ORCID Profile
0000-0002-9282-2743
Current Organisations
Birjand University of Medical Sciences
,
Florey Institute of Neuroscience and Mental Health
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Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology) | Psychology
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in Psychology and Cognitive Sciences |
Publisher: Elsevier BV
Date: 06-2022
Publisher: BMJ
Date: 15-08-2012
DOI: 10.1136/ANNRHEUMDIS-2012-201691
Abstract: This study describes the longitudinal association between objectively assessed physical activity (PA) and knee structural change measured using MRI. 405 community-dwelling adults aged 51–81 years were measured at baseline and approximately 2.7 years later. MRI of the right knee at baseline and follow-up was performed to evaluate bone marrow lesions (BMLs), meniscal pathology, cartilage defects, and cartilage volume. PA was assessed at baseline by pedometer (steps/day). Doing ≥10 000 steps/day was associated with BML increases (RR 1.97, 95% CI 1.19 to 3.27, p=0.009). Participants doing ≥10 000 steps/day had a 1.52 times (95% CI 1.05 to 2.20, p=0.027) greater risk of increasing meniscal pathology score, which increased to 2.49 (95% CI 1.05 to 3.93, p=0.002) in those with adverse meniscal pathology at baseline. Doing ≥10 000 steps/day was associated with a greater risk of increasing cartilage defect score in those with prevalent BMLs at baseline (RR 1.36, 95% CI 1.03 to 1.69, p=0.013). Steps/day was protective against volume loss in those with more baseline cartilage volume but led to increased cartilage loss in those with less baseline cartilage volume. (p=0.046 for interaction). PA was deleteriously associated with knee structural change, especially in those with pre-existing knee structural abnormalities. This suggests in iduals with knee abnormalities should avoid doing ≥10 000 steps/day. Alternatives to weight-bearing activity may be needed in order to maintain PA levels required for other aspects of health.
Publisher: Research Square Platform LLC
Date: 10-09-2020
DOI: 10.21203/RS.3.RS-31807/V2
Abstract: Background: To describe demographic and clinical factors associated with the prevalence and incidence of depression and explore the temporal relationship between depression and joint symptoms in patients with symptomatic knee osteoarthritis (OA). Methods: 413 participants were selected from a randomized controlled trial in people with symptomatic knee OA and vitamin D deficiency (age 63.2 ± 7.0 year, 50.4% female). Depression severity and knee joint symptoms were assessed using the patient health questionnaire (PHQ-9) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively, at baseline and 24 months. Results: The prevalence and incidence of depression was 25.4% and 11.2%, respectively. At baseline, having younger age, a higher body mass index (BMI), greater scores of WOMAC pain (PR: 1.05, 95%CI:1.03, 1.07), dysfunction (PR: 1.02, 95%CI:1.01, 1.02) and stiffness (PR: 1.05, 95%CI: 1.02, 1.09), lower education level, having more than one comorbidity and having two or more painful body sites were significantly associated with a higher prevalence of depression. Over 24 months, being female, having a higher WOMAC pain (RR: 1.05, 95%CI: 1.02, 1.09) and dysfunction score (RR: 1.02, 95%CI: 1.01, 1.03) at baseline and having two or more painful sites were significantly associated with a higher incidence of depression. In contrast, baseline depression was not associated with changes in knee joint symptoms over 24 months. Conclusion: Knee OA risk factors and joint symptoms, along with co-existing multi-site pain are associated with the prevalence and development of depression. This suggests that managing common OA risk factors and joint symptoms may be important for prevention and treatment depression in patients with knee OA. Trial registration: ClinicalTrials.gov identifier: NCT01176344Anzctr.org.au identifier: ACTRN12610000495022
Publisher: Research Square Platform LLC
Date: 03-11-2020
DOI: 10.21203/RS.3.RS-31807/V3
Abstract: Background: To describe demographic and clinical factors associated with the presence and incidence of depression and explore the temporal relationship between depression and joint symptoms in patients with symptomatic knee osteoarthritis (OA). Methods: 397 participants were selected from a randomized controlled trial in people with symptomatic knee OA and vitamin D deficiency (age 63.3 ± 7.1 year, 48.6% female). Depression severity and knee joint symptoms were assessed using the patient health questionnaire (PHQ-9) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively, at baseline and 24 months. Results: The presence and incidence of depression was 25.4% and 11.2%, respectively. At baseline, having younger age, a higher body mass index (BMI), greater scores of WOMAC pain (PR: 1.05, 95%CI:1.03, 1.07), dysfunction (PR: 1.02, 95%CI:1.01, 1.02) and stiffness (PR: 1.05, 95%CI: 1.02, 1.09), lower education level, having more than one comorbidity and having two or more painful body sites were significantly associated with a higher presence of depression. Over 24 months, being female, having a higher WOMAC pain (RR: 1.05, 95%CI: 1.02, 1.09) and dysfunction score (RR: 1.02, 95%CI: 1.01, 1.03) at baseline and having two or more painful sites were significantly associated with a higher incidence of depression. In contrast, baseline depression was not associated with changes in knee joint symptoms over 24 months. Conclusion: Knee OA risk factors and joint symptoms, along with co-existing multi-site pain are associated with the presence and development of depression. This suggests that managing common OA risk factors and joint symptoms may be important for prevention and treatment depression in patients with knee OA. Trial registration: ClinicalTrials.gov identifier: NCT01176344Anzctr.org.au identifier: ACTRN12610000495022
Publisher: Elsevier BV
Date: 04-2019
Publisher: The Journal of Rheumatology
Date: 06-2016
Abstract: Knee cartilage defects are a key feature of osteoarthritis (OA) but correlates of hip defects remain unexplored. The aims of this cross-sectional study were to describe the correlates of hip cartilage defects. The study included 194 subjects from the Tasmanian Older Adult Cohort who had right hip short-tau inversion recovery magnetic resonance imaging (MRI). Hip cartilage defects were assessed and categorized as grade 0 = no defects, grade 1 = focal blistering or irregularities on cartilage or partial thickness defect, and grade 2 = full thickness defect. Hip pain was determined by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Hip structural changes were measured on MRI, and hip radiographic OA (ROA) was assessed. Leg strength and physical activity were assessed using dynamometer and pedometers, respectively. Data were analyzed using log binomial and linear regression. Of 194 subjects, 24% (n = 48) had no defects, 34% (n = 66) had grade 1, and 41% (n = 80) had grade 2. In multivariable analyses, any hip defects were associated with greater hip pain [prevalence ratio (PR) 1.20, 95% CI 1.02–1.35] and lower mean leg strength (men mean ratio 0.83, 95% CI 0.67–0.98). Grade 1 defects were associated with hip bone marrow lesions (BML PR 1.42, 95% CI 1.03–1.96) and high cartilage signal (men PR 1.84, 95% CI 1.27–2.70), but not with hip pain or other structural findings. Grade 2 defects were associated with greater hip pain (PR 1.40, 95% CI 1.09–1.80), hip BML (PR 1.45, 95% CI 1.15–1.85), hip effusion cross-sectional area (PR 1.14, 95% CI 1.01–1.30), hip ROA (men PR 1.60, 95% CI 1.13–2.25), and steps/day (PR 0.97, 95% CI 0.96–0.99). Grade 2 defects in both sexes and grade 1 defects (mostly in men) are associated with clinical, demographic, and structural factors relevant for OA. Damage to the hip cartilage could be one of the major causes of rapid disease progression and pathophysiology of hip defects. The topic needs further study.
Publisher: Wiley
Date: 23-08-2017
DOI: 10.1111/BPH.13955
Publisher: Research Square Platform LLC
Date: 11-02-2020
Abstract: Objective To describe associations between hand abnormalities on MRI or radiographs (X-ray) and pain and function in a cross-sectional study of community-based older adults. Methods Distal and proximal interphalangeal index finger joints (n=221) were examined using MRI, X-ray, and hand examination. Hand pain, function, and stiffness were assessed using Australian/Canadian hand osteoarthritis index (AUSCAN) questionnaire. Grip strength was assessed using dynamometer. Models were adjusted for age, sex, and other MRI or X-ray abnormalities. Results Absence of collateral ligament (CLs) on MRI (relative risk RR=3.15 (95% confidence interval 1.33, 7.50), and joint space narrowing (JSN) on X-ray (RR=2.96 (1.33, 6.58)) was associated with having a painful joint after adjustment for confounders. JSN was also associated with tender joints (RR=2.19 (1.01, 4.76)). Effusion-synovitis was associated with better AUSCAN pain scores (OR=0.51 (0.28, 0.94)) and JSN with worse AUSCAN pain scores (odds ratio OR=1.67 (1.13, 2.48)). Absent CLs were also associated with stiffer joints (OR=3.12 (1.26, 7.70)) and weaker grip strength (β=-1.69 (-2.95, -0.43)) independent of pain and other features JSN was also associated with weaker grip strength (β=-0.87 (-1.62, -0.14)). No other MRI or X-ray abnormalities were associated with pain or function independent of age, sex or pain. Conclusion Most MRI abnormalities were not associated with pain and function cross-sectionally. Absent CLs and JSN were associated with painful joints and weak grip strength independent of pain and other imaging features. JSN was also associated with tender joints and absent CLs with stiff joints. Unexpectedly, effusions were associated with reduced odds of pain.
Publisher: Oxford University Press (OUP)
Date: 14-08-2018
Abstract: To describe the associations of between-person and within-person variability in serum 25-hydroxyvitamin D (25(OH)D), physical activity (PA), and knee pain and dysfunction with muscle mass, strength, and muscle quality over 10 years in community-dwelling older adults. Participants (N = 1033 51% women mean age 63 ± 7.4 years) were measured at baseline, 2.5, 5, and 10 years. Lower limb lean mass (LLM) was assessed using dual energy X-ray absorptiometry, lower limb muscle strength (LMS) using a dynamometer, and lower limb muscle quality (LMQ) calculated as LMS/LLM. Knee pain and dysfunction were assessed using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index. PA was measured using pedometers. Linear-mixed effect regression models, with adjustment for confounders, were used to estimate the association of within-person and between-person variability in PA, 25(OH)D, and WOMAC scores with muscle mass, strength, and muscle quality. Both between-person and within-person increases in PA were associated with LLM, LMS, and LMQ (all P < 0.05). Within-person and between-person increases in knee pain and dysfunction were associated with LLS and LMQ, but not with LLM (all P < 0.05). Between-person effects showed that higher average 25(OH)D was associated with a higher 10-year average LLM, LMS, and LMQ (all P < 0.05), whereas within-person increases in average 25(OH)D were associated with a higher LMS and LMQ, but not with LLM. Variability in 25(OH)D, pain, and dysfunction within an in idual over time is related to muscle changes in that in idual. Increasing one's own PA level further increases muscle mass, strength, and quality supporting the clinical recommendation of promoting PA to reduce age-related muscle loss.
Publisher: Research Square Platform LLC
Date: 31-05-2020
DOI: 10.21203/RS.3.RS-31807/V1
Abstract: Background To describe demographic and clinical factors associated with the prevalence and incidence of depression and explore the temporal relationship between depression and joint symptoms in patients with symptomatic knee osteoarthritis (OA). Methods 413 participants were selected from a randomized controlled trial in people with symptomatic knee OA and vitamin D deficiency (age 63.2 ± 7.0 year, 50.4% female). Depression severity and knee joint symptoms were assessed using the patient health questionnaire (PHQ-9) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively, at baseline and 24 months. Results The prevalence and incidence of depression was 25.4% and 11.2%, respectively. At baseline, having a higher body mass index (BMI), greater scores of WOMAC pain (PR: 1.05, 95%CI:1.03, 1.07), dysfunction (PR: 1.02, 95%CI:1.01, 1.02) and stiffness (PR: 1.05, 95%CI: 1.02, 1.09), lower education level, having more than one comorbidity and having two or more painful body sites were significantly associated with a higher prevalence of depression. Over 24 months, being female, having a higher WOMAC pain (RR: 1.04, 95%CI: 1.00, 1.08) and dysfunction score (RR: 1.01, 95%CI: 1.00, 1.02) at baseline and having two or more painful sites were significantly associated with a higher incidence of depression. In contrast, baseline depression was not associated with changes in knee joint symptoms over 24 months. Conclusion Knee OA risk factors and joint symptoms, along with co-existing multi-site pain are associated with the prevalence and development of depression. This suggests that managing common OA risk factors and joint symptoms could be important for prevention and treatment depression in patients with knee OA.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.EXGER.2019.01.008
Abstract: This study aims to describe the associations of low muscle mass, handgrip (HGS) and lower-limb muscle strength (LMS) with health-related quality of life (HRQoL) over 10 years in community-dwelling older adults. Participants (N = 1002 51% women mean age 63 ± 7.4 years) were prospectively followed for 10 years. HRQoL was measured using the validated assessment of quality of life (AQoL) instrument. Appendicular lean mass (ALM) was assessed using dual energy X-ray absorptiometry and normalized to body mass index (BMI). HGS and LMS were assessed using dynamometers. Low ALM/BMI (ALM/BMI Participants with LMS Lower-limb muscle strength and handgrip strength (in women only), which can be easily measured in clinical practice, appear more important than muscle mass for HRQoL.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Wiley
Date: 02-2022
DOI: 10.1111/IMJ.15066
Abstract: A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown. To describe the association between SES and time to THR and TKR. One thousand and seventy-two older adults residing in Tasmania, Australia, were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area-level SES was determined using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) from the Australian Bureau of Statistics' 2001 census data. The IRSAD was analysed in two ways: (i) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group and (ii) the cohort dichotomised at the quartile 1 cut-point. The mean age was 63.0 (±7.5) years and 51% were women. Over the median follow up of 12.9 (interquartile range: 12.2-13.9) years, 56 (5%) participants had a THR and 79 (7%) had a TKR. Compared with the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR hazard ratio (HR): 0.56 95% confidence interval (CI) 0.32, 1.00) but not TKR (HR: 0.90 95% CI 0.53, 1.54). However, the former became non-significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors. The present study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES.
Publisher: Research Square Platform LLC
Date: 18-12-2020
DOI: 10.21203/RS.3.RS-31807/V4
Abstract: Background: To describe demographic and clinical factors associated with the presence and incidence of depression and explore the temporal relationship between depression and joint symptoms in patients with symptomatic knee osteoarthritis (OA). Methods: 397 participants were selected from a randomized controlled trial in people with symptomatic knee OA and vitamin D deficiency (age 63.3 ± 7.1 year, 48.6% female). Depression severity and knee joint symptoms were assessed using the patient health questionnaire (PHQ-9) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively, at baseline and 24 months. Results: The presence and incidence of depression was 25.4% and 11.2%, respectively. At baseline, having younger age, a higher body mass index (BMI), greater scores of WOMAC pain (PR: 1.05, 95%CI:1.03, 1.07), dysfunction (PR: 1.02, 95%CI:1.01, 1.02) and stiffness (PR: 1.05, 95%CI: 1.02, 1.09), lower education level, having more than one comorbidity and having two or more painful body sites were significantly associated with a higher presence of depression. Over 24 months, being female, having a higher WOMAC pain (RR: 1.05, 95%CI: 1.02, 1.09) and dysfunction score (RR: 1.02, 95%CI: 1.01, 1.03) at baseline and having two or more painful sites were significantly associated with a higher incidence of depression. In contrast, baseline depression was not associated with changes in knee joint symptoms over 24 months. Conclusion: Knee OA risk factors and joint symptoms, along with co-existing multi-site pain are associated with the presence and development of depression. This suggests that managing common OA risk factors and joint symptoms may be important for prevention and treatment depression in patients with knee OA. Trial registration: ClinicalTrials.gov identifier: NCT01176344Anzctr.org.au identifier: ACTRN12610000495022
Publisher: Springer Science and Business Media LLC
Date: 12-10-2016
Publisher: Wiley
Date: 29-06-2010
DOI: 10.1002/ART.27467
Abstract: There is limited longitudinal evidence relating subchondral bone changes to cartilage damage and loss. The aim of this study was to describe the association between baseline tibial bone area and tibial subchondral bone mineral density (BMD) with tibial cartilage defect development and cartilage volume loss. A total of 341 subjects (mean age 63 years, range 52-79 years) underwent measurement at baseline and approximately 2.7 years later. Tibial knee cartilage volume, cartilage defects (graded on a scale of 0-4), and bone area were determined using T1-weighted fat suppression magnetic resonance imaging. Tibial subchondral BMD was determined using dual x-ray absorptiometry. In multivariable analysis, baseline bone area positively predicted cartilage defect development at the medial and lateral tibial sites (odds ratio [OR] 1.6 per 1 SD increase, 95% confidence interval [95% CI] 1.0, 2.6, and OR 2.4 per 1 SD increase, 95% CI 1.4, 4.0, respectively) and cartilage volume loss at the medial tibial site (beta = -34.9 per 1 SD increase, 95% CI -49.8, -20.1). In contrast, baseline subchondral BMD positively predicted cartilage defect development at the medial tibial site only (OR 1.6 per 1 SD increase, 95% CI 1.2, 2.1) and was not associated with cartilage loss. The results of this study demonstrated that bone area predicted medial and lateral cartilage defect development and medial cartilage volume loss, while subchondral BMD predicted medial defect development but not cartilage loss. These associations were independent of each other, indicating there are multiple mechanisms by which subchondral bone changes may lead to cartilage damage.
Publisher: Wiley
Date: 12-2009
DOI: 10.1359/JBMR.090532
Abstract: Subchondral bone is hypothesized to be important in the development and progression of osteoarthritis (OA) however, little is known about the determinants of subchondral bone. This study describes the relationship between tibial subchondral BMD (sBMD) and anthropometric, lifestyle, and structural measures in 740 randomly selected subjects (mean age, 62 yr range, 50-80 yr 52% women). We measured medial tibial sBMD by DXA at two regions of interest (ROIs). We also assessed anthropometrics, vitamin D, steps per day by pedometer, joint space narrowing (JSN) and osteophytes (by X-ray), cartilage defects, cartilage volume, and bone marrow lesions (BML by MRI), and hip and spine BMD (by DXA). sBMD using ROI 1 was negatively associated with age and female sex and positively associated with BMI. In multivariable analysis, sBMD was positively correlated with steps per day (r = 0.08, p = 0.025), tibial osteophytes (r = 0.08, p = 0.028), JSN (r = 0.11, p < 0.01), cartilage defects (r = 0.16, p < 0.01), cartilage volume (r = 0.12, p = 0.01), BMLs (r = 0.17, p = 0.013 [tibial] r = 0.16, p = 0.018 [femoral]), and hip and spine BMD (r = 0.36, p < 0.01 and r = 0.38, p < 0.01, respectively). Similar associations were observed using ROI 2, with vitamin D also associated with sBMD (r = 0.10, p < 0.01). In conclusion, this study identified a large number of factors associated with sBMD, of which the most novel is cartilage defects. Longitudinal studies are required to address causality.
Publisher: Wiley
Date: 25-04-2019
DOI: 10.1002/ACR.23713
Abstract: To describe the cross-sectional and longitudinal associations between quantitative measures of infrapatellar fat pad (IPFP) signal-intensity alteration and knee structural abnormalities in patients with symptomatic knee osteoarthritis (OA). A total of 261 patients (mean ± SD age 63.0 ± 7.2 years) with symptomatic knee OA were selected from a randomized controlled trial with a follow-up of 2 years. IPFP signal-intensity alterations at baseline were quantitatively measured on T2-weighted fat-saturated magnetic resonance imaging using MATLAB. These quantitative measures included the SD of whole IPFP signal intensity measurement, the upper quartile value of high signal intensity (UQ Higher baseline SD of the IPFP, UQ Quantitative measures of increased signal intensity in the IPFP were associated with knee structural abnormalities in the tibiofemoral compartment, suggesting that these measurements could be used as an additional entry criterion to enrich studies for faster progressors of knee OA.
Publisher: Springer Science and Business Media LLC
Date: 10-11-2016
Publisher: Wiley
Date: 25-02-2021
DOI: 10.1002/ACR.24128
Abstract: To describe cross-sectional associations between features observed on ultrasound (US) or clinical joint examination and hand symptoms among community-dwelling older adults (n = 519), and to determine whether such associations are independent of age, sex, body mass index, and other imaging features. Hand pain, function, and stiffness were assessed using a visual analog scale (VAS) and the Australian/Canadian Hand Osteoarthritis (AUSCAN) index. Standardized clinical and US examinations were performed, and grip strength was assessed using a dynamometer. Data were analyzed using hurdle and linear models and adjusted for demographic factors and other features. Abnormal findings on joint examination and on US imaging are common in older adults with and without hand pain. Greater numbers of tender joints were associated with greater pain (VAS: β = 2.63 [95% confidence interval (95% CI) 1.88, 3.39] AUSCAN pain: β = 10.57 [95% CI 4.00, 17.13]), poorer AUSCAN function (β = 4.07 [95% CI 1.28, 6.86]), and poorer grip strength (β = -0.15 [95% CI -0.27, -0.03]). Power Doppler imaging (PDI) synovitis was associated with greater pain (VAS: β = 2.61 [95% CI 1.03, 4.19] AUSCAN pain: β = 13.07 [95% CI 3.82, 22.32]), but not function. Joint deformity was associated with poorer function (β = 4.51 [95% CI 1.75, 7.26]) and grip strength (β = -0.23 [95% CI -0.40, -0.05]), but not pain. Gray-scale synovitis was associated only with poorer grip strength (β = -0.22 [95% CI -0.41, -0.04]). Associations with function and grip strength were partially mediated by pain. Joints that are tender on palpation or have US-identified PDI synovitis are potential treatment targets for hand pain. Treating tender joints and preventing hand deformity is required to improve hand function in community-dwelling older adults.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.NEUROPHARM.2016.07.006
Abstract: Alcoholism is a chronic relapsing disorder and a major global health problem. Stress is a key precipitant of relapse in human alcoholics and in animal models of alcohol seeking. The brainstem nucleus incertus (NI) contains a population of relaxin-3 neurons that are highly responsive to psychological stressors and the ascending NI relaxin-3/RXFP3 signalling system is implicated in stress-induced reinstatement of alcohol seeking. The NI receives orexinergic innervation and expresses orexin1 (OX1) and orexin2 (OX2) receptor mRNA. In alcohol-preferring (iP) rats, we examined the impact of yohimbine-induced reinstatement of alcohol seeking on orexin neuronal activation, and the effect of bilateral injections into NI of the OX1 receptor antagonist, SB-334867 (n = 16) or the OX2 receptor antagonist, TCS-OX2-29 (n = 8) on stress-induced reinstatement of alcohol seeking. We also assessed the effects of orexin-A on NI neuronal activity and the involvement of OX1 and OX2 receptors using whole cell patch-cl recordings in rat brain slices. Yohimbine-induced reinstatement of alcohol seeking activated orexin neurons. Bilateral NI injections of TCS-OX2-29 attenuated yohimbine-induced reinstatement of alcohol seeking. In contrast, intra-NI injection of SB-334867 had no significant effect. In line with these data, orexin-A (600 nM) depolarized a majority of NI neurons recorded in coronal brain slices (18/28 cells), effects prevented by bath application of TCS-OX2-29 (10 μM), but not SB-334867 (10 μM). These data suggest an excitatory orexinergic input to NI contributes to yohimbine-induced reinstatement of alcohol seeking, predominantly via OX2 receptor signalling.
Publisher: Springer Science and Business Media LLC
Date: 12-2010
DOI: 10.1186/AR3209
Publisher: Oxford University Press (OUP)
Date: 16-01-2021
DOI: 10.1093/RHEUMATOLOGY/KEAA787
Abstract: To describe the impact of OA on health-related quality of life (HRQoL) in the forms of health state utilities (HSUs) and health-dimension scores, and to compare the longitudinal changes in HRQoL for people with and without OA, using an Australian population-based longitudinal cohort. Participants of the Tasmanian Older Adult Cohort with data on OA diagnosis and HRQoL were included [interviewed at baseline (n = 1093), 2.5 years (n = 871), 5 years (n = 760) and 10 years (n = 562)]. HRQoL was assessed using the Assessment of Quality of Life four-dimensions and analysed using multivariable linear mixed regressions. Compared with participants without OA, HSUs for those with OA were 0.07 (95% confidence interval: 0.09, 0.05) units lower on average over 10 years. HSUs for participants with knee and/or hip OA were similar to those with other types of OA at the 2.5 year follow-up and then erged, with HSUs of the former being up to 0.09 units lower than the latter. Those with OA had lower scores for psychological wellness, independent living and social relationships compared with those without OA. Independent living and social relationships were mainly impacted by knee and/or hip OA, with the effect on the former increasing over time. Interventions to improve HRQoL should be tailored to specific OA types, health dimensions, and times. Support for maintaining psychological wellness should be provided, irrespective of OA type and duration. However, support for maintaining independent living could be more relevant to knee and/or hip OA patients living with the disease for longer.
Publisher: Springer International Publishing
Date: 2016
DOI: 10.1007/7854_2016_55
Abstract: Addiction is a chronic relapsing disorder characterized by compulsive drug seeking and drug taking despite negative consequences. Alcohol abuse and addiction have major social and economic consequences and cause significant morbidity and mortality worldwide. Currently available therapeutics are inadequate, outlining the need for alternative treatments. Detailed knowledge of the neurocircuitry and brain chemistry responsible for aberrant behavior patterns should enable the development of novel pharmacotherapies to treat addiction. Therefore it is important to expand our knowledge and understanding of the neural pathways and mechanisms involved in alcohol seeking and abuse. The orexin (hypocretin) neuropeptide system is an attractive target, given the recent FDA and PMDA approval of suvorexant for the treatment of insomnia. Orexin is synthesized exclusively in neurons located in the lateral (LH), perifornical (PEF), and dorsal medial (DMH) hypothalamus. These neurons project widely throughout the neuraxis with regulatory roles in a wide range of behavioral and physiological responses, including sleep-wake cycle neuroendocrine regulation, anxiety, feeding behavior, and reward seeking. Here we summarize the literature to date, which have evaluated the interplay between alcohol and the orexin system.
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.SEMARTHRIT.2022.152054
Abstract: To evaluate the effect of annual infusions of zoledronic acid (ZA) with or without a single injection of methylprednisolone, compared to placebo, on quantitative magnetic resonance imaging 3-D bone area and bone shape in participants with symptomatic knee osteoarthritis (OA). This was a post-hoc analysis of the ZAP2 trial. Active appearance modelling was used to assess bone area (mm At baseline 65% of participants demonstrated an OA shape. Treatment with ZA plus methylprednisolone but not ZA alone, compared to placebo, was associated with significantly slower expansion in bone area at the medial femoral (-33.9 mm ZA plus methylprednisolone may retard expansion of bone area over 24 months, but ZA alone may not. Neither ZA with or without methylprednisolone slowed progression of bone shape over 6 or 24 months.
Publisher: Springer Science and Business Media LLC
Date: 02-05-2020
Publisher: Wiley
Date: 12-09-2022
DOI: 10.1002/MSC.1700
Abstract: Using a qualitative design this study aimed to (1) explore the experience of people living with osteoarthritis (OA), (2) gain an understanding of their navigation of the health system and, (3) explore their opinions on the role of exercise and joint replacement surgery for the management of OA. Purposive s ling was used to recruit 26 participants with knee OA, aged 45 years and over, from Tasmania, Australia. Semi‐structured interviews were audio‐recorded, transcribed, coded, and thematically analysed to document participant understanding and experience of OA and their opinions on the role of exercise and surgery in managing OA. Of the 26 participants, 80% ( n = 21) were female with a mean age of 66 years. The main theme identified was that in iduals with knee OA were navigating a maze of OA treatments. Three related subthemes were that participants: (i) perceived their general practitioner did not have an ongoing role in their OA care, (ii) self‐directed their management and, (iii) s led from a ‘smorgasbord’ of treatment options, including low‐value care options. Two other major themes were: the role of exercise for OA management, and surgery as a last resort. Our findings suggest that OA patients may not be choosing consistent, high‐value care for their OA. This highlights the importance of an evidence‐based multi‐disciplinary approach to guide patients to self‐manage their OA and support their navigation of the health system. Reducing emphasis on the pathway to surgery and streamlining access to conservative management strategies may assist people to receive high‐value care.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.JOCA.2018.12.023
Abstract: To investigate the longitudinal association between objectively measured ambulatory activity (AA) and knee MRI-detected osteophytes (OPs), and to test whether this relationship was modified by common risk factors for OA including sex, obesity, disease severity and knee injury history. 408 community-dwelling adults aged 51-81 years were assessed at baseline and 2.7 years. T1-weighted fat-suppressed MRI was used to evaluate knee OPs at both time points. AA was assessed at baseline by pedometers and categorized as: less active (≤7499 steps per day), moderately active (7500-9999 steps per day) and highly active (≥10,000 steps per day). Statistically significant interactions were detected between knee OA risk factors and AA on increases in MRI-detected OPs (all P < 0.05). In stratified analyses, being moderately active, compared to being less active, was protective against an increase in MRI-detected OPs (score change of ≥1) in females (relative risk (RR) = 0.42, 95%CI, 0.25-0.70, P < 0.01), those who were obese (RR = 0.50, 95%CI, 0.30-0.83, P < 0.01), those with radiographic OA (ROA) (RR = 0.68, 95%CI, 0.47-0.97, P = 0.02) and those with a history of knee injury (RR = 0.27, 95%CI, 0.08-0.88, P = 0.02) in almost every knee compartment, after adjustment for confounders. No statistically significant associations were found in males, non-obese, non-ROA or non-injury groups. Being moderately active is protective against an increase in MRI-detected OPs in females, those with ROA, those who are obese and those with a history of knee injury. These findings suggest that being moderately active is beneficial for in iduals who are at higher risk of knee OA.
Publisher: Springer Science and Business Media LLC
Date: 07-01-2021
DOI: 10.1186/S12891-020-03875-1
Abstract: To describe demographic and clinical factors associated with the presence and incidence of depression and explore the temporal relationship between depression and joint symptoms in patients with symptomatic knee osteoarthritis (OA). Three hundred ninety-seven participants were selected from a randomized controlled trial in people with symptomatic knee OA and vitamin D deficiency (age 63.3 ± 7.1 year, 48.6% female). Depression severity and knee joint symptoms were assessed using the patient health questionnaire (PHQ-9) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively, at baseline and 24 months. The presence and incidence of depression was 25.4 and 11.2%, respectively. At baseline, having younger age, a higher body mass index (BMI), greater scores of WOMAC pain (PR: 1.05, 95%CI:1.03, 1.07), dysfunction (PR: 1.02, 95%CI:1.01, 1.02) and stiffness (PR: 1.05, 95%CI: 1.02, 1.09), lower education level, having more than one comorbidity and having two or more painful body sites were significantly associated with a higher presence of depression. Over 24 months, being female, having a higher WOMAC pain (RR: 1.05, 95%CI: 1.02, 1.09) and dysfunction score (RR: 1.02, 95%CI: 1.01, 1.03) at baseline and having two or more painful sites were significantly associated with a higher incidence of depression. In contrast, baseline depression was not associated with changes in knee joint symptoms over 24 months. Knee OA risk factors and joint symptoms, along with co-existing multi-site pain are associated with the presence and development of depression. This suggests that managing common OA risk factors and joint symptoms may be important for prevention and treatment depression in patients with knee OA. ClinicalTrials.gov identifier: NCT01176344 . Anzctr.org.au identifier: ACTRN12610000495022 .
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.JOCA.2018.02.899
Abstract: To assess the efficacy of adalimumab in patients with erosive hand osteoarthritis (OA). Patients >50 years old, meeting the American College of Rheumatology (ACR) criteria for hand OA, with pain >50 on 100 mm visual analogue scale (VAS), morning stiffness >30 min and ≥1 erosive joint on X-ray with synovitis present on magnetic resonance imaging (MRI) were included in a randomised double-blind placebo-controlled crossover trial. Patients were randomised to adalimumab (40 mg subcutaneous injections every other week) or identical placebo injections for 12 weeks followed by an 8-week washout and then crossed over treatment groups for another 12 weeks. The primary outcome was change in VAS hand pain over 12 weeks. Secondary outcomes included change in Australian/Canadian Hand OA Index (AUSCAN) pain, function and stiffness subscales from baseline to 4, 8 and 12 weeks, change in MRI-detected synovitis and bone marrow lesions (BMLs) from baseline to 12 weeks and change in VAS from baseline to 4 and 8 weeks. We recruited 51 patients and 43 were randomised to either Group 1 (N = 18, active then placebo) or Group 2 (N = 25, placebo then active). At 12 weeks there was no difference between the groups on the primary outcome measure (mean decrease in VAS pain of 3.2 mm standard deviation (SD 16.7) for adalimumab vs 0.8 mm (SD 29.6) for placebo). The adjusted treatment effect was -0.7 mm (95% confidence interval (CI) -9.3 to 8.0), P = 0.87. No statistically significant differences were found for any secondary outcomes. Adalimumab did not show any effect on pain, synovitis or BMLs in patients with erosive hand OA with MRI-detected synovitis as compared to placebo after 12 weeks. ACTRN12612000791831.
Publisher: Elsevier BV
Date: 04-2018
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.JAMDA.2018.09.006
Abstract: To determine the effect of vitamin D supplementation and maintaining sufficient serum vitamin D on depressive symptoms in patients with knee osteoarthritis (OA) and vitamin D deficiency. A prespecified secondary analysis of a multicentre, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive oral vitamin D This clinical trial was conducted in participants with symptomatic knee OA and vitamin D deficiency from June 2010 to December 2013 in Tasmania and Victoria, Australia. The primary outcome was the depressive symptoms change over 24 months, which was measured using the Patient Health Questionnaire (PHQ-9, 0-27). Of 599 participants who were screened for eligibility, 413 participants were enrolled (mean age: 63.2 years 50.3% female) and 340 participants (intervention n = 181, placebo n = 159, 82.3% retention rate) completed the study. The baseline prevalence of depression (PHQ-9 score ≥5) was 25.4%. Depressive symptoms improved more in the vitamin D supplementation group compared to the placebo group [β: -0.66, 95% confidence interval (CI): -1.22 to -0.11, P for difference = .02] and in the participants who maintained vitamin D sufficiency compared to those who did not (β: -0.73, 95% CI: -1.41 to -0.05, P for difference = .04) over 24 months. These findings suggest that vitamin D supplementation and maintaining adequate vitamin D levels over 24 months may be beneficial for depressive symptoms in patients with knee OA.
Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism
Date: 06-2017
Publisher: Springer Science and Business Media LLC
Date: 31-08-2016
Publisher: Springer Science and Business Media LLC
Date: 12-03-2018
DOI: 10.1007/S00198-018-4446-4
Abstract: Relationships between objectively assessed free-living physical activity (PA) and changes in bone health over time are poorly understood in older adults. This study suggests these relationships are sex-specific and that body composition may influence the mechanical loading benefits of PA. To investigate associations of objectively assessed PA and bone health in community-dwelling older adults. This secondary analysis of a subset of the Tasmanian Older Adult Cohort study included participants with PA assessed utilising ActiGraph GT1M accelerometers over 7 days (N = 209 participants, 53% female mean ± SD age 64.5 ± 7.2 years). Steps/day and PA intensity were estimated via established thresholds. Bone mineral content (BMC) was acquired at the total hip, lumbar spine, legs and whole body by DXA at baseline and approximately 2.2 years later. Relationships between PA and BMC were assessed by multivariable linear regression analyses adjusted for age, smoking status, height and total lean mass. Men with above-median total hip BMC completed significantly less steps per day, but there was no significant difference in PA intensity compared with those with below-median BMC. There were no significant differences in PA in women stratified by median BMC. In women, steps/day were positively associated with leg BMC (B = 0.178 P = 0.017), and sedentary behaviour was negatively associated with leg BMC (- 0.165 0.016) at baseline. After adjustment for confounders including lean mass and height, higher sedentary behaviour at baseline was associated with declines in femoral neck BMC (- 0.286 0.011) but also with increases in pelvic BMC (0.246 0.030) in men and increases in total hip BMC (0.215 0.032) in women, over 2.2 years. No other significant longitudinal associations were observed after adjustment for body composition. Associations of accelerometer-determined sedentary behaviour and PA with bone health in older adults differ by sex and anatomical site and are mediated by body composition.
Publisher: Informa UK Limited
Date: 15-03-2020
Publisher: BMJ
Date: 21-02-2012
DOI: 10.1136/ANNRHEUMDIS-2011-200970
Abstract: To compare the effect of a single infusion of zoledronic acid (ZA) with placebo on knee pain and bone marrow lesions (BMLs). Adults aged 50-80 years (n=59) with clinical knee osteoarthritis and knee BMLs were randomised to receive either ZA (5 mg/100 ml) or placebo. BMLs were determined using proton density-weighted fat saturation MR images at baseline, 6 and 12 months. Pain and function were measured using a visual analogue scale (VAS) and the knee injury and osteoarthritis outcome score (KOOS) scale. At baseline, mean VAS score was 54 mm and mean total BML area was 468 mm(2). VAS pain scores were significantly reduced in the ZA group compared with placebo after 6 months (-14.5 mm, 95% CI -28.1 to -0.9) but not after 3 or 12 months. Changes on the KOOS scales were not significant at any time point. Reduction in total BML area was greater in the ZA group compared with placebo after 6 months (-175.7 mm(2), 95% CI -327.2 to -24.3) with a trend after 12 months (-146.5 mm(2), 95% CI -307.5 to +14.5). A greater proportion of those in the ZA group achieved a clinically significant reduction in BML size at 6 months (39% vs 18%, p=0.044). Toxicity was as expected apart from a high rate of acute phase reactions in treatment and placebo arms. ZA reduces knee pain and areal BML size and increases the proportion improving over 6 months. Treatment of osteoarthritis may benefit from a lesion specific therapeutic approach. ACTRN 12609000399291.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2022
DOI: 10.1186/S13063-022-06715-W
Abstract: There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis. We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0–3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses. This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype. Australian and New Zealand Clinical Trial Registry ACTRN12618001656224 . Registered on 08 October 2018.
Publisher: eLife Sciences Publications, Ltd
Date: 14-09-2022
DOI: 10.7554/ELIFE.82453
Abstract: A neural pathway involved in goal-oriented behaviours becomes dysregulated during binge drinking and alcohol use disorder.
Publisher: Elsevier BV
Date: 04-2020
Publisher: American Medical Association (AMA)
Date: 21-04-2020
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.JSAMS.2016.02.002
Abstract: To evaluate the associations between an objective measure of different intensities of physical activity, upper- and lower-limb muscle strength and psychomotor performance and set-shifting domains of cognitive executive function in older adults. A cross-sectional study. From the Tasmanian Older Adult Cohort Study, 188 community-dwelling older adults (53.7% female mean age±SD 63.98±7.3 years) undertook 7-day physical activity behaviour monitoring using an accelerometer. Dynamometers were used to assess leg extension strength. The Trail Maker Tests were used to measure psychomotor processing speed and set-shifting performance. When controlling for age, smoking history, alcohol intake, educational achievement and neuropsychological functioning, higher levels of light physical activity, but not sedentary behaviour or moderate or vigorous physical activity, was found to be associated with better set-shifting performance. Neither physical activity behaviour or muscle strength were found to be associated with psychomotor performance. In addition, older age, greater alcohol intake, and lower levels of educational attainment, verbal learning and memory performance were significantly associated with lower scores on the set-shifting task whereas older age and reduced neuropsychological functioning were associated with lower psychomotor processing speed scores. Light physical activity is associated with higher executive functioning in community-dwelling older adults and this strengthens the evidence supporting exercise as a neuroprotective agent. Further studies are needed to understand why light physical activity behaviour positively influences executive functioning, and how such physical activity can be implemented into the daily routine of older adults.
Publisher: Elsevier BV
Date: 04-2019
Publisher: Springer Science and Business Media LLC
Date: 2010
DOI: 10.1186/AR3210
Publisher: Wiley
Date: 11-01-2022
DOI: 10.1002/ACR.24478
Abstract: Health state utility values (HSUVs) are a key input in health economic modeling, but HSUVs of people with osteoarthritis (OA)–related conditions have not been systematically reviewed and meta‐analyzed. Our objective was to systematically review and meta‐analyze the HSUVs for people with OA. Searches within health economic/biomedical databases were performed to identify eligible studies reporting OA‐related HSUVs. Data on study design, participant characteristics, affected OA joint sites, treatment type, HSUV elicitation method, considered health states, and the reported HSUVs were extracted. HSUVs for people with knee, hip, and mixed OA in pre‐ and posttreatment populations were meta‐analyzed using random effects models. A total of 151 studies were included in the systematic review, and 88 in meta‐analyses. Of 151 studies, 56% were conducted in Europe, 75% were in people with knee and/or hip OA, and 79% were based on the EuroQoL 5‐dimension instrument. The pooled mean baseline HSUVs for knee OA core interventions, medication, injection, and primary surgery treatments were 0.64 (95% confidence interval [95% CI] 0.61–0.66), 0.56 (95% CI 0.45−0.68), 0.58 (95% CI 0.50–0.66), and 0.52 (95% CI 0.49–0.55), respectively. These were 0.71 (95% CI 0.59–0.84) for hip OA core interventions and 0.52 (95% CI 0.49–0.56) for hip OA primary surgery. For all knee OA treatments and hip OA primary surgery, pooled HSUVs were significantly higher in the post‐ than the pretreatment populations. This study provides a comprehensive summary of OA‐related HSUVs and generates an HSUV database for people with different affected OA joint sites undergoing different treatments to guide HSUV choices in future health economic modeling of OA interventions.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 15-05-2014
DOI: 10.1007/S00223-014-9863-6
Abstract: Studies examining the association between muscle size, muscle strength, and bone mineral density (BMD) are limited. Thus, this study aimed to describe the association between hip muscles cross-sectional area (CSA), muscle strength, and BMD of the hip and spine. A total of 321 subjects from the Tasmanian Older Adult Cohort study with a right hip MRI scan conducted between 2004 and 2006 were included. Hip muscles were measured on MR images by OsiriX (Geneva) software measuring maximum muscle CSA (cm(2)) of gluteus maximus, obturator externus, gemelli, quadratus femoris, piriformis, pectineus, sartorius, and iliopsoas. Dual-energy X-ray absorptiometry measured total hip, femoral neck, and spine BMD, and lower limb muscle strength was assessed by dynamometer. Muscle CSA of the hip flexors (pectineus, sartorius, and iliopsoas) and the hip rotators, obturator externus, and quadratus femoris were associated with both total hip and femoral neck BMD (all p < 0.05). The associations between CSA of pectineus and sartorius and BMD were stronger in women (p = 0.01-0.001) compared to men (p = 0.12-0.54). Additionally, only gemelli CSA was associated with BMD of the spine (p = 0.002). Gluteus maximus and piriformis showed no relationship with BMD. CSA of most hip muscles (except gluteus maximus and gemelli) were positively associated with leg strength (p = 0.02 to <0.001). Lastly, leg strength was weakly associated with BMD (p = 0.11-0.007). Hip muscle CSA, and to a lesser extent muscle strength, were positively associated with hip BMD. These data suggest that both higher muscle mass and strength may contribute to the maintenance of bone mass and prevention of disease progression in older adults.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.JOCA.2013.10.022
Abstract: There is evidence to suggest vascular involvement in the initiation and progression of osteoarthritis (OA). The relationship between large artery characteristics and pathogenesis of OA has not been investigated and was the aim of this study. Large artery characteristics (i.e., aortic stiffness, brachial and central blood pressure (BP) variables) and bone marrow lesions (BMLs measured by magnetic resonance imaging as a surrogate index of OA) were recorded in 208 participants (aged 63 ± 7 years mean ± SD) with symptomatic knee OA. Relationships between large artery characteristics and BML were assessed by multiple regression adjusting for age, sex and body mass index. There was a high prevalence of BML presence in the study population (70%), but no significant difference between participants with and without BML for all large artery and BP variables (P > 0.05 all). Furthermore, there were no significant relationships between BML size and aortic stiffness (r = -0.033, P = 0.71), central pulse pressure (r = 0.028, P = 0.74), augmentation index (r = 0.125, P = 0.14), brachial pulse pressure (r = 0.005, P = 0.95) or brachial systolic BP (r = -0.066, P = 0.44). When participants were stratified according to high or low aortic stiffness, there was no significant difference between groups regarding the proportion of those with a BML (64% vs. 70% respectively P = 0.69). Variables indicative of large artery characteristics are not significantly correlated with BML size or presence in people with symptomatic knee OA. Thus, large artery characteristics may not have a causative influence in the development of OA, but this needs to be confirmed in prospective studies.
Publisher: Wiley
Date: 20-07-2016
DOI: 10.1111/ADB.12426
Abstract: Alcoholism is a chronic relapsing disorder, and stress is a key precipitant of relapse. The nucleus incertus (NI) is highly responsive to corticotrophin-releasing factor (CRF) and psychological stressors, receives a CRF innervation and expresses CRF
Publisher: Springer Science and Business Media LLC
Date: 08-01-2020
DOI: 10.1007/S10067-019-04920-8
Abstract: To identify subgroups of community-dwelling older adults and to assess their longitudinal associations with long-term osteoarthritis (OA) outcomes. 1046 older adults aged 50-80 years were studied. At baseline, body mass index (BMI), pedometer-measured ambulatory activity (AA), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) determined knee pain and information on comorbidities were obtained. Tibial cartilage volume and bone-marrow lesions (BMLs) were assessed using MRI at baseline and 10 years and total knee replacements (TKR) by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. Latent class analysis was used to determine participant subgroups, considering baseline BMI, AA, pain and comorbidities, and linear mixed-effects or log-binomial models were used to assess the associations. Three subgroups/classes were identified: subgroup 1 (43%): Normal/overweight participants with higher AA, lower pain and lower comorbidities subgroup 2 (32%): Overweight participants with lower AA, mild pain and higher comorbidities subgroup 3 (25%): Obese participants with lower AA, mild pain and higher comorbidities. Subgroup 3 had greater cartilage volume loss (β - 60.56 mm Our findings suggest the existence of homogeneous subgroups of participants and support the utility of identifying patterns of characteristics/risk factors that may cluster together and using them to identify subgroups of people who may be at a higher risk of developing and/or progressing OA. Key Points • Complex interplay among characteristics/factors leads to conflicting evidence between ambulatory activity and knee osteoarthritis. • Distinct subgroups are identifiable based on ambulatory activity, body mass index, knee pain, and comorbidities. • Identifying subgroups can be used to determine those who are at risk of developing rogressing osteoarthritis.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.EXGER.2018.01.026
Abstract: To describe the longitudinal associations between physiological falls risk, and between-person and within-person effects of 25-hydroxyvitamin D (25OHD), physical activity (PA), knee pain and dysfunction in community-dwelling older people. Data for 1053 participants (51% women mean age 63 ± 7.4 years) studied at baseline, 2.5, 5, and 10 years were analysed. Falls risk (Z-score) was measured using the Physiological Profile Assessment. Knee pain and dysfunction were assessed using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC). Moderate-to-vigorous PA (MVPA) was measured using accelerometer. Linear mixed-effect regression models, with adjustment for confounders, were used to estimate the association between physiological falls risk and between-person and within-person effects of PA, 25OHD and WOMAC score. Between-person effects showed that 10-year average physiological falls risk was lower in participants who had a higher 10-year average 25OHD (β = -0.005 per nmol/l, 95% CI: -0.008, -0.002), log-MVPA (β = -0.16 per minute, 95% CI: -0.22, -0.10) and lower mean WOMAC score (β = 0.005 per-unit score, 95% CI: 0.003, 0.01). Within-person effects showed that a higher physiological falls risk at any time-point was associated with higher than average WOMAC score (β = 0.002 per-unit score, 95% CI: 0.0003, 0.004) and lower than average log-MVPA (β = -0.15 per minute, 95% CI: -0.24, -0.06), but not 25OHD, at the same time-point. Having higher WOMAC global score above an in idual's average increases the risk of falling, whereas, increasing one's own MVPA level further reduces their risk of falling. The presence of between-person but not within-person associations for 25OHD suggests the former may be confounded by other factors.
Publisher: Elsevier BV
Date: 04-2018
Publisher: Wiley
Date: 03-02-2021
DOI: 10.1111/JNC.15301
Abstract: The central nucleus of the amygdala (CeA) is widely implicated as a structure that integrates both appetitive and aversive stimuli. While intrinsic CeA microcircuits primarily consist of GABAergic neurons that regulate amygdala output, a notable feature of the CeA is the heterogeneity of neuropeptides and neuropeptide/neuromodulator receptors that it expresses. There is growing interest in the role of the CeA in mediating psychopathologies, including stress and anxiety states and their interactions with alcohol use disorders. Within the CeA, neuropeptides and neuromodulators often exert pro‐ or anti‐ stress actions, which can influence anxiety and alcohol associated behaviours. In turn, alcohol use can cause adaptions within the CeA, which may render an in idual more vulnerable to stress which is a major trigger of relapse to alcohol seeking. This review examines the neurocircuitry, neurochemical phenotypes and how pro‐ and anti‐stress peptide systems act within the CeA to regulate anxiety and alcohol seeking, focusing on preclinical observations from animal models. Furthermore, literature exploring the targeting of genetically defined populations or neuronal ensembles and the role of the CeA in mediating sex differences in stress x alcohol interactions are explored. image
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.JOCA.2018.11.009
Abstract: To describe associations between presence of patellar tendon enthesis (PTE) abnormalities and symptoms, structural abnormalities, and total knee replacement (TKR) in older adult cohort. PTE abnormalities (presence of abnormal bone signal and/or bone erosion), were measured on T2-weighted magnetic resonance (MR) images at baseline in 961 community-dwelling older adults. Knee pain and function limitation were assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Bone marrow lesions (BMLs), cartilage volume and defects score, and infrapatellar fat pad (IPFP) area were measured using validated methods. Incidence of TKR was determined by data linkage. Participants with abnormal PTE bone signal and/or erosion was 20%. Cross-sectionally, presence of PTE abnormalities was associated with greater pain intensity while going up and down stairs (β = 0.22 (95% confidence interval (CI) 0.03, 0.41)), greater risk of femoral BMLs (RR = 1.46 (1.12, 1.90)) and worse tibial cartilage defects score (RR = 1.70 (1.16, 2.47), and smaller IPFP area (β = -0.27 (-0.47, -0.06) cm PTE abnormalities are common in older adults. Presence of cross-sectional but not longitudinal associations suggests they are commonly co-exist with other knee structural abnormalities but may not play a major role in symptom development or structural change, excepting tibial BMLs.
Publisher: Wiley
Date: 23-06-2019
DOI: 10.1111/EJN.14431
Abstract: Alcohol use disorders represent an extensive socioeconomic burden, yet effective treatment options are suboptimal. A major hurdle in treating alcohol use disorders is the high rate of relapse. Stress is a major factor that promotes relapse in abstinent drug users therefore, understanding neural mechanisms that underpin the effects of stress on alcohol seeking is critical. In rodent models of stress-induced relapse, the α
Publisher: Wiley
Date: 10-08-2021
DOI: 10.1111/ADB.13079
Abstract: Stimulant use disorder is associated with significant global health burden. Despite evidence for sex differences in the development and maintenance of stimulant use disorder, few studies have focused on mechanisms underpinning distinct trajectories in females versus males, including the effect of the ovarian sex hormones estrogen and progesterone. This review aimed to identify and synthesise the existing preclinical and clinical literature on the effect of ovarian sex hormones on stimulant consumption in females. A systematic search of peer‐reviewed literature identified 1593 articles, screened using the following inclusion criteria: (1) adult female humans or animals, (2) using stimulant drugs, (3) ovarian sex hormones were administered exogenously OR were measured in a validated manner and (4) with stimulant consumption as an outcome measure. A total of 50 studies (3 clinical and 47 preclinical) met inclusion criteria. High‐estrogen (low progesterone) phases of the menstrual/estrus cycle were associated with increased stimulant use in preclinical studies, while there were no clinical studies examining estrogen and stimulant consumption. Consistent preclinical evidence supported progesterone use reducing stimulant consumption, which was also identified in one clinical study. The review was limited by inconsistent data reporting across studies and different protocols across preclinical laboratory paradigms. Importantly, almost all studies examined cocaine use, with impact on meth hetamine use a significant gap in the existing evidence. Given the safety and tolerability profile of progesterone, further research is urgently needed to address this gap, to explore the potential therapeutic utility of progesterone as a treatment for stimulant use disorder.
Publisher: Informa UK Limited
Date: 27-07-2018
DOI: 10.1080/13543784.2018.1502269
Abstract: Alcohol use disorder (AUD) is a complex psychiatric condition characterized by craving, compulsive seeking, loss of control of alcohol consumption as well as the emergence of negative emotional states during withdrawal. Despite the large socioeconomic burden of AUD, therapeutic treatment options lag behind. This review covers pharmacotherapies currently in phase I/II clinical trials for the treatment of AUDs listed on clinicaltrials.gov. We discuss drug therapies that modulate monoamine, GABA/Glutamate, neuropeptide and neuroimmune systems. We examine in depth preclinical and clinical evidence of a select range of these compounds and consider their utility in treating AUDs. Current therapeutic options to treat AUD are inadequate at a population level. Currently there are 30 different compounds and one compound combination in phase I/II clinical trials for AUD. These compounds target various aspects of neurotransmitter signaling, neuroimmune modulation, and alcohol metabolism. Almost 75% of these compounds under trial are Food and Drug Administration (FDA) approved for other indications, which may save time and costs in treatment development. Further, development of therapeutics focused on genetic biomarkers and behavioral screening may improve how treatment decisions are made in the future on a case-by-case basis.
Publisher: Elsevier
Date: 2020
Publisher: Oxford University Press (OUP)
Date: 30-11-2020
DOI: 10.1093/RHEUMATOLOGY/KEAA716
Abstract: To describe the association between change in subchondral bone marrow lesions (BMLs) and change in tibiofemoral cartilage volume and knee symptoms in patients with symptomatic knee OA. In total, 251 participants (mean 61.7 years, 51% female) were included. Tibiofemoral cartilage volume was measured at baseline and 24 months, and BML size at baseline, 6 and 24 months. Knee pain and function scores were evaluated at baseline, 6 and 24 months. Change in total and compartment-specific BML size was categorized according to the Least Significance Criterion. Linear mixed-effects models were used to evaluate the associations of change in BMLs over 6 and 24 months with change in cartilage volume over 24 months and knee symptoms over 6 and 24 months. Total BML size enlarged in 26% of participants, regressed in 31% and remained stable in 43% over 24 months. Compared with stable BMLs in the same compartment, enlarging BMLs over 24 months were associated with greater cartilage loss (difference: −53.0mm3, 95% CI: −100.0, −6.0), and regressing BMLs were not significantly associated with reduced cartilage loss (difference: 32.4mm3, 95% CI: −8.6, 73.3) over 24 months. Neither enlargement nor regression of total BML size over 6 and 24 months was associated with change in knee pain and function over the same time intervals. In subjects with symptomatic knee osteoarthritis and BMLs, enlarging BMLs may lead to greater cartilage loss but regressing lesions are not associated with reduced cartilage loss while neither is associated with change in knee symptoms.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2018
Publisher: Elsevier BV
Date: 04-2020
Publisher: Cambridge University Press (CUP)
Date: 15-11-2018
Publisher: Elsevier BV
Date: 04-2021
DOI: 10.1016/J.JOCA.2020.12.023
Abstract: To examine the cross-sectional and longitudinal associations of dietary patterns with knee symptoms and structures in patients with knee osteoarthritis (OA). Participants with symptomatic knee OA were recruited from a randomised, placebo-controlled trial conducted in Tasmania (N = 259) and Victoria (N = 133). Diet was assessed by the Anti-Cancer Council of Victoria food frequency questionnaire. Factor analysis was used to identify dietary patterns. Knee symptoms were assessed using Western Ontario and McMaster Universities Arthritis Index (WOMAC) and structures using MRI. Multivariable linear regressions were used to examine associations. Three dietary patterns ("high-fat", "healthy" and "mixed") were identified in whole s le. Participants with higher "healthy pattern" score had lower total WOMAC, pain, function and stiffness scores at baseline but the associations were not significant over 24 months. Three ("western", "vegetable and meat" and "mediterranean") and two ("processed" and "vegetable") patterns were identified in Tasmania and Victoria, respectively. Cross-sectionally, only "mediterranean pattern" and "vegetable pattern" scores were significantly and negatively associated with total WOMAC or function scores. Longitudinally, participants with higher "western pattern" had worsening function (β: 0.35, 95%CI: 0.03, 0.67) and total WOMAC (β: 0.40, 95%CI: 0.07, 0.72) scores furthermore, "vegetable pattern" was associated with decreased WOMAC stiffness score (β: -0.47, 95%CI: -0.93, -0.02). In contrast, dietary patterns were largely not associated with structural changes. Some healthy dietary patterns were associated with reduced joint symptoms but dietary patterns were not associated with joint structure in this s le with knee OA. Further studies are required to confirm these findings.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.ARCHGER.2019.01.015
Abstract: To determine whether older adults with low muscle mass (sarcopenia) and strength (dynapenia), in the presence of osteoporosis/osteopenia, have an increased risk of fracture and mortality over 10 years, compared to those with low muscle or low bone mass alone or with neither condition. 1032 participants (52% women mean age 62.9 ± 7.4 years) were prospectively followed for 10 years. Mortality was ascertained from the death registry and fractures were self-reported. Baseline appendicular lean mass (ALM) was assessed using dual-energy X-ray absorptiometry and normalised to body mass index (BMI). Hand grip strength (HGS) was assessed by dynamometer. Osteosarcopenia and osteodynapenia were defined as having T-scores of the total hip and/or lumbar spine bone mineral density (BMD) < -1 combined with being in the lowest 20% of the sex-specific distribution for ALM/BMI or HGS respectively. Incident fracture risk was significantly higher in participants who were osteodynapenic (RR = 2.07, 95% CI: 1.26-3.39), dynapenic alone (RR = 1.74, 95% CI: 1.05-2.87), and osteopenic alone (RR = 1.63, 95% CI: 1.15-2.31), compared to those without dynapenia or osteopenia. Mortality risk was significantly higher only in participants with osteosarcopenia (RR = 1.49, 95% CI: 1.01-2.21) compared to those without sarcopenia or osteopenia. However, osteosarcopenia and osteodynapenia did not lead to a significantly greater fracture or mortality risk compared to having these conditions on their own. These findings suggest that the combined effect of osteopenia and sarcopenia or dynapenia on fracture and mortality risk, respectively, may not be greater than that of each in idual condition.
Publisher: Wiley
Date: 02-02-2018
DOI: 10.1002/JBMR.3376
Abstract: The aim of this study was to evaluate the effect of zoledronic acid (ZA) and denosumab on low back pain (LBP) and Modic change (MC) over 6 months. Adults aged ≥40 years with significant LBP for at least 6 months duration and MC (type 1, 2, or mixed) were randomized to receive ZA (5 mg/100 mL), denosumab (60 mg), or placebo. LBP was measured monthly by visual analogue scale (VAS) and the LBP Rating Scale (RS). MC was measured from MRIs of T
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.NEUROPHARM.2018.09.037
Abstract: Corticotropin releasing factor (CRF) is a key component of stress responsivity, modulating related behaviors including anxiety and reward. Difficulties identifying CRF neurons, using traditional approaches including immunohistochemistry, has led to the development of a number of transgenic CRF reporter mice. The Crh-IRES-Cre::Ai14 (tdTomato) reporter mouse is increasing in popularity as a useful tool to assess the localization, connectivity and function of CRF neurons in various stress-related behaviors. However, without proper characterization of reporter expression, the in vivo and in vitro manifestations resulting from the manipulation of these cells must be interpreted with caution. Here we mapped the distribution of tdTomato-expressing CRF cells throughout the rostro-caudal extent of the Crh-IRES-Cre::Ai14 mouse brain. To determine if reporter expression faithfully reproduced native CRF expression, we assessed the colocalization of CRF expression with tdTomato reporter expression across several brain regions. Good concordance was observed in the extended amygdala and paraventricular nucleus of the hypothalamus (PVN), while discrepancies were observed within the lateral hypothalamus and hippoc us. Finally, we examined the activation of CRF neurons in Crh-IRES-Cre::Ai14 mice in response to different types of stressors using Fos immunohistochemistry. Acute psychological (swim) and pharmacological (yohimbine) stress stimulated Fos-protein expression in PVN CRF neurons. Interestingly though, exposure to four daily restraint stress sessions followed by a novel acute stressor did not further recruit CRF neurons across any brain region examined. Our results highlight the importance of thoroughly characterizing reporter mice before use and suggest that acute versus repeated stress may differentially impact the CRF system. This article is part of the Special Issue entitled 'Hypothalamic Control of Homeostasis'.
Publisher: Wiley
Date: 27-12-2021
DOI: 10.1002/PRP2.907
Abstract: Muscarinic acetylcholine receptors (mAChRs) have been shown to mediate alcohol consumption and seeking. Both M 4 and M 5 mAChRs have been highlighted as potential novel treatment targets for alcohol use disorders (AUD). Similarly, M 1 mAChRs are expressed throughout reward circuitry, and their signaling has been implicated in cocaine consumption. However, whether the same effects are seen for alcohol consumption, or whether natural reward intake is inadvertently impacted is still unknown. To determine the role of M 1 mAChRs in alcohol consumption, we tested operant self‐administration of alcohol under both fixed ratio (FR3) and progressive ratio (PR3‐4) schedules. Enhancing M 1 mAChR signaling (via the M 1 PAM‐Agonist PF‐06767832, 1 mg/kg, i.p.) reduced operant alcohol consumption on a fixed schedule but had no effect on motivation to acquire alcohol. To determine whether these actions were specific to alcohol, we examined the effects of M 1 enhancement on natural reward (sucrose) self‐administration. Systemic administration of PF‐06767832 (1 mg/kg, i.p.) also reduced operant sucrose self‐administration, suggesting the actions of the M 1 receptor may be non‐selective across drug and natural rewards. Finally, to understand whether this reduction extended to natural consummatory behaviors, we assessed home cage standard chow and water consumption. M 1 enhancement via systemic PF‐06767832 administration reduced food and water consumption. Together our results suggest the M 1 PAM‐agonist, PF‐06767832, non‐specifically reduces consummatory behaviors that are not associated with motivational strength for the reward. These data highlight the need to further characterize M 1 agonists, PAMs, and PAM‐agonists, which may have varying degrees of utility in the treatment of neuropsychiatric disorders including AUD.
Publisher: Springer Science and Business Media LLC
Date: 2010
DOI: 10.1186/AR3022
Publisher: Wiley
Date: 07-2014
DOI: 10.1111/BPH.12692
Publisher: Springer Science and Business Media LLC
Date: 18-11-2017
DOI: 10.1007/S12603-016-0843-6
Abstract: Purpose: To compare the performance of low muscle mass and function with falls risk, incident fracture and mortality over 10 years. 1041 participants (50% women mean age 63±7.5 years) were prospectively followed for 10 years. Falls risk was measured using the Physiological Profile Assessment, fractures were self-reported and mortality was ascertained from the death registry. Appendicular lean mass (ALM) was assessed using dual energy X-ray absorptiometry. Four anthropometric: (ALM/height2, ALM/body mass index, ALM/weight×100, a residuals method of ALM on height and total body fat) and four performance-based measures: (handgrip strength, lower-limb muscle strength, upper and lower-limb muscle quality) were examined. Participants in the lowest 20% of the sex-specific distribution for each anthropometric and performance-based measure were classified has having low muscle mass or function. Regression analyses were used to estimate associations between each anthropometric and performance-based measure at baseline and 10-year falls risk, incident fractures and mortality. Mean falls risk z-score at 10 years was 0.64 (SD 1.12), incident fractures and mortality over 10 years were 16% and 14% respectively. All baseline performance-based measures were significantly associated with higher falls risk score at 10 years. Low handgrip (RR 1.55, 95% CI: 1.09, 2.20) and ALM/body mass index (RR 1.54, 95% CI: 1.14, 2.08) were the only significant predictors of fracture and mortality respectively. Low handgrip strength, a simple and inexpensive test could be considered in clinical settings for identifying future falls and fractures. ALM/ body mass index could be most suitable in estimating 10-year mortality risk, but requires specialised equipment.
Publisher: Cambridge University Press (CUP)
Date: 25-06-2018
DOI: 10.1017/S0007114518001174
Abstract: The aim of this study was to determine whether vitamin D supplementation and maintaining vitamin D sufficiency are associated with changes in inflammatory and metabolic biomarkers in patients with knee osteoarthritis (OA) and vitamin D deficiency. A total of 413 participants with symptomatic knee OA and vitamin D deficiency were enrolled in a randomised, placebo-controlled trial and received 1·25 mg vitamin D 3 or placebo monthly for 24 months across two sites. In this post hoc analysis, 200 participants from one site (ninety-four from the placebo group and 106 from the vitamin D group mean age 63·1 ( sd 7·3) years, 53·3 % women) were randomly selected for measurement of serum levels of inflammatory and metabolic biomarkers at baseline and 24 months using immunoassays. In addition, participants were classified into two groups according to serum 25-hydroxyvitamin D (25(OH)D) levels at months 3 and 24: (1) not consistently sufficient (25(OH)D≤50 nmol/l at either month 3 or 24, n 61), and (2) consistently sufficient (25(OH)D nmol/l at both months 3 and 24, n 139). Compared with placebo, vitamin D supplementation had no significant effect on change in serum high-sensitive C-reactive protein, IL-6, IL-8, IL-10, leptin, adiponectin, resistin, adipsin and apelin. Being consistently vitamin D sufficient over 2 years was also not associated with changes in these biomarkers compared with not being consistently sufficient. Vitamin D supplementation and maintaining vitamin D sufficiency did not alter serum levels of inflammatory and metabolic biomarkers over 2 years in knee OA patients who were vitamin D insufficient, suggesting that they may not affect systemic inflammation in knee OA patients.
Publisher: Springer Science and Business Media LLC
Date: 13-02-2018
DOI: 10.1007/S00223-018-0402-8
Abstract: The aim of this study is to describe the association of bone marrow lesions (BMLs) present on two different MRI sequences with clinical outcomes, cartilage defect progression, cartilage volume loss over 2.7 years, and total knee replacement (TKR) over 13.3 years. 394 participants (50-80 years) were assessed at baseline and 2.7 years. BML presence at baseline was scored on T1-weighted fat-suppressed 3D gradient-recalled acquisition (T1) and T2-weighted fat-suppressed 2D fast spin-echo (T2) sequences. Knee pain, function, and stiffness were assessed using WOMAC. Cartilage volume and defects were assessed using validated methods. Incident TKR was determined by data linkage. BMLs were mostly present on both MRI sequences (86%). BMLs present on T2, T1, and both sequences were associated with greater knee pain and functional limitation (odds ratio = 1.49 to 1.70 all p < 0.05). Longitudinally, BMLs present on T2, T1, and both sequences were associated with worsening knee pain (β = 1.12 to 1.37, respectively p < 0.05) and worsening stiffness (β = 0.45 to 0.52, respectively all p < 0.05) but not worsening functional limitation or total WOMAC. BMLs present on T2, T1, and both sequences predicted site-specific cartilage defect progression (relative risk = 1.22 to 4.63 all p < 0.05) except at the medial tibial and inferior patellar sites. Lateral tibial and superior patellar BMLs present on T2, T1, and both sequences predicted site-specific cartilage volume loss (β = - 174.77 to - 140.67 p < 0.05). BMLs present on T2, T1, and both sequences were strongly associated with incident TKR. BMLs can be assessed on either T2- or T1-weighted sequences with no clinical predictive advantage of either sequence.
Publisher: Springer Science and Business Media LLC
Date: 24-11-2017
DOI: 10.1038/NRN.2016.158
Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism
Date: 06-2018
Publisher: BMJ
Date: 09-2021
DOI: 10.1136/BMJSEM-2021-001097
Abstract: The clinical relevance of MRI knee abnormalities in athletes is unclear. This study aimed to determine the prevalence of MRI knee abnormalities in Australian Rules Football (ARF) players and describe their associations with pain, function, past and incident injury and surgery history. 75 male players (mean age 21, range 16–30) from the Tasmanian State Football League were examined early in the playing season (baseline). History of knee injury/surgery and knee pain and function were assessed. Players underwent MRI scans of both knees at baseline. Clinical measurements and MRI scans were repeated at the end of the season, and incident knee injuries during the season were recorded. MRI knee abnormalities were common at baseline (67% bone marrow lesions, 16% meniscal tear/extrusion, 43% cartilage defects, 67% effusion synovitis). Meniscal tears/extrusion and synovial fluid volume were positively associated with knee symptoms, but these associations were small in magnitude and did not persist after further accounting for injury history. Players with a history of injury were at a greater risk of having meniscal tears/extrusion, effusion synovitis and greater synovial fluid volume. In contrast, players with a history of surgery were at a greater risk of having cartilage defects and meniscal tears/extrusion. Incident injuries were significantly associated with worsening symptoms, BML development and incident meniscal damage. MRI abnormalities are common in ARF players, are linked to a previous knee injury and surgery history, as well as incident injury but do not dictate clinical symptomatology.
Publisher: Society for Neuroscience
Date: 03-12-2018
DOI: 10.1523/JNEUROSCI.1596-18.2018
Abstract: Humans with alcohol use disorder typically abstain because of the negative consequences associated with excessive drinking, and exposure to contexts previously associated with alcohol use can trigger relapse. We used a rat model that captures a characteristic of this human condition: namely voluntary abstinence from alcohol use because of contingent punishment. There is substantial variability in the propensity to relapse following extended periods of abstinence, and this is a critical feature preventing the successful treatment of alcohol use disorder. Here we examined relapse following acute or prolonged abstinence. In male alcohol preferring P rats, we found an increased propensity to relapse in Context B, the punishment context after prolonged abstinence. Next, we found that neither alcohol intake history nor the motivational strength of alcohol predicted the propensity to relapse. We next examined the putative circuitry of context-induced relapse to alcohol seeking following prolonged abstinence using Fos as a marker of neuronal activation. The anterior insular cortex (AI) was the only brain region examined where Fos expression correlated with alcohol seeking behavior in Context B after prolonged abstinence. Finally, we used local infusion of GABA A and GABA B receptor agonists (muscimol + baclofen) to show a causal role of the AI in context-induced relapse in Context B, the punishment context after prolonged abstinence. Our results show that there is substantial in idual variability in the propensity to relapse in the punishment-associated context after prolonged abstinence, and this is mediated by activity in the AI. SIGNIFICANCE STATEMENT A key feature of alcohol use disorder is that sufferers show an enduring propensity to relapse throughout their lifetime. Relapse typically occurs despite the knowledge of adverse consequences including health complications or relationship breakdowns. Here we use a recently developed rodent model that recapitulates this behavior. After an extended period of abstinence, relapse propensity is markedly increased in the “adverse consequence” environment, akin to humans with alcohol use disorder relapsing in the face of adversity. From a circuitry perspective, we demonstrate a causal role of the anterior insular cortex in relapse to alcohol seeking after extended abstinence following punishment imposed voluntary cessation of alcohol use.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.EXGER.2014.04.006
Abstract: The aim of this study was to describe the relationship between accelerometer-determined physical activity (PA) and adiposity in community-dwelling older adults. In addition, we were interested in comparing the extent of correlation between questionnaire and accelerometer determined PA. 636 community-dwelling older adults (66±7years) were studied. Adiposity was measured using dual-energy X-ray absorptiometry and BMI was calculated. We measured minutes/day spent in sedentary, light, moderate and vigorous intensity activity using both questionnaires and Actigraph GT1M accelerometers. Participants spent a median of 583(IQR 522-646), 225(176-271), 27(12-45) and 0(0-0) minutes in sedentary, light, moderate and vigorous activities respectively. There was a non linear dose-response inverse relationship between activity intensity and adiposity. After adjusting for age, sex and other levels of PA, for every 10minute increase in activity, total body fat decreased by 169g(95% CI 61-277), 905g(632-1178), and 2208g(759-3657) for light, moderate and vigorous activities respectively. There was an interaction between age and activity as age increased, the magnitude of the effects of light and moderate activities on adiposity decreased. Sedentary minutes were not associated with adiposity after adjusting for time spent at other PA intensities. Questionnaire measures of PA were weakly correlated with body fat measures when compared to accelerometer determined PA. Both the amount and intensity of PA, but not sedentary time, have an independent dose-response association with adiposity. The association is much stronger using objective assessment compared to questionnaire. The magnitude of these associations decrease with age suggesting that physical activity programmes may need to be modified with increasing age.
Publisher: Elsevier BV
Date: 04-2019
Publisher: Elsevier BV
Date: 08-2020
Publisher: Springer Science and Business Media LLC
Date: 21-08-2020
Publisher: Elsevier BV
Date: 12-2021
Publisher: Elsevier BV
Date: 04-2016
Publisher: Authorea, Inc.
Date: 16-10-2023
Publisher: BMJ
Date: 26-11-2015
DOI: 10.1136/ANNRHEUMDIS-2015-208360
Abstract: To describe the associations between infrapatellar fat pad (IPFP) signal intensity alteration at baseline and knee symptoms and structural changes in older adults. A total of 874 subjects (mean 62.1 years, 50.1% female) selected randomly from local community were studied at baseline and 770 were followed up (only 357 had MRI at follow-up) over 2.6 years. T1-weighted or T2-weighted fat suppressed MRI was used to assess IPFP signal intensity alteration (0-3), cartilage volume, cartilage defects and bone marrow lesions (BMLs) at baseline and 2.6 years later. Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index questionnaire. Radiographic osteoarthritis (OA) was assessed. In cross-sectional analyses, IPFP signal intensity alteration was significantly and positively associated with total knee pain as well as knee cartilage defects, BMLs and knee radiographic OA and negatively associated with patellar cartilage volume after adjustment for age, sex, body mass index and/or radiographic OA. Longitudinally, baseline signal intensity alteration within IPFP was significantly and positively associated with increases in knee pain when going upstairs/downstairs as well as increases in tibiofemoral cartilage defects and BMLs, and negatively associated with change in lateral tibial cartilage volume in multivariable analyses. IPFP signal intensity alteration at baseline was associated with knee structural abnormalities and clinical symptoms cross-sectionally and longitudinally in older adults, suggesting that it may serve as an important imaging biomarker in knee OA.
Publisher: Wiley
Date: 05-2023
DOI: 10.1111/BPH.16081
Abstract: Emerging evidence suggests muscarinic acetylcholine receptors represent novel targets to treat alcohol use disorder. In this review, we draw from literature across medicinal chemistry, molecular biology, addiction and learning/cognition fields to interrogate the proposition for muscarinic receptor ligands in treating various aspects of alcohol use disorder, including cognitive dysfunction, motivation to consume alcohol and relapse. In support of this proposition, we describe cholinergic dysfunction in the pathophysiology of alcohol use disorder at a network level, including alcohol‐induced adaptations present in both human post‐mortem brains and reverse‐translated rodent models. Preclinical behavioural pharmacology implicates specific muscarinic receptors, in particular, M 4 and M 5 receptors, as potential therapeutic targets worthy of further interrogation. We detail how these receptors can be selectively targeted in vivo by the use of subtype‐selective allosteric modulators, a strategy that overcomes the issue of targeting a highly conserved orthosteric site bound by acetylcholine. Finally, we highlight the intense pharma interest in allosteric modulators of muscarinic receptors for other indications that provide an opportunity for repurposing into the alcohol use disorder space and provide some currently unanswered questions as a roadmap for future investigation.
Publisher: Springer Science and Business Media LLC
Date: 07-11-2013
DOI: 10.1007/S10067-013-2394-0
Abstract: The objective of this study was to describe the cross-sectional and longitudinal relationship between hip bone marrow lesions (BMLs), high cartilage signal, and hip and knee pain. One hundred ninety-eight participants in the Tasmanian Older Adult Cohort Study with right hip MRI conducted at two time points, approx. 2.3 years apart, were included. Short T1 Inversion Recovery MR images were used to quantitatively measure hip BML size and determine high cartilage signal presence. Hip and knee pain were in idually assessed using the Western Ontario and McMaster Universities Osteoarthritis index pain score. Fifty-five participants (28%) had either femoral and/or acetabular BMLs. Cross-sectionally, the presence of large femoral, acetabular, or any hip BMLs was associated with higher odds of hip pain (OR = 4.42, 95% CI = 1.37-19.7 OR = 5.23, 95% CI = 1.17-22.9 OR = 4.43, 95% CI = 1.46-13.2, respectively). High cartilage signal was strongly associated with hip BMLs (OR = 6.45, 95% CI = 3.37-12.6), but not with pain. Longitudinally, incident acetabular (Mean diff = +5.90, 95% CI = +3.78 to +8.15) and femoral BMLs (Mean diff = +1.18, 95% CI = 0.23-1.94) were associated with worsening hip pain, while resolving femoral BMLs were associated with a decrease in knee pain (Mean diff = -3.18, 95% CI = -5.99 to -0.50). The evidence is consistent for hip, but not knee pain, and strongly suggests that large hip BMLs are associated with hip pain. Furthermore, high cartilage signal is asymptomatic, but strongly associated with hip BMLs. These findings suggest that hip BMLs play an important role in hip osteoarthritis.
Publisher: Springer Science and Business Media LLC
Date: 2014
DOI: 10.1186/AR4607
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.JAMDA.2019.07.001
Abstract: Resistin acts as an endogenous ligand of Toll-like receptor (TLR)-4 that triggers major inflammatory pathways and mediates inflammatory processes. The role of resistin in osteoarthritis (OA) pathogenesis is unclear. The aim of this study is to describe the longitudinal associations of serum levels of resistin with knee synovitis measures and structural abnormalities in patients with knee OA. A prospective cohort study. Patients (n = 200) with symptomatic knee OA (mean age 63.1 years, range 49-79 female 46.5%) participated. All measures were performed at baseline and 2 years later. Serum resistin was measured using enzyme-linked immunosorbent assay. Infrapatellar fat pad (IPFP) high signal intensity alteration and effusion synovitis were measured from magnetic resonance imaging (MRI). Knee structures including cartilage volume, cartilage defects, and bone marrow lesions (BMLs) were also assessed by MRI semiquantitatively or quantitatively. Linear or logistic mixed effects regression analyses were used in longitudinal analyses. Serum resistin was positively associated with high signal intensity alteration measures of IPFP as well as the presence [relative risk = 1.06, 95% confidence interval (CI) 1.02, 1.10] and volume (β = 0.77, 95% CI 0.01, 1.53) of effusion synovitis in multivariable analyses. Serum levels of resistin were also positively associated with higher tibiofemoral cartilage defect (β = 1.98, 95% CI 0.34, 3.57) and BML scores (β = 3.18, 95% CI 0.99, 5.37) after adjustment for covariates. Higher serum levels of resistin are associated with knee synovitis surrogate measures and structural abnormalities, suggesting that obesity may promote OA not only by increasing weight loading on joints but also by triggering 1 or more inflammatory pathways.
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.JOCA.2013.06.002
Abstract: To describe the cross-sectional and longitudinal association between hip Bone marrow lesions (BMLs) and bone density. 198 subjects with a right hip MRI and dual-energy X-ray absorptiometry (DXA) scans conducted at two time points, approximately 2.6 years apart were included. MR images were used to assess hip BML presence and size (cm(2)) while DXA scans were used to determine bone mineral density (BMD) of the total hip, spine and femoral neck. Fifty-five subjects (28%) had either a femoral and/or acetabular BML. Cross-sectionally, acetabular BMLs were associated with 5-6% lower total hip [P = 0.01] and femoral neck BMD [P < 0.001]. Resolving acetabular BMLs were associated with a 1-2% increase in BMD at hip [P = 0.05] and femoral neck [P = 0.01]. In contrast, resolving femoral BMLs were associated with a 4% lower and incident femoral BMLs with 3% higher femoral neck BMD [P = 0.04, P < 0.001 resp.]. Finally, each 1 cm(2) change femoral BMLs was associated with increase in femoral neck BMD: +0.03 g/cm(2), 95% confidence intervals (CI): +0.00, +0.05, and enlarging acetabular BMLs was associated with decrease in hip: -0.01 g/cm(2), 95% CI: -0.03, -0.00 and femoral neck BMD: -0.01 g/cm(2), 95% CI: -0.03, -0.001. Hip BMLs were associated with local BMD (hip and femoral neck) but not with spine BMD and these associations vary according to site. BML prevalence and change was low in this study, hence these findings need confirmation. However, we hypothesize that these associations represent a combination of changes related directly to the BML pathology or changes adjacent to the disease process.
Publisher: Wiley
Date: 05-2017
DOI: 10.1111/IMJ.5_13463
Publisher: Elsevier BV
Date: 04-2016
Publisher: Wiley
Date: 03-06-2021
DOI: 10.1111/BPH.15513
Abstract: Muscarinic acetylcholine receptors mediate alcohol consumption and seeking in rats. While M 4 and M 5 receptors have recently been implicated to mediate these behaviours in the striatum, their role in other brain regions remain unknown. The ventral tegmental area (VTA) and ventral subiculum (vSub) both densely express M 4 and M 5 receptors and modulate alcohol‐seeking, via their projections to the nucleus accumbens shell (AcbSh). In Indiana alcohol‐preferring (iP) male rats, we examined Chrm4 (M 4 ) and Chrm5 (M 5 ) expression in the VTA and vSub following long‐term alcohol consumption and abstinence using RT‐qPCR. Using a combination of retrograde tracing and RNAscope, we examined the localisation of Chrm4 and Chrm5 on vSub cells that project to the AcbSh. Using selective allosteric modulators, we examined the functional role of M 4 and M 5 receptors within the vSub in alcohol consumption, context‐induced alcohol‐seeking, locomotor activity, and food/water consumption. Long‐term alcohol and abstinence dysregulated the expression of genes for muscarinic receptors in the vSub, not in the VTA. Chrm4 was down‐regulated following long‐term alcohol and abstinence, while Chrm5 was up‐regulated following long‐term alcohol consumption. Consistent with these data, a positive allosteric modulator (VU0467154) of intra‐vSub M 4 receptors reduced context‐induced alcohol‐seeking, but not motivation for alcohol self‐administration, while M 5 receptor negative allosteric modulator (ML375) reduced initial motivation for alcohol self‐administration, but not context‐induced alcohol‐seeking. Collectively, our data highlight alcohol‐induced cholinergic dysregulation in the vSub and distinct roles for M 4 and M 5 receptor allosteric modulators to reduce alcohol consumption or seeking.
Publisher: Wiley
Date: 24-09-2021
DOI: 10.1002/ACR.24410
Abstract: To comprehensively synthesize the evolution of health‐economic evaluation models (HEEMs) of all osteoarthritis (OA) interventions, including preventions, core treatments, adjunct nonpharmacologic interventions, pharmacologic interventions, and surgical treatments. The literature was searched within health‐economic/biomedical databases. Data extracted included OA type, population characteristics, model setting/type/events, study perspective, and comparators the reporting quality of the studies was also assessed. The review protocol was registered at the International Prospective Register of Systematic Reviews (CRD42018092937). Eighty‐eight studies were included. Pharmacologic and surgical interventions were the focus in 51% and 44% of studies, respectively. Twenty‐four studies adopted a societal perspective (with increasing popularity after 2013), but most (63%) did not include indirect costs. Quality‐adjusted life years was the most popular outcome measure since 2008. Markov models were used by 62% of studies, with increasing popularity since 2008. Until 2010, most studies used short‐to‐medium time horizons subsequently, a lifetime horizon became popular. A total of 86% of studies reported discount rates (predominantly between 3% and 5%). Studies published after 2002 had a better coverage of OA‐related adverse events (AEs). Reporting quality significantly improved after 2001. OA HEEMs have evolved and improved substantially over time, with the focus shifting from short‐to‐medium‐term pharmacologic decision‐tree models to surgical‐focused lifetime Markov models. Indirect costs of OA are frequently not considered, despite using a societal perspective. There was a lack of reporting sensitivity of model outcome to input parameters, including discount rate, OA definition, and population parameters. While the coverage of OA‐related AEs has improved over time, it is still not comprehensive.
Location: Iran (Islamic Republic of)
Location: Australia
Start Date: 2014
End Date: 2014
Funder: Tasmanian Community Fund
View Funded ActivityStart Date: 2016
End Date: 2016
Funder: Menzies Institute for Medical Research
View Funded ActivityStart Date: 01-2022
End Date: 01-2025
Amount: $410,399.00
Funder: Australian Research Council
View Funded Activity