Ultrasound-guided platelet-rich plasma injections for post-traumatic greater occipital neuralgia: study protocol for a pilot randomized controlled trial.

BACKGROUND: Post-traumatic headaches (PTH) are a common sequelae of traumatic brain injury (TBI) and greatly impact patient function and quality of life. Post-traumatic greater occipital neuralgia (GON) is a type of post-traumatic headache. Conventional treatment includes steroid/anesthetic injections which typically alleviate pain but have a short duration of effect. Platelet-rich plasma (PRP) is an emerging biological treatment for numerous degenerative disorders, including peripheral nerve disorders. The primary aim of this pilot study is to evaluate whether a randomized control trial of PRP for the treatment of GON in patients with post-traumatic headaches is feasible in regard to recruitment, adherence, retention, and adherence and adverse events. Exploratory aims include improvement in pain, function, and quality of life in patients with post-traumatic GON receiving PRP compared to steroid/anesthetic and normal saline injections. METHODS: Thirty adults (over 18 years of age) with post-traumatic GON will be randomized into one of three groups: (1) autologous PRP injection, (2) steroid/anesthetic injection (standard care), or (3) placebo injection with normal saline. Injections will be performed to the greater occipital nerve under ultrasound guidance by a trained physician. Daily headache intensity and frequency data will be collected pre-injection and for the duration of the study period. Feasibility will be defined as greater than 30% recruitment, 70% completion of intervention, 70% retention, and less than 2 minor adverse events. Exploratory outcomes will be explored using the Headache Impact Test-6 (HIT-6, a valid and reliable 6-item questionnaire for assessment of the impact of headaches across different diagnostic groups of headaches) and the quality of life in following brain injury questionnaire (QOILIBRI). DISCUSSION: This pilot study will be the first to evaluate the feasibility of PRP as a potential treatment of GON in patients with post-traumatic headache. TRIAL REGISTRATION: ClinicalTrials.gov - NCT04051203 (registered August 9, 2019).

Characterizing Physical Activity and Sedentary Behavior in Adults With Persistent Postconcussive Symptoms After Mild Traumatic Brain Injury.

OBJECTIVE: To evaluate physical activity (PA) and sedentary behavior and their associations with symptom and quality of life outcomes in adults with persistent postconcussive symptoms (PPCS) after mild traumatic brain injury (mTBI). DESIGN: Cross-sectional cohort study. SETTING: Outpatient brain injury clinic. PARTICIPANTS: Consecutive sample of adults (N=180) with a diagnosis of mTBI and PPCS. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: PA and sedentary behavior were assessed using the Godin Leisure-Time Exercise Questionnaire and Rapid Assessment Disuse Index, respectively. Participants were dichotomized according to whether they completed 150 minutes of moderate-to-vigorous PA per week, based on Canadian guidelines. Postinjury moderate-to-vigorous PA was also analyzed as a continuous variable. RESULTS: Prior to injury, 85% of participants reported meeting PA guidelines, compared with 28% postinjury. Individuals meeting PA guidelines postinjury reported higher quality of life (η2p=0.130; P<.001) and lower scores on measures of functional impact of headache (η2p=0.065; P=.009), fatigue (η2p=0.080; P=.004), depression (η2p=0.085; P=.001), and anxiety (η2p=0.046; P=.031), compared with those not meeting guidelines. Sedentary behavior postinjury was negatively correlated with quality of life (rs[127]=-0.252; P=.004) and positively correlated with symptom burden (rs[167]=0.227; P=.003), fatigue (rs[127]=0.288; P=.001), depression (rs[174]=0.319; P<.001), and anxiety (rs[127]=0.180; P=.042). CONCLUSIONS: PA was significantly decreased in individuals with PPCS compared to preinjury levels. Meeting PA guidelines postinjury was associated with better clinical outcomes, suggesting that returning individuals to PA should be considered in the treatment of this patient population.

Growth hormone deficiency testing and treatment following mild traumatic brain injury.

Pituitary dysfunction, specifically growth hormone (GH) deficiency, can occur following traumatic brain injury. Our objective was to characterize the prevalence of GH deficiency (GHD) testing and response to recombinant human GH (rhGH) treatment in adults with persistent symptoms following mild traumatic brain injury (mTBI) referred for assessment of pituitary dysfunction. A retrospective chart review was conducted of patients seen at an outpatient brain injury clinic with a diagnosis of mTBI and persistent post-concussive symptoms who were referred to endocrinology. Clinical assessments of symptoms were collected. Investigations and results of GHD were collected, including initiation of rhGH treatment and treatment response. Of the 253 patients seen in both brain injury and endocrinology clinics, 97 with mTBI were referred for investigation of pituitary dysfunction and 73 (75%) had dynamic testing for assessment of GHD. Of the 26 individuals diagnosed with GHD, 23 (88%) started rhGH. GH therapy was inconsistently offered based on interpretation of GH dynamic testing results. Of those who started rhGH, 18 (78%) had a useful treatment response. This study suggests that clinical management of these patients is varied, highlighting a need for clear guidelines for the diagnosis and management of GHD following mTBI.

Improving symptom burden in adults with persistent post-concussive symptoms: a randomized aerobic exercise trial protocol.

BACKGROUND: Persistent post-concussive symptoms (PPCS) affect up to 30% of individuals following mild traumatic brain injury. PPCS frequently includes exercise intolerance. Sub-symptom threshold aerobic exercise has been proposed as a treatment option for symptom burden and exercise intolerance in this population. The primary aim of this study is to evaluate whether a progressive, sub-symptom threshold aerobic exercise program can alleviate symptom burden in adults with PPCS. METHODS: Fifty-six adults (18-65) with PPCS (>3mos-5 yrs) will be randomized into two groups: an immediate start 12-week aerobic exercise protocol (AEP) or delayed start 6-week placebo-like stretching protocol (SP), followed by AEP. Aerobic or stretching activities will be completed 5x/week for 30 mins during the intervention. Online daily activity logs will be submitted. Exercise prescriptions for the AEP will be 70-80% of heart rate at the point of symptom exacerbation achieved on a treadmill test with heart rate monitoring. Exercise prescription will be updated every 3-weeks with a repeat treadmill test. The Rivermead Post-concussion Symptom Questionnaire will be the primary outcome measure at 6 and 12-weeks of intervention. Secondary outcomes include assessments of specific symptoms (headache, quality of life, mood, anxiety, fatigue, dizziness, sleep parameters, daytime sleepiness) in addition to blood biomarkers and magnetic resonance imaging and spectroscopy data for quantification of brain metabolites including γ-aminobutyric acid (GABA), glutathione, glutamate and N-acetyl aspartate (NAA) all measured at 6 and 12-weeks of intervention. DISCUSSION: This trial will evaluate the use of aerobic exercise as an intervention for adults with PPCS, thus expanding our knowledge of this treatment option previously studied predominantly for adolescent sport-related concussion. TRIAL REGISTRATION: ClinicalTrials.gov - NCT03895450 (registered 2019-Feb-11).

The Effects of Exercise on Physical and Psychological Outcomes in Cancer Caregivers: Results From the RECHARGE Randomized Controlled Trial.

Background: Family caregivers to cancer patients are at risk for physical and psychological morbidity as a direct result of being in the caregiver role. Exercise as an intervention to support caregiver health and well-being has been tested in other caregiver populations; however, no randomized controlled trials testing the effects of an aerobic and resistance training program have been conducted where cancer caregivers only have participated. Purpose: To examine the effects of a 12-week exercise program on quality of life (Short Form 36 v2), psychological outcomes, physical activity levels, and physical fitness in caregivers to cancer patients. Methods: Seventy-seven caregivers were randomized to either an exercise intervention or wait-list control. Two participants in the exercise arm dropped out immediately after their baseline assessment. Outcome data for n = 77 participants were analyzed using intention-to-treat analysis with linear mixed models. Results: Significant group by time interaction effects were detected for exercise on the mental health component score of quality of life, self-reported weekly exercise levels, and the six-minute walk test. Small to medium effect sizes were detected on several outcomes including physical health component of quality of life (d = 0.36), mental health component of quality of life (d = 0.74), depression (d = 0.41), anxiety (d = 0.35), physical activity levels (d = 0.80), and the six-minute walk test (d = 0.21). Conclusions: The findings suggest that exercise may improve health and well-being and could be considered as an additional type of support offered to cancer caregivers. Clinical trial registration no: NCT02580461.

A validation of dynamic causal modelling for 7T fMRI.

BACKGROUND: There is growing interest in ultra-high field magnetic resonance imaging (MRI) in cognitive and clinical neuroscience studies. However, the benefits offered by higher field strength have not been evaluated in terms of effective connectivity and dynamic causal modelling (DCM). NEW METHOD: In this study, we address the validity of DCM for 7T functional MRI data at two levels. First, we evaluate the predictive validity of DCM estimates based upon 3T and 7T in terms of reproducibility. Second, we assess improvements in the efficiency of DCM estimates at 7T, in terms of the entropy of the posterior distribution over model parameters (i.e., information gain). RESULTS: Using empirical data recorded during fist-closing movements with 3T and 7T fMRI, we found a high reproducibility of average connectivity and condition-specific changes in connectivity - as quantified by the intra-class correlation coefficient (ICC = 0.862 and 0.936, respectively). Furthermore, we found that the posterior entropy of 7T parameter estimates was substantially less than that of 3T parameter estimates; suggesting the 7T data are more informative - and furnish more efficient estimates. COMPARED WITH EXISTING METHODS: In the framework of DCM, we treated field-dependent parameters for the BOLD signal model as free parameters, to accommodate fMRI data at 3T and 7T. In addition, we made the resting blood volume fraction a free parameter, because different brain regions can differ in their vascularization. CONCLUSIONS: In this paper, we showed DCM enables one to infer changes in effective connectivity from 7T data reliably and efficiently.

Perceptions of masculinity and body image in men with prostate cancer: the role of exercise.

PURPOSE: The goal of this study was to explore the association between levels of exercise and patterns of masculinity, body image, and quality of life in men undergoing diverse treatment protocols for prostate cancer. METHODS: Fifty men with prostate cancer (aged 42-86) completed self-report measures. Self-reported measures included the following: the Godin Leisure Time Exercise Questionnaire (GLTEQ), Masculine Self-esteem Scale (MSES), Personal Attributes Questionnaire (PAQ), Body Image Scale (BIS), and the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Masculinity, body image, and quality of life scores were compared between men obtaining recommended levels of exercise (aerobic or resistance) and those not obtaining recommended level of exercise. Secondary outcomes included the association between masculinity, body image, and quality of life scores as they relate to exercise levels. RESULTS: There were significantly higher scores of masculinity (p < 0.01), physical well-being (p < 0.05), prostate cancer specific well-being (p < 0.05), and overall quality of life (p < 0.05) in those obtaining at least 150 min of moderate to vigorous aerobic exercise. In the 48% of men who had never received androgen deprivation therapy, significantly higher levels of masculinity, body image, and quality of life were observed in those meeting aerobic guidelines. CONCLUSIONS: Whether treatment includes androgen deprivation or not, men who participate in higher levels of aerobic exercises report higher levels of masculinity, improved body image, and quality of life than those who are inactive. Future longitudinal research is required evaluating exercise level and its effect on masculinity and body image.

Comparison of Polar M600 Optical Heart Rate and ECG Heart Rate during Exercise.

PURPOSE: The purpose of this study was to evaluate the accuracy of the Polar M600 optical heart rate (OHR) sensor compared with ECG heart rate (HR) measurement during various physical activities. METHODS: Thirty-six subjects participated in a continuous 76-min testing session, which included rest, cycling warm-up, cycling intervals, circuit weight training, treadmill intervals, and recovery. HR was measured using a three-lead ECG configuration and a Polar M600 Sport Watch on the left wrist. Statistical analyses included OHR percent accuracy, mean difference, mean absolute error, Bland-Altman plots, and a repeated-measures generalized estimating equation design. OHR percent accuracy was calculated as the percentage of occurrences where OHR measurement was within and including ±5 bpm from the ECG HR value. RESULTS: Of the four exercise phases performed, the highest OHR percent accuracy was found during cycle intervals (91.8%), and the lowest OHR percent accuracy occurred during circuit weight training (34.5%). OHR percent accuracy improved steadily within exercise transitions during cycle intervals to a maximum of 98.5% and during treadmill intervals to a maximum of 89.0%. Lags in HR calculated by the Polar M600 OHR sensor existed in comparison to ECG HR, when exercise intensity changed until steady state occurred. There was a tendency for OHR underestimation during intensity increases and overestimation during intensity decreases. No statistically significant interaction effect with device was found in this sample on the basis of sex, body mass index, V˙O2max, skin type, or wrist size. CONCLUSIONS: The Polar M600 was accurate during periods of steady-state cycling, walking, jogging, and running, but less accurate during some exercise intensity changes, which may be attributed to factors related to total peripheral resistance changes and pulse pressure.

Dietary Intake and Associated Body Weight in Canadian Undergraduate Students Enrolled in Nutrition Education.

The primary purpose of this study was to describe dietary intakes among Canadian undergraduate students enrolled in an Introductory Nutrition course. A secondary objective was to determine food group servings associated with meeting more Dietary Reference Intakes (DRIs) of select nutrients and with a lower body mass index (BMI). Participants (n = 124, 20.7±3.2yrs) provided output from a 3-day dietary record and completed a physical activity/demographics questionnaire. Linear regression showed that the dietary intake associated with meeting the most DRIs included vegetables, fruits, protein foods, and dairy (p = 0.001). Protein foods were a positive predictor and fruit a negative predictor of BMI (p = 0.001 and p = 0.023 respectively). Males consumed more grains (p = 0.001), dairy (p = 0.04), protein foods (p < 0.001), empty calories (p = 0.007) and total calories than females (p < 0.001). A diet characterized by greater intake of vegetables, fruits, protein foods, and dairy was associated with a Canadian undergraduate population meeting the greatest number of nutrient requirements.

Sensor space group analysis for fNIRS data.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) is a method for monitoring hemoglobin responses using optical probes placed on the scalp. fNIRS spatial resolution is limited by the distance between channels defined as a pair of source and detector, and channel positions are often inconsistent across subjects. These challenges can lead to less accurate estimate of group level effects from channel-specific measurements. NEW METHOD: This paper addresses this shortcoming by applying random-effects analysis using summary statistics to interpolated fNIRS topographic images. Specifically, we generate individual contrast images containing the experimental effects of interest in a canonical scalp surface. Random-effects analysis then allows for making inference about the regionally specific effects induced by (potentially) multiple experimental factors in a population. RESULTS: We illustrate the approach using experimental data acquired during a colour-word matching Stroop task, and show that left frontopolar regions are significantly activated in a population during Stroop effects. This result agrees with previous neuroimaging findings. COMPARED WITH EXISTING METHODS: The proposed methods (i) address potential misalignment of sensor locations between subjects using spatial interpolation; (ii) produce experimental effects of interest either on a 2D regular grid or on a 3D triangular mesh, both representations of a canonical scalp surface; and (iii) enables one to infer population effects from fNIRS data using a computationally efficient summary statistic approach (random-effects analysis). Significance of regional effects is assessed using random field theory. CONCLUSIONS: In this paper, we have shown how fNIRS data from multiple subjects can be analysed in sensor space using random-effects analysis.

Thonzonium bromide inhibits RANKL-induced osteoclast formation and bone resorption in vitro and prevents LPS-induced bone loss in vivo.

Osteoclasts (OCs) play a pivotal role in a variety of lytic bone diseases including osteoporosis, arthritis, bone tumors, Paget's disease and the aseptic loosening of orthopedic implants. The primary focus for the development of bone-protective therapies in these diseases has centered on the suppression of OC formation and function. In this study we report that thonzonium bromide (TB), a monocationic surface-active agent, inhibited RANKL-induced OC formation, the appearance of OC-specific marker genes and bone-resorbing activity in vitro. Mechanistically, TB blocked the RANKL-induced activation of NF-κB, ERK and c-Fos as well as the induction of NFATc1 which is essential for OC formation. TB disrupted F-actin ring formation resulting in disturbances in cytoskeletal structure in mature OCs during bone resorption. Furthermore, TB exhibited protective effects in an in vivo murine model of LPS-induced calvarial osteolysis. Collectively, these data suggest that TB might be a useful alternative therapy in preventing or treating osteolytic diseases.

Patient-reported outcomes, body composition, and nutrition status in patients with head and neck cancer: Results from an exploratory randomized controlled exercise trial.

BACKGROUND: Patients with head and neck cancer experience loss of weight and muscle mass, decreased functioning, malnutrition, depression, and declines in quality of life during and after treatment. The purpose of this exploratory randomized study was to determine the optimal timing for the initiation of a lifestyle and progressive resistance exercise training intervention (during or after radiation therapy), as determined by intervention adherence and by comparing between-group outcomes across 24 weeks. METHODS: Sixty patients with head and neck cancer were randomized to engage in a 12-week lifestyle intervention and progressive resistance-training program either during radiation treatment or immediately after completion. The primary outcome of body composition--specifically, lean body mass, body mass index, and body fat--as well as secondary outcomes of fitness, quality of life, depression, and nutrition status were evaluated. RESULTS: The progressive resistance-training intervention carried out during treatment did not significantly influence the primary outcome of body composition, despite a significant increase in weekly physical activity reported by the intervention group. A small-to-medium intervention effect was noted for some secondary outcomes, including fitness, quality of life, and nutrition status. Regardless of whether patients received the immediate or delayed progressive resistance-training intervention, the analysis revealed a main effect of time on body composition, fitness, quality of life, depression, and nutritional scores. CONCLUSIONS: Although the intervention during treatment did not reduce the loss of lean body mass, delaying the exercise program until after treatment completion was associated with improved intervention adherence, a finding with important clinical implications.

Alexidine Dihydrochloride Attenuates Osteoclast Formation and Bone Resorption and Protects Against LPS-Induced Osteolysis.

Aseptic loosening and periprosthetic infection leading to inflammatory osteolysis is a major complication associated with total joint arthroplasty (TJA). The liberation of bacterial products and/or implant-derived wear particles activates immune cells that produce pro-osteoclastogenic cytokines that enhance osteoclast recruitment and activity, leading to bone destruction and osteolysis. Therefore, agents that prevent the inflammatory response and/or attenuate excessive osteoclast (OC) formation and bone resorption offer therapeutic potential by prolonging the life of TJA implants. Alexidine dihydrochloride (AD) is a bisbiguanide compound commonly used as an oral disinfectant and in contact lens solutions. It possesses antimicrobial, anti-inflammatory and anticancer properties; however, its effects on OC biology are poorly described. Here, we demonstrate that AD inhibits OC formation and bone resorption in vitro and exert prophylatic protection against LPS-induced osteolysis in vivo. Biochemical analysis demonstrated that AD suppressed receptor activator of NF-κB ligand (RANKL)-induced activation of mitogen-activated protein kinases (ERK, p38, and JNK), leading to the downregulation of NFATc1. Furthermore, AD disrupted F-actin ring formation and attenuated the ability of mature OC to resorb bone. Collectively, our findings suggest that AD may be a promising prophylactic anti-osteoclastic/resorptive agent for the treatment of osteolytic diseases caused by excessive OC formation and function.

Early Quantification of Hematoma Hounsfield Units on Noncontrast CT in Acute Intraventricular Hemorrhage Predicts Ventricular Clearance after Intraventricular Thrombolysis.

BACKGROUND AND PURPOSE: Thrombolytic efficacy of intraventricular rtPA for acute intraventricular hemorrhage may depend on hematoma composition. We assessed whether hematoma Hounsfield unit quantification informs intraventricular hemorrhage clearance after intraventricular rtPA. MATERIALS AND METHODS: Serial NCCT was performed on 52 patients who received intraventricular rtPA as part of the Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage trial and 12 controls with intraventricular hemorrhage, but no rtPA treatment. A blinded investigator calculated Hounsfield unit values for intraventricular hemorrhage volumes on admission (t0), days 3-4 (t1), and days 6-9 (t2). Controls were matched uniquely to 12 rtPA-treated patients for comparison. RESULTS: Median intraventricular hemorrhage volume on admission for patients treated with intraventricular rtPA was 31.9 mL (interquartile range, 34.1 mL), and it decreased to 4.9 mL (interquartile range, 14.5 mL) (t2). Mean (±standard error of the mean) Hounsfield unit for intraventricular hemorrhage was 52.1 (0.59) at t0 and decreased significantly to 50.1 (0.63) (t1), and to 45.1 (0.71) (t2). Total intraventricular hemorrhage Hounsfield unit count was significantly correlated with intraventricular hemorrhage volume at all time points (t0: P = .002; t1: P < .001; t2: P < .001). On serologic and CSF analysis at t0, only higher CSF protein was positively correlated with intraventricular hemorrhage Hounsfield units (P = .03). In 24 matched patients treated with rtPA and controls, total intraventricular hemorrhage Hounsfield units were significantly lower in patients treated with rtPA at t2 (P = .02). Higher Hounsfield unit quantification of fourth ventricle hematomas independently predicted slower clearance of this ventricle (95% CI, 0.02-0.14; P = .02), along with higher intraventricular hemorrhage volume (95% CI, 0.02-0.41; P = .03) and lower CSF protein levels (95% CI, -0.003 to -0.002; P < .001). CONCLUSIONS: Intraventricular hemorrhage Hounsfield unit counts decrease significantly in the acute phase and to a greater extent with intraventricular rtPA treatment. Intraventricular hemorrhage Hounsfield units are correlated significantly with CSF protein and not with serum erythrocyte or platelet concentrations. Hounsfield unit counts may reflect intraventricular hemorrhage clot composition and rtPA sensitivity.

Disulfiram attenuates osteoclast differentiation in vitro: a potential antiresorptive agent.

Disulfiram (DSF), a cysteine modifying compound, has long been clinically employed for the treatment of alcohol addiction. Mechanistically, DSF acts as a modulator of MAPK and NF-κB pathways signaling pathways. While these pathways are crucial for osteoclast (OC) differentiation, the potential influence of DSF on OC formation and function has not been directly assessed. Here, we explore the pharmacological effects of DSF on OC differentiation, activity and the modulation of osteoclastogenic signaling cascades. We first analyzed cytotoxicity of DSF on bone marrow monocytes isolated from C57BL/6J mice. Upon the establishment of optimal dosage, we conducted osteoclastogenesis and bone resorption assays in the presence or absence of DSF treatment. Luciferase assays in RAW264.7 cells were used to examine the effects of DSF on major transcription factors activation. Western blot, reverse transcription polymerase chain reaction, intracellular acidification and proton influx assays were employed to further dissect the underlying mechanism. DSF treatment dose-dependently inhibited both mouse and human osteoclastogenesis, especially at early stages of differentiation. This inhibition correlated with a decrease in the expression of key osteoclastic marker genes including CtsK, TRAP, DC-STAMP and Atp6v0d2 as well as a reduction in bone resorption in vitro. Suppression of OC differentiation was found to be due, at least in part, to the blockade of several key receptor activators of nuclear factor kappa-B ligand (RANKL)-signaling pathways including ERK, NF-κB and NFATc1. On the other hand, DSF failed to suppress intracellular acidification and proton influx in mouse and human osteoclasts using acridine orange quenching and microsome-based proton transport assays. Our findings indicate that DSF attenuates OC differentiation via the collective suppression of several key RANKL-mediated signaling cascades, thus making it an attractive agent for the treatment of OC-mediated disorders.

Influence of age and gender on microarchitecture and bone remodeling in subchondral bone of the osteoarthritic femoral head.

INTRODUCTION: Age and gender have been reported to have a remarkable impact on bone homeostasis. However, subchondral bone, which plays a pivotal role in the initiation and progression of OA, has been poorly investigated. This study was to investigate age- and gender-related changes of microarchitecture and bone remodeling in subchondral bone in OA. METHODS: Subchondral trabecular bone (STB) and deeper trabecular bone (DTB) specimens were extracted in the load-bearing region of femoral heads from 110 patients with OA. Micro-CT and histomorphometry were performed to analyze microarchitectural and bone remodeling changes of all specimens. RESULTS: Compared to DTB, STB showed more sclerotic microarchitecture, more active bone remodeling and higher frequency of bone cysts. There were no gender differences for both microarchitecture and bone remodeling in STB. However, gender differences were found in DTB, with thinner Tb.Th, higher Tb.N, higher OS/BV and ES/BV in males. In both STB and DTB, no correlation between microarchitecture and age was found in both genders. However, bone remodeling of STB increased significantly with age in males, while bone remodeling of DTB increased significantly with age in females. No age or gender preference was found in subchondral bone cyst (SBC) frequency. The cyst volume fraction was correlated with neither age nor gender. CONCLUSIONS: There were differences in microarchitecture and bone remodeling between STB and DTB, which may be due to the distinct biomechanical and biochemical functions of these two bone structures in maintaining joint homeostasis. OA changed the normal age- and gender-dependence of bone homeostasis in joints, in a site-specific manner.

Dynamic causal modelling for functional near-infrared spectroscopy.

Functional near-infrared spectroscopy (fNIRS) is an emerging technique for measuring changes in cerebral hemoglobin concentration via optical absorption changes. Although there is great interest in using fNIRS to study brain connectivity, current methods are unable to infer the directionality of neuronal connections. In this paper, we apply Dynamic Causal Modelling (DCM) to fNIRS data. Specifically, we present a generative model of how observed fNIRS data are caused by interactions among hidden neuronal states. Inversion of this generative model, using an established Bayesian framework (variational Laplace), then enables inference about changes in directed connectivity at the neuronal level. Using experimental data acquired during motor imagery and motor execution tasks, we show that directed (i.e., effective) connectivity from the supplementary motor area to the primary motor cortex is negatively modulated by motor imagery, and this suppressive influence causes reduced activity in the primary motor cortex during motor imagery. These results are consistent with findings of previous functional magnetic resonance imaging (fMRI) studies, suggesting that the proposed method enables one to infer directed interactions in the brain mediated by neuronal dynamics from measurements of optical density changes.

Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes.

Osteoarthritis (OA) is a major cause of disability in the adult population. As a progressive degenerative joint disorder, OA is characterized by cartilage damage, changes in the subchondral bone, osteophyte formation, muscle weakness, and inflammation of the synovium tissue and tendon. Although OA has long been viewed as a primary disorder of articular cartilage, subchondral bone is attracting increasing attention. It is commonly reported to play a vital role in the pathogenesis of OA. Subchondral bone sclerosis, together with progressive cartilage degradation, is widely considered as a hallmark of OA. Despite the increase in bone volume fraction, subchondral bone is hypomineralized, due to abnormal bone remodeling. Some histopathological changes in the subchondral bone have also been detected, including microdamage, bone marrow edema-like lesions and bone cysts. This review summarizes basic features of the osteochondral junction, which comprises subchondral bone and articular cartilage. Importantly, we discuss risk factors influencing subchondral bone integrity. We also focus on the microarchitectural and histopathological changes of subchondral bone in OA, and provide an overview of their potential contribution to the progression of OA. A hypothetical model for the pathogenesis of OA is proposed.

Mindfulness-based stress reduction for the treatment of irritable bowel syndrome symptoms: a randomized wait-list controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional disorder of the lower gastrointestinal (GI) tract affected by stress, which may benefit from a biopsychosocial treatment approach such as mindfulness-based stress reduction (MBSR). PURPOSE: A treatment as usual (TAU) wait-list controlled trial was conducted in Calgary, Canada to investigate the impact of MBSR on IBS symptoms. It was hypothesized that MBSR patients would experience greater reduction in overall IBS symptom severity and self-reported symptoms of stress relative to control patients. METHOD: Ninety patients diagnosed with IBS using the Rome III criteria were randomized to either an immediate MBSR program (n = 43) or to wait for the next available program (n = 47). Patients completed IBS symptom severity, stress, mood, quality of life (QOL), and spirituality scales pre- and post-intervention or waiting period and at 6-month follow-up. Intent-to-treat linear mixed model analyses for repeated measures were conducted, followed by completers analyses. RESULTS: While both groups exhibited a decrease in IBS symptom severity scores over time, the improvement in the MBSR group was greater than the controls and was clinically meaningful, with symptom severity decreasing from constantly to occasionally present. Pre- to post-intervention dropout rates of 44 and 23 % for the MBSR and control groups, respectively, were observed. At 6-month follow-up, the MBSR group maintained a clinically meaningful improvement in overall IBS symptoms compared to the wait-list group, who also improved marginally, resulting in no statistically significant differences between groups at follow-up. Improvements in overall mood, QOL, and spirituality were observed for both groups over time. CONCLUSIONS: The results of this trial provide preliminary evidence for the feasibility and efficacy of a mindfulness intervention for the reduction of IBS symptom severity and symptoms of stress and the maintenance of these improvements at 6 months post-intervention. Attention and self-monitoring and/or anticipation of MBSR participation may account for smaller improvements observed in TAU patients.