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Background Progressive nonsteroidal anti-inflammatory drug ( NSAID) dose reduction appears logical; however, there is no evidence-based medicine indicating that efficacy is maintained as dose is reduced. Objective To determine if NSAID dose can be reduced and pain relief and mobility can be maintained in dogs with osteoarthritis ( OA). Animals Client-owned dogs (n = 59) with OA-associated impaired mobility and pain. Methods Prospective, randomized, blinded study. After 14 days wash-out, dogs were randomized to reducing dose ( RDG) (n = 30) or maintenance dose ( MDG) (n = 29). MDG received standard dose meloxicam. RDG received a reducing dose from D28 onward, reducing to 0% of maintenance for the final 2 weeks. Assessments were at D14, 28, 42, 56, 70, 84, 98 and 112 using subjective owner assessments, accelerometry ( AM), and standing percent body weight distribution (% BW). A Kaplan- Meier survival curve described how dogs dropped out because of insufficient pain control. A Log-rank test compared the groups. Results More dogs in RDG (13) dropped out because of owner-evaluated insufficient pain control compared with MDG (5) ( P = .029; odds ratio: 3.67; median dropout time: 84 days in each group). For the dogs that did not drop out (n = 41), there were no significant differences between groups in owner assessments ( P > .2 for each), % BW placed on the index limb ( P = .750), or accelerometer-measured activity ( P = .14). Conclusion and Clinical Relevance Dose reduction is a less effective means of pain control compared with maintained dosing. However, NSAID dose reduction with maintained efficacy is possible, but success appears to be individual dog dependent. [ABSTRACT FROM AUTHOR]

The AASHTO LRFD Bridge Design Specifications, in versions up to and including the 2003 interim, limit the shear resistance of hybrid steel I-girders to the shear buckling or shear yield load and prevent consideration of the additional capacity due to tension field action, which homogeneous girders are allowed to include. This limitation severely affected the economy of girders utilizing high-performance steel, whose optimum configuration is often hybrid. Therefore, an experimental investigation was initiated by the National Bridge Research Organization at the University of Nebraska-Lincoln to address the limitation on the consideration of tension field action in hybrid girders. This paper presents the findings of that research. Eight simply supported steel I-girders were designed, constructed, and loaded to failure to investigate their failure mechanisms and shear capacities. All girders tested were capable of supporting loads greater than those predicted, considering full contribution from tension field action. Further, despite the coincidence of high levels of both shear and moment, relative to their respective capacities, the specimens were all capable of supporting loads greater than those predicted if shear and moment interaction were ignored. Due in part to the results of the research being presented, modifications appeared in the 2004 version of the AASHTO LRFD bridge design specifications such that the shear strength provisions apply equally to both hybrid and homogeneous girders. [ABSTRACT FROM AUTHOR]

The objectives of this investigation were to (1) identify elements that comprise an acceptable quality of life (Q-L) post-traumatic brain injury (TBI) from the perspectives of patients and families, and (2) explore patient and family satisfaction with treatment decisions relevant to QoL. The authors created, tested, and administered two forms (patient; family) of a 35-question interview to 33 participants in a longitudinal TBI study (14 women, 19 men) and 33 associated family members. Men associated ratings of QoL with numerous variables, while women's responses revealed no significant relationships shared by QoL and other variables. Women reported a poorer QoL than did men. Older patients reported a better QoL than did younger patients. Families emphasized the family relationship, emotional control, and ability to concentrate when considering overall QoL. Patients did not. The majority of patients and families expressed satisfaction with decisions made about acute treatment. QoL research is essential to illuminate best practice models. [ABSTRACT FROM AUTHOR]

A discontinuous preparative polyacrylamide gel electrophoresis system has been developed and used to purify both the nicked and unnicked forms of tetanus toxin. The system was also used to prepare purified H and L chain peptides from the nicked toxin. The results show that the endogenous protease(s), which convert unnicked toxin to the nicked form, produce multiple species of nicked toxin, and heterogeneity in the H and L chains. The major amino termini of the toxins and their peptide components are: extract toxin, proline; filtrate toxin, proline, serine and asparagine; L chain, proline; and H chain, serine and asparagine. The L chain is located in the amino terminal position of the toxin molecule and the H chain the carboxy terminal end. A model is proposed to explain these results. Using the analytical ultracentrifuge, we have determined the molecular weights of extract and filtrate toxins to be 140 000 ± 5 000 and 128 000 ± 3 000, respectively. Using S DS-polyacrylamide gel electrophoresis we estimate the molecular weights of the H and L chains to be 87 000 and 48 000 daltons, respectively. Circular dichroic spectra of the toxins and their peptide components indicate that: the major tryptophanyl band in the toxin is contributed almost entirely by the H chain, the microenvironments of all the aromatics and disulfides in the two toxins appear to have small if any differences, the two toxins show little difference in their ordered secondary structure, and the two peptides when separated from one another still retain 80% of the helical structure that is present in the intact toxin but show a considerable loss of β-structure. The crystalline form of the nicked toxin has a hexagonal symmetry with two dimensional reciprocal lattice constants of 1/150 Å and 1/150 Å. The crystals appear to belong to the two dimensional plane group P6 suggesting that each unit cell contains 6 or a multiple of 6 toxin molecules. [ABSTRACT FROM AUTHOR]

Backgrounds: Exposure to adverse childhood experiences (ACEs) is associated with adverse neurobiological, developmental, cognitive, behavioral, psychological, and social consequences among children and adolescents. Psychosocial interventions hold promise for mitigating the negative impacts of ACEs, but there is a lack of updated and comprehensive evidence summarizing their effects qualitatively and quantitatively., Aims: We performed a systematic review and meta-analysis of existing evidence on the effectiveness of psychosocial interventions on children's outcomes, including internalizing and externalizing problems., Methods: We searched five database sources from inception to April 2024 for studies on the effectiveness of any psychosocial intervention in any outcome among children and adolescents aged 6-18 who experienced ACEs. We qualitatively synthesized the characteristics of the studies, samples, interventions, and outcomes. We quantitatively estimated the pooled effects of psychosocial interventions on a range of outcomes encompassing internalizing problems, externalizing problems, family relationships, coping, and self-esteem using meta-analysis. Additionally, we conducted a series of subgroup meta-analyses to compare the intervention effects based on sample and intervention characteristics., Results: Forty-four studies were included, with 20 randomized controlled trials, nine controlled trials, and 15 pre-post trials. Significant intervention effects were observed in internalizing problems (standardized mean difference, SMD = -0.36) and externalizing problems (SMD = -0.57), but not in family relationships, coping, or self-esteem. Subgroup analyses have identified various effective interventions for internalizing problems and externalizing problems, respectively., Conclusions: The evidence suggests that psychosocial interventions are effective in preventing internalizing and externalizing problems among children and adolescents who have experienced ACEs. Recommendations are provided for designing and evaluating future psychosocial interventions., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Sleep problems are reported for up to 80% of autistic individuals. We examined whether parsimonious sets of items derived from the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) and the Brief Infant Sleep Questionnaire (BISQ) are superior to the standard M-CHAT-R in predicting subsequent autism spectrum disorder (ASD) diagnoses., Methods: Participants from 11 Environmental influences on Child Health Outcomes (ECHO) cohorts were included. We performed logistic LASSO regression models with 10-fold cross-validation to identify whether a combination of items derived from the M-CHAT-R and BISQ are superior to the standard M-CHAT-R in predicting ASD diagnoses., Results: The final sample comprised 1552 children. The standard M-CHAT-R had a sensitivity of 44% (95% CI: 34, 55), specificity of 92% (95% CI: 91, 94), and AUROC of 0.726 (95% CI: 0.663, 0.790). A higher proportion of children with ASD had difficulty falling asleep or resisted bedtime during infancy/toddlerhood. However, LASSO models revealed parental reports of sleep problems did not improve the accuracy of the M-CHAT-R in predicting ASD diagnosis., Conclusion: While children with ASD had higher rates of sleep problems during infancy/toddlerhood, there was no improvement in ASD developmental screening through the incorporation of parent-report sleep metrics., Impact: Parental-reported sleep problems are common in autism spectrum disorder (ASD). We investigated whether the inclusion of parental-reports of infant/toddler sleep patterns enhanced the effectiveness of developmental screening for autism. We reported higher rates of difficulty falling asleep and resisting bedtime during infancy and toddlerhood among children later diagnosed with ASD; however, we did not find an improvement in ASD developmental screening through the incorporation of parent-report sleep metrics. In our sample, the standard M-CHAT-R had a sensitivity of 39% among children of mothers with government insurance compared with a sensitivity of 53% among children of mothers with employer-based insurance., Competing Interests: Competing interests: The authors declare no competing interests. Consent to participate: The study protocol was approved by the single ECHO institutional review board, WCG IRB. Written informed consent or parent’s/guardian’s permission was obtained along with child assent as appropriate, for the ECHO Cohort Data and Biospecimen Collection Protocol participation and for participation in specific study sites., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Introduction: The response to medical management of young dogs with osteoarthritis (OA) associated pain has not been evaluated. Using an open-label design, the effectiveness, over a 4-month period, of standardized management (grapiprant/fish oil/exercise) for treating OA pain in young dogs was evaluated., Methods: Included dogs were 9 months-4 years of age; ≥3.6 kg body weight; had ≥1 appendicular joint with radiographic OA and obvious joint pain; had a Liverpool Osteoarthritis in Dogs (LOAD) score of ≥5. The non-steroidal anti-inflammatory piprant (grapiprant) was given at the recommended dose daily, omega-3 fatty acid supplementation was initiated at 100 mg/kg and then increased to 200 mg/kg daily, and leash exercise was gradually increased to a target of 60 min daily. Client-reported outcome measures (CROMs) and force plate gait analysis were collected at baseline and monthly for 4 months. The index limb was defined as the most severely affected limb at baseline., Results: Forty-eight dogs were enrolled (mean ± SD age of 30.7 ± 10.7 months). Hips, elbows, and stifles were commonly affected. Medication and supplement compliance was excellent (≥95% of target administered), and treatments were well-tolerated. CROMs showed significant improvement over time and at each time point. Overall, peak vertical force (PVF) increased significantly (<0.001), and vertical impulse increased numerically. Increase in PVF from baseline was significant at all time points except 4-months., Discussion: This study demonstrates a clinically meaningful benefit of a multimodal treatment regimen over a 4-month period for young dogs (<4 years old) with OA-pain. Future work should determine if early, effective treatment is of long-term benefit., Competing Interests: The authors declare that this study received funding from Elanco Animal Health (NC State Grant # 2020-0044). The funder was not involved in the study design, collection, analysis, interpretation of data, or the decision to submit it for publication. However, the manuscript went through an internal review and approval process at Elanco Animal Health before submission to check for potential disclosure of confidential information. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Enomoto, Hash, Cole, Porcel Sanchez, Thomson, Perry, Aker, Nakanishi-Hester, Haupt, Opperman, Roe, Thompson, Innes and Lascelles.)

This study aimed to determine the prevalence of osteoarthritis (OA) and associated clinical signs in young dogs. Owners of dogs aged 8 months-4 years from a single practice, were contacted in random order, to participate in a general health screen. Clinical and orthopedic examinations were performed. Each joint was scored for pain reactions (0-4). Orthogonal radiographs of all joints were made under sedation. Each joint was scored for radiographic OA (rOA) severity on an 11-point scale. Clinical OA (cOA) was defined as an overlap of rOA and joint pain in ≥ 1 joint. Owners completed OA questionnaires. The owners of 123 dogs agreed to participate. Overall, 39.8% (49/123) of dogs had rOA in ≥ 1 joint, and 16.3% (20/123) or 23.6% (29/123) dogs had cOA, depending on the cut-off value of joint pain; moderate (2), or mild (1), respectively. Owners of dogs with cOA observed signs of impairment in approximately 30% of cases. Only 2 dogs with cOA were receiving OA pain management. The most commonly affected joints in descending order of frequency were elbow, hip, tarsus, and stifle. Radiographically visible OA is common in young dogs, and 40-60% of dogs with rOA had cOA. However, OA-pain appears underdiagnosed and undertreated in young dogs., (© 2024. The Author(s).)

Theoretical Principles: Social Cognitive Theory (SCT) is a middle-range theory with triadic determinism between behavioral, environmental, and personal. SCT has been a guiding framework in health promotion research as it helps understand people's behaviors., Phenomena Addressed: Behavioral Insomnia of Childhood (BIC) is highly prevalent, affecting up to 45% of typically developing children and 80% of children with special healthcare needs. BIC leads to sleep deficiency, disrupted physical and psychological health, poor school performance, behavioral dysfunction, and negatively affects parental and family functioning. Using Fawcett's framework, we analyzed and evaluated SCT in a pediatric sleep context and propose a reformulation of SCT to better inform sleep research., Research Linkages: SCT is individually focused and does not account for interdependence within relationships. Pediatric sleep interventions have limited long-term effects and sustainability without considering the parent-child dyadic interdependency. We advance the argument that the parent-child shared management (PCSM) perspective is beneficial for understanding pediatric sleep health. PCSM is a concept that reflects the shared responsibility and interdependence that parent and child have for managing child health. It assumes that with parents' ongoing support, children's responsibility for their health management increases over time, along with developmental progression and health-related experiences. We propose reformulating SCT by integrating PCSM in the pediatric sleep context: SCT with Shared Management (SCT-SM). The proposed SCT-SM accounts for parent-child interdependence and role transition. Shared management interventions that engage parents and children in active roles in managing sleep have potential sustainable effects in improving sleep and quality of life. (250)., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Accelerometry has been used to evaluate activity in dogs with osteoarthritis (OA) pain, especially in relation to effect of treatment; however no studies have compared accelerometry-measured activity in dogs with OA-pain and healthy dogs. The aims of this study were to (1) compare activity output from the PetPace collar with the validated Actical monitor and (2) determine if PetPace collar outputs (overall activity, activity levels, body position, and vital signs) differed between healthy dogs and dogs with OA-pain., Methods: This was an observational, non-interventional study in healthy dogs and dogs with OA-pain. All dogs were outfitted with the PetPace collar and the Actical monitor simultaneously for 14 days. Output from these devices was compared (correlations), and output from the PetPace device was used to explore differences between groups across the activity and vital sign outputs (including calculated heart rate variability indices)., Results: There was moderate correlation between the PetPace collar and Actical monitor output ( R 2 = 0.56, p < 0.001). Using data generated by the PetPace collar, OA-pain dogs had lower overall activity counts and spent less time standing than healthy dogs. Healthy dogs spent more time at higher activity levels than OA-pain dogs. Certain heart rate variability indices in OA-pain dogs were lower than in healthy dogs., Conclusions and Clinical Relevance: The results of this study suggest that the PetPace collar can detect differences between healthy dogs and those with OA-pain, and that OA-pain negatively impacts overall activity levels in dogs, and especially higher intensity activity., Competing Interests: Author BDXL has been a paid consultant for Boehringer Ingelheim Animal Health. This work was funded by Boehringer Ingelheim Animal Health (Duluth, GA, USA) (grant number 2017-0917) and the PetPace collars and data were supplied by PetPace Ltd (Burlington, MA, USA). The funders had no involvement in the study design, collection, analysis, interpretation of data, the writing of the article or the decision to submit it for publication. However, the funders were shown the results as a courtesy, and their input/comments were taken into consideration. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rowlison de Ortiz, Belda, Hash, Enomoto, Robertson and Lascelles.)

Background: Various studies show that sleep quality, life skills, and cortisol are associated with depressive symptoms, separately. However, the relationships between sleep quality, life skills, cortisol, and depressive symptoms remain unclear. Thus, this study aims to examine the mediating or moderating roles of life skills and cortisol in the relationship between sleep quality and depressive symptoms., Methods: A retrospective cross-sectional study was performed among 212 adolescents with childhood household dysfunction (CHD) from August to October 2020 in China. We used the Pittsburgh Sleep Quality Index, the Secondary School Student Life Skills Rating Scale, and the Center for Epidemiologic Studies Depression Scale to measure sleep quality, life skills, and depressive symptoms, respectively. Additionally, 65 participants provided blood samples to assess their blood cortisol levels. Analyses included correlations, regressions, and structural equation models. Bootstrapping was performed to examine the mediation effect. Multiple regression analysis was performed to examine the moderation effect., Results: The results showed that sleep quality and life skills were significantly associated with depressive symptoms ( p < 0.01). Life skills mediated the relationship between sleep quality and depressive symptoms. Cortisol moderated the relationship between sleep quality and depressive symptoms., Conclusion: Our findings support potential mediating and moderating roles of life skills and cortisol in the relationship between sleep quality and depressive symptoms, which suggests improving sleep quality, life skills are of great significance in the prevention and intervention of depression in adolescents with CHD, and disseminating knowledge about the high risk of developing increased depressive symptoms among adolescents with CHD with higher cortisol levels is indicated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mao, Peng, Yuwen, Liu, Yan, Chen, Long and Hash.)

Endogenous Pain Modulation (EPM) impairment is a significant contributor to chronic pain. Conditioned pain modulation (CPM) testing assesses EPM function. Osteoarthritic (OA) dogs are good translational models, but CPM has not been explored. Our aim was to assess EPM impairment in OA dogs compared to controls using CPM. We hypothesized that CPM testing would demonstrate EPM impairment in OA dogs compared to controls. Dogs with stifle/hip OA and demographically-matched controls were recruited. The pre-conditioning test stimulus, using mechanical/thermal quantitative sensory testing (MQST or TQST), were performed at the metatarsus. A 22N blunt probe (conditioning stimulus) was applied to the contralateral antebrachium for 2 minutes, followed by MQST or TQST (post-conditioning test stimulus). The threshold changes from pre to post-conditioning (∆MQST and ∆TQST) were compared between OA and control dogs. Twenty-four client-owned dogs (OA, n = 11; controls, n = 13) were recruited. The ∆MQST(p < 0.001) and ∆TQST(p < 0.001) increased in control dogs but not OA dogs (∆MQST p = 0.65; ∆TQST p = 0.76). Both ∆MQST(p < 0.001) and ∆TQST(p < 0.001) were different between the OA and control groups. These are the first data showing that EPM impairment is associated with canine OA pain. The spontaneous OA dog model may be used to test drugs that normalize EPM function.

Background: Lower urinary tract transitional cell carcinoma (TCC) is an important but rarely described disease of cats., Objectives: To report the clinical characteristics, treatments, and outcomes in a cohort of cats with lower urinary tract TCC and to test identified variables for prognostic relevance., Animals: One-hundred eighteen client-owned cats with lower urinary tract carcinoma., Methods: Medical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes. Recorded variables were analyzed statistically., Results: Median age of affected cats was 15 years (range, 5.0-20.8 years) and median duration of clinical signs was 30 days (range, 0-730 days). The trigone was the most common tumor location (32/118; 27.1%) as assessed by ultrasound examination, cystoscopy, or both. Treatment was carried out in 73 of 118 (61.9%) cats. Metastatic disease was documented in 25 of 118 (21.2%) cats. Median progression-free survival and survival time for all cats were 113 days (95% confidence interval [CI], 69-153) and 155 days (95% CI, 110-222), respectively. Survival increased significantly (P < .001) when comparing cats across the ordered treatment groups: no treatment, treatment without partial cystectomy, and treatment with partial cystectomy. Partial cystectomy (hazard ratio [HR], 0.31; 95% CI, 0.17-0.87) and treatment with nonsteroidal anti-inflammatory drugs (HR, 0.55; 95% CI, 0.33-0.93) were significantly associated with longer survival times., Conclusions and Clinical Importance: The results support treatment using partial cystectomy and NSAIDs in cats with TCC., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

The present study examines how different chronic illnesses and mental illness comorbidity (chronic illness with complexity [CIC]) associate with components of advance care planning (ACP). We also explore the role self-perceived burden plays in the relationship between illness and ACP. Data were gathered from a cross-sectional survey of 305 elderly participants from the New Jersey End-of-Life study. Participants with diabetes and those with cardiovascular disease (CVD) are less likely, while participants with CIC are more likely, to plan for the end-of-life. Participants with diabetes are less likely to make formal plans, whereas those with CVD are less likely to hold informal discussions. CIC is associated with increased odds of having an advance directive, but no other form of ACP. Self-perceived burden did not appear to be the gateway by which illness groups differentially engaged in ACP. Future research should investigate what aspects of illnesses drive ACP.

Study of all flies (Diptera) collected for one year from a four-hectare (150 x 266 meter) patch of cloud forest at 1,600 meters above sea level at Zurquí de Moravia, San José Province, Costa Rica (hereafter referred to as Zurquí), revealed an astounding 4,332 species. This amounts to more than half the number of named species of flies for all of Central America. Specimens were collected with two Malaise traps running continuously and with a wide array of supplementary collecting methods for three days of each month. All morphospecies from all 73 families recorded were fully curated by technicians before submission to an international team of 59 taxonomic experts for identification.        Overall, a Malaise trap on the forest edge captured 1,988 species or 51% of all collected dipteran taxa (other than of Phoridae, subsampled only from this and one other Malaise trap). A Malaise trap in the forest sampled 906 species. Of other sampling methods, the combination of four other Malaise traps and an intercept trap, aerial/hand collecting, 10 emergence traps, and four CDC light traps added the greatest number of species to our inventory. This complement of sampling methods was an effective combination for retrieving substantial numbers of species of Diptera. Comparison of select sampling methods (considering 3,487 species of non-phorid Diptera) provided further details regarding how many species were sampled by various methods.        Comparison of species numbers from each of two permanent Malaise traps from Zurquí with those of single Malaise traps at each of Tapantí and Las Alturas, 40 and 180 km distant from Zurquí respectively, suggested significant species turnover. Comparison of the greater number of species collected in all traps from Zurquí did not markedly change the degree of similarity between the three sites, although the actual number of species shared did increase.        Comparisons of the total number of named and unnamed species of Diptera from four hectares at Zurquí is equivalent to 51% of all flies named from Central America, greater than all the named fly fauna of Colombia, equivalent to 14% of named Neotropical species and equal to about 2.7% of all named Diptera worldwide. Clearly the number of species of Diptera in tropical regions has been severely underestimated and the actual number may surpass the number of species of Coleoptera.        Various published extrapolations from limited data to estimate total numbers of species of larger taxonomic categories (e.g., Hexapoda, Arthropoda, Eukaryota, etc.) are highly questionable, and certainly will remain uncertain until we have more exhaustive surveys of all and diverse taxa (like Diptera) from multiple tropical sites.        Morphological characterization of species in inventories provides identifications placed in the context of taxonomy, phylogeny, form, and ecology. DNA barcoding species is a valuable tool to estimate species numbers but used alone fails to provide a broader context for the species identified.

Estimations of tropical insect diversity generally suffer from lack of known groups or faunas against which extrapolations can be made, and have seriously underestimated the diversity of some taxa. Here we report the intensive inventory of a four-hectare tropical cloud forest in Costa Rica for one year, which yielded 4332 species of Diptera, providing the first verifiable basis for diversity of a major group of insects at a single site in the tropics. In total 73 families were present, all of which were studied to the species level, providing potentially complete coverage of all families of the order likely to be present at the site. Even so, extrapolations based on our data indicate that with further sampling, the actual total for the site could be closer to 8000 species. Efforts to completely sample a site, although resource-intensive and time-consuming, are needed to better ground estimations of world biodiversity based on limited sampling., Competing Interests: The authors declare no competing interests.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs), transdermal fentanyl patches, and transmucosal buprenorphine are probably the most commonly used options for providing post-operative analgesia in the early at-home period. However, these require daily administration or are associated with abuse concerns. One of the significant unmet needs in veterinary surgery and pain management is for longer acting opioids for cats to effectively bridge the gap between the in-hospital and at-home recovery periods. A proof of concept study of an extended release formulation of buprenorphine HCL (ER-Bup) was conducted using objective kinetic measures and a unilateral onychectomy model. Using a blinded, randomized, two period crossover design, four cats were allocated to control (saline) or ER-Bup (0.6 mg/kg, subcutaneously [SC]) treatment groups. All animals underwent a unilateral forelimb onychectomy per period with a washout/recovery period in between. Observational pain scores and kinetic data (using a pressure sensitive walkway [PSW]) were collected prior to (baseline) and at intervals for 72 h following surgery. Symmetry indices were derived for kinetic variables (peak vertical force [PVF]; vertical impulse [VI]) of each forelimb for landing following a jump and for walking. A rescue analgesic protocol was in place. Effect of surgery and treatment were evaluated using a mixed model statistical approach., Results: No cats required rescue analgesics based on subjective pain score. ER-Bup had a positive influence on subjective pain scores during the 72 h postsurgery (p = 0.0473). PVF and VI of the operated limb were significantly decreased for both landing (p < 0.0001 and p < 0.0001) and walking (p < 0.0001 and p < 0.0001 respectively) compared to control. ER-Bup resulted in significantly decreased asymmetry in limb use during landing (PVF, p < 0.0001; VI, p < 0.0001) and walking (PVF, p = 0.0002, VI, p < 0.0001). The novel use of data collected following a jump from an elevated platform appeared to provide all desired information and was easier to collect than walking data., Conclusion: This study demonstrates that SC administration of ER-Bup may be an effective analgesic for a 72 h period postoperatively. Furthermore, landing onto a PSW from an elevated perch may be a useful and efficient way to assess analgesics in cats using a unilateral model of limb pain.

Background: The hip is one of the most common sites of osteoarthritis in the body, second only to the knee in prevalence. However, current animal models of hip osteoarthritis have not been assessed using many of the functional outcome measures used in orthopaedics, a characteristic that could increase their utility in the evaluation of therapeutic interventions. The canine hip shares similarities with the human hip, and functional outcome measures are well documented in veterinary medicine, providing a baseline for pre-clinical evaluation of therapeutic strategies for the treatment of hip osteoarthritis. The purpose of this study was to evaluate a surgical model of hip osteoarthritis in a large laboratory animal model and to evaluate functional and end-point outcome measures., Methods: Seven dogs were subjected to partial surgical debridement of cartilage from one femoral head. Pre- and postoperative pain and functional scores, gait analysis, radiographs, accelerometry, goniometry and limb circumference were evaluated through a 20-week recovery period, followed by histological evaluation of cartilage and synovium., Results: Animals developed histological and radiographic evidence of osteoarthritis, which was correlated with measurable functional impairment. For example, Mankin scores in operated limbs were positively correlated to radiographic scores but negatively correlated to range of motion, limb circumference and 20-week peak vertical force., Conclusions: This study demonstrates that multiple relevant functional outcome measures can be used successfully in a large laboratory animal model of hip osteoarthritis. These measures could be used to evaluate relative efficacy of therapeutic interventions relevant to human clinical care.

Objective: To perform algometric readings in normal dogs in a design that would assess possible confounding factors., Study Design: Prospective study., Animals: Skeletally mature spayed female, intact male and castrated male retriever or retriever mix dogs without orthopedic or neurologic disease (n = 19)., Methods: Twelve common surgical sites were selected for algometric pressure testing. Threshold response was defined as a conscious recognition of the stimulus, and recorded in Newtons. Sites were tested in the same order, and the testing sequence repeated 3 times on each side of the dog. Dogs were tested in the morning and evening of the same day and was repeated 10-14 days later, allowing 4 separate data collections for each dog., Results: Data were analyzed using ANOVA or ANCOVA. When all the data were included in the analysis, dog (P < .0001), order (P < .0001), site (P < .0001), site order (P = .0217), time (P < .0001), day (P < .0001) and repetition (P < .0001) all significantly affected the algometer readings. When only the first reading for each site was included in the analysis, dog (P < .0001), site (P < .0001) and sex (P < .0001) all significantly affected algometer readings., Conclusion: These results suggest that learning occurred over repeated collection time points, with dogs anticipating the stimulus and reacting at lower thresholds., (© Copyright 2014 by The American College of Veterinary Surgeons.)

The objectives of this study were to determine whether thermal quantitative sensory testing (QST) can be performed in client-owned dogs, is repeatable and whether QST differs between normal dogs and dogs with hind limb osteoarthritis (OA). This clinical, prospective, observational study used clinically normal dogs (n=23) and dogs with OA-associated hind limb pain (n=9). Thermal QST was performed in standing dogs using a high-powered light source delivered by a previously validated system. Dogs were tested on two occasions, 2 weeks apart. Five tests were performed on each hind limb at each time point. Repeated measures analysis of variance was used to evaluate the effects of leg, time point and OA/normal status on thermal threshold latencies (TTL). Additionally, paired t tests were used to compare the TTL of left and right limbs within groups and between time points. Thermal thresholds were successfully measured in 32 client-owned dogs without prior training. TTL were significantly different between normal and OA dogs (P=0.012). There was no difference between limbs (P=0.744) or time periods (P=0.572), when analyzed by repeated measures analysis of variance, and no interactions between group and limb, visit and limb, or visit and group. In conclusion, thermal thresholds can be measured in client owned dogs with no prior training and are repeatable from week to week. Further data are required to determine if OA results in thermal hypoalgesia as measured at the distal hind limb and whether this is an indication of central sensitization., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Osteoarthritis (OA) is a clinically important and common disease of older cats. The pathological changes and molecular mechanisms which underpin the disease have yet to be described. In this study we evaluated selected histological and transcriptomic measures in the articular cartilage and subchondral bone (SCB) of the humeral condyle of cats with or without OA., Results: The histomorphometric changes in humeral condyle were concentrated in the medial aspect of the condyle. Cats with OA had a reduction in articular chondrocyte density, an increase in the histopathological score of the articular cartilage and a decrease in the SCB porosity of the medial part of the humeral condyle. An increase in LUM gene expression was observed in OA cartilage from the medial part of the humeral condyle., Conclusions: Histopathological changes identified in OA of the feline humeral condyle appear to primarily affect the medial aspect of the joint. Histological changes suggest that SCB is involved in the OA process in cats. Differentiating which changes represent OA rather than the aging process, or the effects of obesity and or bodyweight requires further investigation.

The objective of this study was to develop a surgical technique for sensory denervation of the canine elbow joint and to assess the effects of denervation on limb function in normal dogs. Twenty cadavers (40 elbows) were used to characterize innervation and design the surgical protocol which was tested in 13 cadavers (26 normal elbows). The effect of denervation on limb function was assessed in vivo in four dogs with the elbow randomly selected for the procedure. Primary outcome measures were static bodyweight distribution and distal limb mechanical sensory thresholds; secondary outcome measures were subjectively scored lameness, neurological function and pain on manipulation. Histology was performed on all resected tissues to determine whether nerves had been resected. Denervation was achieved by separate medial and lateral surgical approaches. In testing the developed surgical protocol, 111/130 resected samples contained nerve tissue in the healthy cadaveric elbows and 18/20 in the in vivo study. Limb function and sensation were not altered by elbow joint denervation. The protocol developed for denervation of the canine elbow appears feasible and does not result in any sensory or motor deficits of the forelimb., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Degenerative joint disease (DJD) is common in domesticated cats. Our purpose was to describe how radiographic findings thought to indicate feline DJD relate to macroscopic cartilage degeneration in appendicular joints. Thirty adult cats euthanized for reasons unrelated to this study were evaluated. Orthogonal digital radiographs of the elbow, tarsus, stifle, and coxofemoral joints were evaluated for the presence of DJD. The same joints were dissected for visual inspection of changes indicative of DJD and macroscopic cartilage damage was graded using a Total Cartilage Damage Score. When considering all joints, there was statistically significant fair correlation between cartilage damage and the presence of osteophytes and joint-associated mineralizations, and the subjective radiographic DJD score. Most correlations were statistically significant when looking at the different joints individually, but only the correlation between the presence of osteophytes and the subjective radiographic DJD score with the presence of cartilage damage in the elbow and coxofemoral joints had a value above 0.4 (moderate correlation). The joints most likely to have cartilage damage without radiographic evidence of DJD are the stifle (71% of radiographically normal joints) followed by the coxofemoral joint (57%), elbow (57%), and tarsal joint (46%). Our data support radiographic findings not relating well to cartilage degeneration, and that other modalities should be evaluated to aid in making a diagnosis of feline DJD., (© 2011 Veterinary Radiology & Ultrasound.)

Objective: To evaluate a technique for midhumeral peripheral nerve blockade in the dog., Study Design: Cadaveric technique development; in vivo placebo-controlled, prospective crossover study., Animals: Canine cadavers (n=38) and 8 clinically healthy, adult hound dogs., Methods: A technique for peripheral block of the radial, ulnar, musculocutaneous, and median nerves (RUMM block) was evaluated using cadaver limbs. Eight purpose-bred, research dogs were anesthetized; a RUMM block was performed on each thoracic limb. One limb from each dog randomly received 0.5% bupivacaine and the opposite limb was assigned to receive sterile saline solution as a control. After recovery from anesthesia, skin sensation at selected dermatomes was evaluated for 24 hours using a mechanical stimulus. Weight-bearing, conscious proprioception, and withdrawal reflex were also evaluated. One month after initial testing, each dog was reanesthetized and each limb received the opposite treatment., Results: Sensory thresholds were significantly increased over baseline measurements when compared with control limbs for all nerves. Complete sensory block was achieved in radial (15/16), ulnar (3/16), musculocutaneous (8/16), and median (11/16) nerves, using a mechanical stimulus of analgesia. Complete simultaneous block of all nerves was only obtained in 1 of 16 limbs., Conclusion: RUMM block resulted in desensitization of the skin in the associated dermatomes for 4-10 hours. Complete sensory block of the dermatomes supplied by the radial nerve was most consistent., Clinical Relevance: RUMM block may be an effective technique to provide adjunctive analgesia for dogs undergoing surgery of the distal aspect of the thoracic limb., (© Copyright 2010 by The American College of Veterinary Surgeons.)

Objective: To (1) determine prevalence of radiographically detectable meniscal mineralization in domestic cats and (2) to evaluate the association between meniscal mineralization and degenerative joint disease (DJD)., Study Design: Prospective study., Animals: Client-owned cats (n=100) and 30 feline cadavers., Methods: Randomly selected client-owned cats were used to determine the prevalence of meniscal mineralization. Stifles from feline cadavers were used to evaluate the relationship between meniscal mineralization (using high-resolution X-ray), radiographic DJD, and cartilage damage. Menisci were evaluated histologically., Results: Forty-six percent of the client-owned cats had meniscal mineralization detected in 1 or both stifles. Pain scores were not significantly different between stifles with meniscal mineralization and those with no radiographic pathology (P=.38). Thirty-four of 57 cadaver stifles had meniscal mineralization, which was always located in the cranial horn of the medial meniscus. Percentage mineralization of the menisci was significantly correlated with the cartilage damage score of the medial femoral (r(2)=0.6; P<.0001) and tibial (r(2)=0.5; P<.0001) condyles as well as with the total joint cartilage damage (r(2)=0.36; P<.0001) score and DJD score (r(2)=0.8; P<.0001)., Conclusion: Meniscal mineralization is a common condition in domestic cats and seems to indicate medial compartment DJD., Clinical Relevance: Clinical significance of meniscal mineralization is uncertain. Further work is needed to determine if the meniscal mineralization is a cause, or a consequence of joint degeneration.

The objectives of this investigation were to (1) identify elements that comprise an acceptable quality of life (Q-L) post-traumatic brain injury (TBI) from the perspectives of patients and families, and (2) explore patient and family satisfaction with treatment decisions relevant to QoL. The authors created, tested, and administered two forms (patient; family) of a 35-question interview to 33 participants in a longitudinal TBI study (14 women, 19 men) and 33 associated family members. Men associated ratings of QoL with numerous variables, while women's responses revealed no significant relationships shared by QoL and other variables. Women reported a poorer QoL than did men. Older patients reported a better QoL than did younger patients. Families emphasized the family relationship, emotional control, and ability to concentrate when considering overall QoL. Patients did not. The majority of patients and families expressed satisfaction with decisions made about acute treatment. QoL research is essential to illuminate best practice models.

Lysozyme Ch was hydrolyzed with trypsin in 2 M urea and the resulting peptides were separated by a combination of gel filtration and ion exchange chromatography. Ten peptides and free lysine were produced by tryptic action. The enzyme has 5 arginine and 4 lysine residues per molecule and one of the peptides arose from a chymotryptic-like cleavage of a tyrosyl-seryl bond near the amino-terminal end of the enzyme. The entire molecule is accounted for by the tryptic peptides, which have been ordered withing the peptides obtained by cyanogen bromide cleavage of the molecule.

Purified filtrate tetanus toxin was subjected to limited digestion with papain and the resulting fragments were separated by gel exclusion chromatography and characterized. One atoxic fragment was shown to react with antiserum against tetanus toxoid and was capable of inducing antibodies in rabbits that neutralized native tetanus toxin, The fragment had an estimated molecular weight of 56,000 by SDS polyacrylamide gel electrophoresis and 62,000 by sedimentation equilibrium. In the presence of a reducing agent, the fragment yielded two components with approximatec molecular weights of 23,000 and 32,000. Thus, it appears that the atoxic, immunogenic fragment is composed of two peptides joined by at least one disulfide bond. The fragment was examined by circular dichroism and data analysis indicated the presence of considerable beta-structure, but little, if any, alpha-helicity. This is significantly different from the estimates for filtrate toxin. 29% alpha-helicity and 23% beta-structure. Above 250 nm, the circular dichroic spectrum of the fragment was also distinct from that of intact toxin.

The anomeric configuration of the sugar residues of the capsular polysaccharide antigen of Staphylococcus aureus M were established by 13C-n.m.r. spectroscopy, and the linkage positions by g.l.c.-m.s. after methylation, indicating a leads to 4)-O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyluronic acid)-(1 leads to 4)-O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyluronic acid)-(1 leads to 3)-O-(2-acetamido-2-deoxy-alpha-D-fucopyranosyl)-(1 leads to repeating unit. A taurine residue is linked by an amide bond, on the average, to every fourth 2-acetamido-2-deoxy-D-galactopyranosyluronic acid residue.

The chemical structure of the surface polysaccharide from Staphylococcus aureus M was investigated by a combination of methanolytic, hydrolytic, and chromatographic techniques. The repeating unit that was most consistent with the data was a hexasaccharide composed of N-acetyl-D-aminogalacturonic acid, N-acetyl-D-fucosamine, and taurine in molar ratios of 4:2:1. A disaccharide was isolated and characterized, by combined gas-liquid chromatography-mass spectrometry, as N-acetyl-D-aminogalacturonyl-(1 leads to 3)-N-acetyl-D-fucosamine. Taurine is linked to a carboxyl group of N-acetyl-D-aminogalacturonic acid via an amide bond.

The complete amino acid sequence of lysozyme Ch has been established by a combination of automated and manual Edman degradation and carboxypeptidase digestion.(see article)There is a single disulfide bond in the center of the molecule. The enzyme has 211 residues with a calculated molecular weight of 22,415. Lysozyme Ch has an amino acid sequence that is totally different from all other lysozymes whose sequences are known.

Two forms of tetanus toxin have been purified from Clostridium tetani cultures. These forms, obtained from filtrate and cellular extracts, were characterized by analytical ultracentrifugation using both conventional and meniscus-depletion sedimentation equilibrium. The molecular weight of filtrate toxin was found to be 128,000 +/- 3,000, while the extract toxin, which tended to self-associate, appeared somewhat larger, 140,000 +/- 5,000. The heavy and light chains were prepared from filtrate toxin, and their molecular weights were estimated to be 87,000 and 48,000, respectively, using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The circular dichroic spectra of the extract and filtrate toxins are quite similar between 200-300 nm indicating that no major conformational difference exists between the two. The toxins contain both alpha-helicity and beta-structure. Interestingly, the isolated chains contain appreciable helicity (e.g., the sum of the chain helicities is over 80% of that found in filtrate toxin), but they appear to have relatively low contents of beta-structure. The sum of the spectra of the chains in both the near- and far-ultraviolet does not yield that found for filtrate toxin, although the similarity is far more striking than the difference. The prominent 293.5 nm negative circular dichroic band of tetanus toxin can be assigned to tryptophanyl residues almost exclusively in the heavy chain. The similarity in the magnitude of this band in the separated chain and toxin suggests that the microenvironments of the contributing tryptophans change very little when toxin is dissociated into its constituent chains.

Strain M, classified as a Staphylococcus aureus, behaves like the other rare encapsulated staphylococcal strains. It was clumping-factor negative, grew in diffuse-type colonies in serum-soft agar, and produced rapidly fatal disease in mice. Strain M was highly resistant to phagocytosis by human or mouse leukocytes and required both specific antibody and heat-labile serum factor(s) for efficient ingestion by human polymorphonuclear leukocytes. Electron micrographs confirmed the presence of a large capsule. Agglutination studies, active or passive mouse protection experiments, and opsonic studies revealed that strain M represents a new, immunologically distinct strain of encapsulated staphylococcus. Strain M differs from other known encapsulated staphylococci in several other respects: its cellular and colonial morphology is atypical; its LD(50) in the mouse peritoneal model is 100 times less than that of other mouse lethal strains; it is poorly opsonized by normal human serum; and, finally, it possesses an unusually large capsule as seen in electron micrographs.