Patterning Chronic Active Demyelination in Slowly Expanding/Evolving White Matter MS Lesions.

BACKGROUND AND PURPOSE: Slowly expanding/evolving lesions measured by conventional T1-weighted/T2-weighted brain MR imaging may contribute to progressive disability accumulation in MS. We evaluated the longitudinal change in myelin and axonal tissue integrity in white matter slowly expanding/evolving lesions by means of the magnetization transfer ratio and DTI radial diffusivity. MATERIALS AND METHODS: Slowly expanding/evolving lesions were detected within the Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Participants With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY) Phase 2 clinical trial dataset (NCT01864148), comprising patients with relapsing-remitting and secondary-progressive MS (n = 299) with T1-weighted/T2-weighted MR imaging at all trial time points (baseline to week 72). RESULTS: Compared with non-slowly expanding/evolving lesions (areas not classified as slowly expanding/evolving lesion) of baseline nonenhancing T2 lesions, slowly expanding/evolving lesions had a lower normalized magnetization transfer ratio and greater DTI radial diffusivity, both in patients with relapsing-remitting MS (n = 242) and secondary-progressive MS (n = 57, P < .001 for all). Although the changes with time in both the normalized magnetization transfer ratio and DTI radial diffusivity between slowly expanding/evolving lesions and non-slowly expanding/evolving lesions were positively correlated (P < .001), a decrease in the normalized magnetization transfer ratio and a greater increase in DTI radial diffusivity were observed in slowly expanding/evolving lesions versus non-slowly expanding/evolving lesions from baseline to week 72 in relapsing-remitting MS and secondary-progressive MS (P < .001 for all). CONCLUSIONS: Patterns of longitudinal change in the normalized magnetization transfer ratio and DTI radial diffusivity in slowly expanding/evolving lesions were consistent with progressive demyelination and tissue loss, as seen in smoldering white matter MS plaques.

Improvement in lipids after switch to boosted atazanavir or darunavir in children/adolescents with perinatally acquired HIV on older protease inhibitors: results from the Pediatric HIV/AIDS Cohort Study.

OBJECTIVES: Dyslipidaemia is common in perinatally HIV-infected (PHIV) youth receiving protease inhibitors (PIs). Few studies have evaluated longitudinal lipid changes in PHIV youth after switch to newer PIs. METHODS: We compared longitudinal changes in fasting lipids [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and TC:HDL-C ratio] in PHIV youth enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) study who switched to atazanavir/ritonavir (ATV/r)- or darunavir/ritonavir (DRV/r)-based antiretroviral therapy (ART) from an older PI-based ART and those remaining on an older PI. Generalized estimating equation models were fitted to assess the association of a switch to ATV/r- or DRV/r-based ART with the rate of change in lipids, adjusted for potential confounders. RESULTS: From 2007 to 2014, 47 PHIV children/adolescents switched to ATV/r or DRV/r, while 120 remained on an older PI [primarily lopinavir/r (72%) and nelfinavir (24%)]. Baseline age ranged from 7 to 21 years. After adjustment for age, Tanner stage, race/ethnicity, and HIV RNA level, a switch to ATV/r or DRV/r was associated with a more rapid annual rate of decline in the ratio of TC:HDL-C. (ß = -0.12; P = 0.039) than remaining on an older PI. On average, TC declined by 4.57 mg/dL/year (P = 0.057) more in the switch group. A switch to ATV/r or DRV/r was not associated with the rate of HDL-C, LDL-C, or TG change. CONCLUSIONS: A switch to ATV/r or DRV/r may result in more rapid reduction in TC and the TC:HDL-C ratio in PHIV youth, potentially impacting long-term cardiovascular disease risk.

Bilateral midshaft femoral fractures in an adolescent baseball player.

Bone disease, specifically low bone mineral density, is a common and undertreated complication that begins during childhood in patients with cystic fibrosis (CF). This case describes a male baseball player, aged 14years, with undiagnosed CF who sustained a left midshaft femoral fracture while running toward base; 8months later, he sustained a right midshaft femoral fracture under similar conditions. After the second fracture, further evaluation revealed low bone mineral density and CF. There is no previously published report of pathologic fractures occurring in the femoral shaft in an athlete with undiagnosed CF. Patients with CF have a higher fracture rate. Low-energy fractures of major bones in athletically active individuals should be viewed with suspicion for an underlying process.

Glenoid notch MRI findings do not predict normal variants of the anterior and superior labrum.

AIM: To determine (1) the relationship of a glenoid notch to the presence of a normal labral variant in the anterior-superior glenoid labrum; (2) the inter- and intra-observer reliability of recognising a glenoid notch; and (3) whether magnetic resonance arthrography (MRA) is more reliable than non-contrast magnetic resonance imaging (MRI) in visualising a glenoid notch. MATERIALS AND METHODS: From 1995 through 2010, 104 patients underwent MRI or MRA before diagnostic shoulder arthroscopy by the senior author. Five blinded musculoskeletal radiologists independently read the images twice to evaluate for the presence or absence of a glenoid notch. Fifty-nine (57%) patients had normal anterior-superior labral variants. The authors calculated the relationship of the readings to the arthroscopically determined presence or absence of a normal labral variant and the reading's diagnostic performance and rater reliability. RESULTS: On average, 38% (range 9-65%) of the glenoid scans were read as notched. The sensitivity, specificity, positive predictive value, and negative predictive value of the notch relative to the presence of a normal variant were 43.1%, 71.2%, 70.2%, and 48% versus 44.3%, 77.5%, 79.4%, and 56.1% for MRI and MRA, respectively. The overall average intra-observer κ-values were 0.438 (range 0.203-0.555) and 0.346 (range -0.102 to 0.570) for MRI and MRA, respectively. The average interobserver intra-class correlation coefficient reliability values were 0.730 (range 0.693-0.760) and 0.614 (range 0.566-0.662) for MRI and MRA, respectively. CONCLUSIONS: A notched glenoid on MRI lacks sufficient diagnostic performance and rater reliability for the clinical detection and prediction of normal anterior-superior labral variants.

Complications of rotator cuff surgery-the role of post-operative imaging in patient care.

When pain or disability occurs after rotator cuff surgery, post-operative imaging is frequently performed. Post-operative complications and expected post-operative imaging findings in the shoulder are presented, with a focus on MRI, MR arthrography (MRA) and CT arthrography. MR and CT techniques are available to reduce image degradation secondary to surgical distortions of native anatomy and implant-related artefacts and to define complications after rotator cuff surgery. A useful approach to image the shoulder after surgery is the standard radiography, followed by MRI/MRA for patients with low "metal presence" and CT for patients who have a higher metal presence. However, for the assessment of patients who have undergone surgery for rotator cuff injuries, imaging findings should always be correlated with the clinical presentation because post-operative imaging abnormalities do not necessarily correlate with symptoms.

Metabolic abnormalities and viral replication are associated with biomarkers of vascular dysfunction in HIV-infected children.

OBJECTIVES: HIV-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction in HIV-infected children (with and without hyperlipidaemia) with those in HIV-exposed, uninfected (HEU) children enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers. METHODS: A prospective cohort study was carried out. Biomarkers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP1)], coagulant dysfunction (fibrinogen and P-selectin), endothelial dysfunction [soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM) and E-selectin], and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded. RESULTS: The median ages of the children were 12.3 years in the HIV-infected group and 10.1 years in the HEU group. Body mass index (BMI) z-scores, waist and hip circumferences, and percentage body fat were lower in the HIV-infected children. Total and non-high-density lipoprotein (HDL) cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children also had higher MCP-1, fibrinogen, sICAM and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavourable lipid profiles were positively associated with IL-6, MCP-1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP-1 and CRP) and endothelial dysfunction (sICAM and sVCAM). CONCLUSIONS: HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavourable lipid levels and active HIV replication.

Manipulation of gold nanoparticles: influence of surface chemistry, temperature, and environment (vacuum versus ambient atmosphere).

We have manipulated raw and functionalized gold nanoparticles (with a mean diameter of 25 nm) on silicon substrates with dynamic atomic force microscopy (AFM). Under ambient conditions, the particles stick to silicon until a critical amplitude is reached by the oscillations of the probing tip. Beyond that threshold, the particles start to follow different directions, depending on their geometry and adhesion to the substrate. Higher and lower mobility were observed when the gold particles were coated with methyl- and hydroxyl-terminated thiol groups, respectively, which suggests that the adhesion of the particles to the substrate is strongly reduced by the presence of hydrophobic interfaces. Under ultrahigh vacuum conditions, where the water layer is absent, the particles did not move, even when operating the atomic force microscope in contact mode. We have also investigated the influence of the temperature (up to 150 degrees C) and of the geometrical arrangement of the particles on the manipulation process. Whereas thermal activation has an important effect in enhancing the mobility of the particles, we did not find differences when manipulating ordered versus random distributions of particles.

Experimental model for cartilage tissue engineering to regenerate the zonal organization of articular cartilage.

OBJECTIVE: Regeneration of the zonal organization of articular cartilage may be an important advancement for cartilage tissue engineering. The first goal of this study was to validate our surgical technique as a method to selectively isolate chondrocytes from different zones of bovine articular cartilage. The second goal was to confirm that chondrocytes from different zones would have different proliferative and metabolic activities in two-dimensional (2-D) and 3-D cultures. Finally, to regenerate the zonal organization, we sought to make multi-layered constructs by encapsulating chondrocytes from different zones of articular cartilage. DESIGN: Cartilage slices were removed from three (upper, middle, and lower) zones of articular cartilage of young bovine legs. Histology and biochemical composition of the cartilage slices were analyzed to confirm that they had been obtained from the proper zone. Growth kinetics and gene expression in monolayer culture and matrix formation in photopolymerizing hydrogels were evaluated. Multi-layered photopolymerizing hydrogels were constructed with chondrocytes from each zone of native cartilage encapsulated. Cell viability and maintenance of the cells in the respective layer were evaluated using the Live/Dead Viability kit and cell tracking protocols, respectively. After 3 weeks, the multi-layered constructs were harvested for histologic examination including immunohistochemistry for type II collagen. RESULTS: Analysis of histology and biochemical composition confirmed that the cartilage slices had been obtained from the specific zone. Chondrocytes from different zones differed in growth kinetics and gene expression in monolayer and in matrix synthesis in 3-D culture. Cells encapsulated in each of the three layers of the hydrogel remained viable and remained in the respective layer in which they were encapsulated. After 3-week culture, each zone of multi-layered constructs had similar histologic findings to that of native articular cartilage. CONCLUSION: We present this as an experimental model to regenerate zonal organization of articular cartilage by encapsulating chondrocytes from different layers in multi-layered photopolymerizing gels.

[Results of repair of SLAP lesion]. / Refixation von SLAP-Läsionen.

The surgical repair of SLAP lesions has become increasingly more common as the techniques and instrumentation have improved. However, there are few studies examining the results of repair of SLAP lesions. The goals of this paper are to summarize the recommended treatment for SLAP lesions and to report upon the studies available to date which report the results of SLAP repair.

Combinatorial electrochemical synthesis and characterization of tungsten-based mixed-metal oxides.

Automated systems for electrochemical synthesis and high-throughput screening of photoelectrochemical materials were developed and used to prepare tungsten-based mixed-metal oxides, W(n)O(m)M(x) [M = Ni, Co, Cu, Zn, Pt, Ru, Rh, Pd, and Ag], specifically for hydrogen production by photoelectrolysis of water. Two-dimensional arrays (libraries) of diverse metal oxides were synthesized by automated cathodic electrodeposition of the oxides on Ti foil substrates. Electrolytes for the mixed oxides were prepared from various metal salts added to a solution containing tungsten stabilized as a peroxo complex. Electrodeposition of the peroxo-stabilized cations gave rise to three distinguishable oxide groups: (1) mixed-metal oxides [Ni], (2) metal-doped tungsten oxides [Pt, Ru, Rh, Pd, Ag], and (3) metal-metal oxide composites [Co, Cu, Zn]. The oxides typically showed n-type semiconducting behavior. Automated measurement of photocurrent using a scanning photoelectrochemical cell showed the W-Ni mixed oxide had the largest relative zero bias photocurrent, particularly at a low Ni concentration (5-10 atomic percent Ni). Pt and Ru were also found to increase the photoactivity of bulk tungsten oxide at relatively low concentrations; however, at concentrations above 5 atomic percent, crystallization of WO(3) was inhibited and photoactivity was diminished. Addition of Co, Cu, and Zn to WO(3) was not found to improve the photoelectrochemical activity.

The injury risk associated with pes planus in athletes.

Despite the common prophylactic use of rigid orthotics in athletes with flat feet to prevent subsequent injury, there is little scientific data in the literature examining the relationship between pes planus and athletic injuries to the lower extremity. The current prospective study was undertaken to establish what relationship, if any, exists between foot morphology and subsequent lower extremity injury. A total of 196 subjects were enrolled in the study, of which 143 (73%) were male and 53 (27%) were female. Forty-two percent of the participants (83) engaged in contact sports. There were a total of 227 episodes of injury involving the lower extremity. Logistic regression using contact sports, gender, and all of the different foot contact areas that were measured at the beginning of the study was undertaken. Although gender and participation in contact sports was predictive of some lower extremity injuries, the existence of pes planus as measured by medial midfoot contact area as a percentage of total contact area was not a risk factor for any injury of the lower extremity. This study shows that in an athletic population that is representative of collegiate athletics, the existence of flat footedness does not predispose to subsequent lower extremity injury. The routine prophylactic use of orthotics in flat-footed athletes to prevent future injury may therefore not be justified based on the data available.

The anatomic relationship of the brachial plexus and axillary artery to the glenoid. Implications for anterior shoulder surgery.

Iatrogenic brachial plexus injury is an uncommon but potentially severe complication of shoulder reconstruction for instability that involves dissection near the subscapularis muscle and potentially near the brachial plexus. We examined the relationship of the brachial plexus to the glenoid and the subscapularis muscle and evaluated the proximity of retractors used in anterior shoulder surgical procedures to the brachial plexus. Eight fresh-frozen cadaveric shoulders were exposed by a deltopectoral approach. The subscapularis muscle was split in the middle and dissected to reveal the capsule beneath it. The capsule was split at midline, and a Steinmann pin was placed in the equator of the glenoid rim under direct visualization. The distance from the glenoid rim to the brachial plexus was measured with calipers with the arm in 0 degrees, 60 degrees, and 90 degrees of abduction. The brachial plexus and axillary artery were within 2 cm of the glenoid rim, with the brachial plexus as close as 5 mm in some cases. There was no statistically significant change in the distance from the glenoid rim to the musculocutaneous nerve, axillary artery, medial cord, or posterior cord with the arm in various degrees of abduction. Retractors placed superficial to the subscapularis muscle or used along the scapular neck make contact with the brachial plexus in all positions tested.

Chemically induced electronic excitations at metal surfaces.

The energy released in low-energy chemisorption or physisorption of molecules on metal surfaces is usually expected to be dissipated by surface vibrations (phonons). Theoretical descriptions of competing electronic excitations are incomplete, and experimental observation of excited charge carriers has been difficult except at energies high enough to eject electrons from the surface. We observed reaction-induced electron excitations during gas interactions with polycrystalline silver for a variety of species with adsorption energies between 0.2 and 3.5 electron volts. The probability of exciting a detectable electron increases with increasing adsorption energy, and the measured time dependence of the electron current can be understood in terms of the strength and mechanism of adsorption.

Human immunodeficiency virus type 1 (HIV-1) gp120-specific antibodies in neonates receiving an HIV-1 recombinant gp120 vaccine.

Infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers were immunized at birth and at ages 4, 12, and 20 weeks with low-, medium-, or high-dose recombinant gp120 vaccine with MF59 adjuvant (HIV-1(SF-2); n=52) or with MF59 alone as a placebo (n=9). An accelerated schedule (birth and ages 2, 8, and 20 weeks) was used for an additional 10 infants receiving the defined optimal dose and for 3 infants receiving placebo. At 24 weeks, anti-gp120 ELISA titers were greater for vaccine-immunized than for placebo-immunized infants on both schedules, and 87% of vaccinees had a vaccine-induced antibody response. At 12 weeks, antibody titers of infants on the accelerated vaccine schedule exceeded those of infants receiving placebo (4949 vs. 551; P=.01), and 63% of the vaccinees met the response criteria. Thus, an accelerated schedule of gp120 vaccinations generated an antibody response to HIV-1 envelope distinct from transplacental maternal antibody by age 12 weeks. These results provide support for further studies of vaccine strategies to prevent mother-to-infant HIV-1 transmission.

Scapular and clavicular kinematics during humeral elevation: a study with cadavers.

A combination of kinematic testing and graphic reconstruction of cadaveric shoulders was used to characterize shoulder kinematics during a simulated passive clinical range-of-motion examination. Cadaveric shoulders were elevated in the coronal, scapular, and sagittal planes while the scapula, clavicle, and humerus were kinematically tracked. Graphic models of each shoulder were created from computed tomography data. The models were animated to display the experimental motions. Shoulder kinematics varied between elevation planes. The scapular and clavicular rotations were relatively small until the humerus reached approximately 90 degrees of elevation. Clavicular and scapular rotations that occurred at low humeral elevation angles for elevation in the coronal plane were significantly larger than for the other two planes. The glenohumeral to scapulothoracic ratio was approximately equal to 2 for the entire range of elevation for each elevation plane, but it was dramatically larger during early elevation than during late elevation.

Effects of the NIK aly mutation on NF-kappaB activation by the Epstein-Barr virus latent infection membrane protein, lymphotoxin beta receptor, and CD40.

Homozygosity for the aly point mutation in NF-kappaB-inducing kinase (NIK) results in alymphoplasia in mice, a phenotype similar to that of homozygosity for deletion of the lymphotoxin beta receptor (LTbetaR). We now find that NF-kappaB activation by Epstein-Barr virus latent membrane protein 1 (LMP1) or by an LMP1 transmembrane domain chimera with the LTbetaR signaling domain in human embryonic kidney 293 cells is selectively inhibited by a wild type dominant negative NIK comprised of amino acids 624-947 (DN-NIK) and not by aly DN-NIK. In contrast, LMP1/CD40 is inhibited by both wild type (wt) and aly DN-NIK. LMP1, an LMP1 transmembrane domain chimera with the LTbetaR signaling domain, and LMP1/CD40 activate NF-kappaB in wt or aly murine embryo fibroblasts. Although wt and aly NIK do not differ in their in vitro binding to tumor necrosis factor receptor-associated factor 1, 2, 3, or 6 or in their in vivo association with tumor necrosis factor receptor-associated factor 2 and differ marginally in their very poor binding to IkappaB kinase beta (IKKbeta), only wt NIK is able to bind to IKKalpha. These data are compatible with a model in which activation of NF-kappaB by LMP1 and LTbetaR is mediated by an interaction of NIK or a NIK-like kinase with IKKalpha that is abrogated by the aly mutation. On the other hand, CD40 mediates NF-kappaB activation through a kinase that interacts with a different component of the IKK complex.

Safety of 2 recombinant human immunodeficiency virus type 1 (HIV-1) envelope vaccines in neonates born to HIV-1-infected women.

To determine the safety of 2 candidate vaccines against human immunodeficiency virus type 1 (HIV-1), a randomized, placebo-controlled, multicenter trial compared low, medium, and high doses of the vaccines or an adjuvant among infants born to HIV-infected women. No local or systemic reactions of grade 2 or greater were reported 48 h after the subjects underwent immunization. Grade 3 or 4 chemistry toxicities occurred in 5 (3%) and grade 3 or 4 hematologic toxicities in 17 (11%) of 154 vaccinated subjects (not significantly different from 29 adjuvant recipients). CD4(+) cell percentages of < or = 20% occurred at least once in 9 vaccinated subjects and 1 control subject. Sustained CD4(+) cell percentages of < or = 20% occurred in 4 HIV-infected children. Fourteen infants (8%) were confirmed to be HIV-infected; median CD4(+) cell counts among these children were 2074, 1674, 1584, and 821 cells/mm(3) at birth and weeks 24, 52, and 104, respectively. Thus, both vaccines were safe and well tolerated in neonates, and there was no evidence of accelerated immunologic decline in HIV-infected infants.