Prognostic factors in dogs with common causes of proteinuria

Little is known about the prognostic value of increased urine protein to creatinine ratios (UPC) comparing different underlying diseases in dogs. Therefore, between 2014 and 2015, dogs with a UPC of 2,0 or higher measured were retrospectively analysed at least once. They were divided into groups of the most common underlying diseases, namely primary glomerulopathy, Cushing's disease, leishmaniasis and in a group of different diseases. Possible prognostic factors, like UPC at time of diagnosis, creatinine, urine specific gravity, albumin and haematocrit, were assessed. Eighty-nine dogs with severe proteinuria were included in the study. Median time of survival was 42 days. UPC and time of survival did not differ significantly between the groups. Among the dogs with primary glomerulopathy, identified significant risk factors for death included increased UPC (p=0,03), increased creatinine (p

Does experience matter? Assessing user motivations to accept a vehicle-to-grid charging tariff

Vehicle-to-grid (V2G) could be a cornerstone to ensure the efficient integration of a large number of electric vehicles (EVs) and the resulting electricity demand into the energy system. However, successful V2G adoption requires direct interaction with the EV user. To explore user preferences and requirements in the context of a V2G charging tariff, we conducted a survey (N = 1196). We assess users’ minimum range requirements and willingness to pay for a V2G charging tariff and relate them to users’ experience with EVs. By building a mediation model, we evaluate the importance of three charging strategies to guide users’ minimum range requirements and expected monetary savings. The results reveal EV owners’ preference for a climate-neutral charging strategy, leading to a higher readiness to accept lower minimum ranges and lower monetary savings. These results are especially important to aggregators, aiming to design profitable business models, while accounting for user requirements and preferences

The influence of rotator cuff tear type and weight bearing on shoulder biomechanics in an ex vivo simulator experiment

Glenohumeral biomechanics after rotator cuff (RC) tears have not been fully elucidated. This study aimed to investigate the muscle compensatory mechanism in weight-bearing shoulders with RC tears and asses the induced pathomechanics (i.e., glenohumeral translation, joint instability, center of force (CoF), joint reaction force). An experimental, glenohumeral simulator with muscle-mimicking cable system was used to simulate 30° scaption motion. Eight fresh-frozen shoulders were prepared and mounted in the simulator. Specimen-specific scapular anthropometry was used to test six RC tear types, with intact RC serving as the control, and three weight-bearing loads, with the non-weight-bearing condition serving as the control. Glenohumeral translation was calculated using instantaneous helical axis. CoF, muscle forces, and joint reaction forces were measured using force sensors integrated into the simulator. Linear mixed effects models (RC tear type and weight-bearing) with random effects (specimen and sex) were used to assess differences in glenohumeral biomechanics. RC tears did not change the glenohumeral translation (p > 0.05) but shifted the CoF superiorly (p ≤ 0.005). Glenohumeral translation and joint reaction forces increased with increasing weight bearing (p < 0.001). RC and deltoid muscle forces increased with the presence of RC tears (p ≤ 0.046) and increased weight bearing (p ≤ 0.042). The synergistic muscles compensated for the torn RC tendons, and the glenohumeral translation remained comparable to that for the intact RC tendons. However, in RC tears, the more superior CoF was close to where glenoid erosion occurs in RC tear patients with secondary osteoarthritis. These findings underscore the importance of early detection and precise management of RC tears

Serum Lipidome Signatures of Dogs with Different Endocrinopathies Associated with Hyperlipidemia

Hyperlipidemia (hypertriglyceridemia, hypercholesterolemia) is a common finding in human and veterinary patients with endocrinopathies (e.g., hypothyroidism and hypercortisolism (Cushing’s syndrome; CS)). Despite emerging use of lipidomics technology in medicine, the lipid profiles of these endocrinopathies have not been evaluated and characterized in dogs. The aim of this study was to compare the serum lipidomes of dogs with naturally occurring CS or hypothyroidism with those of healthy dogs. Serum samples from 39 dogs with CS, 45 dogs with hypothyroidism, and 10 healthy beagle dogs were analyzed using a targeted lipidomics approach with liquid chromatography-mass spectrometry. There were significant differences between the lipidomes of dogs with CS, hypothyroidism, and the healthy dogs. The most significant changes were found in the lysophosphatidylcholines, lysophosphatidylethanolamines, lysophosphatidylinositols, phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, ceramides, and sphingosine 1-phosphates. Lipid alterations were especially pronounced in dogs with hypothyroidism. Several changes suggested a more atherogenic lipid profile in dogs with HT than in dogs with CS. In this study, we found so far unknown effects of naturally occurring hypothyroidism and CS on lipid metabolism in dogs. Our findings provide starting points to further examine differences in occurrence of atherosclerotic lesion formation between the two diseases

Reliability of the fluoroscopic assessment of load-induced glenohumeral translation during a 30° shoulder abduction test

Rotator cuff tears are often linked to superior translational instability, but a thorough understanding of glenohumeral motion is lacking. This study aimed to assess the reliability of fluoroscopically measured glenohumeral translation during a shoulder abduction test. Ten patients with rotator cuff tears participated in this study. Fluoroscopic images were acquired during 30° abduction and adduction in the scapular plane with and without handheld weights of 2 kg and 4 kg. Images were labelled by two raters, and inferior-superior glenohumeral translation was calculated. During abduction, glenohumeral translation (mean (standard deviation)) ranged from 3.3 (2.2) mm for 0 kg to 4.1 (1.8) mm for 4 kg, and from 2.3 (1.5) mm for 0 kg to 3.8 (2.2) mm for 4 kg for the asymptomatic and symptomatic sides, respectively. For the translation range, moderate to good interrater (intra-class correlation coefficient ICC [95% confidence interval (CI)]; abduction: 0.803 [0.691; 0.877]; adduction: 0.705 [0.551; 0.813]) and intrarater reliabilities (ICC [95% CI]; abduction: 0.817 [0.712; 0.887]; adduction: 0.688 [0.529; 0.801]) were found. Differences in the translation range between the repeated measurements were not statistically significant (mean difference, interrater: abduction, -0.1 mm, p = 0.686; adduction, -0.1 mm, p = 0.466; intrarater: abduction 0.0 mm, p = 0.888; adduction, 0.2 mm, p = 0.275). This method is suitable for measuring inferior-superior glenohumeral translation in the scapular plane

Plasma endocannabinoids in cocaine dependence and their interaction with cocaine craving and metabotropic glutamate receptor 5 density in the human brain

Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N=103; 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N=92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N=33; controls: N=43). In an additional analysis using$^{11}$C-ABP688 positron emission tomography (PET) in a male subsample (CU: N=18; controls: N=16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence

Plasma endocannabinoids in cocaine dependence and their relation to cerebral metabotropic glutamate receptor 5 density

Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N = 103; 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N = 92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N = 33; controls: N = 43). In an additional analysis using $^{11}$C-ABP688 positron emission tomography (PET) in a male subsample (CU: N = 18; controls: N = 16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence

Load-induced glenohumeral translation after rotator cuff tears : protocol for an in vivo study

Background: Rotator cuff tears are a common shoulder injury, but they sometimes remain undiagnosed, as symptoms can be limited. Altered shoulder biomechanics can lead to secondary damage and degeneration. In biomechanical analyses, the shoulder (ie, the glenohumeral joint) is normally idealized as a ball-and-socket joint, even though a translation is often observed clinically. To date, no conclusive changes in glenohumeral translation have been reported in patients with rotator cuff tears, and it is unknown how an additional handheld weight that is comparable to those used during daily activities will affect glenohumeral translations in patients with rotator cuff tears. Objective: This study aims to assess the load-induced glenohumeral translation (liTr) in patients with rotator cuff tears and its association with the load-induced changes in muscle activation (liMA). Methods: Patients and asymptomatic controls will be recruited. Participants will fill out health questionnaires and perform 30° arm abduction and adduction trials, during which they will hold different handheld weights of a maximum of 4 kg while motion capture and electromyographic data are collected. In addition, fluoroscopic images of the shoulders will be taken for the same movements. Isometric shoulder muscle strength for abduction and rotation will be assessed with a dynamometer. Finally, shoulder magnetic resonance images will be acquired to assess muscle status and injury presence. The dose-response relationship between additional weight, liTr, and liMA will be evaluated. Results: Recruitment and data collection began in May 2021, and they will last until the recruitment target is achieved. Data collection is expected to be completed by the end of 2022. As of November 2022, data processing and analysis are in progress, and the first results are expected to be submitted for publication in 2023. Conclusions: This study will aid our understanding of biological variations in liTr, the influence of disease pathology on liTr, the potential compensation of rotator cuff tears by muscle activation and size, and the association between liTr and patient outcomes. The outcomes will be relevant for diagnosis, treatment, and rehabilitation planning in patients with rotator cuff tears

Hair Cortisol in Twins : Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

A. Palotie on työryhmän jäsen.Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.Peer reviewe