGEN) CeGen-PRB3-ISCIII (AC15/00015); UK Medical Research Council and Wellcome (102215/2/13/2); University of Bristol; Swedish Heart-Lung Foundation, Swedish Research Council; Region Stockholm (ALF project and database maintenance); NHS Chair of Pharmacogenetics via the UK Department of Health; Innovative Medicines Initiative (IMI) (115010); European Federation of Pharmaceutical Industries and Associations (EFPIA); Spanish National Cancer Research Centre; Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC19/17); Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF); U.S. National Institutes of Health (HL07966); European Social Fund "ESF Investing in your future"; Ministerio de Ciencia, Innovación y Universidades; Universidad de La Laguna (ULL); European Academy of Allergy and Clinical Immunology (EAACI); European Respiratory Society (ERS) (LTRF202101-00861); Ministry of Education, Science and Sport of the Republic of Slovenia (C3330-19-252012); Singapore Ministry of Education Academic Research Fund; Singapore Immunology Network (SIgN); National Medical Research Council (NMRC Singapore); Biomedical Research Council (BMRC Singapore); Agency for Science Technology and Research (A*STAR Singapore, N-154-000-038-001, R-154-000-191-112, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, R-154-000-A91-592, R-154-000-A95-592, R-154-000-B99-114, BMRC/01/1/21/18/077, BMRC/04/1/21/19/315, SIgN-06-006, SIgN-08-020, NMRC/1150/2008, H17/01/a0/008); Sime Darby Technology Centre; First Resources Ltd; Genting Plantation; Olam International; U.S. National Institutes of Health (HL138098).Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. Methods: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. Results: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR) = 0.82, p = 9.05 × 10 and replication: OR = 0.89, p = 5.35 × 10) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR = 0.85, p = 3.10 × 10 and replication: OR = 0.89, p = 1.30 × 10). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense

Genome-wide association study of asthma exacerbations despite inhaled corticosteroids use

Rationale Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies. Methods A genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 European-descent children treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed. Results Ten independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10−6). Of those, one variant at the CACNA2D3-WNT5A locus was nominally replicated in Europeans (rs67026078, p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found. Conclusions The intergenic region of CACNA2D3 and WNT5A was revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response

In Vitro and In Vivo Prostaglandin Production by the Gravid Uterus during Late Gestation in the Sow

Note:Prostaglandins (PG) are considered to be mediators of the events that lead to parturition.Final Fifteen sows were randomly divided into 3 groups of 5 each according to gestational age (GA; d 109, d 114 and at labor). Blood from the umbilical artery (FA), umbilical vein (FV), uterine artery (MA) and uterine vein (MV), and amniotic fluid (AMF), fetal urine (U), amnion (AM), allantochorion(ALC) and amniochorion (AMC) were collected from two fetuses per sow per GA. Prostaglandin concentrations in blood plasma IPLl, AMF, U, and 0-4 h incubates from dispersed placental cells were measured by radioimmunoasay. In addition, pre-term amniotic fluid (PAMF), pre-term CFU) or term-fetal urine ITFVI were added to ALC and to bovine seminal vesicle microsomes (BSVM) to assess the effect of these fluids on PG synthesis. […]Les prostaglandines (PG) sont considérées comme les médiatrices finales des évènements qui mènent à la mise basse. Quinze truies ont été divisées au hasard en 3 groupes de 5 chacun selon le stage gestationel (GA; j 109, j 114 et pendant le travail). Du sang de l'artère ombilicale (FA), de la veine ombilicale (FV), de l'artère utérine (MA) et de la veine utérine (MV), et du liquide amniotique (AMF), de l'urine fétale (U), l'amnios (AM), l'allantochorion (ALC) et l'amniochorion (AMC) ont été prélevées sur deux fetus par truie pour chaque GA. Les concentrations des prostaglandines dans le plasma sanguin (PL), AMF, U et des incubations de 0 à 4 heures de cellules placentaires dispersées ont été mesurées par essai radioimmunologique. En plus de liquide amniotique d'avant-terme (PAMF), de l'urine de fetus d'avant-terme (FU) et à pa terme (TFU) ont été ajoutés au ALC et à des microsomes de vesicules séminales bovines (BSVM) afin d'évaluer leurs effets sur la synthèse des prostaglandines. […

Effects of 60 Hz electric and magnetic fields on productivity, reproductive hormones, plasma minerals and minerals and neurotransmitter metabolites in cerebrospinal fluid in dairy cattle

This study was designed to determine the potential biological effects of electric and magnetic fields (EMF), generated by 735 kV alternating current (AC) high tension lines upon the hormonal profile, some health-related parameters, stress response and productivity in dairy cattle. An EMF exposure chamber to house eight animals at one time was constructed. Forty-nine cows were divided according to their production stage; 8 pregnant non-lactating cows, 16 pregnant lactating cows, 16 non-pregnant lactating cows and 9 non-lactating non-pregnant heifers. They were exposed to an EMF of 10 kilovolts per meter (kV/m) and 30 micro-Tesla $( mu T)$ in two different fashions: (a) for three consecutive periods of 28 days in two sequences either with the EMF on/off/on or off/on/off, in a switch back design; (b) for three consecutive periods with the sequence OFF (5 days), ON (30 days) and OFF (5-12 days). The intensity of the EMF chosen for the experiments resembled a situation in which the cattle are standing continuously under a 735 kV AC high tension line when the line has a maximum load of current. In reality, these conditions are found only for a few days during the winter in the Province of Quebec.Milk production and composition, feed consumption, blood hormonal profiles and cerebrospinal fluid (CSF) components were assessed during the different periods of exposure. Most of the variables assessed were not affected by EMF. However, there was a positive association between EMF and feed consumption, milk fat content, blood plasma progesterone during pregnancy and estrous cycle length. Also, there were changes in the mineral and neurotransmitter metabolite concentrations in the CSF that showed a relationship to the EMF.In conclusion, it could be stated that EMF caused a biological response in dairy cattle. It is speculated that these changes do not represent a health hazard for exposed cattle, although they warrant further research

Does modeling causal relationships improve the accuracy of predicting lactation milk yields?

This study compared 3 correlational (best prediction, linear regression, and feed-forward neural networks) and 2 causal models (recursive structural equation model and recurrent neural networks) for estimating lactation milk yields. The correlational models assumed associations between test-day milk yields (health conditions), while the casual models postulated unidirectional recursive effects between these test-day variables. Wood lactation curves were used to simulate the data and served as a benchmark model. Individual Wood lactation curves provided an excellent parametric interpretation of lactation dynamics, with their prediction accuracies depending on the coverage of the lactation curve dynamics. Best prediction outperformed other models in the absence of mastitis but was suboptimal when mastitis was present and unaccounted for. Recurrent neural networks yielded the highest accuracy when mastitis was present. Although causal models facilitated the inference about the causality underlying lactation, precisely capturing the causal relationships was challenging because the underlying biology was complex. Misspecification of recursive effects in the recursive structural equation model resulted in a loss of accuracy. Hence, modeling causal relationships does not necessarily guarantee improved accuracies. In practice, a parsimonious model is preferred, balancing model complexity and accuracy. In addition to the choice of statistical models, the proper accounting for factors and covariates affecting milk yields is equally crucial

Human genetics influences microbiome composition involved in asthma exacerbations despite inhaled corticosteroid treatment.

BACKGROUND: The upper-airway microbiome is involved in asthma exacerbations despite inhaled corticosteroid (ICS) treatment. Although human genetics regulates microbiome composition, its influence on asthma-related airway bacteria remains unknown. OBJECTIVE: We sought to identify genes and biological pathways regulating airway-microbiome traits involved in asthma exacerbations and ICS response. METHODS: Saliva, nasal, and pharyngeal samples from 257 European patients with asthma were analyzed. The association of 6,296,951 genetic variants with exacerbation-related microbiome traits despite ICS treatment was tested through microbiome genome-wide association studies. Variants with 1 × 10-4&nbsp