Cofilin Activation in Peripheral CD4 T Cells of HIV-1 Infected Patients: A Pilot Study

Cofilin is an actin-depolymerizing factor that regulates actin dynamics critical for T cell migration and T cell activation. In unstimulated resting CD4 T cells, cofilin exists largely as a phosphorylated inactive form. Previously, we demonstrated that during HIV-1 infection of resting CD4 T cells, the viral envelope-CXCR4 signaling activates cofilin to overcome the static cortical actin restriction. In this pilot study, we have extended this in vitro observation and examined cofilin phosphorylation in resting CD4 T cells purified from the peripheral blood of HIV-1-infected patients. Here, we report that the resting T cells from infected patients carry significantly higher levels of active cofilin, suggesting that these resting cells have been primed in vivo in cofilin activity to facilitate HIV-1 infection. HIV-1-mediated aberrant activation of cofilin may also lead to abnormalities in T cell migration and activation that could contribute to viral pathogenesis.Department of Defense (National Defense Science and Engineering Fellowship); National Institute of Allergy and Infectious Diseases (AI069981

Reentrant Processing in Intuitive Perception

The process of perception requires not only the brain's receipt of sensory data but also the meaningful organization of that data in relation to the perceptual experience held in memory. Although it typically results in a conscious percept, the process of perception is not fully conscious. Research on the neural substrates of human visual perception has suggested that regions of limbic cortex, including the medial orbital frontal cortex (mOFC), may contribute to intuitive judgments about perceptual events, such as guessing whether an object might be present in a briefly presented fragmented drawing. Examining dense array measures of cortical electrical activity during a modified Waterloo Gestalt Closure Task, results show, as expected, that activity in medial orbital frontal electrical responses (about 250 ms) was associated with intuitive judgments. Activity in the right temporal-parietal-occipital (TPO) region was found to predict mOFC (∼150 ms) activity and, in turn, was subsequently influenced by the mOFC at a later time (∼300 ms). The initial perception of gist or meaning of a visual stimulus in limbic networks may thus yield reentrant input to the visual areas to influence continued development of the percept. Before perception is completed, the initial representation of gist may support intuitive judgments about the ongoing perceptual process

Spitzer Spectral Mapping of Supernova Remnant Cassiopeia A

We present the global distribution of fine structure infrared line emission in the Cassiopeia A supernova remnant using data from the Spitzer Space Telescope's Infrared Spectrograph. We identify emission from ejecta materials in the interior, prior to their encounter with the reverse shock, as well as from the post-shock bright ring. The global electron density increases by >~100 at the shock to ~10^4 cm^-3, providing evidence for strong radiative cooling. There is also a dramatic change in ionization state at the shock, with the fading of emission from low ionization interior species like [SiII], giving way to [SIV] and, at even further distances, high-energy X-rays from hydrogenic silicon. Two compact, crescent-shaped clumps with highly enhanced neon abundance are arranged symmetrically around the central neutron star. These neon crescents are very closely aligned with the "kick" direction of the compact object from the remnant's expansion center, tracing a new axis of explosion asymmetry. They indicate that much of the apparent macroscopic elemental mixing may arise from different compositional layers of ejecta now passing through the reverse shock along different directions.Comment: 9 pages, 8 figures, accepted by Ap

Research priorities for mitochondrial disorders: Current landscape and patient and professional views

Primary mitochondrial disorders encompass a wide range of clinical presentations and a spectrum of severity. They currently lack effective disease-modifying therapies and have a high mortality and morbidity rate. It is therefore essential to know that competitively-funded research designed by academics meets core needs of people with mitochondrial disorders and their clinicians. The Priority Setting Partnerships are an established collaborative methodology that brings patients, carers and families, charity representatives and clinicians together to try to establish the most pressing and unanswered research priorities for a particular disease. We developed a web-based questionnaire, requesting all patients affected by primary mitochondrial disease, their carers, and clinicians to pose their research questions. This yielded 709 questions from 147 participants. These were grouped into overarching themes including basic biology, causation, health services, clinical management, social impacts, prognosis, prevention, symptoms, treatment, and psychological impact. Following the removal of 'answered questions' the process resulted in a list of 42 discrete, answerable questions. This was further refined by web-based ranking by the community to 24 questions. These were debated at a face-to-face workshop attended by a diverse range of patients, carers, charity representatives and clinicians to create a definitive 'Top Ten of unanswered research questions for primary mitochondrial disorders'. These Top Ten questions related to understanding biological processes, including triggers of disease onset, mechanisms underlying progression and reasons for differential symptoms between individuals with identical genetic mutations; new treatments; biomarker discovery; psychological support; and optimal management of stroke-like episodes and fatigue

Epidemiology and Cost of Nosocomial Gastroenteritis, Avon, England, 2002–2003

Implementing control measures rapidly may be effective in controlling gastroenteritis outbreaks

Clinical audit of core podiatry treatment in the NHS

<p>Abstract</p> <p>Background</p> <p>Core podiatry involves treatment of the nails, corns and callus and also giving footwear and foot health advice. Though it is an integral part of current podiatric practice little evidence is available to support its efficacy in terms of research and audit data. This information is important in order to support the current NHS commissioning process where services are expected to provide data on standards including outcomes. This study aimed to increase the evidence base for this area of practice by conducting a multi-centre audit in 8 NHS podiatry departments over a 1-year period.</p> <p>Methods</p> <p>The outcome measure used in this audit was the Podiatry Health Questionnaire which is a self completed short measure of foot health including a pain visual analogue scale and a section for the podiatrist to rate an individual's foot health based on their podiatric problems. The patient questionnaire was completed by individuals prior to receiving podiatry care and then 2 weeks after treatment to assess the effect of core podiatry in terms of pain and foot health.</p> <p>Results</p> <p>1047 patients completed both questionnaires, with an age range from 26–95 years and a mean age of 72.9 years. The podiatrists clinical rating at baseline showed 75% of patients had either slight or moderate podiatric problems. The differences in questionnaire and visual analogue scores before and after treatment were determined according to three categories – <it>better, same, worse </it>and 75% of patients' scores either remained the same or improved after core podiatry treatment. A student t-test showed a statistical significant difference in pre and post treatment scores where P < 0.001, though the confidence interval indicated that the improvement was relatively small.</p> <p>Conclusion</p> <p>Core podiatry has been shown to sustain or improve foot health and pain in 75% of the patients taking part in the audit. Simple outcome measures including pain scales should be used routinely in podiatric practice to assess the affect of different aspects of treatments and improve the evidence base for podiatry.</p

Research priorities for mitochondrial disorders: current landscape and patient and professional views

Primary mitochondrial disorders encompass a wide range of clinical presentations and a spectrum of severity. They currently lack effective disease-modifying therapies and have a high mortality and morbidity rate. It is therefore essential to know that competitively-funded research designed by academics meets core needs of people with mitochondrial disorders and their clinicians. The Priority Setting Partnerships are an established collaborative methodology that brings patients, carers and families, charity representatives and clinicians together to try to establish the most pressing and unanswered research priorities for a particular disease. We developed a web-based questionnaire, requesting all patients affected by primary mitochondrial disease, their carers, and clinicians to pose their research questions. This yielded 709 questions from 147 participants. These were grouped into overarching themes including basic biology, causation, health services, clinical management, social impacts, prognosis, prevention, symptoms, treatment, and psychological impact. Following the removal of ‘answered questions’ the process resulted in a list of 42 discrete, answerable questions. This was further refined by web-based ranking by the community to 24 questions. These were debated at a face-to-face workshop attended by a diverse range of patients, carers, charity representatives and clinicians to create a definitive ‘Top Ten of unanswered research questions for primary mitochondrial disorders’. These Top Ten questions related to understanding biological processes, including triggers of disease onset, mechanisms underlying progression and reasons for differential symptoms between individuals with identical genetic mutations; new treatments; biomarker discovery; psychological support; and optimal management of stroke-like episodes and fatigue

A Trickle‐Down Model Of Abusive Supervision

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91132/1/j.1744-6570.2012.01246.x.pd

The current state-of-the-art of spinal cord imaging: methods.

A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small cross-sectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of "critical mass" of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research

The GAAS Metagenomic Tool and Its Estimations of Viral and Microbial Average Genome Size in Four Major Biomes

Metagenomic studies characterize both the composition and diversity of uncultured viral and microbial communities. BLAST-based comparisons have typically been used for such analyses; however, sampling biases, high percentages of unknown sequences, and the use of arbitrary thresholds to find significant similarities can decrease the accuracy and validity of estimates. Here, we present Genome relative Abundance and Average Size (GAAS), a complete software package that provides improved estimates of community composition and average genome length for metagenomes in both textual and graphical formats. GAAS implements a novel methodology to control for sampling bias via length normalization, to adjust for multiple BLAST similarities by similarity weighting, and to select significant similarities using relative alignment lengths. In benchmark tests, the GAAS method was robust to both high percentages of unknown sequences and to variations in metagenomic sequence read lengths. Re-analysis of the Sargasso Sea virome using GAAS indicated that standard methodologies for metagenomic analysis may dramatically underestimate the abundance and importance of organisms with small genomes in environmental systems. Using GAAS, we conducted a meta-analysis of microbial and viral average genome lengths in over 150 metagenomes from four biomes to determine whether genome lengths vary consistently between and within biomes, and between microbial and viral communities from the same environment. Significant differences between biomes and within aquatic sub-biomes (oceans, hypersaline systems, freshwater, and microbialites) suggested that average genome length is a fundamental property of environments driven by factors at the sub-biome level. The behavior of paired viral and microbial metagenomes from the same environment indicated that microbial and viral average genome sizes are independent of each other, but indicative of community responses to stressors and environmental conditions