Effect of low-intensity long-duration ultrasound on the symptomatic relief of knee osteoarthritis: a randomized, placebo-controlled double-blind study

Background: Wearable long-duration low-intensity ultrasound is an emerging non-invasive and non-narcotic therapy for the daily treatment of musculoskeletal pain. The aim of this randomized, double-blind, placebo-controlled study was to examine whether long-duration low-intensity ultrasound was effective in treating pain and improving function in patients with knee osteoarthritis. Methods: Ninety patients with moderate to severe knee pain and radiographically confirmed knee osteoarthritis (Kellgren-Lawrence grade I/II) were randomized for treatment with active (n = 55) or placebo (n = 35) devices applied daily to the treated knee. Investigators and subjects were blinded to treatment groups. Ultrasound (3 MHz, 0.132 W/cm2, 1.3 W) was applied with a wearable device for 4 h daily for 6 weeks, delivering 18,720 J per treatment. The primary outcome was change in pain intensity (numeric rating scale) assessed prior to intervention (baseline) and after 6 weeks. Secondary outcomes of functional change were measured at baseline and after 6 weeks using the Western Ontario McMaster Osteoarthritis Questionnaire (n = 84), along with range of motion (flexion, extension) and isometric muscle strength (flexion, extension and rotation) tests on the injured knee in a small pilot subset (n =17). Results: The study had a 93% retention rate, and there were no significant differences between the groups regarding demographic variables or baseline outcome measures. Patients treated with active therapy observed a significant mean NRS pain reduction over the 6-week study of 1.96 points for active (p \u3c 0.0001), compared with a 0.85 points reduction for placebo (p = 0.13). The functional score was also significantly improved by 505 points for the active group over the 311-point improvement for placebo group compared to baseline (p = 0.02). In the pilot subset evaluated, rotational strength increased from baseline to 6 weeks (3.2 N, p = 0.03); however, no other measures were significant. Conclusions: Long-duration low-intensity ultrasound significantly reduced pain and improved joint function in patients with moderate to severe osteoarthritis knee pain. The clinical findings suggest that ultrasound may be used as a conservative non-pharmaceutical and non-invasive treatment option for patients with knee osteoarthritis. Additional research is warranted on non-weight bearing joints of the musculoskeletal system as well as extended treatment time frames and follow-up. Trial registration: NCT02083861, registered 11 March 2014, https://clinicaltrials.gov/ct2/show/results/NCT0208386

Tensile energy dissipation and mechanical properties of the knee meniscus: relationship with fiber orientation, tissue layer, and water content

Introduction: The knee meniscus distributes and dampens mechanical loads. It is composed of water (∼70%) and a porous fibrous matrix (∼30%) with a central core that is reinforced by circumferential collagen fibers enclosed by mesh-like superficial tibial and femoral layers. Daily loading activities produce mechanical tensile loads which are transferred through and dissipated by the meniscus. Therefore, the objective of this study was to measure how tensile mechanical properties and extent of energy dissipation vary by tension direction, meniscal layer, and water content.Methods: The central regions of porcine meniscal pairs (n = 8) were cut into tensile samples (4.7 mm length, 2.1 mm width, and 0.356 mm thickness) from core, femoral and tibial components. Core samples were prepared parallel (circumferential) and perpendicular (radial) to the fibers. Tensile testing consisted of frequency sweeps (0.01–1Hz) followed by quasi-static loading to failure. Dynamic testing yielded energy dissipation (ED), complex modulus (E*), and phase shift (δ) while quasi-static tests yielded Young’s Modulus (E), ultimate tensile strength (UTS), and strain at UTS (εUTS). To investigate how ED is influenced by the specific mechanical parameters, linear regressions were performed. Correlations between sample water content (φw) and mechanical properties were investigated. A total of 64 samples were evaluated.Results: Dynamic tests showed that increasing loading frequency significantly reduced ED (p < 0.05). Circumferential samples had higher ED, E*, E, and UTS than radial ones (p < 0.001). Stiffness was highly correlated with ED (R2 > 0.75, p < 0.01). No differences were found between superficial and circumferential core layers. ED, E*, E, and UTS trended negatively with φw (p < 0.05).Discussion: Energy dissipation, stiffness, and strength are highly dependent on loading direction. A significant amount of energy dissipation may be associated with time-dependent reorganization of matrix fibers. This is the first study to analyze the tensile dynamic properties and energy dissipation of the meniscus surface layers. Results provide new insights on the mechanics and function of meniscal tissue

The innervation of the enthesis organ of the rat achilles tendon

PURPOSE: The enthesis (bony insertion of a tendon or ligament) is a common site of overuse injuries in sport. Because enthesopathies can be painful, it is often assumed that the enthesis is highly innervated-but with little evidence to support the assumption. The Achilles tendon has one of the most complex of attachment sites, for together with adjacent tissues, the enthesis itself forms part of an 'enthesis organ' which reduces stress concentration at the bony interface. These adjacent structures include a 'sesamoid fibrocartilage' in the tendon, a 'periosteal fibrocartilage' on the superior tuberosity of the calcaneus, and a fat pad which extends into the retrocalcaneal bursa during plantarflexion. The purpose of the present study is to investigate the innervation of the whole enthesis organ complex. METHODS: The tendon attachment site was removed from one leg of 3 male Wistar rats at each of the following ages-neonates, 4 weeks, 12 weeks, and 24 months. The tissue was fixed in 4% paraformaldehyde, prepared for routine indirect immunohistochemistry and cryosectioned in the sagittal plane. Serial sections were immunolabelled with polyclonal antibodies to protein gene product 9.5, substance P, calcitonin gene related peptide and neurofilament 200. Histology reference sections were stained with toluidine blue. RESULTS: No nerve fibers were detected at the enthesis itself or in the sesamoid and periosteal fib ro cartilages in rats of any age. However, the fat pad was richly supplied by nerve fibers which immunolabelled with all of the antibodies used. It also contained abundant mast cells. The innervation of the fat pad was confirmed in 10 human Achilles tendons obtained from the Department of Forensic Medicine at the Ludwig-Maximilians-Universität, in accordance with the ethical regulations of Munich University. The nerve fibers again immunolabelled with all antibodies and formed an intricate network in which the fibers lay between individual fat cells. CONCLUSION: We suggest that healthy entheses are not innervated because of the high levels of mechanical loading experienced at insertion sites. However, the striking innervation of the adjacent fat pad suggests that it may have an unheralded proprioceptive role monitoring changes in insertional angle between tendon and bone that occur as a result of foot movements

Gender and PTSD: What Can We Learn from Female Police Officers?

Studies of civilians typically find that female gender is a risk factor for posttraumatic stress disorder (PTSD). Police and military studies often find no gender differences in PTSD. We compared 157 female police officers and 124 female civilians on several variables including trauma exposure, peritraumatic emotional distress, current somatization, and cumulative PTSD symptoms. We found that despite greater exposure to assaultive violence in the officer group, female civilians reported significantly more severe PTSD symptoms. Elevated PTSD symptoms in female civilians were explained by significantly more intense peritraumatic emotional distress among female civilians. We also found that female officers showed a stronger direct relationship between peritraumatic emotional distress and current somatization. Our findings suggest that apparent gender differences in PTSD may result from differences in peritraumatic emotionality, which influence subsequent PTSD and somatization symptoms. Emotionality may be more important than biological sex in understanding gender differences in PTSD

Female HPA axis displays heightened sensitivity to pre-pubertal stress

Early life stress (ELS) is a risk factor in the development of psychiatric disorders. The underlying biological mechanisms governing this phenomenon are not fully understood, but dysregulation of stress responses is likely to play a key role. Males and females differ in their propensity to develop psychiatric disorders, with far higher rates of anxiety, major depressive disorder, affective disorders and post-traumatic stress disorder found in women. We hypothesised that sex differences in response to ELS may play a crucial role in differential vulnerability between the sexes. To test this, we evaluated the consequences of pre-pubertal stress (PPS) on the HPA axis in adult female and male Lister Hooded rats. PPS animals were exposed to swim, restraint and elevated platform stress on postnatal days 25-27, controls remained in their home cage. Once adult, animals were either a) sacrificed directly and brains collected or b) sacrificed 20 minutes or 1 week after a social test and trunk blood collected. In the female hippocampal formation, PPS increased expression of FKBP5 and AVPR1a. In the female prefrontal cortex, PPS resulted in increased glucocorticoid receptor expression, increased glucocorticoid:mineralocorticoid (GR:MR) receptor expression ratio and decreased AVPR1a expression. Females exposed to PPS did not show the normal rise in blood corticosterone levels following a social interaction test. In contrast, PPS did not alter the expression of oxytocin or oxytocin receptors, and no effects of PPS were seen in males. However, striking sex differences were found. Females had higher oxytocin receptor expression in the prefrontal cortex and AVPR1a and oxytocin expression in the hypothalamus, whereas males demonstrated higher expression of GR, MR, GR:MR, FKBP5 and oxytocin receptor in the hypothalamus. These results demonstrate heightened reactivity of the female HPA axis to PPS and may help explain why in humans females display an increased susceptibility to certain stress-related psychopathologies. Lay Summary: Women are at greater risk of developing several psychiatric illnesses. Using a rodent model, we show that the female stress system is more reactive to the lasting effects of early life stress. This heightened reactivity of the female stress response may help explain why women are at a greater risk of developing psychiatric disorders

Peripheral blood monocyte gene expression profile clinically stratifies patients with recent-onset type 1 diabetes

Novel biomarkers of disease progression after type 1 diabetes onset are needed. We profiled peripheral blood (PB) monocyte gene expression in six healthy subjects and 16 children with type 1 diabetes diagnosed ∼3 months previously and analyzed clinical features from diagnosis to 1 year. Monocyte expression profiles clustered into two distinct subgroups, representing mild and severe deviation from healthy control subjects, along the same continuum. Patients with strongly divergent monocyte gene expression had significantly higher insulin dose-adjusted HbA 1clevels during the first year, compared with patients with mild deviation. The diabetes-associated expression signature identified multiple perturbations in pathways controlling cellular metabolism and survival, including endoplasmic reticulum and oxidative stress (e.g., induction of HIF1A, DDIT3, DDIT4, and GRP78). Quantitative PCR (qPCR) of a 9-gene panel correlated with glycemic control in 12 additional recent-onset patients. The qPCR signature was also detected in PB from healthy first-degree relatives. A PB gene expression signature correlates with glycemic control in the first year after diabetes diagnosis and is present in at-risk subjects. These findings implicate monocyte phenotype as a candidate biomarker for disease progression pre- and post-onset and systemic stresses as contributors to innate immune function in type 1 diabetes. © 2012 by the American Diabetes Association

Dynamic Perturbations of the T-Cell Receptor Repertoire in Chronic HIV Infection and following Antiretroviral Therapy

HIV infection profoundly affects many parameters of the immune system and ultimately leads to AIDS, yet which factors are most important for determining resistance, pathology, and response to antiretroviral treatment - and how best to monitor them - remain unclear. We develop a quantitative high-throughput sequencing pipeline to characterize the TCR repertoires of HIV-infected individuals before and after antiretroviral therapy, working from small, unfractionated samples of peripheral blood. This reveals the TCR repertoires of HIV(+) individuals to be highly perturbed, with considerably reduced diversity as a small proportion of sequences are highly overrepresented. HIV also causes specific qualitative changes to the repertoire including an altered distribution of V gene usage, depletion of public TCR sequences, and disruption of TCR networks. Short-term antiretroviral therapy has little impact on most of the global damage to repertoire structure, but is accompanied by rapid changes in the abundance of many individual TCR sequences, decreases in abundance of the most common sequences, and decreases in the majority of HIV-associated CDR3 sequences. Thus, high-throughput repertoire sequencing of small blood samples that are easy to take, store, and process can shed light on various aspects of the T-cell immune compartment and stands to offer insights into patient stratification and immune reconstitution

How special are Brightest Group and Cluster Galaxies?

We use the Sloan Digital Sky Survey to construct a sample of 625 brightest group and cluster galaxies (BCGs) together with control samples of non-BCGs matched in stellar mass, redshift, and color. We investigate how the systematic properties of BCGs depend on stellar mass and on their privileged location near the cluster center. The groups and clusters that we study are drawn from the C4 catalogue of Miller et al. (2005) but we have developed improved algorithms for identifying the BCG and for measuring the cluster velocity dispersion. Since the SDSS photometric pipeline tends to underestimate the luminosities of large galaxies in dense environments, we have developed a correction for this effect which can be readily applied to the published catalog data. We find that BCGs are larger and have higher velocity dispersions than non-BCGs of the same stellar mass, which implies that BCGs contain a larger fraction of dark matter. In contrast to non-BCGs, the dynamical mass-to-light ratio of BCGs does not vary as a function of galaxy luminosity. Hence BCGs lie on a different fundamental plane than ordinary elliptical galaxies. BCGs also follow a steeper Faber-Jackson relation than non-BCGs, as suggested by models in which BCGs assemble via dissipationless mergers along preferentially radial orbits. We find tentative evidence that this steepening is stronger in more massive clusters. BCGs have similar mean stellar ages and metallicities to non-BCGs of the same mass, but they have somewhat higher alpha/Fe ratios, indicating that star formation may have occurred over a shorter timescale in the BCGs. Finally, we find that BCGs are more likely to host radio-loud active galactic nuclei than other galaxies of the same mass, but are less likely to host an optical AGN. The differences we find are more pronounced for the less massive BCGs.Comment: Replaced with slightly modified version accepted by MNRAS. 28 pages, 25 figures. Version with full resolution figures available at http://www.mpa-garching.mpg.de/~anja/bcgs_avdl.pd

The role of exercise training on lipoprotein profiles in adolescent males

BACKGROUND: Major cardiovascular disorders are being recognized earlier in life. In this study we examined the effects of swimming and soccer training on male adolescent lipid-lipoprotein profiles relative to a maturity matched control group to determine the effects of these exercises on specific cardiovascular risk and anti-risk factors. METHODS: Forty five adolescent males (11.81 ± 1.38 yr) including swimmers (SW), soccer players (SO), and non-athlete, physically active individuals as controls (C), participated in this study. Training groups completed 12-wk exercise programs on three non-consecutive days per week. Plasma low-density lipoprotein (LDL), very low density lipoprotein (VLDL), high density lipoprotein (HDL), apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), total cholesterol (TC), and triglyceride (TG) levels were measured in control, pre-training, during-training, and post-training. RESULTS: In response to the 12-wk training period, the SO group demonstrated a decrease in the mean LDL level compared to the SW and C (SW: 0.15%; SO: −9.51%; C: 19.59%; p < 0.001) groups. There was an increase in both the SW and SO groups vs. the control in mean HDL (SW: 5.66%; SO: 3.07%; C: −7.21%; p < 0.05) and apoA-I (SW: 3.86%; SO: 5.48%; C: −1.01%; p < 0.05). ApoB was considerably lower in the training groups vs. control (SW: −9.52%; SO: −13.87%; C: 21.09%; p < 0.05). ApoA-I/apoB ratio was significantly higher in training groups vs. control (SW: 16.74%; SO: 23.71%; C: −17.35%; p < 0.001). There were no significant differences between groups for other factors. CONCLUSIONS: The favorable alterations in LDL, HDL, apoA-I, and apoB observed in the training groups suggest that both regular swimming or soccer exercise can potentially mitigate cardiovascular risk in adolescent males

The Na D profiles of nearby low-power radio sources: Jets powering outflows

(abridged) We have analyzed the properties of the Na D doublet lines in a large sample of 691 radio galaxies using the Sloan Digital Sky Survey (SDSS). These radio galaxies are resolved in the FIRST survey, have redshifts less that 0.2 and radio flux densities at 1.4 GHz higher than 40 mJy. Approximately 1/3 of the sources show a significant excess (above that contributed by their stellar populations) of Na D absorption that can be robustly fitted with two Voigt profiles representing the Na D doublet. A further 1/6 of the sources show residual absorption, for which the fits were not well constrained though while ~50% of the sample show no significant residual absorption. The residual absorption is modestly blueshifted, typically by ~50 km/s, but the velocity dispersions are high, generally ~500 km/s. Assuming that the size of the absorbing region is consistent with ~1 kpc for dust lanes in a sample of generally more powerful radio sources and a continuous constant velocity flow (continuity equation), we estimate mass and energy outflow rates of about 10 Msun/yr and few x e42 erg/s. These rates are consistent with those in the literature based on HI absorption line observations of radio galaxies. The energy required to power these outflows is on the order of 1-10% of the jet mechanical power and we conclude that the radio jet alone is sufficient. The mass and energy outflow rates are consistent with what is needed to heat/expel the mass returned by the stellar populations as well as the likely amount of gas from a cooling halo. This suggests that radio-loud AGN play a key role in energizing the outflow/heating phase of the feedback cycle. The deposition of the jet mechanical energy could be important for explaining the ensemble characteristics of massive early type galaxies in the local universe.Comment: To appear in A&A letters. Fig. 3 to appear online onl