Phaidra - University of Veterinary Medicine Vienna
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Heart rate and salivary cortisol as indicators of arousal and synchrony in clients, therapy horses and therapist in equine-assisted therapy
No full textThis exploratory study aimed to analyse physiological interaction processes in equine-assisted-therapy (EAT) between client, therapy horse and therapist.We measured heart rate (HR), heart rate variability (HRV) and cortisol levels before, during and after a standardized therapy session and a control condition in one therapist, four therapy horses and ten female clients in emerging adulthood (Mn = 21.8 years, SD = 3.39). The clients were diagnosed with mild (N = 5) to moderate (N = 5) intellectual disability (ID).There was no significant change in the client\u27s HR, HRV and cortisol levels during an EAT session. No difference was observed between therapy sessions with or without a therapy horse, except during the challenge phase of the EAT protocol, where clients had a significantly lower HR when interacting with the therapy horse. HR between therapist and client correlated significantly, as well as between therapist and horse. This effect was greater when therapists interacted with a familiar horse. Clients\u27 and horses\u27 HRs also correlated, but only when the horse was the clients\u27 familiar and preferred horse.These results indicate that relationship intensity is an important factor for the synchronization process. Moreover, the inclusion of horses in a therapeutic setting can lead to a decreased HR in young adults with intellectual disability while mastering a challenge. Future research should investigate this potential benefit of EAT, considering the reciprocal influences and the relationship between client, therapist and horse
Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γ
No full textAll human herpesviruses establish latency following the resolution of the primary infection. Among these, α-herpesviruses HSV-1, HSV-2 and VZV establish latency in neurons, whereas neurons are not traditionally considered a site of latency for other herpesviruses. Using a combination of in vivo murine models and ex vivo human fetal tissues, we discovered that cytomegalovirus (CMV), a ubiquitous β-herpesvirus, can persist in neurons and that CD4+ T-cell-derived interferon-gamma is critical in restricting active viral replication in this cell type. Furthermore, we show that mouse CMV can establish latency in neurons and that CD4+ T-cells are essential in preventing viral reactivation. Our findings may have translational significance because human cytomegalovirus (HCMV) is the leading cause of congenital viral infections resulting in neurodevelopmental and neuroinflammatory lesions with long-term functional sequelae
Favorable pharmacokinetic and tolerability profiles make carprofen an attractive analgesic for subcutaneous injection and oral self-administration in rats
No full textAs basis for evidence-based analgesia refinement, species-specific pharmacokinetic and tolerability profiles of carprofen were determined in rats for least aversive administration routes and prolonged treatment. Further, potential influence on behavioral pain indicators was evaluated. LC-MS/MS determined plasma concentrations in Sprague-Dawley rats (n?=?21/sex) after subcutaneous (s.c.) injection (5 mg/kg) and during a 5-day treatment via the drinking water (d.w., 10 mg/kg/24 h). Irwin test parameters, clinical scoring, body weight, body temperature, fluid and food intake, grimace scale, burrowing, nesting, hematology, and histopathology were investigated. Plasma concentrations early after injection were higher in females, reached a maximum (Cmax) of 39.16?±?7.38 µg/ml at 3 h after injection and remained above an estimated in-vitro-derived therapeutic threshold (24.3 µg/ml) for at least 6 h with a T1/2 of 7.06 h. Carprofen-medicated d.w. was readily consumed, with constant target dose intake over the 5-day treatment period reaching a Cmax of 38.68?±?8.67 µg/ml at 24 h. Tolerability and behavioral parameters revealed only minor changes, such as transient sedation (s.c.) and decreased body temperature (females). Gastrointestinal adverse effects were not detected. Carprofen\u27s pharmacokinetic profile allows for a practicable s.c. injection interval. Acceptance and tolerability during prolonged oral treatment with the assessed dose of 10 mg/kg/24 h makes its non-invasive administration promising for analgesia refinement in rats
Cell-type-specific requirement for TYK2 in murine immune cells under steady state and challenged conditions
No full textTyrosine kinase 2 (TYK2) deficiency and loss or inhibition of kinase activity in men and mice leads to similar immune compromised phenotypes, predominantly through impairment of interferon (IFN) and interleukin 12 family responses. Here we relate the transcriptome changes to phenotypical changes observed in TYK2-deficient (Tyk2-/-) and TYK2 kinase-inactive (Tyk2K923E) mice in naïve splenic immune cells and upon ex vivo IFN treatment or in vivo tumor transplant infiltration. The TYK2 activities under homeostatic and both challenged conditions are highly cell-type-specific with respect to quantity and quality of transcriptionally dependent genes. The major impact of loss of TYK2 protein or kinase activity in splenic homeostatic macrophages, NK and CD8+ T cells and tumor-derived cytolytic cells is on IFN responses. While reportedly TYK2 deficiency leads to partial impairment of IFN-I responses, we identified cell-type-specific IFN-I-repressed gene sets completely dependent on TYK2 kinase activity. Reported kinase-inactive functions of TYK2 relate
to signaling crosstalk, metabolic functions and cell differentiation or maturation. None of these phenotypes relates to respective enriched gene sets in the TYK2 kinase-inactive cell types. Nonetheless, the scaffolding functions of TYK2 are capable to change transcriptional activities at single gene levels and chromatin accessibility at promoter-distal regions upon cytokine treatment most prominently in CD8+ T cells. The cell-type-specific transcriptomic and epigenetic effects of TYK2 shed new light on the biology of this JAK family member and are relevant for current and future treatment of autoimmune and inflammatory diseases with TYK2 inhibitors
Development and Validation of Targeted Metabolomics Methods Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for the Quantification of 235 Plasma Metabolites
No full textPlasma contains metabolites with diverse physicochemical properties, ranging from highly polar to highly apolar, and concentrations spanning at least nine orders of magnitude. Plasma metabolome analysis is valuable for monitoring health and evaluating medical interventions but is challenging due to the metabolome\u27s diversity and complexity. This study aims to develop and validate targeted LC-MS/MS methods for quantifying 235 mammalian metabolites from 17 compound classes in porcine plasma without prior derivatization. Utilizing reversed-phase and hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry, each analyte is identified and quantified using two selected reaction monitoring (SRM) transitions. Fast polarity switching and scheduled SRM enhance the metabolome coverage and throughput, enabling the analysis of one sample in about 40 min. A simple "dilute and shoot" sample preparation protocol was employed, with samples injected at two dilution levels to align metabolite concentrations within calibration curve ranges. Validation in porcine plasma included assessments of carryover, linearity, detection and quantification limits, repeatability and recovery. The method was further applied to plasma samples from various animal species, demonstrating its applicability to human and animal studies. This study establishes two robust LC-MS/MS methods for comprehensive porcine plasma metabolome quantification, advancing large-scale targeted metabolomics in biomedical research
Accelerated Endosomal Escape of Splice-Switching Oligonucleotides Enables Efficient Hepatic Splice Correction
No full textSplice-switching oligonucleotides (SSOs) can restore protein functionality in pathologies and are promising tools for manipulating the RNA-splicing machinery. Delivery vectors can considerably improve SSO functionality in vivo and allow dose reduction, thereby addressing the challenges of RNA-targeted therapeutics. Here, we report a biocompatible SSO nanocarrier, based on redox-responsive disulfide cross-linked low-molecular-weight linear polyethylenimine (cLPEI), for overcoming multiple biological barriers from subcellular compartments to en-route serum stability and finally in vivo delivery challenges. Intracellularly responsive cross-links of cLPEI significantly accelerated the endosomal escape and offered efficient SSO release to the cell\u27s nucleus, thereby leading to high splice correction in vitro. In vivo performance of cLPEI-SSOs was investigated in a novel transgenic mouse model for splice correction, spatiotemporal tracking of SSO delivery in wild-type mice, and biodistribution in a colorectal cancer peritoneal metastasis model. A single intravenous application of 5 mg kg-1 cLPEI-SSOs induced splice correction in liver, lung, kidney, and bladder, giving functional protein, which was validated by RT-PCR. Near-infrared (NIR) fluorescence imaging and X-ray computed tomography revealed improved organ retention and reduced renal excretion of SSOs. NIR microscopy demonstrated the accumulation of SSOs in angiogenic tumors within the pancreas. Successful nuclear delivery of SSOs was observed in the hepatocytes. Thus, cLPEI nanocarriers resulted in highly efficient splice correction in vivo, highlighting the critical role of the enhanced SSO bioavailability
A MALDI-ToF mass spectrometry database for identification and classification of highly pathogenic bacteria
No full textToday, MALDI-ToF MS is an established technique to characterize and identify pathogenic bacteria. The technique is increasingly applied by clinical microbiological laboratories that use commercially available complete solutions, including spectra databases covering clinically relevant bacteria. Such databases are validated for clinical, or research applications, but are often less comprehensive concerning highly pathogenic bacteria (HPB). To improve MALDI-ToF MS diagnostics of HPB we initiated a program to develop protocols for reliable and MALDI-compatible microbial inactivation and to acquire mass spectra thereof many years ago. As a result of this project, databases covering HPB, closely related bacteria, and bacteria of clinical relevance have been made publicly available on platforms such as ZENODO. This publication in detail describes the most recent version of this database. The dataset contains a total of 11,055 spectra from altogether 1,601 microbial strains and 264 species and is primarily intended to improve the diagnosis of HPB. We hope that our MALDI-ToF MS data may also be a valuable resource for developing machine learning-based bacterial identification and classification methods
Effect of unilateral arytenoid lateralisation on the rima glottidis volume in cats: a cadaveric study
No full textObjectives
This study aimed to document the percentage increase in the rima glottidis volume after unilateral cricoarytenoid lateralisation (CAL) in feline cadavers and establish categories and ranges to evaluate the degree of arytenoid abduction.
Methods
Left CAL was performed in nine cadavers. Pre- and postoperative video endoscopy was performed on each resting and lateralised larynx. The images were analysed using an imaging program. Based on reference markings, the increase in the volume of each rima glottidis was measured, and the penetration of the mucosa by the suture material was documented. Measurements were evaluated using Wilcoxon’s signed-rank test and objectively graded into four categories based on percentile volume increase, which were defined as unchanged (312%).
Results
During laryngoscopic examinations, none of the nine arytenoid cartilages was considered unchanged; one case was considered to be moderate, five were sufficiently lateralised and three were categorised as over abducted. Through objective videoendoscopic evaluations, we found that the mean increase in the rima glottidis volume was 264%. None of the larynxes were categorised as unchanged; two were categorised as moderately lateralised, with volume increases of 169% and 195%, respectively; four were categorised as sufficiently lateralised, with values in the range of 229–303%; and three were categorised as over abducted, with volume increases in the range of 324–335%. There was strong agreement between the objective and subjective evaluations. There was no evidence of mucosal perforation caused by the suture material.
Conclusions and relevance
Unilateral CAL in cats is a feasible option for increasing the rima glottidis volume. Postoperative laryngoscopic values correlated well with objective measurements; therefore, it is a good method to assess the degree of arytenoid abduction. Moderate lateralisation results in a significant volume increase, but values above 324% cause deformation of the larynx
Environmental efficiency and carbon sequestration potential of organic vs. conventional simmental dairy farming systems in Mountain regions: a case study
No full textNumerous studies have investigated the environmental impacts of dairy cattle farming systems using the Life Cycle Assessment (LCA) methodology. However, considering additional related factors can provide a broader perspective and more comprehensive contextualisation of the results. Net food production is a crucial aspect that adds valuable insights to the discussion on sustainable farming practices. Moreover, few studies have focused on mountain dairy farming systems, which differ significantly in structure and management from large-scale dairy operations in the lowlands. This study aims to provide a comprehensive comparison between conventionally and organically managed mountain dairy farms, specifically focusing on dual-purpose Simmental cattle. Six impact categories, Global Warming Potential (GWP100), Marine Eutrophication Potential (ME), Terrestrial Acidification Potential (TA), Land Use (LU), and Water Use (WU), were quantified via the LCA approach and attributed to one kilogram of Energy Corrected Milk (ECM) and one m2 of on-farm agricultural area. To determine the individual farm’s efficiency to provide human edible food, two additional indicators were calculated: milk yield deriving from roughage and net protein provision, based on the amount of human edible protein in the animal diet vs. the amount of human edible protein inside the milk. Further, carbon sequestration by permanent grassland was calculated for each farm. Results showed lower impacts of the organically managed farms (ORG group) for the categories ME (0.0009 vs. 0.0017 kg N eq) and WU (0.02 vs. 0.08 m³ kg ECM−1), while no significant differences could be found for GWP100 and TA, and the conventional farms (CON group) were more efficient in LU (0.97 vs. 1.54 m2a crop eq). In the case of net food production, the CON group showed an overall higher efficiency (0.023 vs. −0.016 NP kg ECM−1), mainly due to maize silage input. No significant difference was found in the C sequestration of permanent grassland between the two groups. This study analysed diverse mountain dairy farms using a single cattle breed, focusing on management, environmental impact, food efficiency, and carbon sequestration. Enhancing sustainability in these systems requires considering not only emissions but also their role in converting non-edible feed into food, maintaining low local environmental impact, preserving grasslands, and supporting ecosystem services
Erythemal UV radiation exposure during jogging
No full textJogging is one of the most popular recreational sport activities over four decades and is done at almost all ages to keep fitness and health. Joggers are exposed to solar UV radiation (UVR) and, due to enhanced heat production by physical activity, body coverage by clothes is reduced. This may imply a health risk due to overexposure. However, little research has been undertaken so far to estimate UVR exposure during jogging. Therefore, UVR exposure was measured at seven body sites during jogging under cloud-free conditions for solar elevations between 20° and 60°. Results show that the top of the shoulder is the most exposed body site by receiving 80% of ambient UVR on average and up to 110% under certain conditions. All other body parts receive up to 55% on average and up to 85% in special cases. This indicates further that monotonous body alignment to the sun holds a higher risk than a frequently alternating alignment. Assuming the longest recommended duration for cardiovascular beneficial jogging of 50 min, photosensitive persons need protection of the shoulders from a UV index of 2 onward on an unvaried path and from a UV index of 3 on an all-directional path. Further, results show that measurements of UVR exposure possess an uncertainty of ±15% including mounting.Online Version of Record before inclusion in an issue