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In Duchenne muscular dystrophy, progressive loss of muscle tissue is accompanied by fibrosis, chronic inflammation and reduced muscle regenerative capacity. Although much is known about the development of fibrosis and chronic inflammation in muscular dystrophy, less is known about how they are mechanistically linked to loss of muscle regenerative capacity. We have developed a proteomics method to discover dystrophy-associated changes in the muscle progenitor cell niche, which identified serine proteases, and especially neutrophil elastase, as candidates. We show that elastase activity is increased in dystrophic ( mdx 4cv ) muscle and impairs myoblast survival in culture. While the effect of elastase on C2C12 cell survival correlates with the kinetics of elastase-mediated degradation of the substrate to which the cells adhere, the effect of elastase on satellite cell-derived primary myoblast growth and differentiation is substrate-independent and even more dramatic than the effect on C2C12 cells, suggesting a detrimental role for elastase on myogenesis in vivo . Additionally, elastase impairs differentiation of both primary and C2C12 myoblasts into myotubes. Our findings evidence the importance of neutrophil-mediated inflammation in muscular dystrophy and indicate elastase-mediated regulation of myoblast behaviour as a potential mechanism underlying loss of regenerative capacity in dystrophic muscle.

This is a cross-sectional, observational study to evaluate the hypothesis that HIV-seropositive (HIV+) apolipoprotein E4 (APOE4) carriers are at increased risk for HIV-associated neurocognitive disorders (HAND) compared to APOE4 noncarriers with HIV in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Group sample. APOE genotype was determined in 466 CHARTER participants with varying disease stages and histories of antiretroviral treatment who did not have severe psychiatric or medical comorbid conditions that preclude diagnosis of HAND. HAND diagnoses were based on results of comprehensive neurobehavioral evaluation and use of current neuroAIDS diagnostic criteria. HAND status consists of two levels: neuropsychologically normal status (i.e., no HAND) and any HAND diagnosis (i.e., asymptomatic neurocognitive impairment, minor neurocognitive disorder, HIV-associated dementia). Logistic regression analyses revealed no association between APOE4 carrier status and HAND, and there were no interactions between APOE4 carrier status and ethnicity, age, substance use disorders, duration of infection, or nadir CD4. Results did not differ when analysis was restricted to symptomatic HAND, and no APOE4 gene dose-dependent relationship to HAND emerged. APOE4 status was not associated with concurrent HAND in this large, well-characterized sample. This does not preclude emergence of an association between APOE4 status and HAND as this population ages. Prospective, longitudinal studies are needed to examine APOE4 as a risk factor for neurocognitive decline, incident HAND at older ages, and potential associations with cerebrospinal fluid amyloid.

Remote sensing technologies have the potential to support monitoring of floating plastic litter in aquatic environments. An experimental campaign was carried out in a large-scale hydrodynamic test facility to explore the detectability of floating plastics in ocean waves, comparing and contrasting different microwave and optical remote sensing technologies. The extensive experiments revealed that detection of plastics was feasible with microwave measurement techniques using X and Ku-bands with VV polarization at a plastic threshold concentration of 1 item/m 2 or 1–10 g/m 2 . The optical measurements further revealed that spectral and polarization properties in the visible and infrared spectrum had diagnostic information unique to the floating plastics. This assessment presents a crucial step towards enabling the detection of aquatic plastics using advanced remote sensing technologies. We demonstrate that remote sensing has the potential for global targeting of plastic litter hotspots, which is needed for supporting effective clean-up efforts and scientific evidence-based policy making.

Background:While spasticity is commonly treated with oral agents or botulinum neurotoxin (BoNT) injection, these treatments have not been systematically compared.Methods:This study performed a randomised, double-blind, placebo-controlled trial to compare injection of BoNT-Type A into spastic upper limb muscles versus oral tizanidine (TZD), or placebo, in 60 subjects with upper-limb spasticity due to stroke or traumatic brain injury (TBI). Wrist flexors were systematically injected, while other upper limb muscles were injected as per investigator judgement. Participants were randomised into three groups: (1) intramuscular BoNT plus oral placebo; (2) oral TZD plus intramuscular placebo; (3) intramuscular placebo plus oral placebo. The primary outcome was the difference in change in wrist flexor modified Ashworth score (MAS) between groups. Other outcome measures included MAS at elbow and finger joints, Disability Assessment Scale (DAS) and adverse events (AE).Results:BoNT produced greater tone reduction than TZD or placebo in finger and wrist flexors at week 3 (p<0.001 vs TZD; p<0.02 vs placebo) and 6 (p = 0.001 vs TZD; p = 0.08 vs placebo), and greater improvement in the cosmesis domain of the DAS at week 6 (p<0.01). TZD was not superior to placebo in tone reduction at either time point (p⩾0.09). The incidence of AE related to study treatment was higher with TZD than in the BoNT (p<0.01) or placebo groups (p = 0.001).Conclusions:BoNT is safer and more effective than TZD in reducing tone and disfigurement in upper-extremity spasticity, and may be considered as first-line therapy for this disorder.

New trait technology incorporating 2,4-D resistance in soybean is dependent upon the ability of the plant to metabolize 2,4-D by the aryloxyalkanoate dioxygenase-12 protein (AAD-12). Our objectives were to determine AAD-12 expression during the daytime, throughout the leaf canopy, and before and after 2,4-D treatment for the events DAS-68416-4 and DAS-21606-3. Field experiments were conducted near Wanatah, IN in 2009 and Fowler, IN in 2009, 2010, and 2011. During the daytime, total AAD-12 expression was lowest between 12:30 and 15:30, averaging 161 ng cm−2, as compared to an average of 245 ng cm−2 in the morning and 243 ng cm−2 in the evening. The youngest fully emerged trifoliate in the DAS-68416-4 event had the highest AAD-12 expression, with means ranging from 369 to 390 ng cm−2, while the older leaves maintained a lower level of expression, 171 to 211 ng cm−2. The youngest leaves of event DAS-21606-3 had the highest level of AAD-12 expression (205 to 225 ng cm−2), while the level of AAD-12 was lower in older leaves (71 to 149 ng cm−2). In general, 2,4-D treatments did not reduce AAD-12 expression at 3, 7, 14, and 21 days after treatment; however, in a few instances AAD-12 expression was increased or decreased by 8 to 11% after 2,4-D treatment. Expression of AAD-12 was between 152 to 390 ng cm−2 for DAS-68416-4 and from 71 to 244 ng cm−2 for DAS-21606-3. Nomenclature: 2,4-D; Glycine max (L.) Merr., soybean.

Three types of HIV-associated neurocognitive disorders (HAND) exist that are distinguished by presence and severity of impairment in cognitive and everyday functioning. Although well-validated neurocognitive measures exist, determining impairment in everyday functioning remains a challenge. We aim to determine whether Self-Report measures of everyday functioning are as effective in characterizing HAND as Performance-Based measures. We assessed 674 HIV-infected participants with a comprehensive neurocognitive battery; 233 met criteria for a HAND diagnosis by having at least mild neurocognitive impairment. Functional decline was measured via Self-Report and Performance-Based measures. HAND diagnoses were determined according to published criteria using three approaches to assess functional decline: (1) Self-Report measures only, (2) Performance-Based measures only, and (3) Dual-method combining Self-Report and Performance-Based measures. The Dual-method classified the most symptomatic HAND, compared to either singular method. Singular method classifications were 76% concordant with each other. Participants classified as Performance-Based functionally impaired were more likely to be unemployed and more immunosuppressed, whereas those classified as Self-Report functionally impaired had more depressive symptoms. Multimodal methods of assessing everyday functioning facilitate detection of symptomatic HAND. Singular Performance-Based classifications were associated with objective functional and disease-related factors; reliance on Self-Report classifications may be biased by depressive symptoms. (JINS, 2012, 18, 79–88)

A variety of peripheral neuropathies are associated with human immunodeficiency virus (HIV) infection. Although the incidence of certain forms of neuropathy is increased in HIV infection, in other cases, the association may be fortuitous. Different forms of peripheral neuropathy occur with increased frequency at particular stages of HIV disease. For example, inflammatory demyelinating neuropathy (IDP) is often the first manifestation of HIV disease, when CD4 lymphocyte counts are relatively high. As immunosuppression progresses and HIV viral load becomes uncontrolled, the incidence of distal symmetrical polyneuropathy (DSP) increases. In advanced stages of HIV disease (CD4 count <50 cells/mm(3)), patients may develop opportunistic cytomegalovirus (CMV) nerve infection, which can present as progressive polyradiculopathy (PP) or mononeuropathy multiplex (MM). In addition to the neuromuscular disorders caused by HIV and its concomitant immunosuppression, the use of antiretroviral (ARV) drugs and other therapeutic agents in HIV disease is frequently limited by neuromuscular side effects. This paper will review the symmetrical forms of polyneuropathy that occur in association with HIV infection and nucleoside analogue therapy. The clinical, electrophysiologic, and pathologic features of these disorders will be described along with a discussion of theories of pathogenesis and results of treatment to date.

Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16–72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research Cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.

Observations from aircraft, an island station, and two research vessels are used to investigate the development of an elevated mixed layer or land plume over the Arabian sea during the Indian Ocean Experiment Intensive Field Phase 1999 (INDOEX) through air mass modification. Much of the transport of aerosols and gases occurs in this plume located above a well-mixed convective marine boundary layer with a depth of 800-1000 m. The depth of the land plume is approximately 2000 m with the peak ozone concentrations occurring near the centre of this land plume. Significant latitudinal variations in the concentration of ozone occur in the marine boundary layer and in the plume. Mean ozone concentrations in the land plume decreased with distance from the Indian coastline.

Human immunodeficiency virus (HIV)-associated dementia (HIVD) has been reported in up to 15% of HIV-infected adult patients. Although the pathogenesis of HIVD remains unclear, HIV probably plays an important role in the syndrome, as evidenced by the correlation between cerebrospinal fluid (CSF) HIV load and neuropsychological functioning. Although a large number of antiretrovirals are used to treat HIVD, zidovudine is the best studied. Zidovudine therapy has been associated with reduced levels of HIV RNA in CSF, fewer HIV-related changes in brain tissue at autopsy, and time-limited improvements in neurological function among AIDS and HIVD patients. More recent studies have investigated the penetration into CSF of other antiretrovirals, including protease inhibitors, and the clinical efficacy of abacavir in the treatment of dementia. HIV encephalopathy may occur in 30%–60% of children with AIDS and causes significant disability. Zidovudine has been associated with improved neuropsychological functioning in children with progressive encephalopathy, but optimum dosing levels, duration of effect, and prophylactic potential remain to be demonstrated.