Objective comparison of a sit to stand test to the walk test for the identification of unilateral lameness caused by cranial cruciate ligament disease in dogs.

OBJECTIVE: The purpose of this study was to evaluate a sit to stand test with the walk test for the identification of unilateral cranial cruciate ligament rupture in dogs. MATERIALS AND METHODS: Peak vertical force and vertical impulse were measured on a pressure-sensitive walkway, during a sit to stand test and walk test, and in 10 dogs with unilateral cranial cruciate ligament rupture and 18 non-lame dogs. Data collected were used to calculate symmetry indices (SI) of ipsilateral and contralateral hindlimbs (HL), diagonal limb pairs (DLP) and ipsilateral limb pairs (ILP). RESULTS: The symmetry indices of peak vertical force of HL during the walk test and sit to stand test were 100% and 90% sensitive for discriminating lame and non-lame dogs respectively. The symmetry indices of vertical impulse of HLs during the walk test and sit to stand test were 100% and 50% sensitive for discriminating lame and non-lame dogs respectively. Analysis of ipsilateral and diagonal limb pairs did not improve the discrimination in either test. The time taken to collect data from the sit to stand test data was shorter than for the walk test. CLINICAL SIGNIFICANCE: Whilst the sit to stand test required a shorter time for collection of data than the walk test, it did not accurately identify all dogs with lameness associated with CCLR, and thus has relatively limited clinical utility in its tested form.

Using global feedback to induce learning of gist of abnormality in mammograms.

Extraction of global structural regularities provides general 'gist' of our everyday visual environment as it does the gist of abnormality for medical experts reviewing medical images. We investigated whether naïve observers could learn this gist of medical abnormality. Fifteen participants completed nine adaptive training sessions viewing four categories of unilateral mammograms: normal, obvious-abnormal, subtle-abnormal, and global signals of abnormality (mammograms with no visible lesions but from breasts contralateral to or years prior to the development of cancer) and receiving only categorical feedback. Performance was tested pre-training, post-training, and after a week's retention on 200 mammograms viewed for 500 ms without feedback. Performance measured as d' was modulated by mammogram category, with the highest performance for mammograms with visible lesions. Post-training, twelve observed showed increased d' for all mammogram categories but a subset of nine, labelled learners also showed a positive correlation of d' across training. Critically, learners learned to detect abnormality in mammograms with only the global signals, but improvements were poorly retained. A state-of-the-art breast cancer classifier detected mammograms with lesions but struggled to detect cancer in mammograms with the global signal of abnormality. The gist of abnormality can be learned through perceptual/incidental learning in mammograms both with and without visible lesions, subject to individual differences. Poor retention suggests perceptual tuning to gist needs maintenance, converging with findings that radiologists' gist performance correlates with the number of cases reviewed per year, not years of experience. The human visual system can tune itself to complex global signals not easily captured by current deep neural networks.

Applying Mendelian randomization to appraise causality in relationships between smoking, depression and inflammation.

Smoking, inflammation and depression commonly co-occur and may be mechanistically linked. However, key questions remain around the direction of association and the influence of residual confounding. We aimed to characterize the association between lifetime smoking and depression, as well as to assess the role that genetically-predicted C-reactive protein (CRP) level, (an archetypal generalized inflammatory marker) and/or IL-6 activity, as a potential explanation for this association. We performed inverse variance weighted Mendelian randomization (MR) analyses using recently published summary-level GWAS data for lifetime smoking index, CRP levels, and depression. A subset of inflammatory-related genetic variants from the lifetime smoking GWAS were also used to assess the potential inflammatory causal pathways between smoking and depression. The analysis indicated reciprocal relationships of lifetime smoking with depression (ORSmk-Dep = 2.01, 95% CI 1.71-2.37, p < 0.001; ORDep-Smk = 1.09, 95% CI 1.06-1.13, p < 0.001), CRP levels and IL-6 activity (ORSmk-CRP = 1.40, 95% CI 1.21-1.55, p < 0.001; ORCRP-Smk = 1.03, 95% CI 1.02-1.05, p < 0.001, ORIL-6/CRP-Smk = 1.06 (1.03-1.09), p < 0.001). These associations were also supported by the majority of the robust MR methods performed. We did not find evidence for a reciprocal relationship between CRP levels (using > 500 genetic instruments for CRP) and depression (ORCRP-Dep = 1.01, 95% CI 0.99-1.04; ORDep-CRP = 1.03, 95% CI 0.99-1.07). We observed little variation in the IVW estimates between smoking and depression when we limited the genetic variants assessed to those related to measures of generalized inflammation, but we found evidence for an attenuation of the smoking-depression association in multivariable mendelian randomization when adjusting for IL-6 activity, suggesting that the IL-6 pathway may be at least in part responsible for the association of smoking and depression. Our study supports potential bidirectional causal associations between lifetime smoking and depression which may be at least in part explained by the IL-6 signalling pathway. The IL-6 pathway may represent a putative therapeutic target for smoking and to mitigate the effects of smoking on depression.

Microbiome and Neurotrauma: Emerging Innovations.

The gut-brain axis plays an important role in bidirectional communication that exists and can be altered by injury. Neurotrauma provides acute alteration in the GI tract and alters autonomic function. In this focused review, we highlight what is known about GI disruption following neurotrauma. We then delve into how this affects recovery. Areas of innovation and emerging pre-clinical results are addressed. Finally, we address the link between neurotrauma induced GI dysfunction and progression to neurodegenerative disease states.

An emotional discrete controller PSO tuned and designed for a real industrial pumping system.

The application of automation techniques to water pump systems, combined with modern control techniques, has been increasing the hydraulic and energy efficiency of such systems. In this context, the objective of this work is to present an intelligent method of flow control based on Brain Emotional Learning Basic Intelligent Control (BELBIC), which will be applied to an experimental workbench of a pumping system, located in the Energy Efficiency and Energy Quality Laboratory (LEEQE) at Federal University of Pernambuco (UFPE). The parameters of this controller are optimized with a particle swarm optimization (PSO) technique with minimization of Integral Absolute Error (IAE). Initial tests were performed in a computational environment so that the system's performance could be pre-tested, thereby the dynamics of the system was modeled from real data generated in the process. The experimental results were obtained through the implementation of this control system in a programmable logic controller (PLC), which was the device responsible for all the automation of the workbench previously mentioned. The data of this workbench were collected using a supervisory system exclusively developed for this work. These data were then used to analyze the performance of the proposed control system, which demonstrated that its behavior was efficient.

Alpha-1 antitrypsin limits neutrophil extracellular trap disruption of airway epithelial barrier function.

Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance and increasing paracellular flux, partially by NET-induced airway cell apoptosis. NETs selectively impact the expression of tight junction genes claudins 4, 8 and 11. Bronchial epithelia exposed to NETs demonstrate visible gaps in E-cadherin staining, a decrease in full-length E-cadherin protein and the appearance of cleaved E-cadherin peptides. Pretreatment of NETs with alpha-1 antitrypsin (A1AT) inhibits NET serine protease activity, limits E-cadherin cleavage, decreases bronchial cell apoptosis and preserves epithelial integrity. In conclusion, NETs disrupt human airway epithelial barrier function through bronchial cell death and degradation of E-cadherin, which are limited by exogenous A1AT.

Early Cytokine-Induced Transient NOX2 Activity Is ER Stress-Dependent and Impacts ß-Cell Function and Survival.

In type 1 diabetes (T1D) development, proinflammatory cytokines (PIC) released by immune cells lead to increased reactive oxygen species (ROS) production in ß-cells. Nonetheless, the temporality of the events triggered and the role of different ROS sources remain unclear. Isolated islets from C57BL/6J wild-type (WT), NOX1 KO and NOX2 KO mice were exposed to a PIC combination. We show that cytokines increase O2•- production after 2 h in WT and NOX1 KO but not in NOX2 KO islets. Using transgenic mice constitutively expressing a genetically encoded compartment specific H2O2 sensor, we show, for the first time, a transient increase of cytosolic/nuclear H2O2 in islet cells between 4 and 5 h during cytokine exposure. The H2O2 increase coincides with the intracellular NAD(P)H decrease and is absent in NOX2 KO islets. NOX2 KO confers better glucose tolerance and protects against cytokine-induced islet secretory dysfunction and death. However, NOX2 absence does not counteract the cytokine effects in ER Ca2+ depletion, Store-Operated Calcium Entry (SOCE) increase and ER stress. Instead, the activation of ER stress precedes H2O2 production. As early NOX2-driven ROS production impacts ß-cells' function and survival during insulitis, NOX2 might be a potential target for designing therapies against early ß-cell dysfunction in the context of T1D onset.

Kyphosis and 3-year fall risk in community-dwelling older men.

Hyperkyhosis is thought to be a fall risk factor in older adults. This large study of older men found that fall risk increased with greater kyphosis measured with the blocks method, but did not find an association between kyphosis and falls when measured by the commonly used the Cobb angle method. INTRODUCTION: Research suggests an association between hyperkyphosis and falls in community-dwelling older adults, though this has not been investigated within large, population-based studies. This study sought to determine whether two measures of kyphosis prospectively predict fall risk over 3 years among older men. METHODS: Within the Osteoporotic Fractures in Men Study (MrOS), we conducted two 3-year prospective studies of 2346 and 2928 men. The first group had kyphosis measured by the Cobb angle at visit 1, while the second group had kyphosis assessed with the blocks method at visit 3; both groups then self-reported falls tri-annually for 3 years. Poisson regression with GEE was used to obtain relative risks (RR) of falls. RESULTS: The fall rates over 3 years were 651/1000 person-years among the visit 1 sample (mean age 74 ± 6 years) and 839/1000 person-years among the visit 3 sample (mean age 79 ± 5 years). In adjusted models of the visit 3 sample, the risk of falls was increased by 12% for each standard deviation increase (1.4 blocks) in the number of blocks required to achieve a neutral head and neck position (RR = 1.12, 95% CI = 1.06, 1.18). The Cobb angle was not associated with falls in the visit 1 sample. CONCLUSIONS: Although the Cobb angle did not predict falls in community-dwelling older men over 3 years, the blocks method of measuring kyphosis was predictive of falls in this population. This difference could be due to the Cobb angle's focus on thoracic kyphosis, whereas the blocks method may additionally capture abnormal cervical spine curvature.