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.

A Standardized Approach to Cesarean Surgical Technique and Its Effect on Operative Time and Surgical Morbidity.

OBJECTIVE: To evaluate the impact of a standardized surgical technique for primary cesarean deliveries (CDs) on operative time and surgical morbidity. MATERIALS AND METHODS: Two-year retrospective chart review of primary CD performed around the implementation of a standardized CD surgical technique. The primary outcome was total operative time (TOT). Secondary outcomes included incision-to-delivery time (ITDT), surgical site infection, blood loss, and maternal and fetal injuries. RESULTS: When comparing pre- versus postimplementation surgical times, there was no significant difference in TOT (76.5 vs. 75.9 minutes, respectively; p = 0.42) or ITDT (9.8 vs. 8.8 minutes, respectively; p = 0.06) when the entire cohort was analyzed. Subgroup analysis of CD performed early versus late in an academic year among the pre- and postimplementation groups showed no significant difference in TOT (79.3 early vs. 73.8 minutes late; p = 0.10) or ITDT (10.8 early vs. 8.8 minutes late; p = 0.06) within the preimplementation group. In the postimplementation group, however, there was significant decrease in TOT (80.5 early vs. 71.3 minutes late; p = 0.02) and ITDT (10.6 early vs. 6.8 minutes late; p < 0.01). Secondary outcomes were similar for both groups. CONCLUSION: A standardized surgical technique combined with surgical experience can decrease TOT and ITDT in primary CD without increasing maternal morbidity.

Bronchoscopic resection of a tracheobronchial leiomyoma in a pregnant patient.

Flexible bronchoscopy, therapeutic bronchoscopy and other procedures requiring anesthesia are generally avoided in pregnancy and postponed until after delivery if possible. We report a case of a parturient with an abnormal chest radiograph and mild obstructive symptoms of unknown etiology. At bronchoscopy, a tumor associated with post-obstructive suppuration was found and excised using electrocautery snare and cryotherapy, for restoration of airway patency. Coordination between pulmonary, obstetric, anesthesia, neonatology and thoracic surgery services was essential in ensuring success and the safety of the mother and fetus.

Proteinase-activated receptor-2 blockade inhibits changes seen in a chronic murine asthma model.

BACKGROUND: Proteinase-Activated Receptor-2 (PAR2 ) is a G protein-coupled receptor activated by serine proteinases. We have shown that PAR2 activation in the airways is involved in the development of allergic inflammation and airway hyperresponsiveness (AHR) in acute murine models. We hypothesized that functional inhibition of PAR2 prevents allergic inflammation, AHR and airway remodeling in chronic allergic airway inflammation models. MATERIAL AND METHODS: We developed and used a 12 week model of cockroach extract (CE)-mediated AHR, airway inflammation and remodeling in BALB/c mice. RESULTS: Mice sensitized and challenged with CE for 12 weeks exhibit AHR, increased numbers of eosinophils in bronchoalveolar lavage (BAL) and increased collagen content in the lung tissue compared to saline controls. Administration of an anti-PAR2 antibody, SAM-11, after the initial development of airway inflammation significantly inhibited all these parameters. CONCLUSIONS: Our data demonstrate that PAR2 signaling plays a key role in CE-induced AHR and airway inflammation/remodeling in long term models of allergic airway inflammation. Targeting PAR2 activation may be a successful therapeutic strategy for allergic asthma.

Kyphosis and incident falls among community-dwelling older adults.

Hyperkyphosis commonly affects older persons and is associated with morbidity and mortality. Many have hypothesized that hyperkyphosis increases fall risk. Within this prospective study of older adults, kyphosis was significantly associated with incident falls over 1 year. Measures of hyperkyphosis could enhance falls risk assessments during primary care office visits. INTRODUCTION: To determine the association between four measures of kyphosis and incident and injurious falls in older persons. METHODS: Community-dwelling adults aged 65 and older (n = 72) residing in southern California were invited to participate in a prospective cohort study. Participants had kyphosis assessed four ways. Two standing measures included a flexicurve ruler placed against the back to derive a kyphotic index and the Debrunner kyphometer, a protractor used to measure the kyphotic angle in degrees. Two lying measures included the blocks method (number of 1.7 cm blocks needed to achieve a neutral head position while lying supine) and traditional Cobb angle calculation derived from DXA based lateral vertebral assessment. Baseline demographic, clinical, and other health information (including a timed up and go (TUG) test) were assessed at a clinic visit. Participants were followed monthly through email or postcard for 1 year, with falls outcomes confirmed through telephone interview. RESULTS: Mean age was 77.8 (± 7.1) among the 52 women and 20 men. Over 12 months, 64% of participants experienced at least one incident fall and 35% experienced an injurious fall. Each standard deviation increase in kyphosis resulted in more than doubling the adjusted odds of an incident fall, even after adjusting for TUG. Odds of injurious falls were less consistent across measures; after adjusting for TUG, only the blocks method was associated with injurious falls. CONCLUSIONS: Each kyphosis measure was independently associated with incident falls. Findings were inconsistent for injurious falls; the blocks measure suggested the strongest association. If these findings are replicated, the blocks measure could be incorporated into office visits as a quick and efficient tool to identify patients at increased fall risk.

Mercury alkylation in freshwater sediments from Scottish canals.

Mercury concentrations were investigated in freshwater sediment from two canals in Scotland, UK. High concentrations found in the Union Canal (35.3-1200 mg kg-1) likely originate from historical munitions manufacture, with lower levels in the Forth & Clyde Canal (0.591-9.14 mg kg-1). Concentrations of methylmercury (MeHg) were low - from 6.02 to 18.6 µg kg-1 (0.001-0.023% of total Hg) in the Union Canal and from 3.44 to 14.1 µg kg-1 (0.11-0.58% of total Hg) in the Forth & Clyde Canal - and there was a significant inverse relationship between total Hg concentration and %MeHg. Total Hg concentration was significantly negatively correlated with pH and positively correlated with Fe content (in the Union Canal only) but not with organic matter, S content or the proportion of clay present. The MeHg concentration was not correlated with any of the above sediment parameters. Ethylmercury was detected in the most highly contaminated sediments from the Union Canal.

Population-based study demonstrating an increase in colorectal cancer in young patients.

BACKGROUND: New Zealand has among the highest rates of colorectal cancer in the world and is an unscreened population. The aim of this study was to determine the trends in incidence and tumour location in the New Zealand population before the introduction of national colorectal cancer screening. METHODS: Data were obtained from the national cancer registry and linked to population data from 1995 to 2012. Incidence rates for colorectal cancer by sex, age (less than 50 years, 50-79 years, 80 years or more) and location (proximal colon, distal colon and rectum) were assessed by linear regression. RESULTS: Among patients aged under 50 years, the incidence of distal colonic cancer in men increased by 14 per cent per decade (incidence rate ratio (IRR 1·14), 95 per cent c.i. 1·00 to 1·30; P = 0·042); the incidence of rectal cancer in men increased by 18 per cent (IRR 1·18, 1·06 to 1·32; P = 0·002) and that in women by 13 per cent (IRR 1·13, 1·02 to 1·26; P = 0·023). In those aged 50-79 years, there was a reduction in incidence per decade of proximal, distal and rectal cancers in both sexes. In the group aged 80 years and over, proximal cancer incidence per decade increased by 19 per cent in women (IRR 1·19, 1·13 to 1·26; P < 0·001) and by 25 per cent in men (IRR 1·25, 1·18 to 1·32; P < 0·001); among women, the incidence of distal colonic cancer decreased by 8 per cent (IRR 0·92, 0·86 to 0·98); P = 0·012), as did that of rectal cancer (IRR 0·92, 0·86 to 0·97; P = 0·005). CONCLUSION: The increasing incidence of rectal cancer among younger patients needs to be considered when implementing screening strategies.

Hypersexuality in Psychiatric Conditions Observer-Rated Scale (HIPCORS): Evaluation of Reliability and Validity.

Hypersexual behavior is not uncommon in psychiatric presentations. Most available scales that measure hypersexual behavior are self-rated, often containing sexually explicit questions, unsuitable for use in mentally unwell people. Lack of a clinically suitable instrument may have resulted in underdetection and under-researching of hypersexuality in people with mental disorders, with potential to cause significant consequences for themselves and those around them, including family members, coclients, and clinicians. To address this need, we developed the Hypersexuality in Psychiatric Conditions Observer-Rated Scale (HIPCORS), a rater-rated, nonintrusive tool, designed for use in mentally unwell people. It has been shown to be a reliable and valid instrument.

Masking in reports of "most serious" events: bias in estimators of sports injury incidence in Canadian children. / Le phénomène du masquage dans le signalement des événements « les plus graves ¼ : biais influant sur les estimations des taux d'incidence des blessures sportives chez les enfants canadiens.

INTRODUCTION: Surveys that collect information on injuries often focus on the single "most serious" event to help limit recall error and reduce survey length. However, this can mask less serious injuries and result in biased incidence estimates for specific injury subcategories. METHODS: Data from the 2002 Health Behaviour in School-aged Children (HBSC) survey and from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) were used to compare estimates of sports injury incidence in Canadian children. RESULTS: HBSC data indicate that 6.7% of children report sustaining a sports injury that required an emergency department (ED) visit. However, details were only collected on a child's "most serious" injury, so children who had multiple injuries requiring an ED visit may have had sports injuries that went unreported. The rate of 6.7% can be seen to be an underestimate by as much as 4.3%. Corresponding CHIRPP surveillance data indicate an incidence of 9.9%. Potential masking bias is also highlighted in our analysis of injuries attended by other health care providers. CONCLUSION: The "one most serious injury" line of questioning induces potentially substantial masking bias in the estimation of sports injury incidence, which limits researchers' ability to quantify the burden of sports injury. Longer survey recall periods naturally lead to greater masking. The design of future surveys should take these issues into account. In order to accurately inform policy decisions and the direction of future research, researchers must be aware of these limitations.

INTRODUCTION: Les enquêtes sur la cueillette de données sur les blessures ciblent souvent « l'événement le plus grave ¼ dans le but de limiter les erreurs de mémoire et de réduire la longueur des questionnaires. Cela risque cependant de masquer des blessures moins graves et d'entraîner un biais dans les estimations des taux d'incidence de certaines sous-catégories de traumatismes. MÉTHODOLOGIE: Nous avons utilisé des données tirées de l'Enquête sur les comportements liés à la santé des enfants d'âge scolaire (ECSEAS) et du Système canadien hospitalier d'information et de recherche en prévention des traumatismes (SCHIRPT) pour comparer les estimations des taux d'incidence des blessures sportives chez les enfants canadiens. RÉSULTATS: D'après les données de l'ECSEAS, 6,7 % des enfants déclarent avoir subi une blessure sportive ayant nécessité une consultation à un service des urgences. N'ont cependant été recueillies que les données sur la blessure « la plus grave ¼ subie par l'enfant, ce qui fait qu'un enfant ayant subi de multiples blessures justifiant une consultation à un service des urgences est susceptible d'avoir subi des blessures sportives passées sous silence. La sous-estimation de ce taux de 6,7 % pourrait atteindre 4,3 %. D'après les données de surveillance du SCHIRPT correspondantes, le taux d'incidence de ces blessures est de 9,9 %. Nous mettons également en lumière dans notre analyse le biais potentiel de masquage lié aux blessures traitées par d'autres prestataires de soins de santé. CONCLUSION: Poser une question sur « la blessure la plus grave ¼ risque d'induire un biais de masquage considérable du taux d'incidence des blessures sportives, limitant ainsi la capacité des chercheurs à estimer l'ampleur réelle du phénomène. Des périodes de rappel plus longues entraînent inévitablement un phénomène de masquage plus important. La conception des enquêtes à venir devrait tenir compte de ces réalités. Si l'on veut faciliter une prise de décisions éclairées et orienter correctement les futures recherches, il faut que les chercheurs soient conscients de ces limitations.