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ATP-binding cassette transporters of the subfamily A (ABCA) are responsible for the translocation of lipids including cholesterol, which is crucial for neurological function. Recent studies suggest that the ABC transporter ABCA7 may play a role in the development of brain disorders such as schizophrenia and Alzheimer's disease. However, Abca7's role in cognition and other behaviours has not been investigated. Therefore, we characterised homozygous Abca7 knockout mice in a battery of tests for baseline behaviours (i.e. physical exam, baseline locomotion and anxiety) and behaviours relevant to schizophrenia (i.e. prepulse inhibition and locomotor response to psychotropic drugs) and Alzheimer's disease (i.e. cognitive domains). Knockout mice had normal motor functions and sensory abilities and performed the same as wild type-like animals in anxiety tasks. Short-term spatial memory and fear-associated learning was also intact in Abca7 knockout mice. However, male knockout mice exhibited significantly impaired novel object recognition memory. Task acquisition was unaffected in the cheeseboard task. Female mice exhibited impaired spatial reference memory. This phenomenon was more pronounced in female Abca7 null mice. Acoustic startle response, sensorimotor gating and baseline locomotion was unaltered in Abca7 knockout mice. Female knockouts showed a moderately increased motor response to MK-801 than control mice. In conclusion, Abca7 appears to play only a minor role in behavioural domains with a subtle sex-specific impact on particular cognitive domains.

The cannabis constituent cannabidiol (CBD) possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET) mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, Δ(9)-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT) received vehicle or CBD (1, 50 or 100 mg/kg i.p.) for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 HET mice displayed locomotor hyperactivity, PPI deficits and reduced 5-HT(2A) receptor binding density in the substantia nigra, but these phenotypes were not reversed by CBD. However, long-term CBD (50 and 100 mg/kg) selectively enhanced social interaction in Nrg1 TM HET mice. Furthermore, acute CBD (100 mg/kg) selectively increased PPI in Nrg1 TM HET mice, although tolerance to this effect was manifest upon repeated CBD administration. Long-term CBD (50 mg/kg) also selectively increased GABA(A) receptor binding in the granular retrosplenial cortex in Nrg1 TM HET mice and reduced 5-HT(2A) binding in the substantia nigra in WT mice. Nrg1 appears necessary for CBD-induced anxiolysis since only WT mice developed decreased anxiety-related behaviour with repeated CBD treatment. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD, which does not reverse the schizophrenia-relevant phenotypes.

Introduction. This study compares hip fracture rates in Long Term Care (LTC) residents with those in the community to determine if their high rate of fracturing reflects the extreme age and predominantly female nature of that population. Methods. Hospital discharge data in London Ontario (population 350,000) and Statistics Canada data were used to correct the hip fracture rate in the LTC setting for age and gender. Results. The risk of hip fracture is 1.8 times greater in LTC than in the community for people of similar age and gender. The rate in women is 1.5 times higher whereas in men it is 4.3 times higher. In the oldest residents, the risk in men exceeds that of women in LTC. Conclusion. The high hip fracture rate in LTC is not just a reflection of the age and predominantly female nature of this population. The oldest men in LTC are a particularly high risk group, deserving more attention.

Background: Approximately 20% of total knee arthroplasty (TKA) patients are found to be dissatisfied or unsure of their satisfaction at 1-year post-surgery. This study attempted to predict 1-year post-surgery dissatisfied/unsure TKA patients with pre-surgery and surgical variables using logistic regression and machine learning methods.Methods: A retrospective analysis of patients who underwent primary TKA for osteoarthritis between 2012 and 2016 at a single institution was completed. Patients were split into satisfied and dissatisfied/unsure groups. Potential predictor variables included the following: demographic information, patella re-surfaced, posterior collateral ligament sacrificed, and subscales from the Knee Society Knee Scoring System, the Knee Society Clinical Rating System, the Western Ontario and McMaster Universities Osteoarthritis Index, and the 12-Item Short Form Health Survey version 2. Logistic regression and 6 different machine learning methods were used to create prediction models. Model performance was evaluated using discrimination (AUC [area under the receiver operating characteristic curve]) and calibration (Brier score, Cox intercept, and Cox slope) metrics.Results: There were 1432 eligible patients included in the analysis, 313 were considered to be dissatisfied/unsure. When evaluating discrimination, the logistic regression (AUC = 0.736) and extreme gradient boosted tree (AUC = 0.713) models performed best. When evaluating calibration, the logistic regression (Brier score = 0.141, Cox intercept = 0.241, and Cox slope = 1.31) and gradient boosted tree (Brier score = 0.149, Cox intercept = 0.054, and Cox slope = 1.158) models performed best.Conclusion: The models developed in this study do not perform well enough as discriminatory tools to be used in a clinical setting. Further work needs to be done to improve the performance of pre-surgery TKA dissatisfaction prediction models. [ABSTRACT FROM AUTHOR]

Abstract Background A hallmark of Alzheimer’s disease is the presence of senile plaques in human brain primarily containing the amyloid peptides Aβ42 and Aβ40. Many drug discovery efforts have focused on decreasing the production of Aβ42 through γ-secretase inhibition. However, identification of γ-secretase inhibitors has also uncovered mechanism-based side effects. One approach to circumvent these side effects has been modulation of γ-secretase to shift Aβ production to favor shorter, less amyloidogenic peptides than Aβ42, without affecting the overall cleavage efficiency of the enzyme. This approach, frequently called γ-secretase modulation, appears more promising and has lead to the development of new therapeutic candidates for disease modification in Alzheimer’s disease. Results Here we describe EVP-0015962, a novel small molecule γ-secretase modulator. EVP-0015962 decreased Aβ42 in H4 cells (IC50 = 67 nM) and increased the shorter Aβ38 by 1.7 fold at the IC50 for lowering of Aβ42. AβTotal, as well as other carboxyl-terminal fragments of amyloid precursor protein, were not changed. EVP-0015962 did not cause the accumulation of other γ-secretase substrates, such as the Notch and ephrin A4 receptors, whereas a γ-secretase inhibitor reduced processing of both. A single oral dose of EVP-0015962 (30 mg/kg) decreased Aβ42 and did not alter AβTotal peptide levels in a dose-dependent manner in Tg2576 mouse brain at an age when overt Aβ deposition was not present. In Tg2576 mice, chronic treatment with EVP-0015962 (20 or 60 mg/kg/day in a food formulation) reduced Aβ aggregates, amyloid plaques, inflammatory markers, and cognitive deficits. Conclusions EVP-0015962 is orally bioavailable, detected in brain, and a potent, selective γ-secretase modulator in vitro and in vivo. Chronic treatment with EVP-0015962 was well tolerated in mice and lowered the production of Aβ42, attenuated memory deficits, and reduced Aβ plaque formation and inflammation in Tg2576 transgenic animals. In summary, these data suggest that γ-secretase modulation with EVP-0015962 represents a viable therapeutic alternative for disease modification in Alzheimer’s disease.

Background: Approximately 20% of patients are dissatisfied with their total knee arthroplasty (TKA) at 1-year post-surgery. Met expectations have been found by some to significantly predict satisfaction. The role of met expectations in determining patient satisfaction has not been exhaustively explored. The primary aim of this study is to evaluate if met expectations moderate the relationship between pain and function variables and satisfaction.Methods: Patients who underwent primary TKA for osteoarthritis were included in the study (n = 304). Patient-reported outcomes at pre-surgery and 1-year post-surgery were collected. The Knee Society Score (KSS) satisfaction subscale was used as the dependent variable. Candidate independent variables included the following: demographics, KSS, Knee injury and Osteoarthritis Outcome Score (KOOS), 12-Item Short Form Health Survey (SF-12), Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, Self-Administered Comorbidity Questionnaire, and University of California Los Angeles activity score. Separate linear regression models were created to test interactions for KSS met expectations with pain and KSS met expectations with function.Results: Significant predictors of satisfaction were KSS symptoms (pain), KOOS activities of daily living (function), KSS met expectations, KOOS pre-surgery activities of daily living, body mass index, and SF-12 general health. A significant interaction between met expectations and pain was found (P = .043) and the met expectations and function interaction approached significance (P = .086). For both interactions, as met expectations increased, pain and function predicted satisfaction less strongly.Conclusion: Met expectations were found to moderate the relationship between pain and satisfaction. There may be more value in improving pain for patients with low met expectations.Level Of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Water resources on the Canadian Prairies are at risk due to human settlement, agricultural intensification, and climatic change. The Red River Valley (RRV), Manitoba, Canada, represents a nexus of these cumulative stressors. Here land use change, combined with a recent increase in precipitation and runoff, imperils the protective function of tributaries draining to Lake Winnipeg. A concerted research effort over the past decade has greatly improved availability of data and knowledge about the RRV. However, a full synthesis of these data and information remain lacking. We undertook a review to identify and compare contemporary and historical land use, climatic, hydrologic, and water quality condition within the RRV. Then, using current knowledge of the ecological condition of streams in the RRV and elsewhere, we completed an ecological causal assessment of RRV tributaries to identify linkages and knowledge gaps between anthropogenic drivers and ecological endpoints. We found wastewater to be the candidate cause of ecological effects in RRV streams best supported by empirical evidence. A lack of complete lines of evidence linking agriculture, the greatest diffuse source of nutrient inputs, and ecological effects in RRV tributaries underscored a need for stressor-specific indicators and improved biomonitoring strategies to better detect likely impacts of land use. We also identified a need for research to connect well-known causal elements in the RRV, such as climatic variables and hydrological alteration, to ecological effects. Our findings provide direction for future research and can aid in development of an adaptive management strategy for tributaries of the RRV. [ABSTRACT FROM AUTHOR]

Abstract Background It is well recognised that the adoption and longer term adherence to physical activity by adults to reduce the risk of chronic disease is a challenge. Interventions, such as group and home based physical activity programs, have been widely reported upon. However few studies have directly compared these interventions over the longer term to determine their adherence and effectiveness. Participant preference for home based or group interventions is important. Some evidence suggests that home based physical activity programs are preferred by middle aged adults and provide better long term physical activity adherence. Physiotherapists may also be useful in increasing physical activity adherence, with limited research on their impact. Methods 'Physical Activity at Home' is a 2 year pragmatic randomised control trial, with a non-randomised comparison to group exercise. Middle-aged adults not interested in, or unable to attend, a group exercise program will be targeted. Sedentary community dwelling 50-65 year olds with no serious medical conditions or functional impairments will be recruited via two mail outs using the Australian federal electoral roll. The first mail out will invite participants to a 6 month community group exercise program. The second mail out will be sent to those not interested in the group exercise program inviting them to take part in a home based intervention. Eligible home based participants will be randomised into a 6 month physiotherapy-led home based physical activity program or usual care. Outcome measures will be taken at baseline, 6, 12, 18 and 24 months. The primary outcome is physical activity adherence via exercise diaries. Secondary outcomes include the Active Australia Survey, accelerometry, aerobic capacity (step test), quality of life (SF-12v2), blood pressure, waist circumference, waist-to-hip ratio and body mass index. Costs will be recorded prospectively and qualitative data will be collected. Discussion The planned 18 month follow-up post intervention will provide an indication of the effectiveness of the group and home based interventions in terms of adherence to physical activity, health benefits and cost. If the physiotherapy-led home based physical activity program is successful it could provide an alternative option for physical activity program delivery across a number of settings. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000890932

Abstract Background Hip fractures are expensive and a frequent cause of morbidity and mortality in the elderly. In most studies hip fractures have been viewed as a unitary fracture but recently the two main types of fracture (intertrochanteric and subcapital) have been viewed as two fractures with a different etiology and requiring a different approach to prevention. The relative proportion of intertrochanteric fractures increases with age in women. In previous studies no particular pattern in men has been noted. In this study, we explored changes in the relative proportion of the two fracture types with age in the two genders. Methods Patients of 50 years and older, with a diagnosis of hip fracture, discharged from two local acute care hospitals over a 5 year period (n = 2150) were analyzed as a function of age and gender to explore the relative proportions of intertrochanteric and subcapital fractures, and the change in relative proportion in the two genders with age. Results Overall, for the genders combined, the proportion of intertrochanteric fractures increases with age (p = .007). In women this increase is significant (p < .001), but in men the opposite pattern is observed, with the proportion of intertrochanteric fractures falling significantly with age (p = .025). Conclusions The pattern of hip fractures is different in men and women with aging. It is likely that the pattern difference reflects differences in type and rate of bone loss in the genders, but it is conjectured that the changing rate and pattern of falling with increasing age may also be important. The two main hip fracture types should be considered distinct and different and be studied separately in studies of cause and prevention.

Abstract Background There is no published evidence of how patient concerns change during the first six weeks following total knee arthroplasty (TKA). An understanding of the recovery process from the patient's perspective will inform clinicians on how to best educate patients about their post-operative concerns. Our objectives were to (1) quantify the level of importance for each of 32 previously identified concerns pre-operatively, and across the first six weeks following primary TKA and, (2) convey this change in importance post-operatively using the components of the International Classification of Functioning, Disability and Health (ICF). Methods The objectives were achieved using a repeated measures design. Convenience sampling was used to recruit 54 consecutive patients undergoing primary TKA at a hospital in Ontario, Canada. Pre-operatively and at two, four and six weeks post-operatively subjects rated the level of importance for each of the 32 previously identified patient concerns Results The importance rating of patient concerns in all four ICF components changed from before surgery to two weeks after surgery. Patient concerns in the Participation component became increasingly important after the first two weeks following surgery. Post-operatively from week two to week four, changes in importance ratings were also found in the Body Function and Activity components, but not in the Environmental Factors component. Conclusion Changes in patient concerns mirror their early recovery from TKA surgery. Consistent with this, Participation restrictions become increasingly important to patients after discharge from acute care suggesting that clinicians should think of managing patient expectations for return to societal roles early in post-operative rehabilitation.

Abstract Background To date, no researchers have investigated patient concerns in the first six weeks following primary total knee arthroplasty (TKA). An understanding of patient concerns at a time when physical therapists are involved in the treatment of these patients will aid clinicians in providing patient-centered care. Linking of items to the International Classification of Functioning, Disability and Health (ICF) allows for comparison and sharing of data amongst researchers, as the ICF is the accepted framework for evaluating disability in rehabilitation. The objective of this study was to identify patient concerns in the first six weeks following primary TKA and link these concerns to components of the ICF and map them to commonly used outcome measures. Methods Individual interviews were conducted to identify patient concerns during their recovery following primary TKA. Concerns identified by patients were analysed for content and linked to the components of the ICF using the operational definitions of the ICF components. These concerns were mapped to the WOMAC, KOOS and Oxford Knee Scale. Results Thirty patients (18 female) with an average age (SD) of 68.4 (11.1) years completed the study. Patients identified 32 concerns. Twenty-two percent (n = 7) of the concerns linked to Body Function and Structure, 47% (n = 15) to Activity, 13% (n = 4) to Participation, and 13% (n = 4) to the Environmental Factors component of the ICF. Six percent (n = 2) of the concerns did not link to the ICF. Of the 32 concerns identified by patients 14 mapped to the KOOS, 11 to the WOMAC and 4 to the Oxford Knee Scale. Conclusion Patient concerns linked to four different components of the ICF indicating that patients are involved in or are thinking of multiple aspects of life even in this early phase of recovery. The KOOS was found to be the most appropriate for use based on the patients' perspective. However, less than half of the concerns identified by patients were covered by the KOOS, WOMAC or Oxford Knee Scale indicating that other existing measures that evaluate the concepts identified as important to patients should be considered when evaluating outcomes during this acute phase of recovery following primary TKA.

Aims: To investigate the effect of the transverse arytenoid ligament (TAL) on abduction of the arytenoid cartilage when performing laryngoplasty. Methods: Modified prosthetic laryngoplasty was performed on right and left sides of 13 cadaver larynges. Increasing force was sequentially applied to the left arytenoid cartilage at 3 N intervals from 0–24 N, when the force on the right arytenoid cartilage was either 0 or 24 N, before and after TAL transection. Digital photographs of the rostral aspect of the larynx were used to determine the left arytenoid abduction angles for these given force combinations and results compared before and after TAL transection. Longitudinal and transverse sections of the TAL from seven other equine larynges were also examined histologically. Results: Increasing force on the left arytenoid cartilage from 0–24 N produced a progressive increase in the angle of the left arytenoid cartilage (p < 0.001) and increasing force on the right arytenoid cartilage from 0–24 N reduced the angle of the left arytenoid cartilage (p < 0.001). Following transection of the TAL the mean angle of the left arytenoid increased from 36.7 (95% CI = 30.5–42.8)° to 38.4 (95% CI = 32.3–44.5)°. Histological examination showed that the TAL was not a discrete ligament between the arytenoid cartilages but was formed by the convergence of the ligament and the left and right arytenoideus transversus muscles. Conclusions: Transection of the TAL in ex vivo equine larynges enabled greater abduction of the left arytenoid cartilage for a given force. These results indicate that TAL transection in conjunction with prosthetic laryngoplasty may have value, but the efficacy and safety of TAL transection under load in vivo, and in horses clinically affected with recurrent laryngeal neuropathy must be evaluated. Abbreviations:Fmax: Force needed to maximally abduct the left or right arytenoid; TAL: Transverse arytenoid ligament [ABSTRACT FROM AUTHOR]

Background: Orthopedic surgeons recognize patient expectations of total knee arthroplasty (TKA) can be managed through education. E-learning is the application of educational technology. The objective of this study was to evaluate whether an e-learning tool could affect whether patients' expectations were met and they were satisfied 1 year following TKA.Methods: Patients with osteoarthritis from the London Health Sciences Centre, Canada, were randomly assigned to either a control group (n = 207) receiving standard patient education or an intervention group (n = 209) using the e-learning tool in addition to the standard. We used a web-based system with permuted block sizes, stratified by surgeon and first or second TKA. Preoperative measures were completed following the patients' preadmission clinic visit. Postoperative patient-reported outcome measures were completed at 6 weeks, 3 months, and 1 year after TKA. One year after TKA, risk difference was used to determine between-group differences for patient satisfaction and expectations being met.Results: One year postoperatively, the risk that expectations of patients were not met was 21.8% in the control group and 21.4% in the intervention group for an adjusted risk difference of 1.3% (95% confidence interval, -7.8% to 10.4%, P = .78). The proportion of patients satisfied with their TKA at 1 year postoperative was 78.6% in the intervention and 78.2% in the control groups.Conclusion: There was no between-group difference at 1 year between intervention and control groups for either the risk that expectations of patients were not met or the proportion of patients who were dissatisfied with their TKA. [ABSTRACT FROM AUTHOR]

Intimate partner violence (IPV) is an urgent public health concern. Despite extensive research that has highlighted the heterogeneity of IPV perpetrators, the majority of treatment programs for perpetrators have taken a “one-size-fits-all” approach, which has rendered high rates of attrition and violence recidivism. More comprehensive intervention approaches are needed to address the individual treatment needs of IPV perpetrators. Intervention should be founded on a problem theory that delineates how the relevant sequelae are connected to the social problem in order to provide guidance on how it may be addressed. Accordingly, the primary aim of this article is to take an initial step toward improving IPV perpetrator intervention by examining current theory and offering a refined theoretical lens with which to view IPV perpetration. After a thorough examination of IPV perpetration, including the epidemiology, etiology, and implications for social welfare and social intervention, an in-depth review is provided on three key theories commonly applied to IPV perpetration: feminist theory, neurobiological theories of trauma, and attachment theory. This article concludes with a critique of each theory and the proposal of a new, more comprehensive conceptual model for understanding the risk factors of IPV perpetration. [ABSTRACT FROM AUTHOR]

Objective: To evaluate 5-year outcomes after lower limb realignment and test the hypothesis that surgery-induced changes in selected biomechanical risk factors for medial knee osteoarthritis (OA) are associated with clinically important improvements.Design: We prospectively evaluated patient-reported outcomes, full-limb standing radiographs and gait biomechanics before, 6 months (surgery-induced change) and 5 years after medial opening wedge high tibial osteotomy (HTO) in 170 patients (46.4 ± 8.9 years, 135 males) with knee OA and varus alignment. Logistic regression tested the associations of 6-month changes in mechanical axis angle and knee adduction moment with achieving an increase of ≥10 points in the Knee injury and Osteoarthritis Outcome Score (KOOS)4 at 5 years, with and without adjusting for covariates. Gait data were also compared to existing data from healthy controls.Results: Mean 5-year changes (95% confidence interval (CI)) were: KOOS4: +14.2 (10.8, 17.6); mechanical axis angle: +8.21° (7.58, 8.83); knee adduction moment: -1.49 %BW*Ht (-1.35, -1.63). The postoperative knee adduction moments were typically lower than values for healthy controls. When divided into quartiles, although all strata improved significantly, patients with reductions in knee adduction moment of 1.14-1.74 %BW*Ht (neither largest nor smallest changes) had highest 5-year KOOS4 scores. The 6-month change in knee adduction moment (odds ratios (OR) = 0.38; 95% CI: 0.22, 0.67), preoperative KOOS4 (OR = 0.96; 95% CI: 0.94, 0.99) and preoperative medial tibiofemoral narrowing grade (OR = 0.62; 95% CI: 0.37, 1.00) were negatively associated with having a 5-year clinically important improvement (C-statistic = 0.70).Conclusions: Substantial improvements in biomechanical risk factors and patient-reported outcomes are observed 5 years after medial opening wedge HTO. The surgery-induced change in load distribution during walking is significantly associated with long-term clinically important improvement. [ABSTRACT FROM AUTHOR]

• Stroke survivors often have unmet physical, psychological and/or social concerns. • Patient Concerns Inventories for other conditions augment clinical consultations. • A Stroke Patient Concerns Inventory has been developed and is ready to be piloted. Stroke survivors often have unmet physical, psychological and/or social concerns. Patient Concerns Inventories (PCIs) have been developed for other health conditions to address concerns. Our objective was to develop a PCI for stroke care. This was a development study, including Modified Delphi study design, with academic and healthcare professionals with stroke care expertise. In Stage 1, a draft Stroke PCI (Version 1a) was created through identifying patient-reported concerns post-stroke from three previous studies and through expert panel discussions using Nominal Group Technique. In Stage 2, Version 1a was sent to 92 academic and healthcare professionals with stroke care expertise. Participants ranked their top 20 Stroke PCI items in order of importance and provided feedback. Rankings were converted into scores, and, with the feedback, used to amend the Stroke PCI. Two further rounds of feedback followed until consensus was reached between participants. A final draft of the Stroke PCI was created. In stage 1, 64 potential Stroke PCI items were generated. In Stage 2, 38 participants (41.3%) responded to the request to rank Stroke PCI items. The three highest ranked items were 'Risk of another stroke', 'Walking', 'Recovery'. After three rounds of feedback and amendments, the final draft of the Stroke PCI consisted of 53 items. A Stroke PCI has been developed using patient-reported concerns in previous studies and input from academic and healthcare professionals. Future work will involve gathering further feedback on the tool and exploring its acceptability and usability in a pilot study. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: Delphi panel study. BACKGROUND: Biomechanical parameters measured during a drop vertical jump task are risk factors for anterior cruciate ligament (ACL) injury and are targeted during rehabilitation after ACL reconstruction. A clinically feasible tool that quantifies observed performance on the drop vertical jump would help inform treatment efforts. The content and scoring of such a tool should be deliberated on by a group of experts throughout its development. OBJECTIVES: To establish consensus on the content and scoring of a clinician-rated drop vertical jump scale (DVJS) for use during rehabilitation after ACL reconstruction. METHODS: Using a modified Delphi process, a panel of experts (researchers and clinicians) on the risk factors, prevention, treatment, and biomechanics of ACL injury anonymously critiqued versions of a DVJS. The DVJS was developed iteratively, based on the feedback from the panel, using Likert scale responses to questions and providing written comments. Three to 5 rounds were planned a priori, with a requirement of 75% agreement on included items after the final round. RESULTS: Twenty of the 31 invited experts (65%) participated. Approximately 93% agreement was achieved after the fourth round. Final items on the scale included the rating of knee valgis collapse (no collapse to extreme collapse) and the presence of other undesirable movements, including lateral trunk lean, insufficient knee flexion, and limb-to-limb asymmetry. CONCLUSION: The Delphi process resulted in a beta version of a DVJS. Expert consensus was achieved on its content and scoring to support further clinical testing of the scale. [ABSTRACT FROM AUTHOR]

Summary Objective This study used a rat model of post-traumatic knee osteoarthritis (OA) created by anterior cruciate ligament transection with partial medial meniscectomy (ACLT + pMMx). In this model, mild to moderate structural changes that are typical of knee OA have been observed within 2 and 8 weeks post-surgery. We aimed to determine whether pain-related behaviours can distinguish between an ACLT + pMMx and a sham surgery group. Design Three-month old male Sprague–Dawley rats underwent ACLT + pMMx on their right hindlimb within two groups of n = 6 each, and sham surgery within two groups of n = 5 each. Assessments evaluated percent ipsilateral weight-bearing for static weight-bearing and 18 different variables of exploratory motor behaviour at multiple time points between 1 and 8 weeks post-surgery. Histology was performed on the right hindlimbs at 4 and 8 weeks post-surgery. Results Histology confirmed mild to moderate knee OA changes in the ACLT + pMMx group and the absence of knee OA changes in the sham group. Compared to the sham group, the ACLT + pMMx group had significantly lower percent ipsilateral weight-bearing from 1 through 8 weeks post-surgery. Compared to the sham group, the ACLT + pMMx group had significantly lower vertical activity (episode count, time, and count) values. Conclusions These findings suggest that ipsilateral weight-bearing deficit and vertical activity limitations resulted from the presence of knee OA-like changes in this model. When using the ACLT + pMMx-induced rat model of knee OA, percent ipsilateral weight-bearing and vertical activity distinguished between rats with and without knee OA changes. These variables may be useful outcome measures in preclinical research performed with this experimental post-traumatic knee OA model. [ABSTRACT FROM AUTHOR]

Objectives To compare self-reported physical activity recorded in physical activity diaries or the Active Australia Survey with objectively measured physical activity using accelerometry in sedentary middle-aged adults completing two physical activity interventions. Design Cross-sectional study. Methods Sedentary 50–65 year olds were recruited to a non-randomized 6-month community group exercise program (G) or a physiotherapist-led home-based physical activity program (HB). Over 7-days, 76 participants (HB 39, G 37) wore an ActiGraph GT1M accelerometer (5 s epochs), completed the Active Australia Survey (AAS) and a daily physical activity diary. Data were analysed using descriptive statistics and Spearman rank-order correlations. Results The two interventions had similar demographic and physical activity characteristics except that home-based participants were younger ( p < 0.01), more likely to be employed full time ( p ≤ 0.001) and reported less moderate-to-vigorous physical activity in the physical activity diaries compared to group exercise participants (HB 29 ± 21 min d −1 vs. G 57 ± 35 min d −1 , p ≤ 0.001). Home-based participants had fair-to-good agreement between the physical activity diaries and AAS or ActiGraph data ( r = 0.39–0.68, p < 0.05). Group exercise physical activity diary data did not correlate significantly with either the AAS or ActiGraph data. In contrast, group exercise AAS data had good correlations with ActiGraph data ( r = 0.49–0.64, p ≤ 0.001). Conclusions Physical activity diaries should be interpreted cautiously unless intervention participants have an adequate understanding of physical activity intensity. The AAS is the preferred self-report measure in middle-aged adults independent of intervention. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To examine the efficacy of exercise intervention in patients with knee osteoarthritis (OA), as directed by Mechanical Diagnosis and Therapy (MDT) assessment, and, secondarily, to explore outcomes between MDT assessment-defined subgroups within the exercise group. BACKGROUND: Due to the high physical and economic burden of knee OA, the effectiveness of conservative interventions and determining those patients who will respond to them should be investigated. METHODS: Patients with knee OA (n = 180) were randomized to an exercise intervention group or a control group. The intervention group, in which patients classified as having knee derangements (MDT derangement) received MDT directional exercises and patients classified as nonresponders (MDT nonresponders) received evidence-based exercises, was compared to a control group that received no exercise intervention. Pain and function were assessed at baseline, 2 weeks, and 3 months, using the P4 pain scale and Knee injury and Osteoarthritis Outcome Score (KOOS) pain and function subscales. Two-way analysis of covariance was used to examine treatment and time effects. Multiple comparisons were examined, and mean differences with 95% confidence intervals (CIs) were reported. RESULTS: The exercise intervention group had significantly improved P4 scores (mean difference, -6; 95% CI: -8, -3), KOOS pain scores (mean difference, 9; 95% CI: 5, 13), and KOOS function scores (mean difference, 11; 95% CI: 7, 15) compared to those of the control group at 2 weeks. At 3 months, the exercise intervention group had significantly improved KOOS pain scores (mean difference, 7; 95% CI: 3, 11) and KOOS function scores (mean difference, 5; 95% CI: 1, 9) compared to controls. CONCLUSION: Patients with knee OA who were prescribed exercises based on an MDT assessment had superior outcomes compared to those of wait-list controls. The MDT subgroup of knee derangement may warrant further investigation in patients with knee OA. [ABSTRACT FROM AUTHOR]

The article looks at a prospective study on the screening algorithm used by the American and British Geriatrics Society to identify and stratify the risks of falls in community-dwelling older adults. The prognostic accuracy values for different at-risk categories are reviewed. Results suggest that the algorithm can be used in identifying fall risks, but the author recommendations further evaluation of the algorithm.

Summary: Objective: To examine the interaction and relative contributions of frontal plane alignment and body mass on dynamic knee joint loading in patients with knee osteoarthritis (OA). Methods: We completed three-dimensional gait analyses and hip-to-ankle standing anteroposterior radiographs on 487 patients with knee OA referred to a tertiary care center specializing in orthopaedics. Results: Using sequential (hierarchical) linear regression, the interaction term (mechanical axis angle×mass) contributed significantly (P <0.001) to a model (total adjusted R 2 =0.70) predicting the external knee adduction moment, that included mechanical axis angle (R 2 =0.37) and mass (R 2 =0.06) while controlling for age, sex, height, Kellgren and Lawrence grade, pain score during walking, gait speed, toe out angle and trunk lean (R 2 =0.25). When the sample was split into tertiles for mass, mechanical axis angle accounted for 32–54% of explained variance in knee adduction moment. In the tertile with greatest mass, results suggest a 3.2Nm increase in knee load for every 1° increase in varus alignment. When split into tertiles for mechanical axis angle, mass accounted for 6–10% of explained variance in the knee adduction moment. In the tertile with the most varus alignment, results suggest a 0.4Nm increase in knee load for every 1kg increase in mass. Conclusion: Our findings describe the interaction between alignment and body mass on dynamic knee joint loading, with the association between alignment and load highest in patients with the highest mass. Our findings also emphasize the role of malalignment on knee load at all levels of mass, and have implications for better understanding risk factors and intervention strategies for knee OA. [Copyright &y& Elsevier]

Abstract: Recent research has highlighted a potential role for neuropeptide Y (NPY) and its Y1 receptor in the development of schizophrenia. Genetic as well as molecular biological studies have demonstrated reduced levels of NPY in schizophrenia patients. Importantly, Y1 receptors may mediate some of the potential effects of NPY on schizophrenia, as decreased Y1 receptor expression has been found in the lymphocytes of schizophrenia patients. To clarify NPY’s role in schizophrenia, we investigated a genetic animal model for Y1 deficiency in regard to (i) acoustic startle response (ASR), (ii) habituation to ASR and (iii) sensorimotor gating [i.e. prepulse inhibition (PPI)] using two different PPI protocols. Mutant and wild type-like mice were screened for baseline behaviours and after pharmacological challenge with the psychotropic drugs dexamphetamine (DEX) and MK-801. Y1 knockout mice (Y1 −/−) showed a moderate reduction of the ASR and an impaired ASR habituation at baseline and after DEX treatment. The baseline PPI performance of Y1 mutant mice was unaltered their response to DEX and MK-801 challenge was moderately different compared to control mice, which was dependent on the PPI protocol used. MK-801 challenge had a protocol-dependent differential effect in Y1 −/− mice and DEX a more pronounced impact at the highest prepulse intensities. In conclusion, it appears that the Y1 receptor influences the acoustic startle response and its habituation but does not play a major role in sensorimotor gating. Further explorations into the effects of Y1 deficiency seem valid. [Copyright &y& Elsevier]

Background: Chronic neuroinflammation has been identified as a common feature of many neurodegenerative diseases, such as Alzheimer's disease (Kempuraj et al., 2016). Sex has been shown to strongly influence the development as well as the clinical expression of neurodegenerative and neuroinflammatory diseases. The GFAP‐IL6 mouse is a useful model to study chronic neuroinflammation and its consequences. These mice exhibit increased levels of neuroinflammatory markers, neurodegeneration, as well as motor deficits (Campbell et al., 1993; Chiang et al., 1994; Gyengesi et al., 2019). Although previous studies have identified some cognitive impairments in these animals (Heyser et al., 1997), more work is needed to fully characterised this model at a behavioural level. Method: Cognitive tests exploring anxiety such as the elevated plus‐maze (EPM), light/dark box, and spatial learning and memory such as the Barnes maze and Y‐maze, were performed on female GFAP‐IL6 mice and their litter mate control wild‐type (WT) from 12 months of age. Tests were recorded using AnyMaze® and results analysed in IBM SPSS® software with one or two‐way ANOVAs. This study was completed with immunochemistry and RT‐qPCR in brain regions implicated in anxiety, learning and memory. Result: We found that the GFAP‐IL6 mice travelled a significantly higher percentage of distance in the opened arm of the EPM than the WT (WT=9.48%, GFAP‐IL6=18.03%, p<0.01), and a lower percentage in the closed arm than the WT (WT=63.13%, GFAP‐IL6=53.70%, p<0.05). No genotype effect was found in the preference for the light compartment during the light/dark box test. In the Y‐maze, the GFAP‐IL6 mice spent a significantly lower percentage of time in the novel arm compared to the WT (WT=45.06%, GFAP‐IL6=27.97%, p<0.01). During the acquisition phase of the Barnes maze, all mice were able to learn the location of the escape hole. However, there was a significant effect of genotype (p<0.01), with the GFAP‐IL6 mice exhibiting higher latencies to enter the escape hole than the WT. No significant difference was found during the probe test Conclusion: These results suggest that female GFAP‐IL6 mice exhibit a less anxious phenotype but seem to present impaired spatial memory compared to female WT. [ABSTRACT FROM AUTHOR]

Abstract: Five hundred fifty patients who underwent primary total knee arthroplasty between 1987 and 2004 with a primary diagnosis of osteoarthritis and 1-year outcome data (Western Ontario and McMaster Osteoarthritis Index [WOMAC]) were evaluated. Patients were stratified into body mass index categories based on the World Health Organization classification of obesity. Patients were dichotomized into a class III morbidly obese group and a non–morbidly obese group. Independent t test and multivariable linear regression were used to determine if a difference existed in the 1-year WOMAC outcome between morbidly obese patients and all other patients. Although 1-year outcomes were worse for morbidly obese patients (P < .05), they showed greater improvement in function compared with non–morbidly obese patients. Morbid obesity does not affect 1-year outcomes in patients who have had a total knee arthroplasty. [Copyright &y& Elsevier]