Analgesic and anti-inflammatory actions of robenacoxib in acute joint inflammation in dog

The objectives of this study were to establish dose-response and blood concentration-response relationships for robenacoxib, a novel nonsteroidal anti-inflammatory drug with selectivity for inhibition of the cyclooxygenase (COX)-2 isoenzyme, in a canine model of synovitis. Acute synovitis of the stifle joint was induced by intra-articular injection of sodium urate crystals. Robenacoxib (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg), placebo and meloxicam (0.2 mg/kg) were administered subcutaneously (s.c.) 3 h after the urate crystals. Pharmacodynamic endpoints included data from forceplate analyses, clinical orthopaedic examinations and time course of inhibition of COX-1 and COX-2 in ex vivo whole blood assays. Blood was collected for pharmacokinetics. Robenacoxib produced dose-related improvement in weight-bearing, pain and swelling as assessed objectively by forceplate analysis (estimated ED(50) was 1.23 mg/kg for z peak force) and subjectively by clinical orthopaedic assessments. The analgesic and anti-inflammatory effects of robenacoxib were significantly superior to placebo (0.25-4 mg/kg robenacoxib) and were non-inferior to meloxicam (0.5-4 mg/kg robenacoxib). All dosages of robenacoxib produced significant dose-related inhibition of COX-2 (estimated ED(50) was 0.52 mg/kg) but no inhibition of COX-1. At a dosage of 1-2 mg/kg administered s.c., robenacoxib should be at least as effective as 0.2 mg/kg of meloxicam in suppressing acute joint pain and inflammation in dogs.

In Vitro and In Vivo Imaging Characteristics Assessment of Polymeric Coils Compared with Standard Platinum Coils for the Treatment of Intracranial Aneurysms

BACKGROUND AND PURPOSE:Conventional platinum coils cause imaging artifacts that reduce imaging quality and therefore impair imaging interpretation on intraprocedural or noninvasive follow-up imaging. The purpose of this study was to evaluate imaging characteristics and artifact production of polymeric coils compared with standard platinum coils in vitro and in vivo.MATERIALS AND METHODS:Polymeric coils and standard platinum coils were evaluated in vitro with the use of 2 identical silicon aneurysm models coiled with a packing attenuation of 20% each. DSA, flat panel CT, CT, and MR imaging were performed. In vivo evaluation of imaging characteristics of polymeric coils was performed in experimentally created rabbit carotid bifurcation aneurysms. DSA, CT/CTA, and MR imaging were performed after endovascular treatment of the aneurysms. Images were evaluated regarding visibility of individual coils, coil mass, artifact production, and visibility of residual flow within the aneurysm.RESULTS:Overall, in vitro and in vivo imaging showed relevantly reduced artifact production of polymeric coils in all imaging modalities compared with standard platinum coils. Image quality of CT and MR imaging was improved with the use of polymeric coils, which permitted enhanced depiction of individual coil loops and residual aneurysm lumen as well as the peri-aneurysmal area. Remarkably, CT images demonstrated considerably improved image quality with only minor artifacts compared with standard coils. On DSA, polymeric coils showed transparency and allowed visualization of superimposed vessel structures.CONCLUSIONS:This initial experimental study showed improved imaging quality with the use of polymeric coils compared with standard platinum coils in all imaging modalities. This might be advantageous for improved intraprocedural imaging for the detection of complications and posttreatment noninvasive follow-up imaging.

Clinical Characteristics of Children with Viral Single- and Co-Infections and a Petechial Rash

BACKGROUND:: Children with petechial rash are more likely to undergo invasive diagnostics, to be treated with antibiotics for potential bacterial infection and to be hospitalized. However, viruses have also been associated with petechial rash. Nonetheless, a systematic analysis of viral infections with modern available techniques as quantitative real time polymerase chain reaction (q-PCR) in the context of petechial rash is lacking. The purpose of this pediatric study was to prospectively uncover viral pathogens that may promote the emergence of petechiae and to analyze the correlation with the clinical characteristics and course. METHODS:: We conducted a prospective study in children (0 to 18 years) presenting with petechiae and signs or symptoms of infection at the emergency department between November 2009 and March 2012. In nasopharyngeal aspirates the following viruses were analyzed by q-PCR: Cytomegalovirus, Epstein-Barr virus, parvovirus B19, Influenza A and B, parainfluenza viruses, human respiratory syncytial virus A and B, human metapneumovirus, rhinovirus, enterovirus, adenovirus, human coronavirus OC43, 229E, NL63 and human bocavirus. RESULTS:: A viral pathogen was identified in 67% of the analyzed 58 cases with petechial rash. Virus positive patients showed a significantly higher incidence of lower respiratory tract infections. Forty-one percent were viral co-infections, which were significantly younger than virus negative patients, had a higher leukocyte count and were hospitalized for a longer time. CONCLUSIONS:: A petechial rash is frequently associated viral single- and co-infections and can rapidly be identified via q-PCR.

Distribution of lactate dehydrogenase in healthy and degenerative canine stifle joint cartilage

In dogs, degenerative joint diseases (DJD) have been shown to be associated with increased lactate dehydrogenase (LDH) activity in the synovial fluid. The goal of this study was to examine healthy and degenerative stifle joints in order to clarify the origin of LDH in synovial fluid. In order to assess the distribution of LDH, cartilage samples from healthy and degenerative knee joints were investigated by means of light and transmission electron microscopy in conjunction with immunolabeling and enzyme cytochemistry. Morphological analysis confirmed DJD. All techniques used corroborated the presence of LDH in chondrocytes and in the interterritorial matrix of healthy and degenerative stifle joints. Although enzymatic activity of LDH was clearly demonstrated in the territorial matrix by means of the tetrazolium-formazan reaction, immunolabeling for LDH was missing in this region. With respect to the distribution of LDH in the interterritorial matrix, a striking decrease from superficial to deeper layers was present in healthy dogs but was missing in affected joints. These results support the contention that LDH in synovial fluid of degenerative joints originates from cartilage. Therefore, we suggest that (1) LDH is transferred from chondrocytes to ECM in both healthy dogs and dogs with degenerative joint disease and that (2) in degenerative joints, LDH is released from chondrocytes and the ECM into synovial fluid through abrasion of cartilage as well as through enhanced diffusion as a result of increased water content and degradation of collagen.

Connectionism as metaphor: Towards an integrated, unified conception of self-system and individual difference

Comments on an article by Kashima et al. (see record 2007-10111-001). In their target article Kashima and colleagues try to show how a connectionist model conceptualization of the self is best suited to capture the self's temporal and socio-culturally contextualized nature. They propose a new model and to support this model, the authors conduct computer simulations of psychological phenomena whose importance for the self has long been clear, even if not formally modeled, such as imitation, and learning of sequence and narrative. As explicated when we advocated connectionist models as a metaphor for self in Mischel and Morf (2003), we fully endorse the utility of such a metaphor, as these models have some of the processing characteristics necessary for capturing key aspects and functions of a dynamic cognitive-affective self-system. As elaborated in that chapter, we see as their principal strength that connectionist models can take account of multiple simultaneous processes without invoking a single central control. All outputs reflect a distributed pattern of activation across a large number of simple processing units, the nature of which depends on (and changes with) the connection weights between the links and the satisfaction of mutual constraints across these links (Rummelhart & McClelland, 1986). This allows a simple account for why certain input features will at times predominate, while others take over on other occasions. (PsycINFO Database Record (c) 2008 APA, all rights reserved)

Transient apical ballooning syndrome--clinical characteristics, ballooning pattern, and long-term follow-up in a Swiss population

BACKGROUND: Transient apical ballooning syndrome (TABS) or Takotsubo cardiomyopathy mimics acute ST-elevation myocardial infarction, but is considered to have a good prognosis with only moderate elevation of myocardial enzymes and full recovery of left ventricular function. Although it is increasingly reported, its exact incidence, clinical presentation, and prognosis in non-Asian populations remain largely unknown. OBJECTIVE: To describe the clinical characteristics and long-term follow-up of patients who presented with TABS at our institution over a 3 year-period. METHODS: Patients were retrospectively retrieved from our local database. Patient charts were carefully reviewed and the diagnosis of TABS was based on the Mayo Clinic diagnostic criteria. Moreover, psychosocial stress or gastrointestinal disease was recorded. RESULTS: During the study period, 13,715 coronary angiographies were performed at our institution, including 2459 patients presenting with an acute coronary syndrome (ACS). Forty-one TABS were diagnosed, which represents an incidence of 1.7% of ACS-patients and 0.3% of all coronary angiographies performed, respectively. Mean age was 65 years, with 85% women. Clinical presentations included chest pain, dyspnoea, and cardiogenic shock. A preceding psychological or physical condition perceived as "stress" was reported in 61%. At a mean follow-up of 675+/-288 days, none of the patients died of cardiac causes, but two patients had a recurrence of symptoms. CONCLUSIONS: This is the largest cohort of TABS patients reported out of Europe so far. The good overall prognosis and low likelihood of recurrence were confirmed.

Wolf habitat selection at the territory level : seasonal and interannual variation and influence on reproductive success

Habitat selection has been one of the main research topics in ecology for decades. Nevertheless, many aspects of habitat selection still need to be explored. In particular, previous studies have overlooked the importance of temporal variation in habitat selection and the value of including data on reproductive success in order to describe the best quality habitat for a species. We used data collected from radiocollared wolves in Yellowstone National Park (USA), between 1996 and 2008, to describe wolf habitat selection. In particular, we aimed to identify i) seasonal differences in wolf habitat selection, ii) factors influencing interannual variation in habitat selection, and iii) the effect of habitat selection on wolf reproductive success. We used probability density functions to describe wolf habitat use and habitat coverages to represent the habitat available to wolves. We used regression analysis to connect habitat use with habitat characteristics and habitat selection with reproductive success. Our most relevant result was discovering strong interannual variability in wolf habitat selection. This variability was in part explained by pack identity and differences in litter size and leadership of a pack between two years (summer) and in pack size and precipitation (winter). We also detected some seasonal differences. Wolves selected open habitats, intermediate elevations, intermediate distances from roads, and avoided steep slopes in late winter. They selected areas close to roads and avoided steep slopes in summer. In early winter, wolves selected wetlands, herbaceous and shrub vegetation types, and areas at intermediate elevation and distance from roads. Surprisingly, the habitat characteristics selected by wolves were not useful in predicting reproductive success. We hypothesize that interannual variability in wolf habitat selection may be too strong to detect effects on reproductive success. Moreover, prey availability and competitor pressure may also have an influence on wolf reproductive success, which we did not assess. This project demonstrated how important temporal variation is in shaping patterns of habitat selection. We still believe in the value of running long-term studies, but the effect of temporal variation should always be taken into account.

Functions and effects of creatine in the central nervous system

Creatine kinase catalyses the reversible transphosphorylation of creatine by ATP. In the cell, creatine kinase isoenzymes are specifically localized at strategic sites of ATP consumption to efficiently regenerate ATP in situ via phosphocreatine or at sites of ATP generation to build-up a phosphocreatine pool. Accordingly, the creatine kinase/phosphocreatine system plays a key role in cellular energy buffering and energy transport, particularly in cells with high and fluctuating energy requirements like neurons. Creatine kinases are expressed in the adult and developing human brain and spinal cord, suggesting that the creatine kinase/phosphocreatine system plays a significant role in the central nervous system. Functional impairment of this system leads to a deterioration in energy metabolism, which is phenotypic for many neurodegenerative and age-related diseases. Exogenous creatine supplementation has been shown to reduce neuronal cell loss in experimental paradigms of acute and chronic neurological diseases. In line with these findings, first clinical trials have shown beneficial effects of therapeutic creatine supplementation. Furthermore, creatine was reported to promote differentiation of neuronal precursor cells that might be of importance for improving neuronal cell replacement strategies. Based on these observations there is growing interest on the effects and functions of this compound in the central nervous system. This review gives a short excursion into the basics of the creatine kinase/phosphocreatine system and aims at summarizing findings and concepts on the role of creatine kinase and creatine in the central nervous system with special emphasis on pathological conditions and the positive effects of creatine supplementation.

Relationship between instream habitat characteristics, emergent insects, and riparian bird communities

Streams and riparian areas can be intricately connected via physical and biotic interactions that influence habitat conditions and supply resource subsidies between these ecosystems. Streambed characteristics such as the size of substrate particles influence the composition and the abundance of emergent aquatic insects, which can be an important resource for riparian breeding birds. We predict fine sediment abundance in small headwater streams directly affects the composition and number of emergent insects while it may indirectly affect riparian bird assemblages. Streams with abundant fine sediments that embed larger substrates should have lower emergence of large insects such as phemeroptera, Plecoptera and Trichoptera. Streams with lower emergent insect abundance are predicted to support fewer breeding birds and may lack certain bird species that specialize on aquatic insects. This study examined relationships between streambed characteristics, and emergent insects (composition, abundance and biomass), and riparian breeding birds (abundance and richness) along headwater streams of the Otter River Watershed. The stream bed habitats of seven stream reaches were characterized using longitudinal surveys. Malaise traps were deployed to sample emergent aquatic insects. Riparian breeding birds were surveyed using fixed-radius point-counts. Streams differed within a wide range of fine sediment abundances. Total emergent aquatic insect abundance increased as coverage by instream substrates increased in diameter, while bird community was unresponsive to insect or stream features. Knowledge of stream and riparian relationships is important for understanding of food webs in these ecosystems, and it is useful for riparian forest conservation and improving land-use management to reduce sediment pollution in these systems.

Early diagnosis of temporomandibular joint involvement in juvenile idiopathic arthritis: a pilot study comparing clinical examination and ultrasound to magnetic resonance imaging

OBJECTIVES: To study the validity of both rheumatological and orthodontic examinations and ultrasound (US) as screening methods for early diagnosis of TMJ arthritis against the gold standard MRI. METHODS: Thirty consecutive juvenile idiopathic arthritis (JIA) patients were included in this pilot study. Rheumatological and orthodontic examinations as well as US were performed within 1 month of the MRI in a blinded fashion. Joint effusion and/or increased contrast enhancement of synovium or bone were considered signs of active arthritis on MRI. RESULTS: A total of 19/30 (63%) patients and 33/60 (55%) joints had signs of TMJ involvement on MRI. This was associated with condylar deformity in 9/19 (47%) patients and 15/33 (45%) joints. Rheumatological, orthodontic and US examinations correctly diagnosed 11 (58%), 9 (47%) and 6 (33%) patients, respectively, with active TMJ arthritis, but misdiagnosed 8 (42%), 10 (53%) and 12 (67%) patients, respectively, as having no signs of inflammation. The best predictor for active arthritis on MRI was a reduced maximum mouth opening. CONCLUSION: None of the methods tested was able to reliably predict the presence or absence of MRI-proven inflammation in the TMJ in our cohort of JIA patients. US was the least useful of all methods tested to exclude active TMJ arthritis.

Phenotypes and echocardiographic characteristics of a European population of domestic shorthair cats with idiopathic hypertrophic cardiomyopathy

111 Domestic Shorthair cats with idiopathic hypertrophic cardiomyopathy were reviewed retrospectively. Two-dimensional echocardiography was used to classify cases in 6 established phenotypes. Hypertrophy was diffuse in 61 % of cats and involved major portions of the ventricular septum and the left ventricular free wall (phenotype D). In the remaining cats, distribution of hypertrophy was more segmental and was identified on the papillary muscles exclusively (phenotype A, 6 %), on the anterior and basal portion of the ventricular septum (phenotype B, 12 %), on the entire septum (phenotype C, 14 %), or on the left ventricular free wall (phenotype E, 7 %). Echocardiographic characteristics and clinical findings were determined for each phenotype to study the correlation between distribution of hypertrophy and clinical implications. 31 cats demonstrated systolic anterior motion of the mitral valve, 75 % of them belonged to phenotype C of hypertrophy. Left ventricular-outflow turbulences were identified more frequently with patterns of hypertrophy involving the ventricular septum (65.5 %), while prevalence of mitral regurgitation was higher when hypertrophy included the papillary muscles (phenotypes A and E, 85 % and 87 %, respectively). Left atrial dilatation occurred more frequently when hypertrophy was diffuse or confined to the left ventricular free wall (61 % of cats with phenotype D or E) rather than to the ventricular septum (31 % of cats with phenotype B or C).

Characteristics of visual hallucinations in Parkinson disease dementia and dementia with Lewy bodies

OBJECTIVE Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) have overlapping clinical and pathologic features. Recurrent visual hallucinations (RVH) are common in both disorders. The authors have compared details of hallucination characteristics and associated neuropsychiatric features in DLB and PDD. METHODS This is a descriptive, cross-sectional study using the Institute of Psychiatry Visual Hallucinations Interview (IP-VHI) to explore self-reported frequency, duration, and phenomenology of RVH in PDD and DLB. The caregivers' ratings of hallucinations and other neuropsychiatric features were elicited with the Neuropsychiatric Inventory (NPI). RESULTS Fifty-six patients (35 PDD; 21 DLB) with RVH were assessed. Hallucination characteristics were similar in both disorders. Simple hallucinations were rare. Most patients experienced complex hallucinations daily, normally lasting minutes. They commonly saw people or animals and the experiences were usually perceived as unpleasant. NPI anxiety scores were higher in PDD. Neuropsychiatric symptoms coexisting with hallucinations were apathy, sleep disturbance, and anxiety. CONCLUSIONS Patients with mild to moderate dementia can provide detailed information about their hallucinations. Characteristics of RVH were similar in PDD and DLB, and phenomenology suggests the involvement of dorsal and ventral visual pathways in their generation. The coexistence of RVH with anxiety, apathy, and sleep disturbance is likely to impair patients' quality of life and may have treatment implications.

Changes in situational and dispositional factors as predictors of job satisfaction

Arguably, job satisfaction is one of the most important variables with regard to work. When explaining job satisfaction, research usually focuses on predictor variables in terms of levels but neglects growth rates. Therefore it remains unclear how potential predictors evolve over time and how their development affects job satisfaction. Using multivariate latent growth modeling in a study with 1145 young workers over five years, we analyzed how well job satisfaction is predicted a) by levels of situational (i.e., job control) and dispositional (i.e., Core Self-Evaluations (CSE)) factors and b) by growth per year of these predictors. Results showed both intercepts and slopes to be related to each other, suggesting a joint growth of job control and CSE during early careers. Job satisfaction after five years was best predicted by the slopes of job control (β = .31, p < .001) and CSE (β = .34, p < .01). These findings provide further longitudinal evidence for the role of situational as well as dispositional factors for predicting job satisfaction. In addition, growth rates per year were better predictors than initial levels. Furthermore, a lack of change in job control or CSE went along with a drop in job satisfaction, implying that young workers need to perceive things to be improving in order to increase, or at least maintain, their level of job satisfaction. In terms of theory, the relative importance of levels versus changes deserves more attention. In terms of practical implications, our results suggest a double emphasis on job design (i.e., granting sufficient, and increasing, control) and on personal development (e.g., through training) so that people experience a match between both. Finally, negative associations between initial levels and growth rates suggest that people are quite successful in achieving a reasonable fit between their job characteristics and their needs and goals.

FUNCTIONS OF DEADENYLATION FACTORS IN MRNA DECAY AND MRNA PROCESSING BODY FORMATION

Most newly synthesized messenger RNAs possess a 5’ cap and a 3’ poly(A) tail. The process of poly(A) tail shortening, also termed deadenylation, is important for post-transcriptional gene regulation, because deadenylation not only leads to mRNA translational inhibition but also is the first step of major mRNA degradation. Translationally inhibited mRNAs can be stored and/or degraded in dynamic cytoplasmic foci termed mRNA processing bodies, or P bodies, which are conserved in eukaryotes. To shed new light on the mechanisms of P body formation and P body functions, I focused on the link between deadenylation factors and P bodies. I found that the two major deadenylation complexes, Pan3-Pan2 and Ccr4-Caf1, can both be enriched in P bodies. The deadenylase activity of the Ccr4-Caf1 complex is prerequisite for P body formation. Pan3, but not the deadenylase Pan2, is essential for P body formation. While the C-terminal domain of Pan3 is important for interaction with Pan2, Pan3 N-terminal domain is important for Pan3 to form cytoplasmic foci colocalizing with P bodies and to promote mRNA decay. Interestingly, Pan3 N-terminal domain may be phosphorylated to regulate Pan3 localization and functions. Aside from the functions of the two deadenylation complexes in P bodies, I also studied all reported human P body proteins as a whole using bioinformatics. This effort not only has generated a comprehensive picture of the functions of and interactions among human P body proteins, but also has predicted proteins that may regulate P body formation and/or functions. In summary, my study has established a direct link between mRNA deadenylation and P body formation and has also led to new hypotheses to guide future research on how P body dynamics are controlled.

Characteristics of a spina bifida population including North American Caucasian and Hispanic individuals.

BACKGROUND: Meningomyelocele (MM) is a common human birth defect. MM is a disorder of neural development caused by contributions from genes and environmental factors that result in the NTD and lead to a spectrum of physical and neurocognitive phenotypes. METHODS: A multidisciplinary approach has been taken to develop a comprehensive understanding of MM through collaborative efforts from investigators specializing in genetics, development, brain imaging, and neurocognitive outcome. Patients have been recruited from five different sites: Houston and the Texas-Mexico border area; Toronto, Canada; Los Angeles, California; and Lexington, Kentucky. Genetic risk factors for MM have been assessed by genotyping and association testing using the transmission disequilibrium test. RESULTS: A total of 509 affected child/parent trios and 309 affected child/parent duos have been enrolled to date for genetic association studies. Subsets of the patients have also been enrolled for studies assessing development, brain imaging, and neurocognitive outcomes. The study recruited two major ethnic groups, with 45.9% Hispanics of Mexican descent and 36.2% North American Caucasians of European descent. The remaining patients are African-American, South and Central American, Native American, and Asian. Studies of this group of patients have already discovered distinct corpus callosum morphology and neurocognitive deficits that associate with MM. We have identified maternal MTHFR 667T allele as a risk factor for MM. In addition, we also found that several genes for glucose transport and metabolism are potential risk factors for MM. CONCLUSIONS: The enrolled patient population provides a valuable resource for elucidating the disease characteristics and mechanisms for MM development.