A three-experiment examination of iliotibial band strain characteristics during different conditions using musculoskeletal simulation.

PURPOSE: Iliotibial band syndrome (ITBS) is a common chronic pathology mediated via excessive Iliotibial band (ITB) strain. The purpose using a three-experiment approach is to provide insight into the differences in strain between different athletic movements, the incidence of ITBS in females, the efficacy of different prophylactic modalities for ITBS and also the kinematic parameters associated with ITB strain. METHODS: Experiment 1 examined male and female athletes performing run, 45° cut and one-legged hop movements, experiment 2 observed males and females, whilst running in five different orthotic conditions and experiment 3 examined males and females riding a cycle ergometer at 70, 80 and 90RPM whilst in prophylactic knee brace and no-brace conditions. In each experiment, kinematics were obtained using a motion capture system and ITB strain was measured using a musculoskeletal simulation approach. RESULTS: In experiment 1 ITB strain was greater in the run (male=3.87% & female=4.37%; P<0.001) and cut (male=3.12% & female=4.06%; P<0.001) movements compared to hop (male=0.87% & female=1.54%). Experiment 2 showed that females exhibited increased ITB strain (male=6.34% & female=8.91%; P<0.05) and ITB strain velocity (male=57.17%/s & female=77.41%/s; P<0.05) and also in females that ITB strain velocity was greater (P≤0.01) in lateral (80.22%/s) and no-orthotic (83.01%/s) conditions compared to medial (72.58%/s) and off the shelf orthoses (74.52%/s). The regression analyses across movements showed that ITB strain was predicted by sagittal and coronal plane mechanics at the hip (R2=0.15-0.30; P<0.05) and sagittal, coronal and transverse plane kinematics at the knee joint (R2=0.15-0.22; P<0.05). CONCLUSION: Further insight is provided into differences in ITB strain across functional athletic movements, the increased incidence of ITBS in females and the parameters linked most strongly with ITB strain during different movements is provided; whilst also highlighting the prophylactic efficacy of medial and off the shelf orthoses in female runners

Enhancement of Vaccinia Virus Based Oncolysis with Histone Deacetylase Inhibitors

Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells

Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses.

The neonatal crystallizable fragment receptor (FcRn) functions as an intracellular protection receptor for immunoglobulin G (IgG). Recently, several clinical studies have reported the lowering of circulating monomeric IgG levels through FcRn blockade for the potential treatment of autoimmune diseases. Many autoimmune diseases, however, are derived from the effects of IgG immune complexes (ICs). We generated, characterized, and assessed the effects of SYNT001, a FcRn-blocking monoclonal antibody, in mice, nonhuman primates (NHPs), and humans. SYNT001 decreased all IgG subtypes and IgG ICs in the circulation of humans, as we show in a first-in-human phase 1, single ascending dose study. In addition, IgG IC induction of inflammatory pathways was dependent on FcRn and inhibited by SYNT001. These studies expand the role of FcRn in humans by showing that it controls not only IgG protection from catabolism but also inflammatory pathways associated with IgG ICs involved in a variety of autoimmune diseases

A vegetation control on seasonal variations in global atmospheric mercury concentrations

International audienceAnthropogenic mercury emissions are transported through the atmosphere as gaseous elemental mercury (Hg(0)) before they are deposited to Earth’s surface. Strong seasonality in atmospheric Hg(0) concentrations in the Northern Hemisphere has been explained by two factors: anthropogenic Hg(0) emissions are thought to peak in winter due to higher energy consumption, and atmospheric oxidation rates of Hg(0) are faster in summer. Oxidation-driven Hg(0) seasonality should be equally pronounced in the Southern Hemisphere, which is inconsistent with observations of constant year-round Hg(0) levels. Here, we assess the role of Hg(0) uptake by vegetation as an alternative mechanism for driving Hg(0) seasonality. We find that at terrestrial sites in the Northern Hemisphere, Hg(0) co-varies with CO$_2$, which is known to exhibit a minimum in summer when CO$_2$ is assimilated by vegetation. The amplitude of seasonal oscillations in the atmospheric Hg(0) concentration increases with latitude and is larger at inland terrestrial sites than coastal sites. Using satellite data, we find that the photosynthetic activity of vegetation correlates with Hg(0) levels at individual sites and across continents. We suggest that terrestrial vegetation acts as a global Hg(0) pump, which can contribute to seasonal variations of atmospheric Hg(0), and that decreasing Hg(0) levels in the Northern Hemisphere over the past 20 years can be partly attributed to increased terrestrial net primary production