Genetic background and sex influence somatosensory sensitivity and oxycodone analgesia in the Hybrid Rat Diversity Panel.

Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD. Understanding the genetic contributions to oxycodone-induced analgesia could provide insight into the early stages of OUD development. Here, we present findings from a behavioral phenotyping protocol using several inbred strains from the Hybrid Rat Diversity Panel. Our behavioral protocol included a modified "up-down" von Frey procedure to measure inherent strain differences in the sensitivity to a mechanical stimulus on the hindpaw. We also performed the tail immersion assay, which measures the latency to display tail withdrawal in response to a hot water bath. Initial withdrawal thresholds were taken in drug-naïve animals to record baseline thermal sensitivity across the strains. Oxycodone-induced analgesia was measured after administration of oxycodone over the course of 2 h. Both mechanical and thermal sensitivity are shaped by genetic factors and display moderate heritability (h2 = 0.23-0.40). All strains displayed oxycodone-induced analgesia that peaked at 15-30 min and returned to baseline by 2 h. There were significant differences between the strains in the magnitude and duration of their analgesic response to oxycodone, although the heritability estimates were quite modest (h2 = 0.10-0.15). These data demonstrate that genetic background confers differences in mechanical sensitivity, thermal sensitivity, and oxycodone-induced analgesia.

The diabetes community exercise programme plus usual care versus usual care in patients with type 2 diabetes: A randomised, two-arm, parallel, open-label trial.

Background: Exercise is important in type 2 diabetes (T2D) management. Focussing on Maori and Pacific people and those from deprived circumstances, the Diabetes Community Exercise Programme (DCEP) was developed to engage people with T2D in exercise. We report the evaluation of whether being offered DCEP (plus usual care) was more effective than usual care in improving glycaemic control at 1-year. Methods: A randomised, two-arm, parallel, open-label trial with blinding of outcome assessor and data analyst. Adults (age ≥35 years) with T2D recruited from two New Zealand (NZ) communities were randomised, using opaque sealed envelopes and stratified by centre with random block lengths, to DCEP or usual care. DCEP comprises twice-weekly, two-hour sessions of exercise and education over 12-weeks, followed by a twice-weekly maintenance exercise class. The primary outcome was between-group differences in mean changes of glycated haemoglobin (HbA1c) from baseline to 1-year follow-up with intention-to treat analysis. This trial is registered with the Australian NZ Clinical Trials Registry (ANZCTR): ACTRN12617001624370p and is closed to new participants. Findings: From 2018 - 2019, of 294 people screened, 165 (mean age 63·8, SD16·2 years, 56% female, 78·5% European, 14% Maori, 6% Pacific, 27% most deprived) were baseline evaluated, randomised, and analysed at study end (DCEP = 83, control = 82). Multimorbidity (≥2) and polypharmacy (>5 medications) were high (82%, 69%). We found no statistically significant between-groups differences in HbA1c (mmol/mol) change at 15 months (mean 3% higher in DCEP, 95% CI 2% lower to 8% higher, p = 0·23). Twelve-week intervention adherence was good (41% attended >80% available sessions). No adverse events were reported. Interpretation: DCEP was not effective in improving glycaemic control, possibly due to insufficient exercise intensity. Our attendance demonstrated DCEP's cultural accessibility. DCEP might be good to engage in exercise marginalised people with high Hb1Ac levels, multimorbidity, and high polypharmacy. Funding: Health Research Council of New Zealand.

'I think there is nothing . . . that is really comprehensive': healthcare professionals' views on recommending online resources for pain self-management.

OBJECTIVES: To explore healthcare professionals' views on, and attitudes, towards recommending online resources for persistent pain self-management. METHODS: This study was the qualitative phase of a two-phase mixed method study. Thirty-one New Zealand health professionals involved in the management of persistent pain were interviewed via focus groups and individual interviews. Data were analysed using the general inductive approach. RESULTS: The major themes were as follows: (1) risks and limits of online information outweigh benefits, (2) a blended model, of online resources with healthcare professional support, could work, (3) only trustworthy resources can be recommended, (4) need for personalisation and (5) perceived barriers to adoption. CONCLUSION: Online resources were perceived as a useful adjunct to support pain self-management; however, due to potential risks of misinterpretation and misinformation, healthcare professionals proposed a 'blended model' where curated online resources introduced during face-to-face consultations could be used to support self-management. Participants needed 'trustworthy online resources' that provide evidence-based, updated information that is personalised to clients' health literacy and cultural beliefs. PRACTICE IMPLICATIONS: Training for healthcare professionals on critical appraisal of online resources or curation of evidence-based online resources could increase recommendation of online resources to support pain self-management as an adjunct to in-person care.

Perfect absorption in GaAs metasurfaces near the bandgap edge.

Perfect optical absorption occurs in a metasurface that supports two degenerate and critically-coupled modes of opposite symmetry. The challenge in designing a perfectly absorbing metasurface for a desired wavelength and material stems from the fact that satisfying these conditions requires multi-dimensional optimization often with parameters affecting optical resonances in non-trivial ways. This problem comes to the fore in semiconductor metasurfaces operating near the bandgap wavelength, where intrinsic material absorption varies significantly. Here we devise and demonstrate a systematic process by which one can achieve perfect absorption in GaAs metasurfaces for a desired wavelength at different levels of intrinsic material absorption, eliminating the need for trial and error in the design process. Using this method, we show that perfect absorption can be achieved not only at wavelengths where GaAs exhibits high absorption, but also at wavelengths near the bandgap edge. In this region, absorption is enhanced by over one order of magnitude compared a layer of unstructured GaAs of the same thickness.

Unraveling the dislocation core structure at a van der Waals gap in bismuth telluride.

Tetradymite-structured chalcogenides such as bismuth telluride (Bi2Te3) are of significant interest for thermoelectric energy conversion and as topological insulators. Dislocations play a critical role during synthesis and processing of such materials and can strongly affect their functional properties. The dislocations between quintuple layers present special interest since their core structure is controlled by the van der Waals interactions between the layers. In this work, using atomic-resolution electron microscopy, we resolve the basal dislocation core structure in Bi2Te3, quantifying the disregistry of the atomic planes across the core. We show that, despite the existence of a stable stacking fault in the basal plane gamma surface, the dislocation core spreading is mainly due to the weak bonding between the layers, which leads to a small energy penalty for layer sliding parallel to the van der Waals gap. Calculations within a semidiscrete variational Peierls-Nabarro model informed by first-principles calculations support our experimental findings.

Vacancy dissociation in body-centered cubic screw dislocation cores.

The interaction between screw dislocations and vacancies in body-centered cubic metals is investigated using molecular dynamics simulations. For thirteen different classical interatomic potentials, materials properties relating to vacancies, dislocations, and the interaction between the two are evaluated. The potentials include six for iron, two for molybdenum, and five for tantalum, and they are a mix of embedded atom method (EAM), modified embedded atom method (MEAM), and angular dependent potential (ADP) styles. A previously unknown behavior was identified during the interaction simulations. Out of the thirteen potentials investigated, ten predict a vacancy on the dislocation core to no longer remain as a discrete point defect, but rather to dissociate along the dislocation line. The structure of the dissociation is dependent on the potential and is characterized here. As this vacancy dissociation alters the core structure of the dislocation, it may prove to be a new mechanism for dislocation pinning and pipe diffusion.

Negotiated autonomy in diabetes self-management: the experiences of adults with intellectual disability and their support workers.

BACKGROUND: The basic human right of autonomy is underpinned by the ability to practice decision-making. The rights of people with disabilities to engage in autonomous decision-making are promoted as best practice and includes decisions around health and self-care. Little is known about autonomy in the field of long-term condition management. This paper explores how people with intellectual disabilities (ID) and their support workers experience and practice autonomy in relation to the management of diabetes. METHODS: Semi-structured interviews were completed in residential and independent living settings with people living with an ID and type 1 (N = 8) or type 2 (N = 6) diabetes and their support workers (N = 17). The participant with ID's support worker was present as requested; however, the interviews were run separately with each participant rather than jointly. Thematic analysis was undertaken, and a constructivist lens informed both data collection and analysis. RESULTS: The analysis revealed a strong process of negotiated autonomy between people with ID and their support workers in relation to the daily management of diabetes. During times of transition, roles in relation to diabetes management were renegotiated, and the promotion of autonomy was prefaced within the context of risk and client safety. Goals to increase independence were drivers for negotiating greater autonomy. CONCLUSIONS: The successful negotiation of autonomy in relation to diabetes illustrates the potential for people with ID to play a key role in the management of long-term health conditions. The study highlights the primacy of developing decision-making skills among people with ID. Promoting opportunities for decision-making and an ethos of supported decision-making through person-centred planning are all vital in working towards enhancing autonomy.

Perceptions of physiotherapists towards research: a mixed methods study.

OBJECTIVES: To explore the perceptions of physiotherapists towards the use of and participation in research. DESIGN: Concurrent mixed methods research, combining in-depth interviews with three questionnaires (demographics, Edmonton Research Orientation Survey, visual analogue scales for confidence and motivation to participate in research). SETTING: One physiotherapy department in a rehabilitation hospital, consisting of seven specialised areas. PARTICIPANTS: Twenty-five subjects {four men and 21 women, mean age 38 [standard deviation (SD) 11] years} who had been registered as a physiotherapist for a mean period of 15 (SD 10) years participated in this study. They were registered with the New Zealand Board of Physiotherapy, held a current practising certificate, and were working as a physiotherapist or physiotherapy/allied health manager at the hospital. MAIN OUTCOME MEASURE: The primary outcome measure was in-depth interviews and the secondary outcome measures were the three questionnaires. RESULTS: Physiotherapists were generally positive towards research, but struggled with the concept of research, the available literature and the time to commit to research. Individual confidence and orientation towards research seemed to influence how these barriers were perceived. CONCLUSION: This study showed that physiotherapists struggle to implement research in their daily practice and become involved in research. Changing physiotherapists' conceptions of research, making it more accessible and providing dedicated research time could facilitate increased involvement in the physiotherapy profession.

Ethnic variation in the association between sleep and body mass among US adolescents.

OBJECTIVE: We investigate whether differences in sleep duration help explain ethnic disparities in body mass index (BMI) among US adolescents. We also evaluate the functional form of the association between sleep duration and BMI, and investigate whether this association varies by sex and ethnicity. PARTICIPANTS AND METHODS: We analyzed restricted-use data from the first two waves of the National Longitudinal Study of Adolescent Health (n=30 133) to evaluate linear and quadratic associations between sleep duration and BMI. Through a series of models that incorporated interaction terms between sex, ethnicity and sleep duration, we also assessed whether (1) sleep duration mediates associations between ethnicity and BMI, and (2) associations between sleep duration and BMI differ for girls and boys from different ethnic groups. RESULTS: A linear association between sleep duration and BMI best fits the data in this large sample of US adolescents. We find no evidence that sleep duration contributes substantially to ethnic disparities in BMI. However, we detect significant differences in the association between sleep duration and BMI by sex and ethnicity. Sleep duration is negatively associated with BMI among White, Hispanic and Asian boys, positively associated with BMI among Black girls and is not related to BMI among Black boys or girls from White, Hispanic or Asian ethnic groups. CONCLUSIONS: Despite significant associations between sleep duration and BMI for certain groups of adolescents, we find no evidence that ethnic differences in sleep duration exacerbate ethnic disparities in BMI. Future research should explore mechanisms that underlie ethnic differences in the association between sleep and BMI.

First reported clinical pregnancy following heterotopic grafting of cryopreserved ovarian tissue in a woman after a bilateral oophorectomy.

Ovarian tissue cryopreservation and transplantation is a form of fertility preservation offered to young women at high risk of losing ovarian function after cancer treatment. While there have been successful births resulting from orthotopic site grafts, we report the first case of an ongoing pregnancy from a heterotopic graft in a patient who had previously undergone bilateral oopherectomy for a granulosa cell tumour. Frozen-thawed ovarian tissue was transplanted to the anterior abdominal wall. Subsequent ovarian stimulation and transabdominal ultrasound-guided oocyte retrieval from the grafts resulted in two oocytes. These were fertilized with ICSI and two embryos were transferred. Serial ultrasounds have confirmed an ongoing 26-week intrauterine twin pregnancy. Thus, this first demonstration of a pregnancy from a heterotopic graft site provides unequivocal evidence that cryopreservation preserves complete follicle development and that normal ovarian function can occur at a non-ovarian site. This provides optimism for further efforts to assist women who have had oophorectomy and pelvic surgery or radiotherapy, without an appropriate orthotopic site for grafting.

Insulin directly stimulates VEGF-A production in the glomerular podocyte.

Podocytes are critically important for maintaining the integrity of the glomerular filtration barrier and preventing albuminuria. Recently, it has become clear that to achieve this, they need to be insulin sensitive and produce an optimal amount of VEGF-A. In other tissues, insulin has been shown to regulate VEGF-A release, but this has not been previously examined in the podocyte. Using in vitro and in vivo approaches, in the present study, we now show that insulin regulates VEGF-A in the podocyte in both mice and humans via the insulin receptor (IR). Insulin directly increased VEGF-A mRNA levels and protein production in conditionally immortalized wild-type human and murine podocytes. Furthermore, when podocytes were rendered insulin resistant in vitro (using stable short hairpin RNA knockdown of the IR) or in vivo (using transgenic podocyte-specific IR knockout mice), podocyte VEGF-A production was impaired. Importantly, in vivo, this occurs before the development of any podocyte damage due to podocyte insulin resistance. Modulation of VEGF-A by insulin in the podocyte may be another important factor in the development of glomerular disease associated with conditions in which insulin signaling to the podocyte is deranged.

Insulin-like growth factor-II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse.

Podocytes are crucial for preventing the passage of albumin into the urine and, when lost, are associated with the development of albuminuria, renal failure and cardiovascular disease. Podocytes have limited capacity to regenerate, therefore pro-survival mechanisms are critically important. Insulin-like growth factor-II (IGF-II) is a potent survival and growth factor; however, its major function is thought to be in prenatal development, when circulating levels are high. IGF-II has only previously been reported to continue to be expressed in discrete regions of the brain into adulthood in rodents, with systemic levels being undetectable. Using conditionally immortalized human and ex vivo adult mouse cells of the glomerulus, we demonstrated the podocyte to be the major glomerular source and target of IGF-II; it signals to this cell via the IGF-I receptor via the PI3 kinase and MAPK pathways. Functionally, a reduction in IGF signalling causes podocyte cell death in vitro and glomerular disease in vivo in an aged IGF-II transgenic mouse that produces approximately 60% of IGF-II due to a lack of the P2 promoter of this gene. Collectively, this work reveals the fundamental importance of IGF-II in the mature podocyte for glomerular health across mammalian species.

Sleep duration and incidence of colorectal cancer in postmenopausal women.

BACKGROUND: Sleep duration is dependent on circadian rhythm that controls a variety of key cellular functions. Circadian disruption has been implicated in colorectal tumorigenesis in experimental studies. We prospectively examined the association between sleep duration and risk of colorectal cancer (CRC). METHODS: In the Women's Health Initiative Observational Study, 75 828 postmenopausal women reported habitual sleep duration at baseline 1993-1998. We used Cox proportional hazards regression model to estimate the hazard ratio (HR) of CRC and its associated 95% confidence interval (CI). RESULTS: We ascertained 851 incident cases of CRC through 2010, with an average 11.3 years of follow-up. Compared with 7 h of sleep, the HRs were 1.36 (95% CI 1.06-1.74) and 1.47 (95% CI 1.10-1.96) for short (≤5 h) and long (≥9 h) sleep duration, respectively, after adjusting for age, ethnicity, fatigue, hormone replacement therapy (HRT), physical activity, and waist to hip ratio. The association was modified by the use of HRT (P-interaction=0.03). CONCLUSION: Both extreme short and long sleep durations were associated with a moderate increase in the risk of CRC in postmenopausal women. Sleep duration may be a novel, independent, and potentially modifiable risk factor for CRC.

The feasibility and short-term benefits of Blue Prescription: a novel intervention to enable physical activity for people with multiple sclerosis.

PURPOSE: Participation in physical activity for people with Multiple sclerosis (MS) is important but can be difficult to sustain long-term. Facilitators for long-term adherence include choice over activity and control over level of engagement, coupled with support, advice and encouragement from a physiotherapist. This is the basis of Blue Prescription, a novel physiotherapy approach aimed at optimising long-term adherence with physical activity. We evaluated the feasibility and short-term benefits of Blue Prescription in people with MS. METHODS: Twenty-seven people with MS (mean age: 51 ± 11 years, with a range of MS type and disability) were assessed at baseline and immediately post-intervention with the MS Impact Scale, MS Self-efficacy Scale, and European Quality of Life Questionnaire. Change in outcomes were analysed with Wilcoxon signed ranks tests. RESULTS: All participants, irrespective of level of disability, were able to choose a physical activity and to engage in it. The physical component MS Impact Scale score significantly improved by a median change of 6.5 (95% CI = -10.5 to -2.0; p = 0.007; effect size = 0.38). There were no other significant changes in outcomes. CONCLUSION: Blue Prescription appears feasible and potentially beneficial, particularly in reducing the negative impacts of MS upon individuals, and thus warrants further evaluation.

Relative abundance and size of coastal sharks derived from commercial shark longline catch and effort data.

In the north-west Atlantic Ocean, stock assessments conducted for some commercially harvested coastal sharks indicate declines from 64 to 80% with respect to virgin population levels. While the status of commercially important species is available, abundance trend information for other coastal shark species in the north-west Atlantic Ocean are unavailable. Using a generalized linear modelling (GLM) approach, a relative abundance index was derived from 1994 to 2009 using observer data collected in a commercial bottom longline fishery. Trends in abundance and average size were estimated for bull shark Carcharhinus leucas, spinner shark Carcharhinus brevipinna, tiger shark Galeocerdo cuvier and lemon shark Negaprion brevirostris. Increases in relative abundance for all shark species ranged from 14% for C. brevipinna, 12% for C. leucas, 6% for N. brevirostris and 3% for G. cuvier. There was no significant change in the size at capture over the time period considered for all species. While the status of shark populations should not be based exclusively on abundance trend information, but ultimately on stock assessment models, results from this study provide some cause for optimism on the status of these coastal shark species.

Promoting physical activity for individuals with neurological disability: indications for practice.

PURPOSE: This study explored processes that influenced involvement in recreational exercise for individuals with neurological disability, to identify strategies to promote physical activity for health and well-being in this population. METHOD: Nineteen participants (11 males and eight females), aged 20-71 years, with a range of neurological conditions and functional limitations, were recruited in one large metropolitan area in New Zealand. Individual semi-structured interviews explored participants' views, perceptions, and experiences of undertaking recreational exercise. Data were analysed for themes. RESULTS: For some individuals, recreational exercise is undertaken for its physical, psychological, or social benefits, despite the physical activity itself feeling relatively unsatisfactory. In contrast, individuals who are able to undertake their preferred choice of recreational exercise experience intense satisfaction. This motivates self-maintenance of physical activity, even for those individuals who require carer support or assistance to do so. CONCLUSIONS: This study has identified that there can be two forms of involvement in recreational exercise that allows individuals with neurological disability to become more physically active. The information could be further developed and tested in intervention studies to provide strategies for health professionals to facilitate engagement in physical activity for people with neurological disability.

The relationship between physical activity and low back pain outcomes: a systematic review of observational studies.

Although clinical guidelines advocate exercise and activity in the management of non-specific low back pain (NSLBP), the link between levels of physical activity and outcomes is unclear. This systematic review investigated the relationships between free living activity levels after onset of low back pain (LBP) and measures of pain, and disability in patients with NSLBP. Cohort and cross-sectional studies were located using OVID, CINAHL, Medline, AMED, Embase, Biomed, PubMed-National Library of Medicine, Proquest and Cochrane Databases, and hand searches of reference lists. Studies were included if a statistical relationship was investigated between measures of free living physical activity (PA) in subjects with LBP and LBP outcome measures. Twelve studies (seven cohort and five cross-sectional) were included. One prospective study reported a statistically significant relationship between increased leisure time activity and improved LBP outcomes, and one cross-sectional study found that lower levels of sporting activity were associated with higher levels of pain and disability. All other studies (n = 10) found no relationship between measures of activity levels and either pain or disability. Heterogeneity of study designs, particularly in terms of activity measurement, made comparisons between studies difficult. These data suggest that the activity levels of patients with NSLBP are neither associated with, nor predictive of, disability or pain levels. Validated activity measurement in prospective research is required to better evaluate the relationships between PA and LBP.

Analysis of early changes in the articular cartilage transcriptisome in the rat meniscal tear model of osteoarthritis: pathway comparisons with the rat anterior cruciate transection model and with human osteoarthritic cartilage.

OBJECTIVE: The purpose of this study was to use microarray technology to: (1) understand the early molecular events underlying the damage of articular cartilage initiated by this surgical procedure, and (2) determine whether these changes mimic those that are occurring in human osteoarthritic (OA) cartilage. DESIGN: Cartilage was harvested from both medial and lateral sides of the tibial plateaus and femoral condyles of both meniscal tear (MT) and sham surgery groups on days 3, 7 and 21 post-surgery. mRNA prepared from these rat cartilage samples was used for microarray analysis. RESULTS: Statistical analysis identified 475 genes that were differentially expressed between the sham and MT groups, at one or more of the time points that were analyzed. By integrating these genes with OA-related genes reported previously in a rat OA model and in human OA array studies, we identified 20 commonly changed genes. Six out of these 20 genes (Col5A1, Col6A2, INHBA, LTBP2, NBL1 and SERPINA1) were differentially expressed in two animal models and in human OA. Pathway analysis identified some key features of OA pathology, namely cartilage extracellular matrix remodeling, angiogenesis, and chondrocyte cell death that were recapitulated in the animal models. The rat models suggested increased inflammation and cholesterol metabolic pathways may play important role in early cartilage degeneration. CONCLUSION: We identified a large number of differentially expressed genes in the articular cartilage of the MT model. While there was lack of overall identity in cartilage gene expression between the rat models and human OA, several key biological processes were recapitulated in the rat MT OA model.

Osteoporosis and gait and balance disturbances in older sarcopenic obese New Zealanders.

UNLABELLED: Bone, muscle, and fat may affect gait and balance in older adults. Osteoporosis was prevalent in low muscle mass participants and related to gait and balance deficits. Low muscle combined with high fat mass had more functional deficits and poorer bone health, which has implications for falls risk and fractures. INTRODUCTION: Decreasing bone density and muscle mass and increasing fat mass may act synergistically to affect gait and balance in older adults. METHODS: One hundred eighty-three older adults (age 72.7 +/- 6 years, range 56-93; body mass index 28.2 +/- 4.9, range 16.6-46.0) were recruited from a New Zealand falls prevention intervention trial. Total and appendicular skeletal muscle mass (ASM), percent fat, and bone mineralization were assessed by dual energy X-ray absorptiometry and used to characterize normal lean (NL, n = 51), sarcopenic (SS, n = 18), sarcopenic obese (SO, n = 29), and obese (OO, n = 85) phenotypes. Functional performance was assessed using timed up and go, chair stand, single leg stand, and step test. Regression models were adjusted for age, sex, medications, and physical activity. RESULTS: Femoral neck osteoporosis was present in 22% SS, 17% SO, 12% NL, and 7% OO. Femoral neck osteoporosis with low ASM predicted poor chair stand performance (beta -3.3, standard error 1.6, p = 0.04). SO scored lowest on the chair stand (p = 0.03) and step test (p = 0.03). Higher ASM predicted faster timed up and go performance (p = 0.001). CONCLUSIONS: Osteoporosis was prevalent in low ASM groups (SS and SO) and related to gait and balance deficits, particularly in the SO. This has implications for falls risk, fractures, and interventions.