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Abstract Background RNA editing at the Q/R site of GluA2 occurs with ~99% efficiency in the healthy brain, so that the majority of AMPARs contain GluA2(R) instead of the exonically encoded GluA2(Q). Reduced Q/R site editing increases AMPA receptor calcium permeability and leads to dendritic spine loss, neurodegeneration, seizures and learning impairments. Furthermore, GluA2 Q/R site editing is impaired in Alzheimer’s disease (AD), raising the possibility that unedited GluA2(Q)-containing AMPARs contribute to synapse loss and neurodegeneration in AD. If true, then inhibiting expression of unedited GluA2(Q), while maintaining expression of GluA2(R), may be a novel strategy of preventing synapse loss and neurodegeneration in AD. Methods We engineered mice with the ‘edited’ arginine codon (CGG) in place of the unedited glutamine codon (CAG) at position 607 of the Gria2 gene. We crossbred this line with the J20 mouse model of AD and conducted anatomical, electrophysiological and behavioural assays to determine the impact of eliminating unedited GluA2(Q) expression on AD-related phenotypes. Results Eliminating unedited GluA2(Q) expression in AD mice prevented dendritic spine loss and hippocampal CA1 neurodegeneration as well as improved working and reference memory in the radial arm maze. These phenotypes were improved independently of Aβ pathology and ongoing seizure susceptibility. Surprisingly, our data also revealed increased spine density in non-AD mice with exonically encoded GluA2(R) as compared to their wild-type littermates, suggesting an unexpected and previously unknown role for unedited GluA2(Q) in regulating dendritic spines. Conclusion The Q/R editing site of the AMPA receptor subunit GluA2 may act as an epigenetic switch that regulates dendritic spines, neurodegeneration and memory deficits in AD.

This paper introduces RSoANU, a dataset of real multichannel room impulse responses (RIRs) obtained in a recording studio. Compared to the current publicly available datasets, RSoANU distinguishes itself by featuring RIRs captured using both a 32-channel spherical microphone array (mh acoustics em32 Eigenmike) and a B-format soundfield microphone array (Rode NT-SF1). The studio incorporates variable wall panels in felt and wood options, with measurements conducted for two configurations: all panels set to wood or felt. Three source positions that emulate typical performance locations were considered. RIRs were collected over a planar receiver grid spanning the room, with the microphone array centered at a height of 1.7 m. The paper includes an analysis of acoustic parameters derived from the dataset, revealing notable distinctions between felt and wood panel environments. Felt panels exhibit faster decay, higher clarity, and superior definition in mid-to-high frequencies. The analysis across the receiver grid emphasizes the impact of room geometry and source–receiver positions on reverberation time and clarity. The study also notes spatial variations in parameters obtained from the two microphone arrays, suggesting potential for future research into their specific capabilities for room acoustic characterization.

IntroductionNeuroinflammation is a common feature of many psychiatric disorders as well as a common underlying mechanism of neurodegenerative diseases. Sex has been shown to strongly influence the development as well as the clinical expression of these pathologies. However, there is still a neglect regarding the consideration of sex effects in rodent experiments, and a substantial underrepresentation of females in studies. This work set out to expand our knowledge of neuroinflammatory mechanisms in female mice, at both a behavioral and molecular level.MethodsThis study used GFAP-IL6 mice, a model of chronic neuroinflammation, in which interleukin-6 (IL6) is overexpressed in the central nervous system under the control of the glial fibrillary acidic protein (GFAP) promoter. We evaluated aged (11-15-month-old) wild type-like (WT) and GFAP-IL6 female mice in behavioral tests assessing anxiety (elevated plus-maze, EPM, Light/dark box), and spatial learning and memory (Y-maze, YM and Barnes Maze, BM) and associative learning (fear conditioning, FC). We also examined gene expression of markers linked to neuroinflammation, neurodegeneration and neurotransmission via RT-qPCR in brain regions involved in motor control, anxiety, learning and memory.ResultsFemale GFAP-IL6 mice exhibited reduced anxiety-like behavior in the EPM, and hypolocomotion in the light-dark test and EPM. Short-term memory impairment was evident in the YM but associative learning in FC was intact in GFAP-IL6 mice, suggesting domain-specific cognitive deficits in female GFAP-IL6 mice. In the BM, all mice showed intact learning and memory, but GFAP-IL6 mice exhibited higher latencies to enter the escape hole than WT mice. We analyzed the search strategy and found differences in the way GFAP-IL6 mice searched for the escape hole compared to WTs. RT-qPCR showed increased mRNA levels for molecules involved in pro-inflammatory pathways in the cerebellum, motor cortex, hippocampus, and amygdala in GFAP-IL6 mice. Of the regions examined, the cerebellum and the hippocampus showed upregulation of neuroinflammatory makers as well as dysregulation of glutamatergic and GABAergic neurotransmission gene expression in GFAP-IL6 mice compared to WTs.ConclusionIn conclusion, we showed that chronic neuroinflammation via IL6 overexpression in aged female mice led to a less anxious-like phenotype, hypolocomotion and impaired intermediate-term spatial learning and memory in the YM.

For most of us, learning to communicate is as effortless as breathing, and like air, communication skills are elemental; integral to our human existence in this world. Our communicative competencies might be seen as a bridge, facilitating our relationship with the world we are immersed in. But what happens when a child has difficulty learning to communicate effectively? What happens when their most basic messages of hunger or thirst fail to be understood or they are unable to jointly share in everyday experiences of curiosity, joy, frustration, or anger? In these situations, it is the role of the Speech-Language Pathologist (SLP) to span the distance between a child and their family, a child and the world, building a route for life experiences and understandings to cross over. An SLP often begins with assessment and after a brief interaction, an SLP may come to a ‘naming’ such as delay or disorder. While the caring professional may intend this naming to be helpful in better understanding a child or facilitating access to valuable support, this naming may also place an immeasurable weight upon the child and their family. The act of naming is therefore an ethical concern. Through observation and interviews, this paper presentation explores SLP’s experiences of coming to a diagnosis through the human lens of phenomenological inquiry. It seeks to enhance thoughtful and conscientious practice by considering the ‘ethical experience of caring responsibility’ as applied to SLP (van Manen, 2016).

Since 2004 and the enlargement of the EU, increased migration from Central and Eastern European (CEE) countries to the UK necessitates sustained research on the implications for children, their families and practitioners in the early years. This paper draws upon a sociocultural approach to bring into focus family story-sharing practices. We report findings from an interpretivist study to foreground the experiences of two families living in Scotland. The findings indicate that story-sharing practices can potentially be a meeting place for early childhood practitioners to engage with children's linguistic and cultural heritage and can provide opportunities to listen to and build upon diverse cultural traditions. The findings also highlight that children's sense of their cultural and individual identities, as well as their sense of belonging, entail a complex set of interactions and that embedding them into curricula and pedagogy requires a sensitive criticality and open dialogue between practitioners, children and families. As a result of the findings, it is recommended that early years practitioners build upon story-sharing practices as a means to engage critically with issues of culture and identity and to facilitate the participation of CEE children and families in early years settings.

Commercial sexual exploitation of children (CSEC) is an urgent public health concern. Given the dire consequences for exploited youth, growing attention has been focused on the importance of preventing, identifying, and responding to CSEC in school settings. Despite calls for schools to be prepared to identify and respond to CSEC, limited specific guidance is available to prepare and inform school personnel about how to recognize and address CSEC. In this article, we will describe a sample protocol that delineates how schools can respond to CSEC concerns, identifications, and disclosures. Our protocol was created as part of a larger project to develop CSEC awareness and response materials to be used within middle and high schools. It is our intention that this sample protocol will stimulate additional practice, policy, and research attention on how to effectively recognize and address CSEC in schools.

Summary: Background: People living with overweight or obesity (PLwO) can be stigmatised by healthcare professionals (HCPs). Reducing focus on weight is a proposed strategy to provide less threatening healthcare experiences. Given the lack of research on weight bias within obesity services, this study aimed to explore implicit bias among obesity specialist HCPs and explore views on non-weight focused approaches. Methods: Obesity specialist HCPs were invited to a webinar, “An exploration of non-weight focused approaches within bariatric services”, held in October 2021. Implicit weight bias was examined using the BiasProof mobile device test, based on the Implicit Association Test. Poll data was analysed descriptively, and qualitative data was analysed using framework analysis. Findings: 82 of the 113 HCPs who attended the webinar consented to contribute data to the study. Over half (51%) had an implicit weight bias against PLwO. Most (90%) agreed/strongly agreed that obesity services are too weight focused and that patients should not be weighed at every appointment (86%). Perceived benefits of taking a non-weight focused approach included patient-led care, reducing stigma and supporting patient wellbeing, while perceived barriers included loss of objectivity, inducing risk and difficulty demonstrating effectiveness. Interpretation: Our findings indicate that half of obesity specialists HCPs in our sample of 82 providers, who are primarily dieticians and psychologists, have an implicit weight bias against PLwO. HCPs feel that a weight-focused approach within services was a barrier to patient care, but that there is a lack of alternative non-weight focused measures. Further research is needed into substitute outcome measures for clinical practice, also seeking the views of PLwO, and into interventions to address implicit weight bias. Funding: Johnson & Johnson funded the BiasProof licence and publication open access charge.

Cannabidiol (CBD) is a non-intoxicating cannabinoid with antipsychotic-like properties, however it’s potential to prevent schizophrenia development has not been thoroughly investigated. Brain maturation during adolescence creates a window where CBD could potentially limit the development of schizophrenia. The neuregulin 1 transmembrane domain heterozygous (Nrg1 TM HET) mutant mouse shows face, predictive, and construct validity for schizophrenia. Here we sought to determine if CBD given in adolescence could prevent the development of the schizophrenia-relevant phenotype, as well as susceptibility to the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) in Nrg1 TM HET mice. Adolescent male Nrg1 mutants and wild type-like (WT) animals were administered 30 mg/kg CBD i.p. daily for seven weeks, and were tested for locomotion, social behavior, sensorimotor gating and cognition, and sensitivity to acute THC-induced behaviors. GAD67, GluA1, and NMDAR1 protein levels were measured in the hippocampus, striatum, and prefrontal cortex. Chronic adolescent CBD increased locomotion in animals regardless of genotype, was anxiolytic, and increased social behavior when animals were tested for their acute THC response. CBD did not alleviate the schizophrenia-relevant hyperlocomotive phenotype of Nrg1 mutants, nor deficits in social behaviors. Nrg1 mutant mice treated with CBD and THC showed no habituation to a startle pulse, suggesting CBD increased vulnerability to the startle habituation-reducing effects of THC in mutant mice. CBD increased levels of GluA1, but reduced levels of GAD67 in the hippocampus of Nrg1 mutants. These results suggest adolescent CBD is not effective as a preventative of schizophrenia-relevant behavioral deficits in mutants and may actually contribute to pathological changes in the brain that increase sensitivity to THC in particular behavioral domains.

Cannabidiol is a promising potential therapeutic for neurodegenerative diseases, including Alzheimer’s disease (AD). Our laboratory has shown that oral CBD treatment prevents cognitive impairment in a male genetic mouse model of AD, the amyloid precursor protein 1 x presenilin 1 hemizygous (APPxPS1) mouse. However, as sex differences are evident in clinical populations and in AD mouse models, we tested the preventive potential of CBD therapy in female APPxPS1 mice. In this study, 2.5-month-old female wildtype-like (WT) and APPxPS1 mice were fed 20 mg/kg CBD or a vehicle via gel pellets daily for 8 months and tested at 10.5 months in behavioural paradigms relevant to cognition (fear conditioning, FC; cheeseboard, CB; and novel object recognition test, NORT) and anxiety-like behaviours (elevated plus maze, EPM). In the CB, CBD reduced latencies to find a food reward in APPxPS1 mice, compared to vehicle-treated APPxPS1 controls, and this treatment effect was not evident in WT mice. In addition, CBD also increased speed early in the acquisition of the CB task in APPxPS1 mice. In the EPM, CBD increased locomotion in APPxPS1 mice but not in WT mice, with no effects of CBD on anxiety-like behaviour. CBD had limited effects on the expression of fear memory. These results indicate preventive CBD treatment can have a moderate spatial learning-enhancing effect in a female amyloid-β-based AD mouse model. This suggests CBD may have some preventive therapeutic potential in female familial AD patients.

Abstract Background The aim of this study was to identify key indicator symptoms and patient factors associated with correct out of hospital cardiac arrest (OHCA) dispatch allocation. In previous studies, from 3% to 62% of OHCAs are not recognised by Emergency Medical Service call handlers, resulting in delayed arrival at scene. Methods Retrospective, mixed methods study including all suspected or confirmed OHCA patients transferred to one acute hospital from its associated regional Emergency Medical Service in England from 1/7/2013 to 30/6/2014. Emergency Medical Service and hospital data, including voice recordings of EMS calls, were analysed to identify predictors of recognition of OHCA by call handlers. Logistic regression was used to explore the role of the most frequently occurring (key) indicator symptoms and characteristics in predicting a correct dispatch for patients with OHCA. Results A total of 39,136 dispatches were made which resulted in transfer to the hospital within the study period, including 184 patients with OHCA. The use of the term ‘Unconscious’ plus one or more of symptoms ‘Not breathing/Ineffective breathing/Noisy breathing’ occurred in 79.8% of all OHCAs, but only 72.8% of OHCAs were correctly dispatched as such. ‘Not breathing’ was associated with recognition of OHCA by call handlers (Odds Ratio (OR) 3.76). The presence of key indicator symptoms ‘Breathing’ (OR 0.29), ‘Reduced or fluctuating level of consciousness’ (OR 0.24), abnormal pulse/heart rate (OR 0.26) and the characteristic ‘Female patient’ (OR 0.40) were associated with lack of recognition of OHCA by call handlers (p-values

This article contests the emphasis that is frequently placed upon child-friendly methods in research with young children. Focusing upon a series of research encounters from a doctoral study of play in an early years classroom, I examine my interactions with the children and their social and material worlds and draw upon these encounters to highlight some emergent and unpredictable elements of research with young children. I argue that these elements call for a decreased emphasis upon the implementation of method towards an openness to uncertainty and an ethical responsiveness to the researcher's relations with children and their everyday lives. An ethical responsiveness to uncertainty has implications throughout the research process, including through the ways in which we choose to read, interpret and present the data. This article offers original contributions to contemporary debates regarding what might become possible when uncertainty is acknowledged and embraced in research with young children.

Chronic neuroinflammation characterized by microglia reactivity is one of the main underlying processes in the initiation and progression of neurodegenerative diseases such as Alzheimer’s disease. This project characterized spatial memory during healthy aging and prolonged neuroinflammation in the chronic neuroinflammatory model, glial fibrillary acidic protein-interleukin 6 (GFAP-IL6). We investigated whether chronic treatment with the natural flavonoid, apigenin, could reduce microglia activation in the hippocampus and improve spatial memory. GFAP-IL6 transgenic and wild-type-like mice were fed with apigenin-enriched or control chow from 4 months of age and tested for spatial memory function at 6 and 22 months using the Barnes maze. Brain tissue was collected at 22 months to assess microgliosis and morphology using immunohistochemistry, stereology, and 3D single cell reconstruction. GFAP-IL6 mice showed age-dependent loss of spatial memory recall compared with wild-type-like mice. Chronic apigenin treatment decreased the number of Iba-1+ microglia in the hippocampus of GFAP-IL6 mice and changed microglial morphology. Apigenin did not reverse spatial memory recall impairment in GFAP-IL6 mice at 22 months of age. GFAP-IL6 mice may represent a suitable model for age-related neurodegenerative disease. Chronic apigenin supplementation significantly reduced microglia activation, but this did not correspond with spatial memory improvement in the Barnes Maze.

Abstract Background The increased use of electronic medical records (EMRs) in Canadian primary health care practice has resulted in an expansion of the availability of EMR data. Potential users of these data need to understand their quality in relation to the uses to which they are applied. Herein, we propose a basic model for assessing primary health care EMR data quality, comprising a set of data quality measures within four domains. We describe the process of developing and testing this set of measures, share the results of applying these measures in three EMR-derived datasets, and discuss what this reveals about the measures and EMR data quality. The model is offered as a starting point from which data users can refine their own approach, based on their own needs. Methods Using an iterative process, measures of EMR data quality were created within four domains: comparability; completeness; correctness; and currency. We used a series of process steps to develop the measures. The measures were then operationalized, and tested within three datasets created from different EMR software products. Results A set of eleven final measures were created. We were not able to calculate results for several measures in one dataset because of the way the data were collected in that specific EMR. Overall, we found variability in the results of testing the measures (e.g. sensitivity values were highest for diabetes, and lowest for obesity), among datasets (e.g. recording of height), and by patient age and sex (e.g. recording of blood pressure, height and weight). Conclusions This paper proposes a basic model for assessing primary health care EMR data quality. We developed and tested multiple measures of data quality, within four domains, in three different EMR-derived primary health care datasets. The results of testing these measures indicated that not all measures could be utilized in all datasets, and illustrated variability in data quality. This is one step forward in creating a standard set of measures of data quality. Nonetheless, each project has unique challenges, and therefore requires its own data quality assessment before proceeding.

Aging is a complex biological process that increases the risk of age-related cognitive degenerative diseases such as dementia, including Alzheimer’s disease (AD), Lewy Body Dementia (LBD), and mild cognitive impairment (MCI). Even non-pathological aging of the brain can involve chronic oxidative and inflammatory stress, which disrupts the communication and balance between the brain and the immune system. There has been an increasingly strong connection found between chronic neuroinflammation and impaired memory, especially in AD. While microglia and astrocytes, the resident immune cells of the central nervous system (CNS), exerting beneficial effects during the acute inflammatory phase, during chronic neuroinflammation they can become more detrimental. Central cholinergic circuits are involved in maintaining normal cognitive function and regulating signaling within the entire cerebral cortex. While neuronal-glial cholinergic signaling is anti-inflammatory and anti-oxidative, central cholinergic neuronal degeneration is implicated in impaired learning, memory sleep regulation, and attention. Although there is evidence of cholinergic involvement in memory, fewer studies have linked the cholinergic anti-inflammatory and anti-oxidant pathways to memory processes during development, normal aging, and disease states. This review will summarize the current knowledge of cholinergic effects on microglia and astroglia, and their role in both anti-inflammatory and anti-oxidant mechanisms, concerning normal aging and chronic neuroinflammation. We provided details on how stimulation of α7 nicotinic acetylcholine (α7nACh) receptors can be neuroprotective by increasing amyloid-β phagocytosis, decreasing inflammation and reducing oxidative stress by promoting the nuclear factor erythroid 2-related factor 2 (Nrf2) pathways and decreasing the release of pro-inflammatory cytokines. There is also evidence for astroglial α7nACh receptor stimulation mediating anti-inflammatory and antioxidant effects by inhibiting the nuclear factor-κB (NF-κB) pathway and activating the Nrf2 pathway respectively. We conclude that targeting cholinergic glial interactions between neurons and glial cells via α7nACh receptors could regulate neuroinflammation and oxidative stress, relevant to the treatment of several neurodegenerative diseases.

Children's interests are widely recognised as pivotal to meaningful learning and play in the early years. However, less is known about how children's diverse interests may contribute to relationships and interactions within peer cultures. This article builds upon previous studies to argue that participation in sociocultural activity generates interests informed by funds of knowledge that children reconstruct in their play. It reports findings from an interpretive study that used filmed footage of children's play as a provocation to explore the perspectives of children, parents and teachers. The article presents original insights regarding some ways in which mutually constituted funds of knowledge afford opportunities for children to co-construct meaning. The findings also indicate that interests arising from diverse funds of knowledge may contribute to the interplay of power, agency and status within peer cultures. This raises some issues regarding how matters of inclusion and exclusion are understood and responded to within early years settings. The article recommends that teachers and researchers engage critically with children's individual and collective funds of knowledge in order to better understand the complexities of play cultures.

College instructors often teach scientific thinking by asking students to review and analyze a primary research article. The main purpose of this study was to explore how classroom response systems (CRS) could help impact the quality of written analysis papers submitted for this assignment by students taking 100-level biology courses at a medium-sized suburban, two-year college in the northeastern United States. Students in all participating course sections received written instructions on five key elements of critical analysis (CA) to include in scientific study analysis papers. Classroom instruction on recognizing these key elements in primary research papers was provided either via CRS or via an instructor-facilitated classroom discussion enhanced by the same PowerPoint presentation. A rubric, designed specifically for this assignment, was validated prior to its use in this study. Fifty students participated in the study, and those who received the CRS intervention achieved significantly higher CA scores for identifying implications of study findings, while the group that received only written instructions achieved significantly higher CA scores for discussing the credibility of the references used by the authors in planning the critiqued study. The implications of this study are discussed along with ideas for future research.

The use of cannabis is a well-established component risk factor for schizophrenia, particularly in adolescent individuals with genetic predisposition for the disorder. Alterations to the endocannabinoid system have been found in the prefrontal cortex of patients with schizophrenia. Thus, we assessed whether molecular alterations exist in the endocannabinoid signalling pathway during brain development in a mouse model for the schizophrenia risk gene neuregulin 1 (Nrg1). We analysed transcripts encoding key molecules of the endocannabinoid system in heterozygous transmembrane domain Nrg1 mutant mice (Nrg1 TM HET), which is known to have increased sensitivity to cannabis exposure. Tissue from the prelimbic cortex and hippocampus of male and female Nrg1 TM HET mice and wild type-like littermates was collected at postnatal days (PNDs) 7, 10, 14, 21, 28, 35, 49, and 161. Quantitative polymerase chain reaction was conducted to assess mRNA levels of cannabinoid receptor 1 (CB1R) and enzymes for the synthesis and breakdown of the endocannabinoid 2-arachidonoylglycerol [i.e., diacylglycerol lipase alpha (DAGLα), monoglyceride lipase (MGLL), and α/β-hydrolase domain-containing 6 (ABHD6)]. No sex differences were found for any transcripts in either brain region; thus, male and female data were pooled. Hippocampal and cortical mRNA expression of DAGLα, MGLL, and ABHD6 increased until PND 21–35 and then decreased and stabilised for the rest of postnatal development. Hippocampal CB1R mRNA expression increased until PND 21 and decreased after this age. Expression levels of these endocannabinoid markers did not differ in Nrg1 TM HET compared to control mice at any time point. Here, we demonstrate dynamic changes in the developmental trajectory of several key endocannabinoid system transcripts in the mouse brain, which may correspond with periods of endocannabinoid system maturation. Nrg1 TM HET mutation did not alter the developmental trajectory of the endocannabinoid markers assessed, suggesting that other mechanisms may be responsible for the exaggerated cannabinoid susceptibility in these mice.

A key challenge in the development of precision medicine is defining the phenotypic consequences of pharmacological modulation of specific target macromolecules. To address this issue, a variety of genetic, molecular and chemical tools can be used. All of these approaches can produce misleading results if the specificity of the tools is not well understood and the proper controls are not performed. In this paper we illustrate these general themes by providing detailed studies of small molecule inhibitors of the enzymatic activity of two members of the SMYD branch of the protein lysine methyltransferases, SMYD2 and SMYD3. We show that tool compounds as well as CRISPR/Cas9 fail to reproduce many of the cell proliferation findings associated with SMYD2 and SMYD3 inhibition previously obtained with RNAi based approaches and with early stage chemical probes.

WHSC1 is a histone methyltransferase that is responsible for mono- and dimethylation of lysine 36 on histone H3 and has been implicated as a driver in a variety of hematological and solid tumors. Currently, there is a complete lack of validated chemical matter for this important drug discovery target. Herein we report on the first fully validated WHSC1 inhibitor, PTD2, a norleucine-containing peptide derived from the histone H4 sequence. This peptide exhibits micromolar affinity towards WHSC1 in biochemical and biophysical assays. Furthermore, a crystal structure was solved with the peptide in complex with SAM and the SET domain of WHSC1L1. This inhibitor is an important first step in creating potent, selective WHSC1 tool compounds for the purposes of understanding the complex biology in relation to human disease.

Approximately 20% of patients are dissatisfied with their total knee arthroplasty (TKA). Identifying patients likely to be dissatisfied early in the recovery process could help reduce the number of dissatisfied patients. The purpose of this study was to create an easily administered short questionnaire to identify patients likely to be dissatisfied at 1 year post surgery early in the recovery process. The study included 275 patients who underwent primary TKA for osteoarthritis. Individual 3-month postsurgery questionnaire items from the Knee Injury and Osteoarthritis Outcome Score and Knee Society Knee Scoring System were pooled together and used as candidate items to create 3 different short questionnaires. Items included in each questionnaire were selected using least absolute shrinkage and selection operator logistic regressions, a backward elimination method, and theory-based approaches. The area under the curve for each short questionnaire was calculated to evaluate predictive performances. All 3 questionnaires contained a small number of items and appeared to successfully predict 1-year postsurgery dissatisfaction early in the recovery process. The least absolute shrinkage and selection operator logistic regression, backward elimination, and theory-based questionnaires were comprised of 4, 7, and 5 items and had the area under the curve scores of 0.893, 0.902, and 0.890, respectively. A question evaluating rising from sitting and activities of daily living appeared in all of the created questionnaires. A short questionnaire that is easy to administer and interpret can effectively predict TKA patient dissatisfaction at 1 year post surgery early in the recovery process. [ABSTRACT FROM AUTHOR]

As water organizations adopt green infrastructure for stormwater management to increase sustainability, new types of professionals are needed that were not previously widespread in the industry. Ecologists and other ecologically-oriented employees are being brought into these organizations that have long been mostly oriented around an engineering knowledge system. This study examines how these two different knowledge systems interact within a water organization, outlining the differences in their underlying assumptions and orientations that can cause friction. The research used a case study approach to examine implementation of asset management within a water organization that has been building and managing green infrastructure for over thirty years. It found that integration around a common decision process can occur, but that it is a slow process filled with continuous negotiation. The research suggests that water organizations looking to establish green infrastructure programs should be more aware and intentional about discussing differences in professional knowledge systems when bringing new types of professions into an established organization. • Green infrastructure requires engineers and ecologists to work together. • Engineers and ecologists see the world and solve problems differently. • Professional diversity can change decision processes in the water sector. • Professional diversity should be acknowledged and addressed in organizations. [ABSTRACT FROM AUTHOR]

Introduction: Following hip fracture surgery, patients often experience multiple transitions through different care settings, with resultant challenges to the quality and continuity of patient care. Family caregivers can play a key role in these transitions, but are often poorly engaged in the process. We aimed to: (1) examine the characteristics of the family caregivers’ experience of communication and information sharing and (2) identify facilitators and barriers of effective information sharing among patients, family caregivers and health care providers.Methods: Using an ethnographic approach, we followed 11 post-surgical hip fracture patients through subsequent care transitions in rural Ontario; in-depth interviews were conducted with patients, family caregivers (n = 8) and health care providers (n = 24).Results: Priority areas for improved information sharing relate to trust and respect, involvement, and information needs and expectations; facilitators and barriers included prior health care experience, trusting relationships and the rural setting.Conclusion: As with knowledge translation, effective strategies to improve information sharing and care continuity for older patients with chronic illness may be those that involve active facilitation of an on-going partnership that respects the knowledge of all those involved.

Methamphetamine (METH) is a highly addictive psychostimulant with no therapeutics registered to assist addicts in discontinuing use. Glutamatergic dysfunction has been implicated in the development and maintenance of addiction. We sought to assess the involvement of the metabotropic glutamate 5 receptor (mGlu5) in behaviours relevant to METH addiction because this receptor has been implicated in the actions of other drugs of abuse, including alcohol, cocaine and opiates. mGlu5 knockout (KO) mice were tested in intravenous self-administration, conditioned place preference and locomotor sensitization. Self-administration of sucrose was used to assess the response of KO mice to a natural reward. Acquisition and maintenance of self-administration, as well as the motivation to self-administer METH was intact in mGlu5 KO mice. Importantly, mGlu5 KO mice required more extinction sessions to extinguish the operant response for METH, and exhibited an enhanced propensity to reinstate operant responding following exposure to drug-associated cues. This phenotype was not present when KO mice were tested in an equivalent paradigm assessing operant responding for sucrose. Development of conditioned place preference and locomotor sensitization were intact in KO mice; however, conditioned hyperactivity to the context previously paired with drug was elevated in KO mice. These data demonstrate a role for mGlu5 in the extinction and reinstatement of METH-seeking, and suggests a role for mGlu5 in regulating contextual salience.

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]