Mapping of the Epstein-Barr virus and C3dg binding sites to a common domain on complement receptor type 2.

Complement receptor type 2 (CR2;CD21), a member of the superfamily of proteins containing short consensus repeats (SCRs), is the B cell receptor for both the gp350/220 envelope protein of Epstein-Barr virus (EBV), and for the C3dg protein of complement. By analysis of CR2 deletion mutants and chimeras formed with CR1 (CD35) we determined that of the 15 SCRs in CR2, the NH2-terminal two SCRs are necessary and sufficient to bind both gp350/220 and C3dg with affinities equivalent to those of the wild-type receptor. The epitope for OKB-7, a mAb that blocks binding of both EBV and C3dg and shares with these ligands B cell-activating capabilities, also requires both SCR-1 and SCR-2, whereas mAbs lacking these functions bind to other SCRs. Thus, EBV, a polyclonal activator of B cells, has selected a site that is proximate or identical to the natural ligand binding site in CR2, perhaps reflecting the relative immutability of that site as well as its signal transducing function

The efficacy of a lateral wedge insole for painful medial knee osteoarthritis after prescreening : a randomized clinical trial

OBJECTIVE: Lateral wedge shoe insoles decrease medial knee loading, but trials have shown no effect on pain in medial knee osteoarthritis (OA). However, insoles' loading effects are inconsistent, and they can increase patellofemoral loading. We hypothesized that insoles would reduce pain in preselected patients. METHODS: In persons with painful medial knee OA, we excluded those with patellofemoral OA and those with pain <4/10. We further excluded participants who, in a gait laboratory using lateral wedges, did not show at least a 2% reduction in knee adduction moment (KAM) compared with their shoes and a neutral insole. We then randomized subjects to lateral wedge vs. neutral insole for 8 week periods separated by an 8 week washout. Primary outcome was knee pain over the past week (0-10) and secondary outcomes nominated activity pain and KOOS pain. We carried out mixed model analyses adjusted for baseline pain. RESULTS: Of 83 participants, 21 (25%) were excluded because of insufficient reduction in KAM. Of 62 included, mean age was 64.2 years (SD 9.1); 37.1% were women. Lateral wedge insoles produced a greater reduction in knee pain than neutral insoles (difference 0.7 on 0-10 scale; 95%CI 0.1, 1.2; p = 0.02). Secondary outcomes showed mixed findings. CONCLUSIONS: In persons prescreened to eliminate those with patellofemoral OA and biomechanical non-responders, lateral wedge insoles reduced knee pain, but the effect of treatment was small and is likely of clinical significance in only a minority of patients. Targeting patients may identify those who respond to this treatment

Transport in holographic superfluids

We construct a slowly varying space-time dependent holographic superfluid and compute its transport coefficients. Our solution is presented as a series expansion in inverse powers of the charge of the order parameter. We find that the shear viscosity associated with the motion of the condensate vanishes. The diffusion coefficient of the superfluid is continuous across the phase transition while its third bulk viscosity is found to diverge at the critical temperature. As was previously shown, the ratio of the shear viscosity of the normal component to the entropy density is 1/(4 pi). As a consequence of our analysis we obtain an analytic expression for the backreacted metric near the phase transition for a particular type of holographic superfluid.Comment: 45 pages + appendice

Pointlike probes of superstring-theoretic superfluids

In analogy with an experimental setup used in liquid helium, we use a pointlike probe to study superfluids which have a gravity dual. In the gravity description, the probe is represented by a hanging string. We demonstrate that there is a critical velocity below which the probe particle feels neither drag nor stochastic forces. Above this critical velocity, there is power-law scaling for the drag force, and the stochastic forces are characterized by a finite, velocity-dependent temperature. This temperature participates in two simple and general relations between the drag force and stochastic forces. The formula we derive for the critical velocity indicates that the low-energy excitations are massless, and they demonstrate the power of stringy methods in describing strongly coupled superfluids.Comment: 17 pages, 2 figures, added a figure, a reference, and moved material to an appendi

L-DOPA functionalized, multi-branched gold nanoparticles as brain-targeted nano-vehicles

The blood–brain barrier (BBB) is a protective endothelial barrier lining the brain microvasculature which prevents brain delivery of therapies against brain diseases. Hence, there is an urgent need to develop vehicles which efficiently penetrate the BBB to deliver therapies into the brain. The drug L-DOPA efficiently and specifically crosses the BBB via the large neutral amino acid transporter (LAT)-1 protein to enter the brain. Thus, we synthesized L-DOPA-functionalized multi-branched nanoflower-like gold nanoparticles (L-DOPA-AuNFs) using a seed-mediated method involving catechols as a direct reducing-cum-capping agent, and examined their ability to cross the BBB to act as brain-penetrating nanovehicles. We show that L-DOPA-AuNFs efficiently penetrate the BBB compared to similarly sized and shaped AuNFs functionalized with a non-targeting ligand. Furthermore, we show that L-DOPA-AuNFs are efficiently internalized by brain macrophages without inducing inflammation. These results demonstrate the application of L-DOPA-AuNFs as a non-inflammatory BBB-penetrating nanovehicle to efficiently deliver therapies into the brain

Dissipative superfluid dynamics from gravity

Charged asymptotically AdS black branes in five dimensions are sometimes unstable to the condensation of charged scalar fields. For fields of infinite charge and squared mass -4 Herzog was able to analytically determine the phase transition temperature and compute the endpoint of this instability in the neighborhood of the phase transition. We generalize Herzog's construction by perturbing away from infinite charge in an expansion in inverse charge and use the solutions so obtained as input for the fluid gravity map. Our tube wise construction of patched up locally hairy black brane solutions yields a one to one map from the space of solutions of superfluid dynamics to the long wavelength solutions of the Einstein Maxwell system. We obtain explicit expressions for the metric, gauge field and scalar field dual to an arbitrary superfluid flow at first order in the derivative expansion. Our construction allows us to read off the the leading dissipative corrections to the perfect superfluid stress tensor, current and Josephson equations. A general framework for dissipative superfluid dynamics was worked out by Landau and Lifshitz for zero superfluid velocity and generalized to nonzero fluid velocity by Clark and Putterman. Our gravitational results do not fit into the 13 parameter Clark-Putterman framework. Purely within fluid dynamics we present a consistent new generalization of Clark and Putterman's equations to a set of superfluid equations parameterized by 14 dissipative parameters. The results of our gravitational calculation fit perfectly into this enlarged framework. In particular we compute all the dissipative constants for the gravitational superfluid.Comment: v1: 58 + 1 pages; v2: 83 + 1 page

Life is sexually transmitted: Live with it

This article explores issues of sexual health relevant to client care that is, could, or should be offered by nurses in general practice. Sexual health is often the most important element of a person’s holistic health and well-being to be overlooked during consultations. Sadly, some professional carers consider it is not their job, is too embarrassing, morally ‘problematic’ or outside their area of expertise. Sexual health is part of life: not to address it means that health professionals fail to fully address all aspects of their clients’ holistic health and well-being. The result is selective or reduced—not holistic—care. This article will point to ways for practice nurses to remedy this situation

Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the R6/2 Mouse Model of HD

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6/2 mouse model of HD expresses a mutant version of exon 1 HTT and develops motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Despite the vast number of studies that have been performed on this model, the association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood. In an attempt to link these factors, we have performed longitudinal assessments of behavior (rotarod, open field, passive avoidance) and of regional brain abnormalities determined through magnetic resonance imaging (MRI) (whole brain, striatum, cortex, hippocampus, corpus callosum), as well as an end-stage histological assessment. Detailed correlative analyses of these three measures were then performed. We found a gender-dependent emergence of motor impairments that was associated with an age-related loss of regional brain volumes. MRI measurements further indicated that there was no striatal atrophy, but rather a lack of striatal growth beyond 8 weeks of age. T2 relaxivity further indicated tissue-level changes within brain regions. Despite these dramatic motor and neuroanatomical abnormalities, R6/2 mice did not exhibit neuronal loss in the striatum or motor cortex, although there was a significant increase in neuronal density due to tissue atrophy. The deposition of the mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the brain. End-stage histopathological assessments were not found to be as robustly correlated with the longitudinal measures of brain atrophy or motor impairments. In conclusion, modeling pre-manifest and early progression of the disease in more slowly progressing animal models will be key to establishing which changes are causally related. © 2013 Rattray et al

A treatment applying a biomechanical device to the feet of patients with knee osteoarthritis results in reduced pain and improved function: a prospective controlled study

<p>Abstract</p> <p>Background</p> <p>This study examined the effect of treatment with a novel biomechanical device on the level of pain and function in patients with knee OA.</p> <p>Methods</p> <p>Patients with bilateral knee OA were enrolled to active and control groups. Patients were evaluated at baseline, at 4 weeks and at the 8-week endpoint. A novel biomechanical device was individually calibrated to patients from the active group. Patients from the control group received an identical foot-worn platform without the biomechanical elements. Primary outcomes were the WOMAC Index and ALF assessments.</p> <p>Results</p> <p>There were no baseline differences between the groups. At 8 weeks, the active group showed a mean improvement of 64.8% on the WOMAC pain scale, a mean improvement of 62.7% on the WOMAC function scale, and a mean improvement of 31.4% on the ALF scale. The control group demonstrated no improvement in the above parameters. Significant differences were found between the active and control groups in all the parameters of assessment.</p> <p>Conclusions</p> <p>The biomechanical device and treatment methodology is effective in significantly reducing pain and improving function in knee OA patients.</p> <p>The study is registered at clinicaltrials.gov, identifier NCT00457132, <url>http://www.clinicaltrials.gov/ct/show/NCT00457132?order=1</url></p

Parity-Violating Hydrodynamics in 2+1 Dimensions

We study relativistic hydrodynamics of normal fluids in two spatial dimensions. When the microscopic theory breaks parity, extra transport coefficients appear in the hydrodynamic regime, including the Hall viscosity, and the anomalous Hall conductivity. In this work we classify all the transport coefficients in first order hydrodynamics. We then use properties of response functions and the positivity of entropy production to restrict the possible coefficients in the constitutive relations. All the parity-breaking transport coefficients are dissipationless, and some of them are related to the thermodynamic response to an external magnetic field and to vorticity. In addition, we give a holographic example of a strongly interacting relativistic fluid where the parity-violating transport coefficients are computable.Comment: 39+1 page