Regional annulus fibre orientations used as a tool for the calibration of lumbar intervertebral disc finite element models

The highly organized collagen network of human lumbar a nnulus fibrosus (AF) is fundamental to preserve the mechanical inte grity of the interverte bral discs. In the healthy AF, fibres are embedded in a hydrated matrix and arranged in a criss-cross fashion, giving an anisotropic structure capab le to undergo large st rains. Quantitative anatomical examinations revealed particular fibre orientation patterns, possibly coming from regional adaptations of the AF mechan ics. Based on such hypothesis, this study aimed to show that the regional differen ces in AF mechanical behaviour can be reproduced by considering only fibre orientatio n changes. Using the finite element (FE) method, AF matrix was modelled as a poro-hy perelastic material, where the porous solid was treated as a comp ressible continuum following a Neo-Hookean constitutive law. Strain-dependent permeability was assumed and all material parameters were taken from the literature. Fibre reinforcement wa s accounted for by adding an extra-term to the porous matrix strain energy density func tion, only active along th e fibre directions. Through such term, fibre orientations were then adjusted, to reproduce AF tensile behaviours measured for four different regi ons: posterior outer (PO), anterior outer (AO), posterior inner (PI) and anterior inne r (AI). Curve calibrations resulted in the following optimal angles, calculated with respect to the circumferential axis: 28º for PO, 23º for AO, 43º for PI and 31º for AI. In average, we obtained fibres 30% more transversal in the inner than in the outer AF against 38% as measured by Cassidy et al. (1989). Fibres more axial in the posterior than in the anterior AF were also measured by Holzapfel et al. (2005), with angle values comparable to our computed average values. Since all the hyperelastic and fluid-phase material parameters remained unchanged throughout the AF, calibration based only on fibre patterns variations may be an effective tool to calibrate the regional AF mechanics in a realistic way.Postprint (published version

A micro-macro evaluation of the vertebral bony endplate permeability based on computational fluid dynamics

The intrinsic permeability is an important parameter that describes the resistance of a porous structure to fluid flo w. It has a key role in poroelastic finite element models of spinal segments, especially at the vertebral endplate, i.e. the interface between intervertebral disc and vertebra. In the understanding of the properties of the complex endplate system, an expli cit evaluation for permeability of subchondral bone is missing. Thus, a new method wa s proposed to evaluate the intrinsic permeability of the bony endplate. CT - based reconstruction s of the bony endplate from a lumbar vertebra were analyzed using computational fluid dynamics , and the i ntrinsic permeability and porosity of the structure were calculated. Results showed that the permeability did not depend on the fluid flow direction, and was statistically similar for both the superior and inferior endplates . Permeability values varied within the range of trabecular bone, while porosity values w ere lower than trabecular bone characteristic values. Finally, i ntrins ic permeability correlated well with porosity through the Kozeny - Karman model, which offer s perspectives for parametric studies involving degenerative or age - related changes at the disc - bone interface.Postprint (published version

Depression predicts revascularization procedures for 5 years after coronary angiography.

OBJECTIVE:Depression has been reported to increase cardiac event rates and functional impairment in patients with coronary disease. This article describes the impact of depression on subsequent healthcare utilization for such patients. METHODS:One hundred ninety-eight health maintenance organization patients with stable coronary disease were interviewed after elective angiography using a structured psychiatric diagnostic scale. Cardiac events, hospitalizations, procedures, and costs were monitored for the next 5 years through automated data. Subjects were classified at the time of angiography by modified DSM-IV criteria into those with major, minor, and no depression. RESULTS:In univariate analyses, the no depression group (N = 136) was most likely to receive coronary artery bypass grafting (CABG) (61% vs. 36% in the major depression group vs. 27% in the minor depression group, p =.001), and the major depression group (N = 25) was most likely to receive percutaneous transluminal coronary angioplasty (PTCA) (44% vs. 14% in the minor depression group vs. 24% in the no depression group). The minor depression group (N = 37) was least likely to be hospitalized for cardiac reasons during follow-up (54% vs. 80% in the major depression group vs. 80% in the no depression group, p =.005). Five-year rates of myocardial infarction and death did not differ significantly between groups. Proportional hazard models showed that those in the depression groups differed in time from catheterization to CABG (chi2(2) = 11.9, p =.003) and time to PCTA (chi2(2) = 7.74, p =.02) after controlling for relevant covariates. Median regression showed that patients with no depression had higher costs during the first year but tended to have lower costs in years 2 through 5 than patients with minor or major depression. CONCLUSIONS:Depression status at angiography is associated with the need for revascularization and total healthcare costs for the following year

An Activity Index for Raw Accelerometry Data and Its Comparison with Other Activity Metrics

Accelerometers have been widely deployed in public health studies in recent years. While they collect high-resolution acceleration signals (e.g., 10–100 Hz), research has mainly focused on summarized metrics provided by accelerometers manufactures, such as the activity count (AC) by ActiGraph or Actical. Such measures do not have a publicly available formula, lack a straightforward interpretation, and can vary by software implementation or hardware type. To address these problems, we propose the physical activity index (AI), a new metric for summarizing raw tri-axial accelerometry data. We compared this metric with the AC and another recently proposed metric for raw data, Euclidean Norm Minus One (ENMO), against energy expenditure. The comparison was conducted using data from the Objective Physical Activity and Cardiovascular Health Study, in which 194 women 60–91 years performed 9 lifestyle activities in the laboratory, wearing a tri-axial accelerometer (ActiGraph GT3X+) on the hip set to 30 Hz and an Oxycon portable calorimeter, to record both tri-axial acceleration time series (converted into AI, AC, and ENMO) and oxygen uptake during each activity (converted into metabolic equivalents (METs)) at the same time. Receiver operating characteristic analyses indicated that both AI and ENMO were more sensitive to moderate and vigorous physical activities than AC, while AI was more sensitive to sedentary and light activities than ENMO. AI had the highest coefficients of determination for METs (0.72) and was a better classifier of physical activity intensity than both AC (for all intensity levels) and ENMO (for sedentary and light intensity). The proposed AI provides a novel and transparent way to summarize densely sampled raw accelerometry data, and may serve as an alternative to AC. The AI’s largely improved sensitivity on sedentary and light activities over AC and ENMO further demonstrate its advantage in studies with older adults

Sedentary Behavior and Physical Function Decline in Older Women: Findings from the Women's Health Initiative

Sedentary behavior is associated with deleterious health outcomes. This study evaluated the association between sedentary time and physical function among postmenopausal women in the Women's Health Initiative Observational Study. Data for this prospective cohort study were collected between 1993–1998 (enrollment) and 2009, with an average of 12.3 follow-up years. Analyses included 61,609 women (aged 50–79 years at baseline). Sedentary time was estimated by questionnaire; physical function was measured using the RAND SF-36 physical function scale. Mixed-model analysis of repeated measures was used to estimate the relationship of sedentary time exposures and changes in physical function adjusting for relevant covariates. Compared to women reporting sedentary time of ≤6 hours/day, those with greater amounts of sedentary time (>6–8 hours/day, >8–11 hours/day, >11 hours/day) reported lower physical function between baseline and follow up (coefficient = −0.78, CI = −0.98, −0.57, −1.48, CI = −1.71, −1.25, −3.13, and CI = −3.36, −2.89, respectively P < 0.001). Sedentary time was strongly associated with diminished physical function and most pronounced among older women and those reporting the greatest sedentary time. Maintaining physical function with age may be improved by pairing messages to limit sedentary activities with those promoting recommended levels of physical activity

Antiepileptic Drug Use, Falls, Fractures, and BMD in Postmenopausal Women: Findings From the Women's Health Initiative (WHI)

Antiepileptic drugs (AEDs) are used increasingly in clinical practice to treat a number of conditions. However, the relationship between the use of these medications, particularly the newer AEDs, and fracture risk has not been well characterized. We used data from the Women's Health Initiative (WHI) to determine the relationship bewteen the use of AEDs and falls, fractures, and bone mineral density (BMD) over an average of 7.7 years of follow-up. We included 138,667 women (1,385 users of AEDs and 137,282 nonusers) aged 50 to 79 years in this longitudinal cohort analyses. After adjustment for covariates, use of AEDs was positively associated with total fractures [hazard ratio (HR) = 1.44, 95% confidence interval (CI) 1.30–1.61], all site-specific fractures including the hip (HR = 1.51, 95% CI 1.05–2.17), clinical vertebral fractures (HR = 1.60, 95% CI 1.20–2.12), lower arm or wrist fractures (HR = 1.40, 95% CI 1.11–1.76), and other clinical fractures (HR = 1.46, 95% CI 1.29–1.65) and two or more falls (HR = 1.62, 95% CI 1.50–1.74) but not with baseline BMD or changes in BMD (p ≥ .064 for all sites). Use of more than one and use of enzyme-inducing AEDs were significantly associated with total fractures (HR = 1.55, 95% CI 1.15–2.09 and HR = 1.36, 95% CI 1.09–1.69, respectively). We conclude that in clinical practice, postmenopausal women who use AEDs should be considered at increased risk for fracture, and attention to fall prevention may be particularly important in these women. © 2010 American Society for Bone and Mineral Research

Understanding Barriers and Facilitators to Healthy Eating and Active Living in Rural Communities

Objective. Studies demonstrate that people’s food and physical activity (PA) environments influence behavior, yet research examining this in rural communities is limited. Methods. Focus groups of 8–15 women were conducted in rural communities in seven US states. Questions were designed to identify factors within residents’ food and PA environments they felt helped or hindered them from eating healthfully and being physically active. Results. Participants were aged 30–84 years; mean (SD) = 61 (14) (N=95). On average, communities had fewer than 5,000 residents. Limited time, social norms, and distances from or lack of exercise facilities were common PA barriers. Facilitators for PA included social support, dog walking, and availability of affordable facilities. Healthy eating barriers included the perception that healthy foods were too expensive; calorically dense large portion sizes served at family meals; and frequency of eating foods away from home, which were perceived as generally unhealthy. Healthy eating supports included culture/value around local food gathering (e.g., hunting and gardening) and preservation (e.g., canning and smoking). Friends and family were frequently identified as key influencers of eating and PA behavior. Conclusions. Targeting both social and built environment factors, particularly those unique to rural locales, may enhance support for healthy eating and PA behavior change interventions

Escherichia coli heat-stable enterotoxin mediates Na+/H+ exchanger 4 inhibition involving cAMP in T84 human intestinal epithelial cells

The enterotoxigenic Escherichia coli strains lead to diarrhoea in humans due to heat-labile and heat-stable (STa) enterotoxins. STa increases Cl-release in intestinal cells, including the human colonic carcinoma T84 cell line, involving increased cGMP and membrane alkalization due to reduced Na+/H+ exchangers (NHEs) activity. Since NHEs modulate intracellular pH (pHi), and NHE1, NHE2, and NHE4 are expressed in T84 cells, we characterized the STa role as modulator of these exchangers. pHi was assayed by the NH4Cl pulse technique and measured by fluorescence microscopy in BCECF-preloaded cells. pHi recovery rate (dpHi/dt) was determined in the absence or presence of 0.25 μmol/L STa (30 minutes), 25 μmol/L HOE-694 (concentration inhibiting NHE1 and NHE2), 500 μmol/L sodium nitroprusside (SNP, spontaneous nitric oxide donor), 100 μmol/L dibutyryl cyclic GMP (db-cGMP), 100 nmol/L H89 (protein kinase A inhibitor), or 10 μmol/L forskolin (adenylyl cyclase activator). cGMP and cAMP were measured in cell extracts by radioimmunoassay, and buffering capacity (βi) and H+ efflux (JH +) was determined. NHE4 protein abundance was determined by western blotting. STa and HOE-694 caused comparable reduction in dpHi/dt and JH + (∼63%), without altering basal pHi (range 7.144-7.172). STa did not alter βi value in a range of 1.6 pHi units. The dpHi/dt and JH+ was almost abolished (∼94% inhibition) by STa + HOE-694. STa effect was unaltered by db-cGMP or SNP. However, STa and forskolin increased cAMP level. STa-decreased dpHi/dt and JH + was mimicked by forskolin, and STa + HOE-694 effect was abolished by H89. Thus, incubation of T84 cells with STa results in reduced NHE4 activity leading to a lower capacity of pHi recovery requiring cAMP, but not cGMP. STa effect results in a causal phenomenon (STa/increased cAMP/increased PKA activity/reduced NHE4 activity) ending with intracellular acidification that could have consequences in the gastrointestinal cells function promoting human diarrhoe

Intestinal permeability and gut microbiota interactions of pharmacologically active compounds in valerian and St. John’s wort

Phytomedicines such as valerian and St. John's wort are widely used for the treatment of sleeping disorders, anxiety and mild depression. They are perceived as safe alternatives to synthetic drugs, but limited information is available on the intestinal absorption and interaction with human intestinal microbiota of pharmacologically relevant constituents valerenic acid in valerian, and hyperforin and hypericin in St. John's wort. The intestinal permeability of these compounds and the antidepressant and anxiolytic drugs citalopram and diazepam was investigated in the Caco-2 cell model with bidirectional transport experiments. In addition, interaction of compounds and herbal extracts with intestinal microbiota was evaluated in artificial human gut microbiota. Microbiota-mediated metabolisation of compounds was assessed, and bacterial viability and short-chain fatty acids (SCFA) production were measured in the presence of compounds or herbal extracts. Valerenic acid and hyperforin were highly permeable in Caco-2 cell monolayers. Hypericin showed low-to-moderate permeability. An active transport process was potentially involved in the transfer of valerenic acid. Hyperforin and hypericin were mainly transported through passive transcellular diffusion. All compounds were not metabolized over 24 h in the artificial gut microbiota. Microbial SCFA production and bacterial viability was not substantially impaired nor promoted by exposure to the compounds or herbal extracts

Parameterizing and Validating Existing Algorithms for Identifying Out-of-Bed Time Using Hip-Worn Accelerometer Data from Older Women

Objective: To parameterize and validate two existing algorithms for identifying out-of-bed time using 24-hour hip-worn accelerometer data from older women. Approach: Overall, 628 women (80±6 years old) wore ActiGraph GT3X+ accelerometers 24 hours/day for up to 7 days and concurrently completed sleep-logs. Trained staff used a validated visual analysis protocol to measure in-bed periods on accelerometer tracings (criterion). The Tracy and McVeigh algorithms were adapted for optimal use in older adults. A training set of 314 women was used to choose two key thresholds by maximizing the sum of sensitivity and specificity for each algorithm and data (vertical axis, VA, and vector magnitude, VM) combination. Data from the remaining 314 women were then used to test agreement in waking wear time (i.e., out-of-bed time while wearing the accelerometer) by computing sensitivity, specificity, and kappa comparing the algorithm output with the criterion. Waking wear time-adjusted means of sedentary time, light-intensity physical activity (light PA) and moderate-to-vigorous-intensity physical activity (MVPA) were then estimated and compared. Main results: Waking wear time agreement with the criterion was high for Tracy_VA, Tracy_VM, McVeigh_VA, and highest for McVeigh_VM. Compared to the criterion, McVeigh_VM had mean sensitivity=0.92, specificity=0.87, kappa=0.80, and overall mean difference (±SD) of -0.04±2.5 hours/day. Minutes of sedentary time, light PA, and MVPA adjusted for waking wear time using the criterion measure and McVeigh_VM were not statistically different (p \u3e0.43 | all). Significance: The McVeigh algorithm with optimal parameters using VM performed best compared to criterion sleep-log assisted visual analysis and is suitable for automated identification of waking wear time in older women when visual analysis is not feasible