152 research outputs found
Assessment of Stress in Laboratory Beagle Dogs Constrained by a Pavlov Sling
The 3Rs - Replacement, Reduction and Refinement - have become increasingly
important in designing animal experiments. The Pavlov sling is thought to be a
non-invasive method to restrain dogs for examinations. The aim of our study
was to investigate whether laboratory Beagle dogs that had been trained to
tolerate restraint by a Pavlov sling are stressed by this procedure and,
furthermore, to analyze their behavior during this period. Five male and five
female Beagle dogs were used, each three years of age. Animals were restrained
in the Pavlov sling for 30 min on six days with an interval of at least two
days. The following behaviors were recorded every minute for each session:
postures of body, head, and ears, as well as state of eyes, tail, legs, and
mouth. Additionally, the animals were observed for the occurrence of
particular stress signs, including body shaking, sweating of the paws,
increased saliva production, piloerection, blinking of eyes, snout licking,
yawning, and panting. As an indicator for stress, salivary cortisol levels
were measured before, during, and after each session. Our results show that
for most behavioral parameters, e.g., body, leg, head, tail, and ear posture,
the frequency of changes between different behavior patterns, as well as
cortisol concentration, were not influenced by restraint in the Pavlov sling.
Therefore, the Pavlov sling does not seem to be perceived as a stressful
situation by the Beagle dogs. Our study demonstrates that under certain
conditions the use of the Pavlov sling in trained dogs can substitute for more
ordinary methods of immobilization, e.g., the use of narcotics
Watching or Listening: How Visual and Verbal Information Contribute to Learning a Complex Dance Phrase
While learning from observation is generally regarded as major learning mode for motor actions, evidence from dance practice suggests that learning dance movement through verbal instruction might provide a promising way to support dancers' individual interpretation of and identification with the movement material. In this multidisciplinary project, we conducted a study on the learning of dance movement through two modalities, observation of a human model in a video clip and listening to the audio-recording of a verbal movement instruction. Eighteen second year dance students learned two dance phrases, one from observation and one from verbal instruction, and were video-recorded performing the learned material. In a second learning step, they were presented the complementary information from the other modality, and their performance was recorded again. A third recording was carried out in a retention test 10 days after learning. Completeness scores representing the recall of the dance phrases, expert ratings addressing the performance quality and questionnaires reflecting the participants' personal impressions were used to evaluate and compare the performance at different stages of the learning process. Results show that learning from observation resulted in better learning outcomes in terms of both recall and approximation of the model phrase, whereas individual interpretation of the learned movement material was rated equally good after initially verbal and initially visual learning. According to the questionnaires, most participants preferred learning initially from observation and found it more familiar, which points toward an influence of learning habit caused by common training practice. The findings suggest that learning dance movement initially from observation is more beneficial than from verbal instruction, and add aspects with regards to multimodal movement learning with potential relevance for dance teaching and training
Reldesemtiv in Patients with Spinal Muscular Atrophy: a Phase 2 Hypothesis-Generating Study
This phase 2, double-blind, placebo-controlled, hypothesis-generating study evaluated the effects of oral reldesemtiv, a fast skeletal muscle troponin activator, in patients with spinal muscular atrophy (SMA). Patients â„ 12 years of age with type II, III, or IV SMA were randomized into 2 sequential, ascending reldesemtiv dosing cohorts (cohort 1: 150 mg bid or placebo [2:1]; cohort 2: 450 mg bid or placebo [2:1]). The primary objective was to determine potential pharmacodynamic effects of reldesemtiv on 8 outcome measures in SMA, including 6-minute walk distance (6MWD) and maximum expiratory pressure (MEP). Changes from baseline to weeks 4 and 8 were determined. Pharmacokinetics and safety were also evaluated. Patients were randomized to reldesemtiv 150 mg, 450 mg, or placebo (24, 20, and 26, respectively). The change from baseline in 6MWD was greater for reldesemtiv 450 mg than for placebo at weeks 4 and 8 (least squares [LS] mean difference, 35.6 m [p = 0.0037] and 24.9 m [p = 0.058], respectively). Changes from baseline in MEP at week 8 on reldesemtiv 150 and 450 mg were significantly greater than those on placebo (LS mean differences, 11.7 [p = 0.038] and 13.2 cm H2O [p = 0.03], respectively). For 6MWD and MEP, significant changes from placebo were seen in the highest reldesemtiv peak plasma concentration quartile (Cmax \u3e 3.29 ÎŒg/mL; LS mean differences, 43.3 m [p = 0.010] and 28.8 cm H2O [p = 0.0002], respectively). Both dose levels of reldesemtiv were well tolerated. Results suggest reldesemtiv may offer clinical benefit and support evaluation in larger SMA patient populations
Who uses self-exclusion to regulate problem gambling? A systematic literature review
Background and aims: Self-exclusion programs offer an intervention for individuals with problem gambling
behavior. However, these programs are insufficiently used. This review describes sociodemographic features and gambling behavior of self-excluders as well as goals and motives for initiating self-exclusion from terrestrial and online gambling. In addition, use of further professional help and barriers to self-exclusion are examined. Methods: Based on systematic literature search and quality assessment, n = 16 original studies (13 quantitative, 2 qualitative,
and 1 mixed method) published between 1997 and 2017 in English or German language were analyzed. Results are
presented for online and terrestrial gambling separately. Results: Online self-excluders were on average 10 years younger than terrestrial self-excluders. Self-exclusion was mainly motivated by financial problems, followed by feelings of losing control and problems with significant others. Financial problems and significant others were less
important for online than for terrestrial gamblers. Main barriers for self-exclusion were complicated enrollment processes, lack of complete exclusion from all venues, little support from venue staff, and lack of adequate information on self-exclusion programs. Both self-excluders from terrestrial and online gambling had negative attitudes toward the need of professional addiction care. Conclusion: To exploit the full potential of self-exclusion as a measure of gambler protection, its acceptance and its utilization need to be increased by target-group-specific information addressing financial issues and the role of significant others, simplifying the administrative processes, facilitating self-exclusion at an early stage of the gambling career, offering self-determined exclusion durations, and promoting additional use of professional addiction care
Empathy deficits, callousâunemotional traits and structural underpinnings in autism spectrum disorder and conduct disorder youth
Distinct empathy deficits are often described in patients with conduct disorder (CD) and autism spectrum disorder (ASD) yet their neural underpinnings and the influence of comorbid CallousâUnemotional (CU) traits are unclear. This study compares the cognitive (CE) and affective empathy (AE) abilities of youth with CD and ASD, their potential neuroanatomical correlates, and the influence of CU traits on empathy. Adolescents and parents/caregivers completed empathy questionnaires (Nâ=â148 adolescents, mean ageâ=â15.16âyears) and T1 weighted images were obtained from a subsample (Nâ=â130). Group differences in empathy and the influence of CU traits were investigated using Bayesian analyses and VoxelâBased Morphometry with ThresholdâFree Cluster Enhancement focusing on regions involved in AE (insula, amygdala, inferior frontal gyrus and cingulate cortex) and CE processes (ventromedial prefrontal cortex, temporoparietal junction, superior temporal gyrus, and precuneus). The ASD group showed lower parentâreported AE and CE scores and lower selfâreported CE scores while the CD group showed lower parentâreported CE scores than controls. When accounting for the influence of CU traits no AE deficits in ASD and CE deficits in CD were found, but CE deficits in ASD remained. Across all participants, CU traits were negatively associated with gray matter volumes in anterior cingulate which extends into the mid cingulate, ventromedial prefrontal cortex, and precuneus. Thus, although coâoccurring CU traits have been linked to global empathy deficits in reports and underlying brain structures, its influence on empathy aspects might be disorderâspecific. Investigating the subdimensions of empathy may therefore help to identify disorderâspecific empathy deficits
NLRX1 suppresses tumorigenesis and attenuates histiocytic sarcoma through the negative regulation of NF-κB signaling
Histiocytic sarcoma is an uncommon malignancy in both humans and veterinary species. Research exploring the pathogenesis of this disease is scarce; thus, diagnostic and therapeutic options for patients are limited. Recent publications have suggested a role for the NLR, NLRX1, in acting as a tumor suppressor. Based on these prior findings, we hypothesized that NLRX1 would function to inhibit tumorigenesis and thus the development of histiocytic sarcoma. To test this, we utilized Nlrx1â/â mice and a model of urethane-induced tumorigenesis. Nlrx1â/â mice exposed to urethane developed splenic histiocytic sarcoma that was associated with significant up-regulation of the NF-λB signaling pathway. Additionally, development of these tumors was also significantly associated with the increased regulation of genes associated with AKT signaling, cell death and autophagy. Together, these data show that NLRX1 suppresses tumorigenesis and reveals new genetic pathways involved in the pathobiology of histiocytic sarcoma
Toronto HCC Risk Index::A validated scoring system to predict 10-year risk of HCC in patients with cirrhosis
Background: Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. Aim: To assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk. Methods: A derivation cohort of patients with cirrhosis diagnosed by biopsy or non-invasive measures was identified through retrospective chart review. The disease-specific incidence of HCC was calculated according to etiology of cirrhosis. Factors associated with HCC were identified through multivariable Cox regression and used to develop a scoring system to predict HCC risk. The scoring system evaluated in an external cohort for validation. Results: Of 2,079 patients with cirrhosis and â„6 months follow-up, 226 (10.8%) developed HCC. The 10-year cumulative incidence of HCC varied by etiologic category from 22% in patients with viral hepatitis, to 16% in those with steatohepatitis and 5% in those with autoimmune liver disease (p<0.001). By multivariable Cox regression, age, sex, etiology and platelets were associated with HCC. Points were assigned in proportion to each hazard ratio to create the Toronto HCC Risk Index (THRI). The 10-year cumulative HCC incidence was 3%, 10% and 32% in the low (<120 points) medium (120-240) and high (>240) risk groups respectively, values that remained consistent after internal validation. External validation was performed on a cohort of patients with PBC, HBV and HCV cirrhosis (n= 1,144) with similar predictive ability (Harrellâs c-statistic 0.77) in the validation and derivation cohorts. Conclusion: HCC incidence varies markedly by etiology of cirrhosis. The THRI, using readily available clinical and laboratory parameters, has good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis
Donor NK and T Cells in the Periphery of Lung Transplant Recipients Contain High Frequencies of Killer Cell Immunoglobulin-Like Receptor-Positive Subsets
Introduction For end-stage lung diseases, double lung transplantation (DLTx) is the ultimate curative treatment option. However, acute and chronic rejection and chronic dysfunction are major limitations in thoracic transplantation medicine. Thus, a better understanding of the contribution of immune responses early after DLTx is urgently needed. Passenger cells, derived from donor lungs and migrating into the recipient periphery, are comprised primarily by NK and T cells. Here, we aimed at characterizing the expression of killer cell immunoglobulin-like receptors (KIR) on donor and recipient NK and T cells in recipient blood after DLTx. Furthermore, we investigated the functional status and capacity of donor vs . recipient NK cells. Methods Peripheral blood samples of 51 DLTx recipients were analyzed pre Tx and at T0, T24 and 3wk post Tx for the presence of HLA-mismatched donor NK and T cells, their KIR repertoire as well as activation status using flow cytometry. Results Within the first 3 weeks after DLTx, donor NK and T cells were detected in all patients with a peak at T0. An increase of the KIR2DL/S1-positive subset was found within the donor NK cell repertoire. Moreover, donor NK cells showed significantly higher frequencies of KIR2DL/S1-positive cells (p<0.01) 3wk post DLTx compared to recipient NK cells. This effect was also observed in donor KIR + T cells 3wk after DLTx with higher proportions of KIR2DL/S1 (p<0.05) and KIR3DL/S1 (p<0.01) positive T cells. Higher activation levels of donor NK and T cells (p<0.001) were detected compared to recipient cells via CD25 expression as well as a higher degranulation capacity upon activation by K562 target cells. Conclusion Higher frequencies of donor NK and T cells expressing KIR compared to recipient NK and T cells argue for their origin in the lung as a part of a highly specialized immunocompetent compartment. Despite KIR expression, higher activation levels of donor NK and T cells in the periphery of recipients suggest their pre-activation during the ex situ phase. Taken together, donor NK and T cells are likely to have a regulatory effect in the balance between tolerance and rejection and, hence, graft survival after DLTx
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