Vertebral stabilisation for thoracolumbar vertebral instability associated with cranial and caudal articular process anomalies in pugs: Seven cases (2010-2019).

OBJECTIVES: To describe the diagnostic findings, surgical technique and outcomes in seven pugs with thoracolumbar vertebral instability due to articular process anomalies. MATERIALS AND METHODS: Records (2010 to 2019) of pugs with thoracolumbar vertebral instability associated with articular process anomalies that underwent decompressive laminectomy and vertebral stabilisation were reviewed. Data on preoperative and postoperative neurologic status, diagnostic findings, surgical techniques and outcomes were retrieved. RESULTS: Seven dogs were presented with ambulatory or non-ambulatory paraparesis. Caudal articular process anomalies (three dogs) and concomitant cranial and caudal articular process anomalies (four dogs) were noted. Myelography (six dogs) or magnetic resonance imaging (one dog) showed none to severe spinal cord compression. Dynamic myelography in six dogs demonstrated nine distinct sites of spinal cord dimension reduction positioned in extension and/or flexion (mean reduction: 16.0%, range: 8.5 to 24.0%). These dynamic compressions were located at sites with articular process anomalies (seven sites) and sites with no articular process anomalies (two sites). Vertebral instability was confirmed by intraoperative spinal manipulation in all dogs. All dogs remained ambulatory with improved (five dogs) or static (two dogs) neurological deficits at the last follow-up (median: 16 months; range: 1.5 to 66 months). CLINICAL SIGNIFICANCE: Dynamic myelography and/or intraoperative spinal manipulation demonstrated vertebral instabilities at sites with or without articular process anomalies on imaging. Decompressive laminectomy with vertebral stabilisation resulted in long-term neurological improvement in most dogs.

A computational model of cardiomyocyte metabolism predicts unique reperfusion protocols capable of reducing cell damage during ischemia/reperfusion.

If a coronary blood vessel is occluded and the neighboring cardiomyocytes deprived of oxygen, subsequent reperfusion of the ischemic tissue can lead to oxidative damage due to excessive generation of reactive oxygen species. Cardiomyocytes and their mitochondria are the main energy producers and consumers of the heart, and their metabolic changes during ischemia seem to be a key driver of reperfusion injury. Here, we hypothesized that tracking changes in cardiomyocyte metabolism, such as oxygen and ATP concentrations, would help in identifying points of metabolic failure during ischemia and reperfusion. To track some of these changes continuously from the onset of ischemia through reperfusion, we developed a system of differential equations representing the chemical reactions involved in the production and consumption of 67 molecular species. This model was validated and used to identify conditions present during periods of critical transition in ischemia and reperfusion that could lead to oxidative damage. These simulations identified a range of oxygen concentrations that lead to reverse mitochondrial electron transport at complex I of the respiratory chain and a spike in mitochondrial membrane potential, which are key suspects in the generation of reactive oxygen species at the onset of reperfusion. Our model predicts that a short initial reperfusion treatment with reduced oxygen content (5% of physiological levels) could reduce the cellular damage from both of these mechanisms. This model should serve as an open-source platform to test ideas for treatment of the ischemia reperfusion process by following the temporal evolution of molecular concentrations in the cardiomyocyte.

A computational model of mutual antagonism in the mechano-signaling network of RhoA and nitric oxide.

BACKGROUND: RhoA is a master regulator of cytoskeletal contractility, while nitric oxide (NO) is a master regulator of relaxation, e.g., vasodilation. There are multiple forms of cross-talk between the RhoA/ROCK pathway and the eNOS/NO/cGMP pathway, but previous work has not studied their interplay at a systems level. Literature review suggests that the majority of their cross-talk interactions are antagonistic, which motivates us to ask whether the RhoA and NO pathways exhibit mutual antagonism in vitro, and if so, to seek the theoretical implications of their mutual antagonism. RESULTS: Experiments found mutual antagonism between RhoA and NO in epithelial cells. Since mutual antagonism is a common motif for bistability, we sought to explore through theoretical simulations whether the RhoA-NO network is capable of bistability. Qualitative modeling showed that there are parameters that can cause bistable switching in the RhoA-NO network, and that the robustness of the bistability would be increased by positive feedback between RhoA and mechanical tension. CONCLUSIONS: We conclude that the RhoA-NO bistability is robust enough in silico to warrant the investment of further experimental testing. Tension-dependent bistability has the potential to create sharp concentration gradients, which could contribute to the localization and self-organization of signaling domains during cytoskeletal remodeling and cell migration.

Medical infrared thermal imaging of syringomyelia in the Cavalier King Charles Spaniel.

BACKGROUND: Medical infrared thermal imaging (MITI) is a non-invasive imaging modality gaining popularity in the veterinary field. An infrared camera captures emission of heat and creates a color map in the form of a thermogram. Topical heat emission is influenced by localized disease processes as a result of autonomic nervous system imbalance. The purpose of this study was to determine the utility of using thermography to identify changes in thermographic patterns associated with syringomyelia (SM) presence or absence in Cavalier King Charles Spaniels (CKCS) with Chiari-like Malformation (CLM). RESULTS: In CKCS with CLM, MITI was most accurate at a texture distance of 6. Optimizing imaging feature sets produced a highest accuracy of 69.9% (95% CI: 59.5-79.0%), with 81.3% sensitivity and 57.8% specificity for identifying the presence of syringomyelia. CONCLUSION: Thermographic image analysis is a successful non-invasive, diagnostic test that can be used to screen for syringomyelia presence in a CKCS with CLM.

Medical infrared thermal imaging of canine appendicular bone neoplasia.

BACKGROUND: Medical infrared thermal imaging (MITI) is a noninvasive imaging modality used in veterinary medicine as a screening tool for musculoskeletal and neurological disease processes. An infrared camera measures the surface body heat and produces a color map that represents the heat distribution. Local trauma or disease can impair the autonomic nervous system, which leads to changes in the local dermal microcirculation and subsequent alteration of surface body heat. Disruption of autonomic flow to the cutaneous vasculature at deeper levels can also result in asymmetric thermographic results. The purpose of this study was to evaluate surface temperature differences between limbs affected by bone neoplasia and their normal contralateral limbs. RESULTS: A statistically significant difference in average temperature was noted between regions of interest of the two groups (paired difference: 0.53 C° ± 0.14; P = 0.0005). In addition, pattern recognition analysis yielded a 75-100% success rate in lesion identification. CONCLUSIONS: Significant alterations noted with average temperature and thermographic patterns indicate that MITI can document discernible changes associated with the presence of canine appendicular bone tumors. While MITI cannot be used as the sole diagnostic tool for bone cancer, it can be used as a screening modality and may be applicable in early detection of cancer.

Survival times in dogs with presumptive intracranial gliomas treated with oral lomustine: A comparative retrospective study (2008-2017).

Intracranial gliomas are a common malignancy in dogs, and are associated with a poor prognosis due to their aggressive nature and a lack of clinically effective treatments. The efficacies of various treatment modalities for canine brain tumours have been previously described, though little data exist on the use of cytotoxic chemotherapy. A comparative retrospective study, including 40 cases from 5 northeastern US veterinary hospitals, from 2008 to 2017, was conducted. Variables analysed in this study with relation to overall survival and prognostic significance included: age, sex, clinical signs, clinical sign duration, tumour location and treatment protocol used. Dogs with presumptive intracranial gliomas treated with lomustine chemotherapy lived longer (median, 138 days) than those treated exclusively with symptomatic care (median, 35 days; P = .0026 log-rank, 0.0138 Wilcoxon). Additionally, a duration of clinical signs ≥16 days prior to diagnosis (median, 109 days) was associated with a longer survival than a duration <16 days prior (median, 25 days; P = .0100 log-rank, 0.0322 Wilcoxon). Lomustine-associated side effects included neutropenia in 46% of dogs, anaemia in 15% and thrombocytopenia in 15%. Potential renal and hepatotoxicity based on increased BUN and/or creatinine and ALT values were reported in 15% and 50% of dogs, respectively. This study provides evidence that lomustine therapy may be effective in prolonging survival in dogs with intracranial gliomas and should be considered as a potential treatment option. Although lomustine-related toxicities are fairly common, they are rarely life threatening and often do not result in discontinuation of therapy.

Modeling oxygen requirements in ischemic cardiomyocytes.

Heart disease remains the leading cause of death globally. Although reperfusion following myocardial ischemia can prevent death by restoring nutrient flow, ischemia/reperfusion injury can cause significant heart damage. The mechanisms that drive ischemia/reperfusion injury are not well understood; currently, few methods can predict the state of the cardiac muscle cell and its metabolic conditions during ischemia. Here, we explored the energetic sustainability of cardiomyocytes, using a model for cellular metabolism to predict the levels of ATP following hypoxia. We modeled glycolytic metabolism with a system of coupled ordinary differential equations describing the individual metabolic reactions within the cardiomyocyte over time. Reduced oxygen levels and ATP consumption rates were simulated to characterize metabolite responses to ischemia. By tracking biochemical species within the cell, our model enables prediction of the cell's condition up to the moment of reperfusion. The simulations revealed a distinct transition between energetically sustainable and unsustainable ATP concentrations for various energetic demands. Our model illustrates how even low oxygen concentrations allow the cell to perform essential functions. We found that the oxygen level required for a sustainable level of ATP increases roughly linearly with the ATP consumption rate. An extracellular O2 concentration of ∼0.007 mm could supply basic energy needs in non-beating cardiomyocytes, suggesting that increased collateral circulation may provide an important source of oxygen to sustain the cardiomyocyte during extended ischemia. Our model provides a time-dependent framework for studying various intervention strategies to change the outcome of reperfusion.

Can Bedside Ultrasound Inferior Vena Cava Measurements Accurately Diagnose Congestive Heart Failure in the Emergency Department? A Clin-IQ.

Congestive heart failure (CHF) is a major cause of morbidity and mortality. Early diagnosis of CHF in patients presenting to the emergency department (ED) with undifferentiated dyspnea would allow clinicians to begin appropriate treatment more promptly. Current guidelines recommend B-type natriuretic peptide (BNP) levels for more accurate diagnosis of CHF in dyspneic patients. Although BNP levels are relatively inexpensive, the test is not usually performed at bedside and results may take up to an hour or more. BNP may also have a "gray zone" in which the values can neither confirm nor rule out CHF. BNP has a reported sensitivity of 87% and specificity of 74% at a cutoff of 400 pg/ml. Studies investigating the sensitivity and specificity of bedside ultrasound (US) inferior vena cava (IVC) measurements for identifying CHF report a specificity of 84% to 96% and sensitivity values ranging from 37% to 93%, depending on the study. Given that US IVC measurements are performed at bedside and results are available rapidly, it is reasonable to evaluate whether US IVC measurements, taken by appropriately trained ED clinicians, alone or in combination with BNP, may increase diagnostic accuracy of congestive heart failure.

Neutrophil gelatinase-associated lipocalin in dogs with chronic kidney disease, carcinoma, lymphoma and endotoxaemia.

OBJECTIVES: To measure serum and urine neutrophil gelatinase-associated lipocalin (NGAL) concentrations in healthy dogs and dogs with chronic kidney disease, neoplasia and endotoxaemia. METHODS: Serum and urine NGAL concentrations were measured in 42 healthy dogs, 11 dogs with chronic kidney disease, 12 dogs with carcinoma, 20 dogs with lymphoma and 15 dogs with lipopolysaccharide-induced endotoxaemia. In dogs with chronic kidney disease, NGAL was measured 3 and 6 months later. RESULTS: Compared with healthy controls, dogs with chronic kidney disease (PÄ0·0008), carcinoma (PÄ0·0072) and lymphoma (PÄ0·0008) had elevated serum and urine NGAL and urine NGAL-to-creatinine ratio. Serum and urine NGAL was not significantly different between dogs with chronic kidney disease, carcinoma or lymphoma (Pê0·12). In dogs with non-progressive chronic kidney disease, NGAL concentrations did not change significantly over the 6-month study period. CLINICAL SIGNIFICANCE: NGAL can be elevated by chronic kidney disease and neoplasia, compared with healthy controls. Further research is needed to determine if uNGAL or uNGAL-to-creatinine ratio is more specific than serum levels to detect chronic kidney disease.

Association Between PRRSV ORF5 Genetic Distance and Differences in Space, Time, Ownership and Animal Sources Among Commercial Pig Herds.

The objective of this study was to investigate associations between genetic distance of porcine reproductive and respiratory syndrome virus (PRRSV) detected in Ontario swine herds, and the distance between the herds with respect to space, time, ownership and animal sources. PRRSV sequence data between September 2004 and August 2007 were obtained from the Animal Health Laboratory of the University of Guelph. Geographical coordinates were obtained from the Ontario Pork marketing board, and network information about ownership and animal suppliers was obtained using a telephone interview. The matrices of sequence, spatial, temporal and network distances were generated and were analysed using the Mantel test, and using linear-mixed models with P-values based on random permutations. A total of 438 PRRSV isolates from 329 premises and 232 ownerships were originally included; 57 of the isolates were considered vaccine type. The Mantel correlation test indicated that there was positive correlation between sequence distance and geographic distance (r = 0.11, P = 0.001), as well as sequence distance and temporal distance (r = 0.03, P = 0.03), with similar results reported after adjusting for the ownership distance. Mantel correlogram suggested existence of spatial correlation up to ~30 km distance. Multivariable linear-mixed model for association between genetic distance and space-time distance was characterized by the three-way interaction among space, time and ownership (P < 0.001). It suggested that positive association between sequence similarity and spatial proximity exists in herds under different ownerships, but its magnitude is very small. In contrast, for pairs of herds under identical ownership, the spatial association was more complex. This could be a consequence of interactions within ownerships, or alternatively decisions made about sampling of herds for diagnostic purposes. Of the networks evaluated, ownership (P < 0.001) and gilt supplier (P < 0.001) showed the highest magnitude of association with genetic distance and should be investigated further for their impact on disease spread.

TENET: topological feature-based target characterization in signalling networks.

MOTIVATION: Target characterization for a biochemical network is a heuristic evaluation process that produces a characterization model that may aid in predicting the suitability of each molecule for drug targeting. These approaches are typically used in drug research to identify novel potential targets using insights from known targets. Traditional approaches that characterize targets based on their molecular characteristics and biological function require extensive experimental study of each protein and are infeasible for evaluating larger networks with poorly understood proteins. Moreover, they fail to exploit network connectivity information which is now available from systems biology methods. Adopting a network-based approach by characterizing targets using network features provides greater insights that complement these traditional techniques. To this end, we present Tenet (Target charactErization using NEtwork Topology), a network-based approach that characterizes known targets in signalling networks using topological features. RESULTS: Tenet first computes a set of topological features and then leverages a support vector machine-based approach to identify predictive topological features that characterizes known targets. A characterization model is generated and it specifies which topological features are important for discriminating the targets and how these features should be combined to quantify the likelihood of a node being a target. We empirically study the performance of Tenet from a wide variety of aspects, using several signalling networks from BioModels with real-world curated outcomes. Results demonstrate its effectiveness and superiority in comparison to state-of-the-art approaches. AVAILABILITY AND IMPLEMENTATION: Our software is available freely for non-commercial purposes from: https://sites.google.com/site/cosbyntu/softwares/tenet CONTACT: hechua@ntu.edu.sg or assourav@ntu.edu.sg SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Pharmacokinetics of single-dose rectal zonisamide administration in normal dogs.

BACKGROUND: Few medications are available for parental administration to animals with seizures. Rectal administration of medications is often used if the animal cannot be administered oral medications. HYPOTHESIS/OBJECTIVES: To determine the pharmacokinetic differences in zonisamide when administered rectally in either of 2 vehicles and p.o. to dogs. ANIMALS: Eight healthy research dogs. METHODS: Randomized cross-over design. Zonisamide, 10 mg/kg, was administered rectally in polyethylene glycol (PEG-R), rectally in water (H2O-R), and as an oral capsule. Plasma zonisamide concentrations were measured until 72 hours after administration. Zonisamide was quantitated by HPLC and plasma concentration versus time curve data was analyzed by using noncompartmental modeling. RESULTS: Mean maximum plasma zonisamide concentrations (µg/mL) were significantly higher after oral administration (11.56 ± 4.04) compared to H2O-R (5.00 ± 1.83) (P = .004). Disappearance half-life (hours) and mean time to maximum concentration (hours) were not significantly different between methods of administration. Mean relative bioavailability of PEG-R (85 ± 69%) was significantly higher than that of H2O-R (53 ± 37%) (P = .039). Dogs tolerated all dosing forms with no evidence of adverse effects. CONCLUSIONS AND CLINICAL IMPORTANCE: The vehicle in which zonisamide is dissolved influences rectal bioavailability, with PEG preferred to H2O-R. Because of the prolonged time to maximum concentration, rectal administration of zonisamide should not be used to treat status epilepticus in dogs. A dose higher than what was used in this study might be necessary, if currently recommended minimum therapeutic concentrations (10 µg/mL) are to be achieved with a single-dose administration.

Habitual condom use across partner type and sexual position among younger gay and bisexual men: findings from New Zealand HIV behavioural surveillance 2006-2011.

OBJECTIVES: Our objectives were to investigate demographic and behavioural factors associated with condom use and to examine how habitual condom use was across partner types and sexual positions among younger men who have sex with men (YMSM), aged 16-29, surveyed in New Zealand. METHODS: We analysed the 2006-2011 national HIV behavioural surveillance data from YMSM who reported anal intercourse in four scenarios of partner type and sexual position: casual insertive, casual receptive, regular insertive and regular receptive. For each, respondents' condom use was classified as frequent (always/almost always) or otherwise, with associated factors identified with multivariate mixed-effect logistic regression. Habitual condom use across scenarios was examined using a latent variable technique that estimated the intraclass correlation coefficient (ICC). RESULTS: Frequent condom use was reported for 63.6% of 5153 scenarios reported from 2412 YMSM. Frequent use increased from boyfriend to fuckbuddy to casual partners. Infrequent use was associated with online recruitment, Pacific ethnicity, less education, HIV positivity, sex with women, having ≥20 sexual partners versus 1 and reporting insertive and receptive sexual positions. Frequent condom use was associated with having two to five sexual partners versus one and shorter regular partnerships. The ICC=0.865 indicated highly habitual patterns of use; habitual infrequent condom use was most prevalent with regular partners (53.3%) and habitual frequent condom use was most prevalent with casual partners (70.2%) and for either sexual position (50.5% and 49.1%). CONCLUSIONS: Habitual condom use among YMSM highlights the value of early, engaging and sustained condom promotion. Public health should provide better and more compelling condom education, training and promotion for YMSM.

Three-dimensional conformal radiation therapy alone or in combination with surgery for treatment of canine intracranial meningiomas.

Treatment protocols, treatment planning methods and tumour types in studies evaluating radiotherapy for canine brain tumours have been varied. This case series retrospectively evaluated the outcome of definitive, three-dimensional conformal radiation therapy (3D-CRT) as either a sole modality or as an adjuvant to surgery in 31 dogs diagnosed with meningioma by histopathology (n = 10) or cross-sectional imaging of the head (n = 21, assessed independently by two board certified radiologists). Prescribed dose ranged from 45 to 54 Gy in 2.5 to 3 Gy fractions. Median overall survival was 577 days (interquartile range = 272-829 days; range = 30-1942 days) when all deaths were considered and 906 days (interquartile range = 336-912 days; range = 10 -1942 days) when only dogs dying due to meningioma were considered. No significant difference in survival time was detected for the defined clinical or imaging findings or between treatment with radiotherapy alone versus adjuvant radiotherapy, suggesting that 3D-CRT may be a viable alternative to surgery.

DiffNet: automatic differential functional summarization of dE-MAP networks.

The study of genetic interaction networks that respond to changing conditions is an emerging research problem. Recently, Bandyopadhyay et al. (2010) proposed a technique to construct a differential network (dE-MAPnetwork) from two static gene interaction networks in order to map the interaction differences between them under environment or condition change (e.g., DNA-damaging agent). This differential network is then manually analyzed to conclude that DNA repair is differentially effected by the condition change. Unfortunately, manual construction of differential functional summary from a dE-MAP network that summarizes all pertinent functional responses is time-consuming, laborious and error-prone, impeding large-scale analysis on it. To this end, we propose DiffNet, a novel data-driven algorithm that leverages Gene Ontology (go) annotations to automatically summarize a dE-MAP network to obtain a high-level map of functional responses due to condition change. We tested DiffNet on the dynamic interaction networks following MMS treatment and demonstrated the superiority of our approach in generating differential functional summaries compared to state-of-the-art graph clustering methods. We studied the effects of parameters in DiffNet in controlling the quality of the summary. We also performed a case study that illustrates its utility.

DualAligner: a dual alignment-based strategy to align protein interaction networks.

MOTIVATION: Given the growth of large-scale protein-protein interaction (PPI) networks obtained across multiple species and conditions, network alignment is now an important research problem. Network alignment performs comparative analysis across multiple PPI networks to understand their connections and relationships. However, PPI data in high-throughput experiments still suffer from significant false-positive and false-negatives rates. Consequently, high-confidence network alignment across entire PPI networks is not possible. At best, local network alignment attempts to alleviate this problem by completely ignoring low-confidence mappings; global network alignment, on the other hand, pairs all proteins regardless. To this end, we propose an alternative strategy: instead of full alignment across the entire network or completely ignoring low-confidence regions, we aim to perform highly specific protein-to-protein alignments where data confidence is high, and fall back on broader functional region-to-region alignment where detailed protein-protein alignment cannot be ascertained. The basic idea is to provide an alignment of multiple granularities to allow biological predictions at varying specificity. RESULTS: DualAligner performs dual network alignment, in which both region-to-region alignment, where whole subgraph of one network is aligned to subgraph of another, and protein-to-protein alignment, where individual proteins in networks are aligned to one another, are performed to achieve higher accuracy network alignments. Dual network alignment is achieved in DualAligner via background information provided by a combination of Gene Ontology annotation information and protein interaction network data. We tested DualAligner on the global networks from IntAct and demonstrated the superiority of our approach compared with state-of-the-art network alignment methods. We studied the effects of parameters in DualAligner in controlling the quality of the alignment. We also performed a case study that illustrates the utility of our approach. AVAILABILITY AND IMPLEMENTATION: http://www.cais.ntu.edu.sg/∼assourav/DualAligner/.

The effect of birth weight and age at tail docking and ear notching on the behavioral and physiological responses of piglets.

Selection for high prolificacy has resulted in litters comprising a large number of low-birth-weight (LBW) piglets. Given their presence in over 75% of litters and increased mortality rate, it is clear that a greater understanding of LBW piglet management is required for both animal welfare and productivity. In this study, we compared the effects of tail docking and ear notching LBW and average-birth-weight (ABW) piglets at 1 or 3 d of age on suckling, behavior, passive transfer of immunoglobulins, and growth. Six piglets per litter from 20 litters (n = 120 piglets) were used in a 2 × 2 complete block design. Piglets were weighed at birth and designated as LBW (0.6 to 1.0 kg) or ABW (≥ 1.2 kg) and "processed" (tail docked and ear notched) at either 1 or 3 d of age. Vocalizations were recorded during the procedures. The acute behavioral responses were observed for 10 min after the procedure. Piglets were observed for 6 h after birth and after the procedure to determine their presence at nursing bouts. On d 5, blood samples were collected to determine concentrations of serum immunoglobulins (IgA and IgG) and IGF-I. Piglet weights were recorded at birth and on d 5, 14, and 21. During the procedures, LBW piglets produced fewer (P = 0.03) calls than ABW piglets. Piglets from either birth weight category produced a similar number (calls/s; P = 0.29) of high-frequency calls (≥ 1,000 Hz), which are indicative of pain and distress, although the average frequency (Hz) of these calls was greatest (P = 0.05) for ABW piglets processed on d 3. Immediately following the procedures, LBW piglets spent more (P = 0.005) time dog-sitting and less (P = 0.005) time lying than ABW piglets. When observed with the sow, LBW males spent more (P = 0.001) time alone and had the lowest (P = 0.007) attendance at nursing bouts compared with LBW females and all ABW piglets. Concentrations of serum IgA (P = 0.06) and IgG (P = 0.04) and plasma IGF-I (P = 0.003) were lower for LBW than ABW piglets regardless of age of processing although the magnitude of these differences was likely not of biological significance. Average-birth-weight piglets may be less reactive to the acute effects of the procedures on d 1 than on d 3. Given the decreased likelihood of a LBW piglet surviving to weaning (P = 0.001), delaying processing until 3 d of age for LBW piglets may eliminate unnecessary procedures.